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Genital Herpes

Genital herpes

The Herpes simplex virus infection (common names: herpes, cold sores) is a common, contagious, incurable, and in some cases sexually transmitted disease caused by a double-stranded DNA virus. Herpes is commonly known as "everybody's favourite STD". The infection can also affect the brain, in which case the consequent disease is called herpes simplex encephalitis.

HSV-1 and HSV-2

brain There are two main kinds of herpes simplex virus: type 1 (HSV-1) and type 2 (HSV-2). Although HSV-1 is generally considered to be associated with orofacial infection, and HSV-2 with genital infection, both types can affect any region of the body. There are some differences, however, in the infectivity and severity of infection — HSV-1 infections are more easily acquired and infections are more severe in the orofacial region and similar with HSV-2 in the genital region. HSV-2 infection is of particular concern because of the largely asymptomatic nature of the infection, and the shedding of infective virions even in asymptomatic individuals. (Koutsky et al., 1990; Wald et al., 2000)

HSV disease

The ways in which herpes infections manifest themselves vary tremendously among individuals. The following are general descriptions of the courses outbreaks may take in the oral and genital regions.

Orofacial infection

brain #Prodromal symptoms #Skin appears irritated #Sore or cluster of fluid-filled blisters appear #Lesion begins to heal, usually without scarring These infections may appear on the lips, nose Nasal herpes or in surrounding areas. The sores may appear to be either weeping or dry, and may resemble a pimple, insect bite, or large chickenpox lesion. Lesions typically heal after a few days to a week (or more), but this varies among individuals. In clinical practice herpes outbreaks are likely to be far more subtle than the illustration on this page of an outbreak about the eye.

Genital infection

#Prodromal symptoms #Sore appears #Lesion begins to heal, usually without scarring In men, the lesions may occur on the shaft of the penis, in the genital region, on the inner thigh, buttocks, or anus. In women, lesions may occur on or near the pubis, labia, clitoris, vulva, buttocks, or anus. This may require a very careful examination e.g. during delivery examination by use of a flashlight may be necessary. The appearance of herpes lesions and the experience of outbreaks in these areas varies tremendously among individuals. Herpes lesions on/near the genitals may look like cold sores. An outbreak may look like a paper cut, or chafing, or appear to be a yeast infection. Symptoms of a genital outbreak may include aches and pains in the area, discharge from the penis or vagina, and discomfort when urinating. Initial outbreaks are usually more severe than subsequent ones, and generally also involve flu-like symptoms and swollen glands for a week or so. Subsequent outbreaks tend to be periodic or episodic, typically occur four to five times a year, and can be triggered by stress, illness, fatigue, menstruation, and other changes. The virus sequesters in the nerve ganglia that serve the infected dermatome during non-eruptive periods, where it cannot be conventionally eliminated by the body's immune system.

Other skin infections

Other forms of herpes simplex infection are rarer, but well characterized, and are sometimes given distinctive names, such as herpes gladiatorum, a skin infection spread through wrestling and other sports involving close skin-to-skin contact. Herpetic sycosis is a herpes simplex infection of the beard area in men, which may occur after shaving through a cold sore. In rarer cases, it seems that herpetic sycosis can occur as a primary herpes simplex outbreak.

Herpes simplex encephalitis

Herpes simplex encephalitis is a very serious disorder, thought to be caused by transmission of the infection from a peripheral site by nerve cells. Without treatment, it results in rapid death in around 70% of cases. Even with the best modern treatment, it is fatal in around 20% of cases, and causes serious longterm neurological damage in over half the survivors. A small population (perhaps 20%) of survivors show little long term damage. It is most common in children and middle-aged adults. Although herpes simplex is by no means the most common cause of viral encephalitis (accounting for about 10% of cases in the US), because of the high risk associated with it if it is not treated, patients presenting with encephalitis symptoms are likely to be treated against this disorder without waiting for a positive diagnosis.

Neonatal herpes simplex

Neonatal HSV disease is a rare, but serious, consequence of vertical HSV transmission from mother to newborn child. Prospective active surveillance data indicates an incidence rate of 3.61 per 100,000 live births in Australia, with similar rates in the UK; but much lower than the USA. (Elliot & Rose, 2004; Jones, 2004) Preliminary studies indicates the epidemiology in Canada is closer to Europe than to America. The mortality rate from neonatal HSV disease is high (up to 25%) despite current interventions with antiviral therapies. Death results from disseminated HSV disease and/or HSV encephalitis in the newborn children.

Outbreak triggers

Many people with herpes have reported that stress, increased exposure to the sun, viral infections, facial injuries and eating foods high in arginine, such as chocolate, peanuts and walnuts, may increase the chance and severity of outbreaks.

Prevalence

The incidence of herpes simplex in the United States rose 30% between 1976 and 1994. Data from National Health and Nutrition Examination Surveys (NHANES) indicate an HSV-2 seroprevalence of 21.9% of the United States population. This rate was higher among women (25.9%) than men (17.8%). Independent risk factors for HSV-2 seropositivity were female sex, African American or Mexican-American ethnic background, older age, less education, poverty, cocaine use, and a greater lifetime number of sexual partners. (Fleming et al., 1997) If present trends in America continue, researchers estimate that 49 percent of women aged 15 to 39 will be infected with herpes simplex virus type 2 (HSV-2) versus 39 percent of males aged 15 to 39 by 2025. (Fisman, Lipsitch, Hook, and Goldie, Oct 2002). HSV-1, which is generally considered to be a less serious illness, actually afflicts the majority of the United States population. At the time of puberty, 50% of Americans already test positive for HSV-1 antibodies; over 80% test positive at age 50. (source [http://www.herpes.com/hsv1-2.html American Social Health Association])

Transmission

Herpes is contracted through direct skin contact (not necessarily in the genital area) with an infected person. The virus travels through tiny breaks in the skin or through moist areas, but symptoms may not appear for up to a month or more after infection. Transmission was thought to be most common during an active outbreak, however in the early 1980s scientists and doctors realized that the virus can be shed from the skin in the absence of symptoms. It is estimated that between 50 and 80% of new HSV-2 cases are from asymptomatic viral shedding. HSV asymptomatic shedding is believed to occur on 2.9% of days while on antiviral therapy, versus 10.8% of days without. Shedding is known to be more frequent within the first 12 months of acquiring HSV-2. There are some indications that some individuals may have much lower patterns of shedding, but evidence supporting this is not fully supported. Sex should always be avoided in the presence of symptomic lesions. Women are more susceptible to acquiring genital HSV-2 than men. On an annual basis, without the use of antivirals or condoms, the transmission risk from infected male to female is approximately 8-10%. This is believed to be due to the increased exposure of mucosal tissue to potential infection sites. Transmission risk from infected female to male is approximately 4-5% annually. Supressive antiviral therapy reduces these risks by 50%. Antivirals also help prevent the development of symptomatic HSV in infection scenarios by about 50%, meaning the infected partner will be seropositive but symptom free. Condom use also reduces the transmission risk by 50%. Condom use is much more effective at preventing male to female transmission than vice-versa. (Wald et al., 2001) The effects of combining antiviral and condom use is roughly additive, thus resulting in approximately a 75% combined reduction in annual transmission risk. It is important to note that these figures reflect experiences with subjects having frequently recurring genital herpes (>6 recurrences per year), subjects with low recurrence rates and those with no clinical manifestations were excluded from these studies.

Prevention

Condoms are the recommended way to prevent transmission of herpes simplex infection, as demonstrated in numerous studies. (Wald, et al., 2001; Casper & Wald, 2002) However, this is by no means completely effective. The effectiveness of this method is somewhat limited on a public health scale by the limited use of condoms in the community (de Visser et al., 2003); and on an individual scale because some blisters may not be covered by the condom. Abstinence, including from kissing/oral sex, is another effective way to prevent contracting or spreading this disease. When one partner has herpes simplex infection and the other doesn't, the use of valaciclovir, in conjunction with a condom, has been demonstrated to further decrease the chances of transmission to the uninfected partner, and the FDA approved this as a new indication for the drug in August 2003. Other measures that have been suggested include:
- the use of a lip protectant or lip gloss
- management of stress
- adequate sleep and nutrition
- avoidance of cross-infecting different sites on the body if HSV blisters are present

Future directions

The National Institutes of Health (NIH) in the United States is currently in the midst of phase III trials of a vaccine against HSV-2. The vaccine has only been shown to be effective for women who have never been exposed to HSV-1. Overall, the vaccine is approximately 48% effective in preventing HSV-2 seropositivity and about 78% effective in preventing symptomatic HSV-2. Assuming FDA approval, a commercial version of the vaccine is estimated to become available around 2008. There are indications that a carrageenan based gel may offer some protection against HSV-2 transmission by binding to the receptors on the herpes virus thus preventing the virus from binding to cells. Researchers have shown that a carrageenan-based gel effectively prevented HSV-2 infection at a rate of 85% in a mouse model. (Phillips & Zacharopoulos, 1997) There is an ongoing large-scale trial of the efficacy of a similar formulation on humans results are expected to be published in 2007.

