The that makes up genes consists of 2 long intertwined strands, each consisting of a sequence of 4 different chemicals called nucleotide bases. These 4 bases are adenine, thymine, cytosine, and guanine (often abbreviated to A, T, C, and G). The sequence of these bases along the strands makes up the genetic code.... genetic code
In the ?rst, the information is transcribed from DNA on to a molecule of mRNA. In the second, the messenger RNA-intermediary transports the information to the protein-manufacturing centres of the cell where the information is translated from the linear sequence of codons in the RNA into a linear sequence of amino acids which are concurrently converted into protein. (See also GENES.)... rna
Both HIV-1 and HIV-2 are predominantly sexually transmitted and both are associated with secondary opportunistic infections. However, HIV-2 seems to result in slower damage to the immune system. HIV-1 is known to mutate rapidly and has given rise to other subtypes.
HIV is thought to have occurred in humans in the 1950s, but whether or not it infected humans from another primate species is uncertain. It became widespread in the 1970s but its latency in causing symptoms meant that the epidemic was not noticed until the following decade. Although it is a sexually transmitted disease, it can also be transmitted by intravenous drug use (through sharing an infected needle), blood transfusions with infected blood (hence the importance of e?ective national blood-screening programmes), organ donation, and occupationally (see health-care workers, below). Babies born of HIV-positive mothers can be infected before or during birth, or through breast feeding.
Although HIV is most likely to occur in blood, semen or vaginal ?uid, it has been found in saliva and tears (but not sweat); however, there is no evidence that the virus can be transmitted from these two body ?uids. There is also no evidence that HIV can be transmitted by biting insects (such as mosquitoes). HIV does not survive well in the environment and is rapidly destroyed through drying.
Prevalence At the end of 2003 an estimated 42 million people globally were infected with HIV – up from 40 million two years earlier. About one-third of those with HIV/AIDS are aged 15–24 and most are unaware that they are carrying the virus. During 2003 it is estimated that 5 million adults and children worldwide were newly infected with HIV, and that 3 million adults and children died. In Africa in 2003,
3.4 million people were newly infected and 2.3 million died, with more than 28 million carrying the virus. HIV/AIDS was the leading cause of death in sub-Saharan Africa where over half of the infections were in women and 90 per cent of cases resulted from heterosexual sex. In some southern African countries, one in three pregnant women had HIV.
In Asia and the Paci?c there were 1.2 million new infections and 435,000 deaths. The area with the fastest-growing epidemic is Eastern Europe, especially the Russian Federation where in 2002 around a million people had HIV and there were an estimated 250,000 new infections, with intravenous drug use a key contributor to this ?gure. Seventy-?ve per cent of cases occurred in men, with male-to-male sexual transmission an important cause of infection, though heterosexual activity is a rising cause of infection.
At the end of 2002 the UK had an estimated 55,900 HIV-infected adults aged between 15 and 59. More than 3,600 individuals were newly diagnosed with the infection in 2000, the highest annual ?gure since the epidemic started
– in 1998 the ?gure was 2,817 and in 1999 just over 3,000 (Department of Health and Communicable Disease Surveillance Centre). The incidence of AIDS in the UK has declined sharply since the introduction of highly active antiretroviral therapy (HAART) and HIV-related deaths have also fallen: in 2002 there were 777 reported new AIDS cases and 395 deaths, compared with 1,769 and 1,719 respectively in 1995. (Sources: UNAIDS and WHO, AIDS Epidemic Update, December 2001; Public Health Laboratory Services AIDS and STD Centre Communicable Disease Surveillance and Scottish Centre for Infection and Environmental Health, Quarterly Surveillance Tables.)
Poverty is strongly linked to the spread of AIDS, for various reasons including lack of health education; lack of e?ective public-health awareness; women having little control over sexual behaviour and contraception; and, by comparison with the developed world, little or no access to antiretroviral drugs.
