Hepatocytes Health Dictionary

Rausch.

Synonym: I. arundinacea Cyr.

Family: Gramineae; Poaceae.

Habitat: The hotter parts of India, both in plains and hills, ascending up to 2,300 m in the Himalayas.

English: Thatch Grass.

Ayurvedic: Darbha, Suuchyagra, Yagnika, Yagyabhuushana, Bahir.

Siddha/Tamil: Dharba.

Folk: Daabh.

Action: Diuretic, anti-inflammatory.

The rhizomes contain flavonoids, together with lignans, graminone A and B. A sesquiterpenoid, cylindrene, and biphenylether compounds, cylindol A and B, are also reported.

Cylindrene and graminone B show inhibitory activity on the contractions of vascular smooth muscles and aorta of rabbit respectively; while cylin- dol A exhibits 5-lipoxygenase inhibitory activity.

The hot aqueous extract of the rhizomes show moderate GTP activity on primary cultured rat hepatocytes intoxicated with carbon tetrachloride cy- totoxicity.

The leaves and stem contain cyano- chroic constituents. The roots contain antibacterial substances. The root is used in fevers but does not possess antipyretic activity.

Dosage: Root—50-100 ml decoction. (CCRAS.)... imperata cylindrica

ACUTE LIVER DISEASE The hepatitis viruses (A– F) are of paramount importance. Hepatitis E (HEV) often produces acute hepatic failure in pregnant women; extensive epidemics – transmitted by contaminated drinking-water supplies – have been documented. HBV, especially in association with HDV, also causes acute liver failure in infected patients in several tropical countries: however, the major importance of HBV is that the infection leads to chronic liver disease (see below). Other hepatotoxic viruses include the EPSTEIN BARR VIRUS, CYTOMEGALOVIRUS (CMV), the ?avivirus causing YELLOW FEVER, Marburg/Ebola viruses, etc. Acute liver disease also occurs in the presence of several acute bacterial infections, including Salmonella typhi, brucellosis, leptospirosis, syphilis, etc. The complex type of jaundice associated with acute systemic bacterial infection – especially pneumococcal PNEUMONIA and pyomiositis – assumes a major importance in many tropical countries, especially those in Africa and in Papua New Guinea. Of protozoan infections, plasmodium falciparum malaria, LEISHMANIASIS, and TOXOPLASMOSIS should be considered. Ascaris lumbricoides (the roundworm) can produce obstruction to the biliary system. CHRONIC LIVER DISEASE Long-term disease is dominated by sequelae of HBV and HCV infections (often acquired during the neonatal period), both of which can cause chronic active hepatitis, cirrhosis, and hepatocellular carcinoma (‘hepatoma’) – one of the world’s most common malignancies. Chronic liver disease is also caused by SCHISTOSOMIASIS (usually Schistosoma mansoni and S. japonicum), and acute and chronic alcohol ingestion. Furthermore, many local herbal remedies and also orthodox chemotherapeutic compounds (e.g. those used in tuberculosis and leprosy) can result in chronic liver disease. HAEMOSIDEROSIS is a major problem in southern Africa. Hepatocytes contain excessive iron – derived primarily from an excessive intake, often present in locally brewed beer; however, a genetic predisposition seems likely. Indian childhood cirrhosis – associated with an excess of copper – is a major problem in India and surrounding countries. Epidemiological evidence shows that much of the copper is derived from copper vessels used to store milk after weaning. Veno-occlusive disease was ?rst described in Jamaica and is caused by pyrrolyzidine alkaloids (present in bush-tea). Several HIV-associated ‘opportunistic’ infections can give rise to hepatic disease (see AIDS/HIV).

A localised (focal) form of liver disease in all tropical/subtropical countries results from invasive Entamoeba histolytica infection (amoebic liver ‘abscess’); serology and imaging techniques assist in diagnosis. Hydatidosis also causes localised liver disease; one or more cysts usually involve the right lobe of the liver. Serological tests and imaging techniques are of value in diagnosis. Whilst surgery formerly constituted the sole method of management, prolonged courses of albendazole and/or praziquantel have now been shown to be e?ective; however, surgical intervention is still required in some cases.