Treatments

Pharmacotherapy

There are several prescription antiviral medications for controlling herpes outbreaks, including aciclovir (Zovirax), valaciclovir (Valtrex), famciclovir (Famvir), and penciclovir. Aciclovir was the original and prototypical member of this class and generic brands are now available at a greatly reduced cost. Valaciclovir and famciclovir are prodrugs of aciclovir and penciclovir respectively, with improved oral bioavailability. Valaciclovir has approximately 55% oral bioavailability, versus 20% for generic aciclovir. Famvir has approximately 75% oral bioavailability, versus 5% for generic penciclovir. Both aciclovir and penciclovir work by interfering with viral replication, effectively slowing the replication rate of the virus, and providing a greater opportunity for the immune reponse to intervene. Penciclovir's primary advantage over aciclovir is that it has a far longer cellular half-life, 10 hours (HSV-1) / 20 hours (HSV-2) versus 3 hours (HSV-1/2) for aciclovir. Famvir is currently about 33% more costly than Valtrex. Docosanol (Abreva) is another treatment that may be effective. Docosanol works by preventing the virus from fusing to cell membranes, thus barring entry into the cell for the virus. This may keep an outbreak contained to a smaller area than would otherwise be observed. Tromantadine is another antiviral drug effective against herpes. Non-prescription analgesics can reduce pain and fever during initial outbreaks. Aciclovir is the recommended antiviral for suppressive therapy to prevent transmission of herpes simplex to the neonate. The use of valaciclovir and famciclovir, while potentially improving treatment compliance and efficacy, are still undergoing safety evaluation in this context. (Leung & Sacks, 2003) There is evidence in mice that treatment with famciclovir, rather than aciclovir, during an initial outbreak can help lower the incidence of future outbreaks by reducing the amount of latent virus in the neural ganglia. This potential effect on latency over aciclovir drops to zero a few months post-infection. (Thackray & Field, 1996)

Availability of generic drugs

- Aciclovir is no longer under US patent protection, available in generic form
- Valaciclovir (GlaxoSmithKline) protected under US patent 4957924 protection expiring June 2009
- Famciclovir (Novartis) protected under US patent 5246937 protection expiring Sept 2010
- Penciclovir (GlaxoSmithKline) protected under US patent 5075445 protection expiring Sept 2010
- Docosanol (Avanir) protected under US patent 4874794 protection expiring April 2014

Unproven

Limited evidence suggests that low dose aspirin (125 mg daily) might be beneficial in patients with recurrent HSV infections. A small study of 21 volunteers with recurrent HSV indicated a significant reduction in duration of active HSV infections, milder symptoms, and longer symptom-free periods as compared to a control group. (Karadi, Karpati & Romics, 1998) A recent animal study found that aspirin inhibited thermal stress-induced ocular viral shedding of HSV-1, and a possible benefit in reducing recurrences. (Gebhardt, Varnell, & Kaufman, 2004) Aspirin is not recommended in persons under 18 years of age with herpes simplex due to the increased risk of Reye's syndrome. Cimetidine, a common component of heartburn medication, and probenecid have been shown to reduce the renal clearance of aciclovir. (De Bony, Tod, Bidault,Posner,and Rolan 2001) The study showed these compounds reduce the rate, but not the extent, at which valaciclovir is converted into aciclovir. Renal clearence of aciclovir was reduce by approximately 24% and 33% respectively. In addition, respective increases in the peak plasma concentration of acyclovir of 8% and 22% were observed. Due to the tendency of aciclovir to precipitate in renal tubules, combining these drugs should only occur under the supervision of a physician.

Complementary

Lysine

Lysine supplementation has been proposed as a complementary therapy for the prophylaxis and treatment of herpes simplex. Lysine supplementation is highly dose-dependent, with beneficial effects apparent only at doses exceeding 1000 mg per day. A small randomised controlled trial indicated a decrease in recurrence rates in nonimmunocompromised patients at a dose of 1248 mg of lysine monohydrochloride, but no effect at 624 mg daily. This study did not show any evidence of shortening the healing time compared to placebo. (McCune et al., 1984) Another small randomised controlled trial indicated the benefit of 3000 mg lysine daily for the reduction of occurrence, severity and healing time for recurrent HSV infection. (Griffith et al., 1987) Tissue culture studies have shown the suppression of viral replication when the lysine to arginine ratio in vitro favours lysine. The therapeutic consequence of this finding is unclear, but dietary arginine may affect the effectiveness of lysine supplementation. (Griffith et al., 1978) High doses of lysine (greater than 10 grams daily) are known to cause gastrointestinal adverse effects. Dyspepsia was reported in 3 of 114 subjects treated with L-lysine in one study. (Griffith et al, 1987) Prolonged and/or very high lysine doses may also have adverse effects on renal function, indeed lysine is contraindicated in lysine hypersensitivity and kidney or liver disease. (Anon., 2005) One patient, with a history of risk factors for renal impairment, developed tubulointerstitial nephritis (Fanconi's Syndrome) after taking lysine 3000 mg daily for approximately 5 years. (Lo et al., 1996)

Other

Lactoferrin, a component of whey protein, has been shown to have a synergistic effect with aciclovir against HSV in vitro. (Andersen, Jenssen & Gutteberg, 2003) The study used 50% lactoferrin concentrations. Milk contains about 1% whey protein which in turn contains about 1-2% lactoferrin, suggesting that simple milk or whey protein consumption is likely insufficient to provide similar benefits. The evidence for the effectiveness of zinc and Vitamin C supplementation is poor. (Anon, 2005). Other supplements with anecdotal evidence of benefits include monolaurin, vitamin A, vitamin B12, garlic, and echinacea. Daily multivitamin intake may be beneficial through maintenance of immune system health. High doses of vitamin A should not be taken in early pregnancy due to linkage with birth defects. Resveratrol, a compound in red wine, has been shown by researchers to prevent HSV replication in vitro by inhibiting a protein needed by the virus to replicate. Resveratrol alone was not considered potent enough by the researchers to be an effective treatment. (Docherty et al., 1999) A more recent in vivo study in mice showed the efficacy of topical resveratrol cream in preventing cutaneous HSV lesion formation. (Docherty et al., 2004) Research on a much more potent derivative of resveratol, named stil-5, is ongoing. There is no evidence that red wine consumption provides any similar benefits.

Long-term effects

The long-term effects of herpes are not well known, but the blisters may leave scars, and historically it was thought to contribute to the risk of cervical cancer in women. Subsequently, another virus, human papillomavirus (HPV), has been shown to be the cause of cervical cancer in women. Additionally, people with herpes are at a higher risk of HIV transmission because of open blisters. In newborns, however, herpes can cause serious damage: death, neurological damage, mental retardation, and blindness. Currently, there is no viable cure for herpes. The immune system is able to destroy active herpes virus particles but the herpes virus has the ability to hide from the immune system in an inactive (or latent) state. Current research suggests that this ability to hide may be achieved via modification to cellular enzyme histone deacetylases (HDACs), namely HDAC1 and HDAC2 (Poon, Liang, Roizman 2003). Hypothetically, by interfering with the HDAC enzymes' effectiveness, it may be possible to block the virus's ability to hide from the immune system, leading to a complete elimination of the virus by the immune system. Studies on the impact of HDAC inhibitors on viral latency are ongoing in the HIV arena.

Psychological and social effects

Discovering that a person has genital herpes can have a dramatic effect on that person's mental well being and sexual behaviour.

Quality of life issues

Upon diagnosis of genital herpes, people can experience a number of negative feelings related to the condition. One study (Vezina, Steben: 2001) surveyed people about their first episode of genital herpes. Findings showed proportions of people who experienced
- depression 82%
- fear of rejection 75%
- feeling of isolation 69%
- fear of being found out 55%
- self-destructive feelings 28% All of these proportions reduced over time. The impact of genital herpes included:
- partial or complete cessation of sexual activity
- total or partial loss of interest in sex
- decreased sexual pleasure
- sex life more inhibited and less spontaneous
- anxiety related to sexual desirability
- increased masturbation In order to improve the well-being of people with herpes, a number of support groups exist, both physically and with a presence on the Internet.

Disclosure to new partners

People with genital herpes are often hesitant to divulge that they have the virus to other people, especially new or potential sexual partners. Results from one study (Green et al., 2003) show that people are less likely to inform what they consider to be casual partners. In addition, the perception of the likely reaction is taken into account before making a decision about whether to inform a new partner. An event such as a couple moving in together was found to be the point when some people disclosed their status. The study showed people informed 62% of regular partners and 22% of casual partners, and was unrelated to the gender of the person. Strategies used when telling partners included keeping the issue "low key," choosing a relaxed environment and suggestions of the couple being tested jointly for a range of sexually transmitted infections. The ratio of positive reactions to negative reactions to disclosure was 22:4. Doctors at some hospitals and health clinics actually advise people not to tell their partners unless the partner is pregnant, reasoning that the psychological effects of herpes far outweigh the physical effects in adults. This advice is still controversial.