Pathogenesis The cellular target of HIV infection is a subset of white blood cells called T-lymphocytes (see LYMPHOCYTE) which carry the CD4 surface receptor. These so-called ‘helper T-cells’ are vital to the function of cell-mediated immunity. Infection of these cells leads to their destruction (HIV replicates at an enormous rate – 109) and over the course of several years the body is unable to generate suf?cient new cells to keep pace. This leads to progressive destruction of the body’s immune capabilities, evidenced clinically by the development of opportunistic infection and unusual tumours.
Monitoring of clinical progression It is possible to measure the number of viral particles present in the plasma. This gives an accurate guide to the likely progression rate, which will be slow in those individuals with fewer than 10,000 particles per ml of plasma but progressively more rapid above this ?gure. The main clinical monitoring of the immune system is through the numbers of CD4 lymphocytes in the blood. The normal count is around 850 cells per ml and, without treatment, eventual progression to AIDS is likely in those individuals whose CD4 count falls below 500 per ml. Opportunistic infections occur most frequently when the count falls below 200 per ml: most such infections are treatable, and death is only likely when the CD4 count falls below 50 cells per ml when infection is developed with organisms that are di?cult to treat because of their low intrinsic virulence.
Simple, cheap and highly accurate tests are available to detect HIV antibodies in the serum. These normally occur within three months of infection and remain the cornerstone of the diagnosis.
Clinical features Most infected individuals have a viral illness some three weeks after contact with HIV. The clinical features are often non-speci?c and remain undiagnosed but include a ?ne red rash, large lymph nodes, an in?uenza-like illness, cerebral involvement and sometimes the development of opportunistic infections. The antibody test may be negative at this stage but there are usually high levels of virus particles in the blood. The antibody test is virtually always positive within three months of infection. HIV infection is often subsequently asymptomatic for a period of ten years or more, although in most patients progressive immune destruction is occurring during this time and a variety of minor opportunistic infections such as HERPES ZOSTER or oral thrush (see CANDIDA) do occur. In addition, generalised LYMPHADENOPATHY is present in a third of patients and some suffer from severe malaise, weight loss, night sweats, mild fever, ANAEMIA or easy bruising due to THROMBOCYTOPENIA.
The presentation of opportunistic infection is highly variable but usually involves either the CENTRAL NERVOUS SYSTEM, the gastrointestinal tract or the LUNGS. Patients may present with a sudden onset of a neurological de?cit or EPILEPSY due to a sudden onset of a STROKE-like syndrome, or epilepsy due to a space-occupying lesion in the brain – most commonly TOXOPLASMOSIS. In late disease, HIV infection of the central nervous system itself may produce progressive memory loss, impaired concentration and mental slowness called AIDS DEMENTIA. A wide variety of opportunistic PROTOZOA or viruses produces DYSPHAGIA, DIARRHOEA and wasting. In the respiratory system the commonest opportunistic infection associated with AIDS, pneumonia, produces severe shortness of breath and sometimes CYANOSIS, usually with a striking lack of clinical signs in the chest.
In very late HIV infection, when the CD4 count has fallen below 50 cells per ml, infection with CYTOMEGALOVIRUS may produce progressive retinal necrosis (see EYE, DISORDERS OF) which will lead to blindness if untreated, as well as a variety of gastrointestinal symptoms. At this stage, infection with atypical mycobacteria is also common, producing severe anaemia, wasting and fevers. The commonest tumour associated with HIV is Kaposi’s sarcoma which produces purplish skin lesions. This and nonHodgkin’s lymphoma (see LYMPHOMA), which is a hundred times more frequent among HIV-positive individuals than in the general population, are likely to be associated with or caused by opportunistic viral infections.