Hepato-biliary disease is also a problem in many tropical/subtropical countries. In southeast Asia, Clonorchis sinensis and Opisthorchis viverini infections cause chronic biliary-tract infection, complicated by adenocarcinoma of the biliary system. Praziquantel is e?ective chemotherapy before advanced disease ensues. Fasciola hepatica (the liver ?uke) is a further hepato-biliary helminthic infection; treatment is with bithionol or triclabendazole, praziquantel being relatively ine?ective.... liver disease in the tropics

A type of alkaloid found in many plants of the Composite and Borage families, once termed a Senecio alkaloid. Some of the pyrrolizidine group have been shown to cause several types of liver degeneration and blood vessel disorders. Several deaths have been attributed to improperly identified plant usage of a Senecio, and some of the desert Boraginaceae annuals and Senecio annuals are overtly toxic. Young leaves and spring roots of Comfrey hybrids should be avoided as well. Not all PAs are toxic, but those that are can produce spontaneous necrosis in the liver hepatocytes of a perfectly healthy person.... pyrrolizidine alkaloid

large irregular masses abnormally located in the hepatocytes of the liver. They are found in patients with alcoholic hepatitis, alcoholic cirrhosis, Wilson’s disease, primary biliary cirrhosis, clinical obesity, and hepatoma. [F. B. Mallory (1862–1941), US pathologist]... mallory bodies

n. infiltration of *hepatocytes with fat. This may occur in alcoholism, obesity, metabolic syndrome, pregnancy, malnutrition, viral hepatitis, or certain drugs (such as oestrogens or steroids).... steatosis

A parasitic disease caused by four species of PLASMODIUM: P. falciparum, P. vivax, P. ovale, and P. malariae. Clinically, malaria is characterised by recurrent episodes of high fever, sometimes associated with RIGOR; enlargement of the SPLEEN is common. P. falciparum infection can also be associated with several serious – often fatal – complications (see below): although other species cause chronic disease, death is unusual.

During a bite by the female mosquito, one or more sporozoites – a stage in the life-cycle of the parasite – are injected into the human circulation; these are taken up by the hepatocytes (liver cells). Following division, merozoites (minute particles resulting from the division) are liberated into the bloodstream where they invade red blood cells. These in turn divide, releasing further merozoites. As merozoites are periodically liberated into the bloodstream, they cause the characteristic fevers, rigors, etc.

Malaria occurs in many tropical and subtropical countries; P. falciparum is, however, con?ned very largely to Africa, Asia and South America. Malaria is present in increasingly large areas; in addition, the parasites are developing resistance to various preventative and treatment drugs. The disease constitutes a signi?cant problem for travellers, who must obtain sound advice on chemoprophylaxis before embarking on tropical trips – especially to a rural area where intense transmission can occur. Transmission has also been recorded at airports, and following blood transfusion.

The World Health Organisation (WHO) has listed malaria as one of Europe’s top ten infectious diseases. In 1992, 20,000 cases were reported: this had risen to more than 200,000 by the late 1990s. The resurgence of malaria has been worldwide, in part the result of the development of resistant strains of the disease, and in part because many countries have failed (or been unable) to implement environmental measures to eliminate mosquitoes. Nearly 40 years ago the WHO forecast that by 1980 only four million people would be affected worldwide; now, at the beginning of the 21st century, around 500 million people a year are contracting malaria with about 3,000 people a day dying from the infection – as many as 70 per cent of them children under the age of ?ve, according to WHO ?gures. The apparently steady advance of global warming means that countries with temperate climates may well warm up su?ciently to enable malaria to become established as an ENDEMIC disease. In any case, the great increase in international air travel has exposed many more people to the risk of malaria, and infected individuals may not exhibit symptoms until they are back home. Doctors seeing a recent traveller with unexplained pyrexia and illness should consider the possibility of malarial infection.

Diagnosis is by demonstration of trophozoites – a stage in the parasite’s life-cycle that takes place in red blood cells – in thick/thin blood-?lms of peripheral blood. Serological tests are of value in deciding whether an individual has had a past infection, but are of no value in acute disease.

P. vivax and P. ovale infections cause less severe disease than P. falciparum (see below), although overall there are many clinical similarities; acute complications are unusual, but chronic ANAEMIA is often present. Primaquine is necessary to eliminate the exoerythrocytic cycle in the hepatocyte (liver cell).

P. falciparum Complications of P. falciparum infection include cerebral involvement (see BRAIN – Cerebrum), due to adhesion of immature trophozoites on to the cerebral vascular endothelium; these lead to a high death rate when inadequately treated. Renal involvement (frequently resulting from HAEMOGLOBINURIA), PULMONARY OEDEMA, HYPOTENSION, HYPOGLYCAEMIA, and complications in pregnancy are also important. In complicated disease, HAEMODIALYSIS and exchange TRANSFUSION have been used. No adequate controlled trial using the latter regimen has been carried out, however, and possible bene?ts must be weighed against numerous potential side-effects – for instance, the introduction of a wide range of infections, overload of the circulatory system with infused ?uids, and other complications.