Myths

Some common myths and misconceptions about herpes are that it is fatal (only true for newborns, where it is rare, or if it infects the brain, which is again unusual), that it only affects the genital areas (it can affect any part of the body), that condoms are completely effective in preventing the spread of this disease, that it is transmittable only in the presence of symptoms, that it can make you sterile, that Pap smears detect herpes, and that only promiscuous people get it (it is so common that anyone having sex is at risk). There is a basis in fact that herpes could be transmitted via an inanimate object such as a toilet seat or wet towel but the conditions required for this kind of transmission (high heat, high moisture, and a vulnerable exposure site) make it extremely unlikely. Although there are no confirmed cases of this type of transmission, sharing a towel with somebody with active lesions should be avoided. There are many hoaxes claiming cures for HSV. None of these have been approved by the FDA and all evidence suggests that none work as claimed. Any cure claiming to eradicate the virus by preventing the virus from retreating to the neural ganglia is a hoax. The virus only travels into the neural ganglia once, at the time of primary infection. Once the virus is established in the nucleus of the neuron, it is there for life. All recurrences involve a unidirectional flow of newly replicated viral particles from within the neuron to the site of shedding. There are currently no treatments which are able to act against latent infection. Similarly, there are many claims made by proponents of "hyper-oxygenation" therapies, namely H2O2 and DMSO, that oxygen "kills" HSV infected cells. Although this is true in basis of fact, it is highly misleading. Oxygen in these forms becomes a free radical when absorbed in the body, in simple terms, it is destructive to all cellular structures, healthy or infected. This lack of a targeted delivery mechanism combined with the lack of an ability to target only infected cells implies that it is impossible for these therapies to have any benefit without causing much more damage to otherwise healthy cells.

Other herpes viruses

There are eight members of the herpes virus family that are known to cause human disease, including not only the Herpes Simplex viruses (HSV-1 and HSV-2), but also the varicella-zoster virus (VZV), Epstein-Barr virus (EBV), Kaposi's sarcoma-associated herpesvirus (KSHV), and the cytomegalovirus (CMV).

References

- Anon (2005). Herpes simplex virus oral - AltMedDex Protocols. In: Klasco RK (Ed). AltMedDex System. Greenwood Village (CO): Thomson Micromedex.
- Casper C, Wald A (2002). Condom use and the prevention of genital herpes acquisition. Herpes 9 (1), 10-14. PMID 11916494
- de Visser RO, Smith AM, Rissel CE, Richters J, Grulich AE (2003). Sex in Australia: safer sex and condom use among a representative sample of adults. Aust N Z J Public Health 27 (2), 223-9. PMID 14696715
- Docherty JJ, Fu MM, Stiffler BS, Limperos RJ, Pokabla CM, DeLucia AL (1999). Resveratrol inhibition of herpes simplex virus replication. Antiviral Res 43 (3), 145-55. PMID 10551373
- Docherty JJ, Smith JS, Fu MM, Stoner T, Booth T (2004). Effect of topically applied resveratrol on cutaneous herpes simplex virus infections in hairless mice. Antiviral Res 61 (1), 19-26. PMID 14670590
- Elliott E, Rose D (2004). Australian Paediatric Surveillance Unit. Reporting of communicable disease conditions under surveillance by the APSU, 1 January to 30 September 2003. Commun Dis Intell 28 (1), 90-1. PMID 15072162
- Fleming DT, McQuillan GM, Johnson RE, Nahmias AJ, Aral SO, Lee FK, et al. (1997). Herpes simplex virus type 2 in the United States, 1976 to 1994. New Engl J Med 337 (16), 1105-11. PMID 9329932
- Gebhardt BM, Varnell ED, Kaufman HE (2004). Acetylsalicylic acid reduces viral shedding induced by thermal stress. Curr Eye Res 29 (2-3), 119-25. PMID 15512958
- Green J, Ferrier S, Kocsis A et al., "Determinants of disclosure of genital herpes to partners". Sex. Transm. Inf. 2003;79:42-44 [http://sextrans.bmjjournals.com/cgi/content/full/79/1/42]
- Griffith RS, Norins AL, Kagan C (1978). A multicentered study of lysine therapy in Herpes simplex infection. Dermatologica 156 (5), 257-67. PMID 640102
- Griffith RS, Walsh DE, Myrmel KH, Thompson RW, Behforooz A (1987). Success of L-lysine therapy in frequently recurrent herpes simplex infection. Treatment and prophylaxis. Dermatologica 175 (4), 183-90. PMID 3115841
- Jones CA. (2004). Vaccines to prevent neonatal herpes simplex virus infection. Expert Rev Vaccines 3 (4), 363-4. PMID 15270635
- Karadi I, Karpati S, Romics L (1998). [http://www.annals.org/cgi/content/full/128/8/696-b Aspirin in the management of recurrent herpes simplex virus infection]. Ann Intern Med 128 (8), 696-7.
- Koutsky LA, Ashley RL, Holmes KK, Stevens CE, Critchlow CW, Kiviat N, et al. (1990). The frequency of unrecognized type 2 herpes simplex virus infection among women. Implications for the control of genital herpes. Sex Transm Dis 17 (2), 90-4. PMID 2163115
- Leung DT, Sacks SL (2003). Current treatment options to prevent perinatal transmission of herpes simplex virus. Expert Opin Pharmacother 4 (10), 1809-19. PMID 14521490
- Lo JC, Chertow GM, Rennke H, et al. (1996). Fanconi's syndrome and tubulointerstitial nephritis in association with l-lysine ingestion. Am J Kidney Dis 28 (4), 614-617.
- McCune MA, Perry HO, Muller SA, O'Fallon WM (1984). Treatment of recurrent herpes simplex infections with L-lysine monohydrochloride. Cutis 34 (4), 366-73. PMID 6435961
- Phillips DM, Zacharopoulos VR (1997). Vaginal formulations of carrageenan protect mice from herpes simplex virus infection. Clin Diagn Lab Immunol 4 (4), 465-68. PMID 9220165
- Thackray AM, Field HJ (1996). Differential effects of famciclovir and valaciclovir on the pathogenesis of herpes simplex virus in a murine infection model including reactivation from latency. J Infect Dis 173 (2), 291-9. PMID 8568288
- Vezina C, Steben M (2001). Genital Herpes: Psychosexual Impacts and Counselling The Canadian Journal of CME June 2001, 125-134
- Wald A, Zeh J, Selke S, Warren T, Ryncarz AJ, Ashley, R, et al. (2000). Reactivation of genital herpes simplex virus type 2 infection in asymptomatic seropositive persons. N Engl J Med 342 (12), 844-50. PMID 10727588
- Wald A, Langenberg AG, Link K, Izu AE, Ashley R, Warren T, et al. (2001). Effect of condoms on reducing the transmission of herpes simplex virus type 2 from men to women. JAMA 285 (24), 3100-6. PMID 11427138

External links

- [http://www.arhp.org/healthcareproviders/resources/stdis/index.cfm Sexually Transmitted Diseases/Infections Resource Center from the Association of Reproductive Health Professionals]
- [http://www.cdc.gov/std/Herpes/STDFact-Herpes.htm Center for Diseases Control Genital Herpes Fact Sheet]
- [http://www.journals.uchicago.edu/JID/journal/issues/v186nS1/020145/020145.text.html Genital Shedding of Herpes Simplex Virus among Men]
- [http://www.stdhelper.com/herpes-treatments.html Herpes Treatments]
- [http://www.fact-sheets.com/health/herpes_symptoms_treatment/ Genital Herpes: Symptoms and Treatment]
- [http://www.niaid.nih.gov/dmid/stds/herpevac/default.htm Herpevac Trial for Women]
- http://www.herpes-coldsores-treatment-pictures.com
- [http://www.ashastd.org The American Social Health Organization] Category:Sexually-transmitted diseases Category:Herpesviruses ja:単純ヘルペスウイルス