Prevention There is, as yet, no vaccine to prevent HIV infection. Vaccine development has been hampered
by the large number of new HIV strains generated through frequent mutation and recombination.
because HIV can be transmitted as free virus and in infected cells.
because HIV infects helper T-cells – the very cells involved in the immune response. There are, however, numerous research pro
grammes underway to develop vaccines that are either prophylactic or therapeutic. Vaccine-development strategies have included: recombinant-vector vaccines, in which a live bacterium or virus is genetically modi?ed to carry one or more of the HIV genes; subunit vaccines, consisting of small regions of the HIV genome designed to induce an immune response without infection; modi?ed live HIV, which has had its disease-promoting genes removed; and DNA vaccines – small loops of DNA (plasmids) containing viral genes – that make the host cells produce non-infectious viral proteins which, in turn, trigger an immune response and prime the immune system against future infection with real virus.
In the absence of an e?ective vaccine, preventing exposure remains the chief strategy in reducing the spread of HIV. Used properly, condoms are an extremely e?ective method of preventing exposure to HIV during sexual intercourse and remain the most important public-health approach to countering the further acceleration of the AIDS epidemic. The spermicide nonoxynol-9, which is often included with condoms, is known to kill HIV in vitro; however, its e?ectiveness in preventing HIV infection during intercourse is not known.
Public-health strategies must be focused on avoiding high-risk behaviour and, particularly in developing countries, empowering women to have more control over their lives, both economically and socially. In many of the poorer regions of the world, women are economically dependent on men and refusing sex, or insisting on condom use, even when they know their partners are HIV positive, is not a straightforward option. Poverty also forces many women into the sex industry where they are at greater risk of infection.
Cultural problems in gaining acceptance for universal condom-use by men in some developing countries suggests that other preventive strategies should also be considered. Microbicides used as vaginal sprays or ‘chemical condoms’ have the potential to give women more direct control over their exposure risk, and research is underway to develop suitable products.
Epidemiological studies suggest that male circumcision may o?er some protection against HIV infection, although more research is needed before this can be an established public-health strategy. Globally, about 70 per cent of infected men have acquired the virus through unprotected vaginal sex; in these men, infection is likely to have occurred through the penis with the mucosal epithelia of the inner surface of the foreskin and the frenulum considered the most likely sites for infection. It is suggested that in circumcised men, the glans may become keratinised and thus less likely to facilitate infection. Circumcision may also reduce the risk of lesions caused by other sexually transmitted disease.
Treatment AIDS/HIV treatment can be categorised as speci?c therapies for the individual opportunistic infections – which ultimately cause death – and highly active antiretroviral therapy (HAART) designed to reduce viral load and replication. HAART is also the most e?ective way of preventing opportunistic infections, and has had a signi?cant impact in delaying the onset of AIDS in HIV-positive individuals in developed countries.
Four classes of drugs are currently in use. Nucleoside analogues, including ZIDOVUDINE and DIDANOSINE, interfere with the activity of the unique enzyme of the retrovirus reverse transcriptase which is essential for replication. Nucleotide analogues, such as tenofovir, act in the same way but require no intracellular activation. Non-nucleoside reverse transcriptase inhibitors, such as nevirapine and EFAVIRENZ, act by a di?erent mechanism on the same enzyme. The most potent single agents against HIV are the protease inhibitors, such as lopinavir, which render a unique viral enzyme ineffective. These drugs are used in a variety of combinations in an attempt to reduce the plasma HIV viral load to below detectable limits, which is achieved in approximately 90 per cent of patients who have not previously received therapy. This usually also produces a profound rise in CD4 count. It is likely, however, that such treatments need to be lifelong – and since they are associated with toxicities, long-term adherence is di?cult. Thus the optimum time for treatment intervention remains controversial, with some clinicians believing that this should be governed by the viral load rising above 10,000 copies, and others that it should primarily be designed to prevent the development of opportunistic infections – thus, that initiation of therapy should be guided more by the CD4 count.
It should be noted that the drug regimens have been devised for infection with HIV-1; it is not known how e?ective they are at treating infection with HIV-2.