P. malariae usually produces a chronic infection, and chronic renal disease (nephrotic syndrome) is an occasional sequel, especially in tropical Africa.

Gross SPLENOMEGALY (hyper-reactive malarious splenomegaly, or tropical splenomegaly syndrome) can complicate all four human Plasmodium spp. infections. The syndrome responds to long-term malarial chemoprophylaxis. BURKITT’S LYMPHOMA is found in geographical areas where malaria infection is endemic; the EPSTEIN BARR VIRUS is aetiologically involved.

Prophylaxis Malaria specialists in the United Kingdom have produced guidance for residents travelling to endemic areas for short stays. Drug choice takes account of:

risk of exposure to malaria;

extent of drug resistance;

e?cacy of recommended drugs and their side-effects;

criteria relevant to the individual (e.g. age, pregnancy, kidney or liver impairment). Personal protection against being bitten by

mosquitoes is essential. Permethrinimpregnated nets are an e?ective barrier, while skin barrier protection and vaporised insecticides are helpful. Lotions, sprays or roll-on applicators all containing diethyltoluamide (DEET) are safe and work when put on the skin. Their e?ect, however, lasts only for a few hours. Long sleeves and trousers should be worn after dark.

Drug prophylaxis should be started at least a week before travelling into countries where malaria is endemic (two or three weeks in the case of me?oquine). Drug treatment should be continued for at least four weeks after leaving endemic areas. Even if all recommended antimalarial programmes are followed, it is possible that malaria may occur any time up to three months afterwards. Medical advice should be sought if any illness develops. Chloroquine can be used as a prophylactic drug where the risk of resistant falciparum malaria is low; otherwise, me?oquine or proguanil hydrochloride should be used. Travellers to malaria-infested areas should seek expert advice on appropriate prophylactic treatment well before departing.

Treatment Various chemoprophylactic regimes are widely used. Those commmonly prescribed include: chloroquine + paludrine, me?oquine, and Maloprim (trimethoprim + dapsone); Fansidar (trimethoprim + sulphamethoxazole) has been shown to have signi?cant side-effects, especially when used in conjunction with chloroquine, and is now rarely used. No chemotherapeutic regimen is totally e?ective, so other preventive measures are again being used. These include people avoiding mosquito bites, covering exposed areas of the body between dusk and dawn, and using mosquito repellents.

Chemotherapy was for many years dominated by the synthetic agent chloroquine. However, with the widespread emergence of chloroquine-resistance, quinine is again being widely used. It is given intravenously in severe infections; the oral route is used subsequently and in minor cases. Other agents currently in use include me?oquine, halofantrine, doxycycline, and the artemesinin alkaloids (‘qinghaosu’).

Researchers are working on vaccines against malaria.... malaria

Linn.

Family: Cucurbitaceae.

Habitat: Cultivated all over India for its fruits.

English: Bitter Gourd, Blsam Pear, Carilla.

Ayurvedic: Kaaravellaka, Kaaravella, Kaathilla, Sushaavi.

Unani: Karelaa.

Siddha/Tamil: Paakal, Paharkai.

Action: Seed/fruit—improves diabetic condition. Fruit—stomachic, laxative, antibilious, emetic, anthelmintic. Used in cough, respiratory diseases, intestinal worms, skin diseases, also for gout and rheumatism. Powdered fruit—applied to wounds and ulcers. Leaf— emetic, antibilious, purgative. Fruit, leaf and root—abortifacient. Leaf and seed—anthelmintic. Root— astringent; appled to haemorrhoids.

Immature fruits gave several nonbitter and bitter momordicosides. Fruits, seeds and tissue culture gave a polypeptide containing amino acids. Fruits also gave 5-hydroxytryptamine, charantin (a steroidal glucoside), dios- genin, cholesterol, lanosterol and beta- sitosterol. Bitter principles are cucur- bitacin glycosides.

Hypoglycaemic effects of the fruit have been demonstrated by blood tests in both humans and animal studies.

Researchers have warned that the fruit extract leads to a false negative test for sugar in the urine (due to its ability to maintain the indicator dye in the glucose oxidase strips and the alkaline copper salts in a reduced state).

Chronic administration of the fruit extract (1.75 g/day for 60 days) to dogs led to testicular lesions with mass atrophy of the spermatogenic elements. The extract reduced the testicular content of RNA, protein and sialic acid as also the acid-phosphatase activity. (Medicinal Plants of India, Vol. 2,1987, Indian Council of Medical Research, New Delhi.)