Virus

:This article is concerned with virus as a biological infectious particle; for other uses see virus (disambiguation). virus (disambiguation) A virus is a microscopic parasite that infects cells in biological organisms. Viruses are obligate intracellular parasites; they can reproduce only by invading and controlling other cells as they lack the cellular machinery for self-reproduction. The term virus usually refers to those particles that infect eukaryotes (multi-celled organisms and many single-celled organisms), whilst the term bacteriophage or phage is used to describe those infecting prokaryotes (bacteria and bacteria-like organisms lacking a nucleus). Typically these particles carry a small amount of nucleic acid (either DNA or RNA, but not both) surrounded by some form of protective coat consisting of proteins, lipids, glycoproteins or a combination. Importantly, viral genomes code not only for the proteins needed to package its genetic material, but for proteins needed by the virus during its life cycle (the term "life cycle" is used loosely here—see Living or non-living?).
Origins and Beginnings
The origins of viruses are not entirely clear and there may not be a single mechanism that can account for all viruses. Some of the smaller viruses that have only a few genes may have originated from host organisms. Their genetic material could have been derived from transferrable elements like plasmids or transposons. Viruses with large genomes may represent extremely reduced microbes which established symbiotic relations with host organisms, allowing the loss of some genes needed for existence independent of a host. Other infectious particles which are even simpler in structure than viruses include viroids, virusoids, and prions.
Size, structure, and anatomy
Virus particles comprise a nucleic acid genome that may be either DNA or RNA, single- or double-stranded, and positive or negative sense. This is surrounded (encapsidated) by a protective coat of protein called a capsid. The viral capsid may be either spherical or helical and is composed of proteins encoded by the viral genome. In helical viruses, the capsid protein (frequently called the nucleocapsid protein) binds directly to the viral genome. For example, in the case of the measles virus, one nucleocapsid protein binds every six bases of RNA to form a helix approximately 1.3 micrometers in length. This complex of protein and nucleic acid is called the nucleocapsid, and, in the case of the measles virus, is enclosed in a lipid "envelope" acquired from the host cell, in which virus-encoded glycoproteins are embedded. These are responsible for binding to and entering the host cell at the start of a new infection. Spherical virus capsids completely enclose the viral genome and do not generally bind as tightly to the nucleic acid as helical capsid proteins do. These structures can range in size from less than 20 nanometers up to 400 nanometers and are composed of viral proteins arranged with icosahedral symmetry. Icosahedral architecture is the same principle employed by R. Buckminster-Fuller in his geodesic dome, and it is the most efficient way of creating an enclosed robust structure from multiple copies of a single protein. The number of proteins required to form a spherical virus capsid is denoted by the "T-number" whereby 60t proteins are necessary. In the case of the hepatitis B virus, the T-number is 4, therefore 240 proteins assemble to form the capsid. As in the helical viruses, the spherical virus capsid may be enclosed in a lipid envelope, although frequently spherical viruses are not enveloped, and the capsid proteins themselves are directly involved in attachment and entry into the host cell. The complete virus particle is referred to as a virion. A virion is little more than a gene transporter, and components of the envelope and capsid provide the mechanism for injecting the viral genome into a host cell..
Replication
Because viruses are acellular and do not have their own metabolism, they must utilize the machinery and metabolism of the host to reproduce. Before a virus has entered a host cell, it is called a virion — a package of viral genetic material. Virions can be passed from host to host either through direct contact or through a vector, or carrier. Inside the organism, the virus can enter a cell in various ways. Bacteriophages—bacterial viruses—attach to the cell wall surface in specific places. Once attached, enzymes make a small hole in the cell wall, and the virus injects its DNA into the cell. Other viruses (such as HIV) enter the host via endocytosis, the process whereby cells take in material from the external environment. After entering the cell, the virus's genetic material begins the destructive process of causing the cell to produce new viruses. There are three different ways genetic information contained in a viral genome can be reproduced. The form of genetic material contained in the viral capsid, the protein coat that surrounds the nucleic acid, determines the exact replication process. Some viruses have DNA, which once inside the host cell is replicated by the host along with its own DNA. There are two different replication processes for viruses containing RNA. In the first process, the viral RNA is directly copied using an enzyme called RNA replicase. This enzyme then uses that RNA copy as a template to make hundreds of duplicates of the original RNA. A second group of RNA-containing viruses, called the retroviruses, uses the enzyme reverse transcriptase to synthesize a complementary strand of DNA so that the virus's genetic information is contained in a molecule of DNA rather than RNA. The viral DNA can then be further replicated using the resources of the host cell.
Outline
#Attachment, sometimes called absorption: The virus attaches to receptors on the host cell wall. #Injection: The nucleic acid of the virus moves through the plasma membrane and into the cytoplasm of the host cell. The capsid of a phage, a bacterial virus, remains on the outside. In contrast, many viruses that infect animal cells enter the host cell intact. #Replication: The viral genome contains all the information necessary to produce new viruses. Once inside the host cell, the virus induces the host cell to synthesize the necessary components for its replication. #Assembly: The newly synthesized viral components are assembled into new viruses. #Release: Assembled viruses are released from the cell and can now infect other cells, and the process begins again. When the virus has taken over the cell, it immediately causes the host to begin manufacturing the proteins necessary for virus reproduction. Some viruses, like herpes, cause the host to produce three kinds of proteins: early proteins, enzymes used in nucleic acid replication; late proteins, proteins used to construct the virus coat; and lytic proteins, enzymes used to break open the cell for viral exit. The final viral product is assembled spontaneously, that is, the parts are made separately by the host and are joined together by chance. This self-assembly is often aided by molecular chaperones, or proteins made by the host that help the capsid parts come together. The new viruses then leave the cell either by exocytosis or by lysis. Envelope-bound animal viruses cause the host's endoplasmic reticulum to make certain proteins, called glycoproteins, which then collect in clumps along the cell membrane. The virus is then discharged from the cell at these exit sites, referred to as exocytosis. On the other hand, bacteriophages must break open, or lyse, the cell to exit. To do this, the phages have a gene that codes for an enzyme called lysozyme. This enzyme breaks down the cell wall, causing the cell to swell and burst. The new viruses are released into the environment, killing the host cell in the process.
Lifeform debate
A virus makes use of existing host enzymes and other molecules of a host cell to create more virus particles (virions). Some viruses encode part or all of their own genome replication machinery and are not entirely reliant on host polymerases for replication of their genetic material. Such viruses can be targeted by antiviral drugs that specifically inhibit the virally encoded replicase molecule(s). Viruses rely on host cell ribosomes for the production of viral proteins and utilize several distinct strategies to make the host cell synthesize the viral proteins. For example, at least some +RNA viruses use Internal Ribosome Entry Site IRES segments to drive the translation from their genomic +RNA molecule. Viruses are neither unicellular nor multicellular organisms; they are somewhere between being living and non-living. Viruses have genes and show inheritance, but are reliant on host cells to produce new generations of viruses. Many viruses have similarities to complex molecules. Because viruses are dependent on host cells for their replication they are generally not classified as "living". Whether or not they are "alive", they are obligate parasites, and have no form which can reproduce independently of their host. Like most parasites, they have a specific host range, sometimes specific to one species (or even limited cell types of one species) and sometimes more general. Some viruses form by self-assembly of protein and nucleic acid molecules. These macromolecules are assembled within host cells from smaller organic compounds. Virus self-assembly has implications for the study of the origin of life. Some viruses also incorporate lipids from the host cell membrane when their core protein-nucleic acid complex buds from the surface of a host cell. Concerning whether viruses are alive or not, if the requirement for autonomous self-reproduction is abandoned, it can be argued strongly that viruses are indeed alive. Some small viruses are more efficient than most cellular life forms as their ratio of functions to working parts is so high. If viruses are alive then the prospect of creating artificial life is enhanced or at least the standards required to call something artificially alive are reduced.
Study and applications

