Infection with hepatitis A virus (HAV) can cause severe illness in adult patients with chronic liver disease (CLD) caused by hepatitis C. In endemic areas such as South Asia, however, most adult patients already have been exposed to HAV but could still be susceptible to hepatitis E virus (HEV) infection. We document that HEV superinfection in 4 of our CLD patients caused severe liver decompensation. We then determined the seroprevalence of HAV and HEV in 233 patients with stable CLD, with the goal of defining the need for protection against these viruses in these patients. Overall, 41 ( T he hepatitis A virus (HAV) and the hepatitis E virus (HEV) are endemic in South Asia and are the most common causes of acute hepatitis in this region. 1,2 Both viruses have a number of common characteristics: they are transmitted by the fecal-oral route and generally cause an acute self-limiting illness followed by complete recovery. However, a number of clinical and epidemiologic differences exist between HAV and HEV. For example, HEV can cause a severe fulminant hepatitis in pregnant women if the infection occurs during late pregnancy, 3 whereas exposure to HAV infection during pregnancy does not impose a higher risk. 4,5 Exposure to HAV infection occurs at a very early age in endemic areas, so that by the age of 10 years almost 100% of children show evidence of exposure to HAV, as determined by a positive HAV immunoglobulin G (IgG) antibody test result. 6 This early exposure to HAV is followed by longterm, possibly lifelong, immunity to the virus. 7 On the other hand, in the same community, exposure to HEV commonly takes place during adult life. The duration of HEV immunity is unclear, but it is possibly shorter term than is HAV immunity. 8 This could theoretically lead to recurrent episodes of HEV infection in the same patient. 9 Large-scale epidemics have been described in South Asia attributable to both HAV and HEV. Epidemics caused by HEV have occurred in Kashmir and Kanpur, as well as recently in Islamabad. [10][11][12] The common features of these epidemics were an incubation period of 2 to 9 weeks, highest clinical attack rates in adults between 15 and 40 years old, and low overall mortality of between 0.5% and 4% but high mortality (15%-25%) in pregnant women.Infection with HAV has been shown to cause a severe illness in adult patients with chronic liver disease (CLD), in particular in patients with hepatitis C, in areas where HAV is not endemic. 13 Because of the increased risk of an adverse outcome and low background exposure to HAV in these areas, vaccination against HAV is now routinely

Background: As the hepatitis B genotyping is important for assessing its clinical implications and geographical distribution, the sub-genotypes have been found useful for determination of specific genomic markers related to hepatocarcinogenesis. In Pakistan, there is no reported data on molecular evolutionary analysis of HBV. A study was, therefore, much needed to evaluate the spectra of mutations present in the strains prevalent here.

Orexin A stimulates GnRH release from hypothalamic explants in vitro. The sites of action of orexin A in the regulation of LH release have been investigated in vivo in ovariectomized rats that were given vehicle or estradiol benzoate (EB), with or without an injection of progesterone 48 h later. Orexin A was administered intrahypothalamically under Saffan anesthesia, 50 h after the EB or vehicle; its effects on plasma LH levels were monitored in sequential blood samples. Orexin A (1.0 microg/side) injected into the rostral preoptic area (rPOA) at the level of the organum vasculosum of the lamina terminalis had a stimulatory effect on LH release in EB-treated ovariectomized rats. When orexin A was injected into the medial POA (mPOA) or the arcuate/median eminence, it had an inhibitory effect on the LH surge that occurs in ovariectomized rats primed with EB plus progesterone. Orexin A injected into the mPOA also reduced LH levels in ovariectomized rats untreated with ovarian steroids. Both the stimulatory and inhibitory effects of orexin A were antagonized by SB334867A, a selective orexin 1 receptor antagonist. Furthermore, when given alone into the rPOA, this antagonist attenuated the LH surge induced by EB plus progesterone. Thus, orexin appears to have a dual effect on LH release, being stimulatory in the rPOA and inhibitory in the mPOA or arcuate/median eminence. Both effects may be mediated, at least in part, by the orexin 1 receptor. Double label immunohistochemistry revealed close appositions between orexin A immunoreactive varicosities and a small proportion of GnRH cell bodies in the rPOA. It is suggested that the stimulatory effect of orexin A on LH release may involve direct actions on GnRH neurons.

Leishmaniasis are a group of diseases, endemic in many parts of the world.1,2) Leishmaniasis are mostly prevalent in poor developing countries evident by the growing number of cases seen in AIDS patients 3) and the occurrence of viscerotropic Leishmania tropica disease among Persian Gulf War Participants.2,3) The disease is transmitted by the members of the genus Leishmania which is a protozoal parasite. These parasitic protozoans are digenetic and have two distinct stages in their life cycle. The motile flagellated promastigote stage lives in the alimentary tract of the sand fly vector, while the non-motile amastigote stage resides inside the macrophages of mammalian hosts. 4)Leishmanial infections include three major syndromes: cutaneous, visceral and mucosal leishmaniasis. The basic treatment consists in the administration of sodium stibogluconate (pentostam), meglumine (glucantime) or pentamidine. Common problem with this basic treatment especially in Kalaazar, mucosal leishmaniasis is the developing drug resistance of the parasite.5) In addition, the low efficacy of pentavalent antimony in the treatment of patients coinfected with AIDS is often noticed.6) These problems prompted the development of new anti-leishmanial drugs. [7][8][9][10] Curcumin is a yellow-orange dye derived from the rhizome of the plant Curcuma longa. It has long been used as a naturally occurring medicine for the treatment of inflammatory diseases. Curcumin (difleruloyl methane) is a natural phenolic compound. It is a potent anti-tumor agent having anti-inflammatory and anti-oxidant properties. It induces apoptosis in cancer cells 11,12) and inhibits TPA-induced Protein kinase C (PKC) activity.13) It has also shown anti-bacterial, anti-fungal and anti-trypnosomal activity. 1,14,15) A recent study has also shown action against the promastigote forms of Leishmania major. 16)In this report we evaluated the actions of curcumin against the promastigote forms of different reference and local leishmanial strains in vitro. We also evaluated the activity of curcumin against the axenic amastigote like cells (AALC) of L. major in vitro. MATERIALS AND METHODSParasite Cultures All the promastigote cultures of both the reference and local Pakistani leishmanial strains were maintained in blood agar based bi-phasic Evan's modified Tobie's medium supplemented with RPMI-1640 with 25 mM TES at 25°C. The reference leishmanial strains were obtained from London School of Hygeine and Tropical Medicine. The reference strains of promastigotes that were used include L. major (JISH118), L. tropica (K27) and L. infantum (LEM3437). Local leishmanial strains used in this study include L. major (MHOM/PK/88/DESTO) in the promastigote and AALC stage (see below). Other local strains used in the promastigote stage include L. tropica and L. infantum. The long term continuous culture of axenic amastigote like cells (AALC) of L. major (MHOM/PK/88/DESTO) strain was successfully established. Briefly, AALC cells were obtained from the promastigotes by the gradual adaptation o...