The fruits and seeds yielded a poly- peptide, p-insulin, which was considered similar to bovine insulin. (Fitoter- apia, 60,1989; Chem Abstr 112,1990.)

The seed and fruit contain an inhibitor of HIV, MAP-30 (Momordi- ca anti-HIV-protein) which exhibited antiviral and antitumour activity in vitro. (Chem Abstr, 113, 1990; ibid, 117, 1992.) Another protein, MRK-29, found in the seed and fruit of a smaller var. of Bitter Gourd found in Thailand, was found to inhibit HIV reverse transcriptase and to increase tumour necrosis factor (TNF). (Planta Med, 67, 2001; Natural Medicines Comprehensive Database, 2007.)

The seeds yield alpha-and beta- momorcharins (glycoproteins). When these glycoproteins were co-cultured with isolated hepatocytes, morphological changes in hepatocytes were observed, indicating hepatotoxicity. Another principle with antilipolytic and lipogenic activities, found along with the alpha-and beta-momorcharin in the seed extract, did not show toxic effect.

Vicine is the hypoglycaemic constituent in the seed. Pure vicine has been found to possess 32.6% hypogly- caemic activity as against 22.2% shown by fresh juice, when tested on albino rats. The vicine is non-haemolytic.

Dosage: Fresh fruit—10-15 ml juice (API, Vol. II); 10-20 ml juice (CCRAS.)... momordica charantia

Bennett.

Family: Simaroubaceae.

Habitat: Garhwal, Himachal Pradesh and Kulu.

English: Quassia (substitute for P excelsa Lindtl).

Ayurvedic: Bhurangi, Nimbi. (Clerodendrum serratum and its related species represent Bhaargi or Bhaarangi.)

Folk: Nimatotaa.

Action: Wood—a non-astringent bitter tonic and stomachic, amoe- bicidal, anthelmintic (used as enema), insect repellent. Used as a supporting medicine for temporary relief in cirrhosis of liver.

Many indole alkaloids of beta-car- boline, canthin-6-one and beta-carbo- line dimer type, have been isolated from the wood. These are reported to increase the blood flow rate in the intestine and stomach of rabbit; also exhibited antiviral activity on Herpes simplex virus.

Nigaki lactone and methylnigaki- none, isolated from the wood, showed antigastric ulcer activity in rats. The extract of the wood is reported to prevent the secretion of gastric juice in a dose-dependent manner in rats. The extract also showed the same effects on rats having aspirin-induced gastric ulcer.

Family: Scrophulariaceae.

Habitat: The alpine Himalayas from Kashmir to Sikkim.

English: Picrorhiza.

Ayurvedic: Katukaa, Katurohini, Kattarohini, Katuki, Katukikaa, Krishnabhedaa, Kaandaruhaa, Matsyashakalaa, Chakraangi, Shat- parvaa, Arishta, Ashokarohinya, Shakuldaani.

Unani: Kutki, Kharbaq-e-Hindi.

Siddha/Tamil: Kaduguragini.

Action: Root—stomachic, antidiar- rhoeal, cholagogue, hepatoprotec- tive. Used in hepatitis, chronic dysentery, amoebiasis.

Key application: In jaundice, intermittent fever, dyspnoea and skin diseases. (The Ayurvedic Pharmacopoeia ofIndia.)

The roots yield a glycosidal bitter principle, kutkin, found to be a mixture of two iridoid glycosides, picro- side I and kutkoside. Also obtained were D-mannitol, kutkiol, kutkisterol and a ketone (identical with apocynin).

Kutkin exhibited hepatoprotective activity in CCl4-induced toxic rats.

Picroliv, a standardized fraction from the alcoholic extract of the root and rhizome, containing 55-60% of a mixture of picroside I and kutkoside (1:15) showed dose-dependent protective activity on isolated hepatocytes in vitro against thiocetamide-induced hepatic damage in rat and was found to be more potent than Silymarin, a known hepatoprotective agent. Pi- croliv is reported to show protective effect against rifampicin-induced hep- atotoxicity in rats. It also exerts hy- polipidaemic effect in normal, triton- treated and cholesterol-fed rats.

Kutkin, picroside I and kutkoside exhibit anti-inflammatory property.

The phenolic glycoside, androsin, isolated from the plant, prevents allergen and platelet activating factor- induced bronchial obstruction in guinea-pigs in vitro.

Cucurbitacin glycosides, isolated from the root, exhibit liver protective, tumour inhibitory and anti-inflammatory activity.

Dosage: Root—1-3 g; 3-6 g as purgative. (CCRAS.)... picrasma quassioides