Exploring basic cellular processes
Viruses are important to the study of molecular and cellular biology because they provide simple systems that can be used to manipulate and investigate the functions of cells. The study and use of viruses have provided valuable information about many aspects of cell biology. For example, viruses have further simplified the study of genetics and have deepened our understanding of the basic mechanisms of molecular genetics (DNA replication, transcription, RNA processing), Translation (genetics), protein transport, and immunology.
Genetic engineering
Geneticists regularly use viruses as vectors to introduce genes into cells that they are studying. Attempts to treat human diseases through the use of viruses as tools of genetic engineering is one goal of gene therapy.
Materials science and nanotechnology
Scientists at MIT have recently been able to use viruses to create metallic wires, and they have the potential to be used for binding to exotic materials, self-assembly, liquid crystals, solar cells, batteries, fuel cells, and many other interesting areas. The essential idea is to use a virus with a known protein on its surface. The location of the code for this protein is in a known location in the DNA, and by randomizing that sequence it can create a phage library of millions of different viruses, each with a different protein expressed on its surface. By using natural selection, one can then find a particular strain of this virus which has a binding affinity for a given material. For example, one can isolate a virus which has a high affinity for gold. Taking this virus and growing gold nanoparticles around it results in the gold nanoparticles being incorporated into the virus coat, resulting in a gold wire of precise length and shape with biological origins. Current thinking is that viruses will one day be created which can act as agents on behalf of bio-mechanical healing devices giving humans or other animals extended life.
Human viral diseases
Examples of diseases caused by viruses include the common cold, which is caused by any one of a variety of related viruses; smallpox; AIDS, which is caused by HIV; and cold sores, which are caused by herpes simplex. Other connections are being studied such as the connection of HHV-6 in organic neurological diseases such as Multiple Sclerosis and Chronic Fatigue Syndrome. Recently it has been shown that cervical cancer is caused at least partly by papillomavirus (which causes papillomas, or warts), representing the first significant evidence in humans for a link between cancer and an infective agent. There is current controversy over whether borna virus, previously thought of primarily as the causative agent of neurological disease in horses, could be responsible for psychiatric illness in humans. The relative ability of viruses to cause disease is described in terms of virulence. The ability of viruses to cause devastating epidemics in human societies has led to concern that viruses will be weaponized for biological warfare. Further concern was raised by the successful recreation of a virus in a laboratory. Much concern revolves around the smallpox virus, which has devastated numerous societies throughout history, and today is extinct in the wild. In fact, smallpox has been used in a crude form of biological warfare by British colonists against a tribe of Native Americans. This episode of biological warfare was part of a larger phenomenon of Native American populations being devastated by contagious diseases, particularly smallpox, brought to the Americas by European colonists. It is unclear how many Native Americans were killed by smallpox after the arrival of Columbus in the Americas, but it may have been very large. The damage done by this disease may have significantly aided European attempts to displace or conquer the native population. Jared Diamond argued in his book Guns, Germs, and Steel that highly contagious diseases develop in agricultural societies and regularly aid those societies when they expand into the territories of non-agricultural peoples. Of all types of virus, the most deadly are known as filovirus. The Filovirus group consists of Marburg, first discovered in 1967 in Marburg Germany, and ebola. Filovirus are long, worm-like virus particles that, in large groups, resemble a plate of noodles. As of April 2005, the Marburg virus is attracting widespread press attention for an outbreak in Angola. Beginning in October 2004 and continuing into 2005, the outbreak, which now appears to be coming under control, is the world's worst epidemic of any kind of hemorrhagic fever.
Laboratory diagnosis of pathogenic viruses
Detection and subsequent isolation of viruses from patients is a very specialised laboratory subject. Normally it requires the use of large facilities, expensive equipment, and highly trained specialists such as technicians, molecular biologists, and virologists. Often, this effort is undertaken by state and national governments and shared internationally through organizations like WHO.
Prevention and treatment of viral diseases
Because they use the machinery of their host cells to reproduce, viruses are difficult to kill. The most effective medical approaches to viral diseases, thus far, are vaccination to provide resistance to infection, and drugs that treat the symptoms of viral infections. Patients often ask for antibiotics, which are useless against viruses, and their misuse against viral infections is one of the causes of antibiotic resistance in bacteria. That said, sometimes, in life-threatening situations, the prudent course of action is to begin a course of antibiotic treatment while waiting for test results to determine whether the patient's symptoms are caused by a virus or a bacterial infection.
Etymology
Although the viruses were discovered by the Russian biologist Dmitry Ivanovsky in 1892, the name for them was coined later. The original word comes from the Latin virus referring to poison and other noxious things. Today it is used to describe the biological viruses discussed above and also as a metaphor for other parasitically-reproducing things, such as memes or computer viruses. The word virion or viron is used to refer to a single infective viral particle. The English plural form of virus is viruses. No reputable dictionary gives any other form, including such "reconstructed" Latin plural forms as viri (which actually means men). (No plural form appears in any extant Latin manuscript). (See plural of virus). The word does not have a traditional Latin plural because its original sense, poison is a mass noun like the English word furniture.
See also

- Horizontal gene transfer
- List of viruses
- Microbiology
- Prion
- Viral plaque
- Viroids
- Virology
- Virus classification
See also

- Wikipedia:WikiProject Viruses
- WikiSpecies:Virus
- Wiktionary:en:virus
References

- [http://www.virology.net/ All the Virology on the WWW]
- Radetsky, Peter (1994). The Invisible Invaders: Viruses and the Scientists Who Pursue Them. Backbay Books, ISBNs 0316732168 (hc), 0316732176 (pb).
- Theiler, Max and Downs, W. G. (1973). The Arthropod-Borne Viruses of Vertebrates: An Account of the Rockefeller Foundation Virus Program 1951-1970. Yale University Press.
-
- Chronic Active Human Herpesvirus-6 (HHV-6) Infection: A New Disease Paradigm - Joseph H. Brewer, M.D. http://www.plazamedicine.com/index.html
Numbered references
# Gelderblom, Hans R. (1996). [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mmed.chapter.2252 41. Structure and Classification of Viruses] in [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mmed Medical Microbiology] 4th ed. Samuel Baron ed. The University of Texas Medical Branch at Galveston. ISBN 0963117211 Category:Virology als:Virus (Medizin) ko:바이러스 ms:Virus ja:ウイルス simple:Virus

Disease

A disease is any abnormal condition of the body or mind that causes discomfort, dysfunction, or distress to the person affected or those in contact with the person. Sometimes the term is used broadly to include injuries, disabilities, syndromes, symptoms, deviant behaviors, and atypical variations of structure and function, while in other contexts these may be considered distinguishable categories. Pathology is the study of diseases. The subject of systematic classification of diseases is referred to as nosology. The broader body of knowledge about diseases and their treatments is medicine.

Syndromes, illness and disease

Medical usage sometimes distinguishes a disease, which has a known specific cause or causes (called its etiology), from a syndrome, which is a collection of signs or symptoms that occur together. However, many conditions have been identified, yet continue to be referred to as "syndromes". Furthermore, numerous conditions of unknown etiology are referred to as "diseases" in many contexts. Illness, although often used to mean disease, can also refer to a person's perception of their health, regardless of whether they in fact have a disease. A person without any disease may feel unhealthy and believe he has an illness. Another person may feel healthy and believe he does not have an illness even though he may have a disease such as dangerously high blood pressure which may lead to a fatal heart attack or stroke.

Transmission of disease

Some diseases, such as influenza, are contagious or infectious, and can be transmitted by any of a variety of mechanisms, including droplets from coughs and sneezes, by bites of insects or other vectors, from contaminated water or food, etc. Other diseases, such as cancer and heart disease are not considered to be due to infection, although micro-organisms may play a role.

Social significance of disease

The identification of a condition as a disease, rather than as simply a variation of human structure or function, can have significant social or economic implications. The controversial recognitions as diseases of post-traumatic stress disorder, also known as "shell shock"; repetitive motion injury or repetitive stress injury (RSI); and Gulf War syndrome has had a number of positive and negative effects on the financial and other responsibilities of governments, corporations and institutions towards individuals, as well as on the individuals themselves. The social implication of viewing aging as a disease could be profound, though this classification is not yet widespread. A condition may be considered to be a disease in some cultures or eras but not in others. Oppositional-defiant disorder, attention-deficit hyperactivity disorder, and, increasingly, obesity are conditions considered to be diseases in the United States and Canada today, but were not so-considered decades ago and are not so-considered in some other countries. Conversely, the number of people in the West who consider homosexuality to be a disease became widespread in the 20th century but has been decreasing in the last two decades. To consider a condition to be a disease can sometimes involve a negative social value judgement. Lepers were a group of afflicted individuals who were historically shunned and the term "leper" still evokes social stigma. Fear of disease can still be a widespread social phenomena, though not all diseases evoke extreme social stigma.

Other uses of the term

In biology, disease refers to any abnormal condition of an organism that impairs function. The term disease is often used metaphorically for disordered, dysfunctional, or distressing conditions of other things, as in disease of society.

External links

- [http://www.nlm.nih.gov/medlineplus/healthtopics.html Health Topics], MedlinePlus descriptions of most diseases, with access to current research articles.
- [http://www.cdc.gov/health/default.htm Center for Disease Control Health Topics A-Z], fact sheets about many common diseases
- [http://rarediseases.about.com/ Rare/Orphan Diseases]
- [http://www.national-health.org/rarediseases/ National Organization for Rare Disorders] Extensive, useful information on rare diseases.
- [http://www.merck.com/pubs/mmanual/sections.htm The Merck Manual], detailed description of most diseases, freely searchable online. Category:Diseases Category:Medical terms als:Krankheit zh-min-nan:Pīⁿ ms:Penyakit ja:病気 simple:Disease th:โรค

Brain

In the anatomy of animals, the brain, or encephalon (Greek for "in the head"), is the higher, supervisory center of the nervous system. The term 'brain' is typically used in connection with vertebrate nervous systems, and less often with regard to the nervous system of invertebrates. In the latter, neural control is performed by collections of ganglia. The brain is an extremely complex organ: the human brain is a collection of 100 billion neurons, each linked with up to 25,000 others. This huge number of interconnecting neurons, often referred to as a neural ensemble, is what makes the brain intelligent—enabling humans to analyze sensory signals, control the body, and think. In most animals, the brain is located in the head, close to the primary sensory apparatus and the mouth. Hippocrates considered the brain to be the seat of thought, while Aristotle believed it to be a cooling system for the blood. Today the study of the mind and brain consists of Neuroscience, the field of biology that studies the brain at its various levels of organization (from single neurons to functional systems such as visual system, auditory system, motor system and others); and psychology, the study of the cognition that arises from the neural function of the brain. Attempts have also been made to directly "read" the brain, which has been accomplished in a rudimentary manner through a brain-computer interface. In recent years, several institutions and bodies have undertaken research on recreating the neural structure of the brain with aim to produce human-like cognition and intelligence in computers. The brain controls and coordinates most movement, behavior and homeostatic body functions (such as heartbeat, blood pressure, fluid balance and body temperature). The brain is responsible for cognition, emotion, memory, motor learning and other kinds of learning. However, many behaviors, such as simple reflexes and basic locomotion, can be executed under spinal cord control alone.