HIV and pregnancy An HIV-positive woman can transmit the virus to her fetus, with the risk of infection being particularly high during parturition; however, the risk of perinatal HIV transmission can be reduced by antiviral drug therapy. In the UK, HIV testing is available to all women as part of antenatal care. The bene?ts of antenatal HIV testing in countries where antiviral drugs are not available are questionable. An HIV-positive woman might be advised not to breast feed because of the risks of transmitting HIV via breastmilk, but there may be a greater risk associated with not breast feeding at all. Babies in many poor communities are thought to be at high risk of infectious diseases and malnutrition if they are not breast fed and may thus be at greater overall risk of death during infancy.
Counselling Con?dential counselling is an essential part of AIDS management, both in terms of supporting the psychological wellbeing of the individual and in dealing with issues such as family relations, sexual partners and implications for employment (e.g. for health-care workers). Counsellors must be particularly sensitive to culture and lifestyle issues. Counselling is essential both before an HIV test is taken and when the results are revealed.
Health-care workers Health-care workers may be at risk of occupational exposure to HIV, either through undertaking invasive procedures or through accidental exposure to infected blood from a contaminated needle (needlestick injury). Needlestick injuries are frequent in health care – as many as 600,000 to 800,000 are thought to occur annually in the United States. Transmission is much more likely where the worker has been exposed to HIV through a needlestick injury or deep cut with a contaminated instrument than through exposure of mucous membranes to contaminated blood or body ?uids. However, even where exposure occurs through a needlestick injury, the risk of seroconversion is much lower than with a similar exposure to hepatitis C or hepatitis B. A percutaneous exposure to HIV-infected blood in a health-care setting is thought to carry a risk of about one infection per 300 injuries (one in 1,000 for mucous-membrane exposure), compared with one in 30 for hepatitis C, and one in three for hepatitis B (when the source patient is e-antigen positive).
In the event of an injury, health-care workers are advised to report the incident immediately where, depending on a risk assessment, they may be o?ered post-exposure prophylaxis (PEP). They should also wash the contaminated area with soap and water (but without scrubbing) and, if appropriate, encourage bleeding at the site of injury. PEP, using a combination of antiretroviral drugs (in a similar regimen to HAART – see above), is thought to greatly reduce the chances of seroconversion; it should be commenced as soon as possible, preferably within one or two hours of the injury. Although PEP is available, safe systems of work are considered to o?er the greatest protection. Double-gloving (latex gloves remove much of the blood from the surface of the needle during a needlestick), correct use of sharps containers (for used needles and instruments), avoiding the resheathing of used needles, reduction in the number of blood samples taken from a patient, safer-needle devices (such as needles that self-blunt after use) and needleless drug administration are all thought to reduce the risk of exposure to HIV and other blood-borne viruses. Although there have been numerous cases of health-care workers developing HIV through occupational exposure, there is little evidence of health-care workers passing HIV to their patients through normal medical procedures.... aids/hiv
To allow it to ful?l its vitally important function as the carrier of genetic information in living cells, DNA has the following properties. It is stable, so that successive generations of species maintain their individual characteristics, but not so stable that evolutionary changes cannot take place. It must be able to store a vast amount of information: for example, an animal cell contains genetic information for the synthesis of over a million proteins. It must be duplicated exactly before each cell division to ensure that both daughter cells contain an accurate copy of the genetic information of the parent cells (see GENETIC CODE).... dna
Habitat: Native to tropical Southeast Asia; distributed throughout India; also planted in public parks.
English: Emblic, Indian gooseberry.Ayurvedic: Aaamalaki, Aaamalaka, Dhaatri, Kaayasthaa, Amoghaa, Amritaphala, Amla, Aaamalaa, Dhaatriphala, Vayasyaa, Vrshya, Shiva, Hattha.Unani: Aamalaa, Amlaj.Siddha/Tamil: Nellikkaai, Nelli.Action: Fruit—antianaemic, anabolic, antiemetic, bechic, astringent, antihaemorrhagic, antidiarrhoeal, diuretic, antidiabetic, carminative, antioxidant. Used in jaundice, dyspepsia, bacillary dysentery, eye trouble and as a gastrointestinal tonic. Juice with turmeric powder and honey is prescribed in diabetes insipidus. Seed—antibilious, antiasthmatic. Used in bronchitis. Bark—astringent. Leaf—juice is given in vomiting.