The importance of the brain

The brain in animals

Three groups of animals, with some exceptions, have notably complex brains: the arthropods (insects and crustaceans), the cephalopods (octopuses, squid, and similar mollusks), and the craniates (vertebrates and their cousins). The brain of arthropods and cephalopods arises from twin parallel nerve cords that extend through the body of the animal. In arthropod, the brain consists of a central brain with three divisions and large optical lobes behind each eye for visual processing. eye The brain of craniates develops from the anterior section of a single dorsal nerve cord, which later becomes the spinal cord. In craniates, the brain is protected by the bones of the skull. In vertebrates, increasing complexity in the cerebral cortex correlates with height on the phylogenetic and evolutionary tree. Primitive vertebrates, like fish, reptiles, and amphibians have cortices with fewer than six layers of neurons, a structure known as allocortex (also named heterotypic cortex) (Martin, 1996). More complex vertebrates such as mammals have developed a six-layered neocortex (other terms: homotypic cortex, neocortex, neopallium), in addition to having some parts of the brain that are allocortex (Martin, 1996). In mammals, increasing convolutions of the brain, called gyri, are characteristic of animals with more advanced brains. These convolutions evolved to provide a larger surface area for a greater number of neurons, while keeping the volume of the brain compact enough to fit inside the skull.

The human brain

The structure of the human brain is different from that of other animals in several significant ways. These differences have allowed for many abilities over and above those of other animals, such as advanced cognitive skills. Human encephalization is especially pronounced in the neocortex, the most complex part of the cerebral cortex. The proportion of the human brain that is devoted to the neocortex—and the most advanced part within it, the prefrontal cortex—is larger than in all other animals. Humans enjoy unique neural capacities, but much of the human neuroarchitecture is shared with ancient species. Basic systems that alert the nervous system to stimulus, that sense events in the environment, and that monitor the condition of the body are similar to those of the most basic vertebrates. The neural circuitry underlying human consciousness includes both the advanced neocortex and protypical structures of the brain stem. The human brain also has a a million billion synaptic connections, making it one of the most densely connected network systems in the known universe; however, more complex structures may exist.

Pathology of the brain

The loss of function in the brain fulfills some definitions of death. Injuries to the brain tend to affect large areas of the organ, sometimes causing major deficits in intelligence, memory and control of the body. Head trauma, caused, for example, by vehicle and industrial accidents, is a leading cause of death in youth and middle age. In these cases, more damage is typically caused by resultant swelling (edema) than by the impact itself. Stroke, caused by the blockage of blood vessels in the brain, is another major cause of death from brain damage. Other problems in the brain can be more accurately classified as diseases rather than injuries. Neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, motor neurone disease, and Huntington's disease, are caused by the gradual death of individual neurons, leading to decrements in movement control, memory, and cognition. Currently, only the symptoms of these diseases can be treated, but stem cell research may offer a cure. Mental illness, such as clinical depression, schizophrenia, bipolar disorder, and post-traumatic stress disorder, are brain diseases that impact on the personality and typically on other aspects of mental and somatic function. These disorders may be treated by psychiatric therapy, by pharmaceutical intervention, or by a combination of treatments; therapeutic effectiveness varies significantly among individuals. pharmaceutical Some infectious diseases affecting the brain are caused by viral and bacterial infection(s). Infection of the meninges, the membrane that covers the brain, can lead to meningitis. Bovine spongiform encephalopathy (also known as mad cow disease), is deadly in cattle and is linked to prions. Kuru is a similar prion-borne degenerative brain disease affecting humans. Both are linked to the ingestion of neural tissue, and may be an evolutionary defense against cannibalism. Viral or bacterial causes have been substantiated in multiple sclerosis, Parkinson's disease, Lyme disease, encephalopathy and encephalomyelitis. Some brain disorders are congenital. Tay-Sachs disease, Fragile X syndrome, Down syndrome, and Tourette syndrome are all linked to genetic and chromosomal errors. Malfunctions in the embryonic development of the brain can be caused by genetic factors, by drug use, and disease during a mother's pregnancy.

Other matters

Some philosophers consider that "brain" is synonymous with "mind", while others (such as strong AI theorists) believe that the mind is analogous to software and the brain to hardware. This issue—related to the mind-body problem—and many other issues, are the subjects of the area of the philosophy of mind. Questions asked in this field typically relate to the nature of consciousness and whether non-human animals are conscious beings. Computer scientists have produced computer systems called neural networks, loosely based on the structure of neuron connections in the brain. Artificial intelligence seeks to replicate brain function—although not necessarily brain mechanisms—but as yet is an immature science. Creating algorithms to mimic a biological brain is extremely difficult because the brain is not a static arrangement of circuits, but a network of vastly interconnected neurons that are constantly changing their connectivity and sensitivity. More recent work in both neuroscience and artificial intelligence models the brain using the mathematical tools of chaos theory and dynamical systems. Brain activity can be detected by electrodes, raising the possibility of "brain-computer interface". The reverse path has been demonstrated: brain implants have been used to generate artificial hearing and (crude and experimental) artificial vision for deaf and blind people; brain pacemakers are now commonly used to regulate brain activity in conditions such as Parkinson's disease. Both of these avenues of research are confronted with potentially serious ethical implications. For example, by placing electrodes in the brain and using a remote control, researchers have been able to remotely control the movements of a rat, combining commands of what to do with the stimulation of the brain pleasure centers. This raises the possibility of creating an electronically controlled biological "ratbot" that could be used in dangerous circumstances.

The biology of the brain

Despite the variance of the species in which the brain is found there are many common features in its cellular make-up, its structure and its function. On a cellular level, the brain is composed of two classes of cell, neurons and glia, both of which contain several different cell types which perform different functions. Interconnected neurons form neural networks (or neural ensembles). These networks are similar to man-made electrical circuits in that they contain circuit elements (neurons) connected by biological wires (nerve fibers). Of course, these do not form simple one-to-one electrical circuits (as is the case in many man-made circuits), neurons typically connect to at least a thousand other neurons. These highly specialized circuits make up systems which are the basis of perception, action and higher cognitive function. The brain contains anatomical and functional divides. In mammals, the most obvious partitioning of the brain is into the cerebrum (Latin for "brain", a large, anterior part that consists of two convoluted hemispheres and deep nuclei), cerebellum (Latin for "small brain", a smaller, structure behind the cerebrum with two rippled hemispheres and deep cerebellar nuclei), and brain stem (an elongated structure connecting the brain to the spinal cord). These parts are further divided into hemispheres, lobes, gyri, cortices, cytoarchitectonic and functional areas, nuclei, layers, fiber tracks and so forth. In summary, the chemical and electrical impulses continually passing through the cells of the brain produce all control, action and cognitive function in the body.

Histology

lobe Neurons, the cells that generate action potentials and convey them to other cells, constitute the chief class of brain cells. In each particular brain area, input (or afferent) neurons, output (or efferent) neurons and interneurons are typically found. Input neurons are recipients of projections from other brain areas. Output neurons project to the other areas. Interneurons are the neurons which do not leave the area. In addition to neurons, the brain contains glial cells in the proportion roughly 10 glial cells to every neuron; these are traditionally seen to perform supportive roles to neurons and fill out the space between them (hence its name, Greek for 'glue'). Most types of glia in the brain (and the rest of the central nervous system) are present in the entire nervous system, exceptions include oligodendrocytes which insulate neural axons (a role performed by Schwann cells in the peripheral nervous system). Oligosaccharides are the defining factor between white matter and grey matter in the brain—white matter is composed of myelinated (insulated) axons, whereas grey matter contains mostly cell soma, dendrites and unmyelinated portions of axons and glia and a smaller proportion of myelinated axons. In mammals, the brain also contains a certain amount of connective tissue called the meninges which is a system of membranes that separate the skull from the brain. The three-layered covering is made of, from the outside in, dura mater, arachnoid and pia mater (the latter two are connected and thus often considered as a single layer, the pia-arachnoid). Below the arachnoid is the subarachnoid space which contains cerebrospinal fluid which protects the nervous system. Blood vessels enter the central nervous system through the perivascular space above the pia mater. A blood-brain barrier protects the brain from unwanted substances that might enter it through the blood. The brain is suspended in cerebrospinal fluid, which circulates between layers of the meninges and through cavities in the brain called ventricles. It is important both chemically (metabolism) and mechanically (shock-prevention).

Anatomy

Although the histology of the brain is common to all those who have one, the structural anatomy is not. Apart from the general nature of the brain to order into lobes and suchforth, the lobes into which it has evolved are not common across the vertebrate/invertebrate divide. There are further dissimilarities within invertebrates, though vertebrates tend to share certain commonalities.

Invertebrates

In insects, the brain can be divided into four parts, the optical lobes, the protocerebrum, the deutocerebrum, and the tritocerebrum. The optical lobes are positioned behind each eye and process visual stimuli (Butler, 2000). The protocerebrum contains the mushroom bodies, which respond to smell, and the central body complex. The deutocerebrum includes the antennal lobes, which are similar to the mammalian olfactory bulb, and the mechanosensory neuropils which receive information from touch receptors on the head and antennae. The antennal lobes of flies and moths are quite complex. In cephalopods, the brain is divided into two regions: the supraesophageal mass and the subesophageal mass. These parts are divided by the animal's esophagus. The supra- and subesophageal masses are connected to each other on either side of the esophagus by the basal lobes and the dorsal magnocellular lobes. The large optic lobes are sometimes not considered to be part of the brain proper since the optic lobes anatomically separate from the brain and are joined to the brain by the optic stalks. However, the optic lobes perform much of the visual processing and can be functionally considered to be a part of the brain.

Vertebrates

In vertebrates, a gross division into three major parts is used: hindbrain (medulla oblongata and metencephalon), midbrain (mesencephalon) and forebrain (diencephalon and telencephalon). Varied taxonomies have been used by assorted schools at various times in history for the study of diverse species. An anterior part of the telencephalon called the cerebrum makes up the largest section of the mammalian brain and in humans, its surface has many deep fissures (sulci) and convolutions (gyri), giving a wrinkled appearance to the brain. In most vertebrates the metencephalon is the highest integration center in the brain, whereas in mammals this role has been adopted by the cerebrum. Behind (or in humans, below) the cerebrum is the cerebellum, a convoluted structure whose neural circuitry is often compared with crystal structure. Cerebellum participates in the control of movement. The cerebellum attaches to the hindbrain in a structure called the pons. The cerebrum and the cerebellum consist each of two halves (hemispheres). The corpus callosum connects the two hemispheres of the cerebrum. An outgrowth of the telencephalon called the olfactory bulb is a major structure in many animals, but in humans and other primates, it is relatively small. Vertebrate nervous systems are distinguished by encephalization and bilateral symmetry. Encephalization refers to the tendency for more complex organisms to gain a larger-size brains through evolutionary time. Larger vertebrates develop a complex of layered, networked and convoluted grey matter and white matter. Grey matter refers to tissue mostly comprised of neurons and can be found on the surface of cerebral cortex, as well as in clusters called nuclei deep within the brain. White matter refers to axons and their surrounding myelin insulation, which gives this tissue its white color. White matter is found in bundles of fibers known as tracts which connect the different parts of the brain. In modern species most closely related to the first vertebrates, brains are covered with gray matter that has a three-layer structure. Their brains also contain deep brain nucleus and fiber tracks forming the white matter. Most regions of the human cerebral cortex have six layers of neurons, a structure known as neocortex.

Brain Regions in Vertebrates

According to the hierarchy based on embryonic and evolutionary development, chordate brains are composed of the following regions:
- RHOMBENCEPHALON (Greek for "rhomboid brain")
- Myelencephalon (Greek for "brain marrow", also called medulla oblongata which means "long marrow" in Latin)
- Metencephalon (Greek for "after the brain"; also called hindbrain)
- pons
- cerebellum
- MESENCEPHALON (Greek for "middle brain", also called midbrain)
- tectum
- midbrain tegmentum
- substantia nigra
- crus cerebri (also called cerebral peduncles and pedunculus cerebri)
- PROSENCEPHALON
- Diencephalon (Greek for "brain in between")
- thalamus
- hypothalamus (Greek for "under the thalamus")
- pituitary gland
- epithalamus
- pineal gland
- Telencephalon (Greek for "end brain", i.e. the most rostral part of the brain; also called forebrain)
- TELENCEPHALON NUCLEI
- putamen
- caudate nucleus
- putamen
- globus pallidus
- amygdala
- CEREBRAL CORTEX
- Archipallium (Greek for "first cloak", i.e. cortex that developed first; also called archeocortex)
- hippocampus
- Paleopallium (Greek for "ancient cloak"; also called "paleocortex")
- priform(olfactory) cortex
- parahippocampal gyrus
- Neopallium (Greek for "new cloak"; also called "paleocortex"; also called neocortex and isocortex)
- frontal lobe
- temporal lobe
- parietal lobe
- occipital lobe
- insula
- cingulate cortex In addition, the brain is often subdivided into the following major parts:
- BRAINSTEM
- Medulla
- Pons
- Midbrain
- CEREBELLUM
- Cerebellar cortex
- Cerebellar nuclei
- BASAL GANGLIA (some midbrain nuclei, such as substantia nigra are usually considered as basal ganglia)
- Striatum (caudate nucleus and putamen)
- Globus pallidus
- HIPPOCAMPUS
- AMYGDALA
- THALAMUS
- HYPOTHALAMUS
- CEREBRAL CORTEX Yet alternative classifications arrange brain areas into functional systems:
- Limbic system
- Sensory systems
- Visual system
- Olfactory system
- Gustatory system
- Auditory system
- Somatosensory system
- Motor system
- Associative areas

Function

Associative areas Vertebrate brains receive signals through nerves arriving from the sensors of the organism, interpret those signals and formulate reactions based on built-in programs and learned experiences. A similarly extensive nerve network delivers signals from a brain to control muscles throughout a body. Anatomically, the majority of afferent and efferent nerves (with the exception of cranial nerves) are connected to the spinal cord, which then transfers the signals to the brain. Sensory input is processed by the brain to recognize danger, find food, identify potential mates and perform more sophisticated functions. Visual, touch, and auditory sensory pathways of vertebrates are routed to specific nuclei of the thalamus and then to regions of the cerebral cortex that are specific to each sensory system: the visual system, the auditory system and the somatosensory system. Olfactory pathways are routed to the olfactory bulb, then to various parts of the olfactory system. Taste is routed through the brainstem and then to other portions of the gustatory system. To control movement, the brain has several parallel systems of muscle control. The motor system controls voluntary muscle movement, aided by motor areas of the cerebral cortex, the cerebellum and the basal ganglia — the system that eventually projects to the spinal cord. Nuclei in the brainstem control many involuntary muscle functions such as heartrate and breathing. In addition, many automatic acts (simple reflexes, locomotion) can be controlled by the spinal cord alone. Brains also produce hormones that can influence organs and glands elsewhere in a body - conversely, brains also react to hormones produced elsewhere in the body. In mammals, most of these hormones are released into the circulatory system by a structure called the pituitary gland. It is hypothesized that developed brains derive consciousness from interaction among numerous systems within the brain. Cognitive processing in mammals occurs in the cerebral cortex but relies on mid-brain and limbic functions as well, especially those of the thalamus and hippocampus. Among "younger" (in an evolutionary sense) vertebrates, advanced processing involves progressively rostral (forward) regions of the brain. Hormones, incoming sensory information, and cognitive processing performed by the brain determine the brain state. Stimulus from any source can trigger a general arousal process that focuses cortical operations to processing of the new information. Cognitive priorities are constantly shifted by a variety of factors, such as hunger, fatigue, beliefs, unfamiliar information or threats. The simplest dichotomy related to processing of threats is the fight-or-flight response mediated by the amygdala, among other structures.

The study of the brain

Fields of study

Several areas of science specifically study the brain. Neuroscience seeks to understand the nervous system, including the brain, from a biological perspective. Psychology seeks to understand behavior and the brain. The terms neurology and psychiatry usually refer to medical applications of neuroscience and psychology, respectively. Cognitive science seeks to unify neuroscience and psychology with other fields that concern themselves with the brain, such as computer science (in Artificial intelligence and similar fields) and philosophy.

Methods of observation

Each method for observing activity in the brain has its advantages and drawbacks. Electrophysiology, in which wire electrodes are implanted in the brain, allows scientists to record the electrical activity of individual neurons or fields of neurons, but since it requires invasive surgery, this is a technique usually reserved for lab animals. By placing electrodes on the scalp, electroencephalography (EEG) measures brain waves, which are the mass changes in electrical current from the cerebral cortex, but can only detect changes over large areas of the brain and very little sub-cortical activity. Functional magnetic resonance imaging (fMRI) measures changes in blood flow in the brain, but the activity of neurons is not directly measured, nor can it be distinguished whether this activity is inhibitory or excitatory. Similarly, a PET (Positron Emission Tomography) Scan, is able to monitor glucose intake in different areas within the brain which is correlated the level of activity in that region. Behavioral tests can measure symptoms of disease and mental performance, but only provide indirect measurements of brain function and may not be practical in all animals. Finally, post-mortem analysis of the brain allows for the study of anatomy and protein expression patterns, but is only possible after the human or animal is dead.