A decoction of powdered pericarp is prescribed for paptic ulcer.Key application: As an antacid. (Indian Herbal Pharmacopoeia.).The fruit is an important source of vitamin C, minerals and amino acids. The edible fruit tissue contains protein concentration threefold and vitamin C (ascorbic acid) concentration 160-fold than those of apple. The fruit also contains considerably higher concentration of most minerals and amino acids than apple.The fruit gave cytokinine-like substances identified as zeatin, zeatin ribo- side and zeatin nucleotide; suspension culture gave phyllembin. Phyllem- bin exhibits CNS depressant and spasmolytic activity, potentiates action of adrenaline and hypnotic action of Nembutal.The leaves contain gallic acid (10.8 mg/g dry basis), besides ascorbic and music acid. The methanol extract of the leaves is found to be effective in rat paw inflammation.The bark contains tannin identified as mixed type of proanthocyanidin.The fruit contains superoxide dis- mutase 482.14 units/g fresh weight and exhibits antisenescent (anti-aging) activity. Fruit, juice, its sediment and residue are antioxidant due to gallic acid. EtOH (50%) extract—antiviral.Aqueous extract of the fruit increases cardiac glycogen level and decreases serum GOT, GPT and LDH in rats having induced myocardial necrosis.Preliminary evidence suggests that the fruit and its juice may lower serum cholesterol, LDL, triglycerides and phospholipids without affecting HDL levels and may have positive effect on atherosclerosis. (Eur J clin Nutr, 42, 1988, 939-944; PhytotherRes, 14, 2000, 592-595.)An aqueous extract of the fruit has been reported to provide protection against radiation-induced chromosomal damage in both pre-and postirradiation treatment. The fruit is reported to enhance natural killer cell activity and antibody dependent cellular cytotoxicity in mice bearing Dalton's lymphoma ascites tumour. The extract of the fruit and ascorbic acid prevented hepatotoxic and nephrotoxic effects induced by lead and aluminium. The toxicity could be counteracted to a great extent by the fruit extract than by an amount of ascorbic acid alone equivalent to that contained in fruits. (The fruit can be used as a dietary supplement to counteract prolonged exposure to metals in population in industrial areas.)The fruits are reported to activate trypsin (proteolytic enzyme) activity.The fruits can be used as coagulant in the treatment of water and can purify low turbidity water.The fruits can be consumed safely all round the year.Dosage: Fresh fruit—10-20 g; pulp juice—5-10 ml. (API Vol. I.)... emblica officinalisBen: Amlaki
Guj: AmbalaMal,Tam: NelliKas: AonlaImportance: Indian gooseberry or emblic myrobalan is a medium sized tree the fruit of which is used in many Ayurvedic preparations from time immemorial. It is useful in haemorrhage, leucorrhaea, menorrhagia, diarrhoea and dysentery. In combination with iron, it is useful for anaemia, jaundice and dyspepsia. It goes in combination in the preparation of triphala, arishta, rasayan, churna and chyavanaprash. Sanjivani pills made with other ingredients is used in typhoid, snake-bite and cholera. The green fruits are made into pickles and preserves to stimulate appetite. Seed is used in asthma, bronchitis and biliousness. Tender shoots taken with butter milk cures indigestion and diarrhoea. Leaves are also useful in conjunctivitis, inflammation, dyspepsia and dysentery. The bark is useful in gonorrhoea, jaundice, diarrhoea and myalgia. The root bark is astringent and is useful in ulcerative stomatitis and gastrohelcosis. Liquor fermented from fruit is good for indigestion, anaemia, jaundice, heart complaints, cold to the nose and for promoting urination. The dried fruits have good effect on hair hygiene and used as ingredient in shampoo and hair oil. The fruit is a very rich source of Vitamin C (600mg/100g) and is used in preserves as a nutritive tonic in general weakness (Dey, 1980).Distribution: Indian gooseberry is found through out tropical and