History

Ancient Greeks had differing views on the function of the brain. Hippocrates believed the brain to be the seat of intelligence, but Aristotle held that the brain was a cooling mechanism for the blood, while the heart was the seat of intelligence. He reasoned that humans are more rational than the beasts because they have a proportionally larger brain to cool their hot-bloodedness (Bear, 2001). During the Roman Empire, the anatomist Galen dissected the brains of sheep. He concluded that since the cerebellum was hard on touch, it must control the muscles, while since the cerebrum was soft, it must be where the senses were processed. Galen further theorized that the brain functioned by movement of fluids through the ventricles (Bear, 2001). In the Age of Reason, René Descartes espoused a fluid mechanical view of the brain similar to Galen's theories. However, Descartes thought that although this explanation was adequate to explain the brain functions of animals, the higher mental functions of humans were accomplished by the soul. This theoretical separation of the mind and brain became known as the mind-body problem (Bear, 2001). In the mid-1600s, however, great progress in describing the anatomy of the brain was achieved with the works of English anatomist Thomas Willis and Flemish anatomist Vesalius. They dispelled many of the notions of Galen and Descartes and discovered many facts about the macro structure of the brain of animals and humans. In the 1700s, Luigi Galvani showed that electrically stimulating the sciatic nerve of a dissected frog caused movement of the attached muscle. His experiments led scientists away from the fluid mechanical theory of the brain and toward an electrical theory. In the 19th century, Galvani's work led to the development of research in bioelectricity and to the discovery of the membrane potential and action potential by researchers such as Emil du Bois-Reymond. The scientists of the 1800s debated whether areas of the brain corresponded to specific functions or if the brain functioned as a whole (the "aggregate field theory"). Jean Pierre Flourens championed the aggregate field theory in opposition to the pseudoscience of phrenology, founded by Franz Joseph Gall. However, the work of Paul Pierre Broca, Karl Wernicke, and Korbinian Brodmann eventually helped to show that areas of the brain had specific functions, though some functions were repeated, an idea known as parallel distributed processing (Kandel, 2001). As the 20th century approached, the anatomical works of Santiago Ramon y Cajal and Camillo Golgi laid the foundation for the study of individual neurons in the brain. Charles Scott Sherrington and Edgar Douglas Adrian furthered the study of neurons with the new techniques of electrodes and the electroencephalogram (EEG). Neurotransmitters were discovered and investigated by a number of scientists, including Otto Loewi, Henry Hallett Dale, Arvid Carlsson and many others. Modern Neuroscience experiences rapid development. The scientists use a variety of approaches to study the brain at different levels — from the molecules to systems. Extensive knowledge has been accumulated about the electrophysiological properties of different types of neurons and their responsiveness to neurotransmitters. Recordings from the brain of awake, behaving animals pioneered by Edward Evarts help to decode neuronal firing during different behaviors and cognitive processes. Miguel Nicolelis introduce multielectrode recording techniques which led to creation of brain-computer interfaces. Rapidly developing brain imaging allows scientists to study the brain in living humans and animals in ways that their predecessors could not.

The brain as a food

Like most other internal organs, the brain can serve as nourishment. For example, in the Southern United States canned pork brain in gravy can be purchased for consumption as food. This form of brain is often fried with scrambled egg to produce the famous "Eggs n' Brains". The brain of animals also features in the cuisine of France such as in the dish tête de veau, or head of calf. Although it might consist only of the outer meat of the skull and jaw, the full meal includes the brain, tongue and glands (the latter form being the favorite food of president Jacques Chirac). Similar delicacies from around the world include Mexican tacos de sesos (tacos made with cattle brain) and squirrel brain in the US South. The Anyang tribe of Cameroon practiced a tradition in which a new chief would consume the brain of a hunted gorilla while another senior member of the tribe would eat the heart. Consuming the brain and other nerve tissue of animals is not without its risks. The first problem is that the brain is made up of 60% fat due to the myelin (which by itself is 70% fat) insulating the axons of neurons and glia. As an example, a 5 oz. (0.14 kg) can of "Pork Brains in Milk Gravy", a single serving, contains 3500 milligrams of cholesterol, 1170% of our recommended daily intake. More importantly, humans can contract fatal transmissible spongiform encephalopathies such as Creutzfeldt-Jakob disease and other (prion diseases), as well as Bovine Spongiform Encephalopathy (colloquially known as "mad cow" disease) through the consumption of the infected nerve tissue of cattle and other animals - However, "there is no evidence that people can get mad cow disease from eating muscle meat". Another prion disease called kuru has been traced to a mourning ritual among the Fore people of Papua New Guinea in which those close to the dead would eat their brain to create a sense of immortality. Some archaeological evidence suggests that the mourning rituals of European neanderthals also involved the consumption of the brain. The practice of eating another human's brain has been depicted by Hollywood in Hannibal (film) and countless zombie movies. It is not only humans who eat the brains of other animals. The two species of chimpanzee, though generally vegetarian, are known to eat the brains of monkeys to obtain fat in their diet.

External links

- [http://www.stanford.edu/group/hopes/basics/braintut/ab0.html Brain Tutorial]
- [http://brainmuseum.org/ Comparative Mammalian Brain Collection]
- [http://www.rmcybernetics.com/science/cybernetics/ai_vision_perception_brain.htm RMCybernetics - The Brain and Artificial Intelligence]
- [http://braininfo.rprc.washington.edu BrainInfo for Neuroanatomy]
- [http://faculty.washington.edu/chudler/neurok.html Neuroscience for kids]
- [http://3dscience.com/advancedsearch.asp?stS=brain&cboMatch=Any&selectcategory=0&txtMinPrice=&txtMaxPrice= Free Brain Medical Clip Art].
- [http://purl.net/net/neurowiki neuroscience wiki]
- [http://www.brainmaps.org/ BrainMaps.org], interactive high-resolution digital brain atlas based on scanned images of serial sections of both primate and non-primate brains

References

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Notes

The following are the sources for individual facts, statistics and information included in the article:
- Statistic from page 161 of Basic Histology: Text and Atlas, 10th ed. by L.C. Junqueira, and J. Carneiro.
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- Category:Central nervous system Category:Cerebrum ja:脳 ko:뇌 simple:Brain th:สมอง

Prodromal

A Prodromal symptom is an early symptom indicating the onset of an attack or a disease.

Blister

A blister or bulla is a defense mechanism of the human body. It consists of a pool of lymph and other bodily fluids beneath the upper layers of the skin. It may be formed in response to burns or friction, and helps to repair damage to the skin. If a blister is punctured, it forms an open wound and must be bandaged. If a blister is associated with sub-dermal bleeding, it may partially fill with blood, forming an unpleasant blood blister. Blistering is a distinguishing characteristic of second degree burns. Certain autoimmune diseases feature extensive blistering. These include pemphigus and pemphigoid. Blistering also occurs as part of foodborne illness with Vibrio vulnificus (seafood). The class of chemical weapons known as vesicants acts by causing blisters (often within in the respiratory tract). Mustard gas and lewisite are examples of such agents.

External links

- [http://www.ehow.com/how_3365_care-blister.html How to Care for a Blister] Category:Dermatology

Penis

The penis (plural penises) is in addition to the scrotum one of the external male sexual organs. Other terms for it are: the (male) member or - for the erect state - the phallus. The penis is the male reproductive organ and for mammals additionally serves as the external male organ of urination. The penis is homologous to the female clitoris and in the theory of evolution, it originated from the same embryonic structure.

Linguistics

Etymology

The word is derived from the Latin word for tail, also used to describe the organ, "penis". The Latin word "phallus" (from the Greek "phallos") is sometimes used to describe the penis, though the word originally was used to describe images, pictoral or carved, of the penis [http://www.etymonline.com/index.php?search=penis&searchmode=none]. Some derive the Latin word penis from earlier
- pesnis, and the Greek word peos = "penis" from earlier
- pesos.

Synonyms

For a far more exhaustive and multi-lingual thesaurus, see the entry on [http://en.wiktionary.org/wiki/WikiSaurus:penis WikiSaurus].

The human penis

The human penis differs from those of some other mammals. It has no baculum, or erectile bone; instead it relies entirely on engorgement with blood to reach it

Genital herpes

HSV-1 and HSV-2

HSV disease

Orofacial infection

Genital infection

Other skin infections

Herpes simplex encephalitis

Neonatal herpes simplex

Outbreak triggers

Prevalence

Transmission

Prevention

Future directions

Treatments

Pharmacotherapy

Availability of generic drugs

Unproven

Complementary

Lysine

Other

Long-term effects

Psychological and social effects

Quality of life issues

Disclosure to new partners

Myths

Other herpes viruses

References

External links

Virus

Origins and Beginnings

Size, structure, and anatomy

Replication

Outline

Lifeform debate

Study and applications

Exploring basic cellular processes

Genetic engineering

Materials science and nanotechnology

Human viral diseases

Laboratory diagnosis of pathogenic viruses

Prevention and treatment of viral diseases

Etymology

See also

See also

References

Numbered references

Disease

Syndromes, illness and disease

Transmission of disease

Social significance of disease

Other uses of the term

See also

External links

Brain

The importance of the brain

The brain in animals

The human brain

Pathology of the brain

Other matters

The biology of the brain

Histology

Anatomy

Invertebrates

Vertebrates

Brain Regions in Vertebrates

Function

The study of the brain

Fields of study

Methods of observation

History

The brain as a food

External links

Related topics

References

Notes

Prodromal

Blister

See also

External links

Penis