subtropical India, Sri Lanka and Malaca. It is abundant in deciduous forests of Madhya Pradesh and Darjeeling, Sikkim and Kashmir. It is also widely cultivated.Botany: Phyllanthus emblica Linn. syn. Emblica officinalis Gaertn. belongs to Euphorbiaceae family. It is a small to medium sized deciduous tree growing up to 18m in height with thin light grey, bark exfoliating in small thin irregular flakes. Leaves are simple, many subsessile, closely set along the branchlets, distichous light green having the appearance of pinnate leaves. Flowers are greenish yellow in axillary fascicles, unisexual; males numerous on short slender pedicels; females few, subsessile; ovary 3-celled. Fruits are globose, 1-5cm in diameter, fleshy, pale yellow with 6 obscure vertical furrows enclosing 6 trigonous seeds in 2-seeded 3 crustaceous cocci. Two forms Amla are generally distinguished, the wild ones with smaller fruits and the cultivated ones with larger fruits and the latter are called ‘Banarasi’(Warrier et al, 1995).Agrotechnology: Gooseberry is quite hardy and it prefers a warm dry climate. It needs good sunlight and rainfall. It can be grown in almost all types of soils, except very sandy type. A large fruited variety “Chambakad Large“ was located from the rain shadow region of the Western Ghats for cultivation in Kerala. Amla is usually propagated by seeds and rarely by root suckers and grafts. The seeds are enclosed in a hard seed coat which renders the germination difficult. The seeds can be extracted by keeping fully ripe fruits in the sun for 2-3 days till they split open releasing the seeds. Seeds are soaked in water for 3-4 hours and sown on previously prepared seed beds and irrigated. Excess irrigation and waterlogging are harmful. One month old seedlings can be transplanted to polythene bags and one year old seedlings can be planted in the main field with the onset of monsoon. Pits of size 50 cm3 are dug at 6-8m spacing and filled with a mixture of top soil and well rotten FYM and planting is done. Amla can also be planted as a windbreak around an orchard. Irrigation and weeding are required during the first year. Application of organic manure and mulching every year are highly beneficial. Chemical fertilisers are not usually applied. No serious pests or diseases are generally noted in this crop. Planted seedlings will commence bearing from the 10th year, while grafts after 3-4 years. The vegetative growth of the tree continues from April to July. Along with the new growth in the spring, flowering also commences. Fruits will mature by December-February. Fruit yield ranges from 30-50kg/tree/year when full grown (KAU,1993).Properties and activity: Amla fruit is a rich natural source of vitamin C. It also contains cytokinin like substances identified as zeatin, zeatin riboside and zeatin nucleotide. The seeds yield 16% fixed oil, brownish yellow in colour. The plant contains tannins like glucogallia, corilagin, chebulagic acid and 3,6-digalloyl glucose. Root yields ellagic acid, lupeol, quercetin and - sitosterol (Thakur et al, 1989).The fruit is diuretic, laxative, carminative, stomachic, astringent, antidiarrhoeal, antihaemorrhagic and antianaemic.... indian gooseberryDNA (deoxyribonucleic acid) the genetic material of nearly all living organisms, which controls heredity and is located in the cell nucleus (see chromosome; gene). DNA is a *nucleic acid composed of two strands made up of units called *nucleotides (see illustration). The two strands are wound around each other into a double helix and linked together by hydrogen bonds between the bases of the nucleotides (see base pairing). The genetic information of the DNA is contained in the sequence of bases along the molecule (see genetic code); changes in the DNA cause *mutations. The DNA molecule can make exact copies of itself by the process of *replication, thereby passing on the genetic information to the daughter cells when the cell divides.... dmsa
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