Anup K. Das

Anticancer effect of antimalarial artemisinin compounds

The anti-malarial drug artemisinin has shown anticancer activity in vitro and animal experiments, but experience in human cancer is scarce. However, the ability of artemisinins to kill cancer cells through a variety of molecular mechanisms has been explored. A PubMed search of about 127 papers on anti-cancer effects of antimalarials has revealed that this class of drug, including other antimalarials, have several biological characteristics that include anticancer properties. Experimental evidences suggest that artemisinin compounds may be a therapeutic alternative in highly aggressive cancers with rapid dissemination, without developing drug resistance. They also exhibit synergism with other anticancer drugs with no increased toxicity toward normal cells. It has been found that semisynthetic artemisinin derivatives have much higher antitumor activity than their monomeric counterparts via mechanisms like apoptosis, arrest of cell cycle at G0/G1, and oxidative stress. The exact mechanism of activation and molecular basis of these anticancer effects are not fully elucidated. Artemisinins seem to regulate key factors such as nuclear factor-kappa B, survivin, NOXA, hypoxia-inducible factor-1α, and BMI-1, involving multiple pathways that may affect drug response, drug interactions, drug resistance, and associated parameters upon normal cells. Newer synthetic artemisinins have been developed showing substantial antineoplastic activity, but there is still limited information regarding the mode of action of these synthetic compounds. In view of the emerging data, specific interactions with established chemotherapy need to be further investigated in different cancer cells and their phenotypes and validated further using different semisynthetic and synthetic artemisinin derivatives.The anti-malarial drug artemisinin has shown anticancer activity in vitro and animal experiments, but experience in human cancer is scarce. However, the ability of artemisinins to kill cancer cells through a variety of molecular mechanisms has been explored. A PubMed search of about 127 papers on anti-cancer effects of antimalarials has revealed that this class of drug, including other antimalarials, have several biological characteristics that include anticancer properties. Experimental evidences suggest that artemisinin compounds may be a therapeutic alternative in highly aggressive cancers with rapid dissemination, without developing drug resistance. They also exhibit synergism with other anticancer drugs with no increased toxicity toward normal cells. It has been found that semisynthetic artemisinin derivatives have much higher antitumor activity than their monomeric counterparts via mechanisms like apoptosis, arrest of cell cycle at G 0 /G 1 , and oxidative stress. The exact mechanism of activation and molecular basis of these anticancer effects are not fully elucidated. Artemisinins seem to regulate key factors such as nuclear factor-kappa B, survivin, NOXA, hypoxia-inducible factor-1α, and BMI-1, involving multiple pathways that may affect drug response, drug interactions, drug resistance, and associated parameters upon normal cells. Newer synthetic artemisinins have been developed showing substantial antineoplastic activity, but there is still limited information regarding the mode of action of these synthetic compounds. In view of the emerging data, specific interactions with established chemotherapy need to be further investigated in different cancer cells and their phenotypes and validated further using different semisynthetic and synthetic artemisinin derivatives.

Hepatic and biliary ascariasis.

Ascariasis mainly contributes to the global helminthic burden by infesting a large number of children in the tropical countries. Hepato-biliary ascariasis (HBA) is becoming a common entity now than in the past owing to the frequent usage of ultrasonograms and endoscopic diagnostic procedures in the clinical practice. There are a variety of manifestations in HBA and diagnosis depends on a high index of suspicion in endemic areas coupled with subsequent confirmation by sonographic or endoscopic demonstration of the worm. Most of them present with acute abdomen and jaundice. Oriental or recurrent pyogenic cholangiopathy is possibly the result of HBA, commonly encountered in South-East Asian countries. Conservative treatment with anthelminthic agents is used in the majority. Failure to respond to medical therapy usually indicates the need for endoscopic or surgical interventions. Overall, mortality is low and prognosis is good, but many epidemiological and immunological aspects of Ascaris infection are unclear, meaning our understanding the disease and infection still remains incomplete. Therefore, it is difficult to definitely put down a fixed modality of treatment for HBA. This underscores the need for further studies as ascariasis has the potential to adversely affect the national socio-economy by compromising the health of children and adults alike with its sheer number.

Changing seroepidemiology of hepatitis A infection and its prevention in endemic regions

Hepatitis A is the most common cause of acute viral hepatitis worldwide although a preventive vaccine is available. Infection generally confers life-long immunity. It causes severe, often fatal, disease in adults, especially in those with underlying liver dysfunction, but is mostly asymptomatic in children. Endemicity is determined by anti-hepatitis A seroprevalence in different regions of the world. Hence, industrialized nations fall under hypoendemic category, but tropical, Asian, or African countries are hyperendemic. Hyperendemic countries have an adult population who develop immunity to hepatitis A as they are usually infected in childhood due to poor sanitation, in contrast to developed nations where adults remain susceptible. Vaccination strategies differ across the world depending on the endemicity. Usually, universal vaccination is still not advocated in endemic developing countries, unlike in USA or Europe. However, data are emerging from developing nations such as India where more adults are probably becoming susceptible to hepatitis A due to improving economy, better sanitation, and personal hygiene. Hence, the global seroepidemiology of hepatitis A is changing in many developing nations giving rise to unique nonimmune adolescent and adult populations emerging in endemic regions, thereby conferring a risk of developing severe hepatitis A. Abstracts, articles, and cross references were examined in search engines including PubMed and chapters from standard textbooks and monographs. This narrative review of some relevant recent information on this shifting seroepidemiology in endemic areas discusses changes in national and regional vaccination strategies with public health implications.

Etiological profile of cirrhosis of liver from North‑East India with reference to their anti‑hepatitis A virus seroprevalence

Background: Cirrhosis of liver is common in north-east India. Hepatitis A infection in adults with chronic liver disease can cause acute on chronic liver failure associated with high mortality and morbidity. There have been reports of an epidemiological shift in hepatitis A virus (HAV) seroprevalence from South-East Asia and India. This study evaluated the etiological profile and seroprevalence of anti-HAV IgG in cirrhosis of liver patients. Patients and Methods: 160 hospitalized adult cases of decompensated cirrhosis of liver and 200 healthy controls were assessed for etiology and their anti-HAV IgG status by commercially available kits. Results : Most common cause of cirrhosis of liver in our region is ethanol related. 95% of cases and 89% of controls were seropositive for anti-HAV IgG (P = 0,181, insignificant difference). All cases above the age of 40 years were seropositive. Seroprevalence between sexes (M 97% and F 83.3%) was statistically insignificant. Only age showed a high coefficient of correlation (r = 0.854, statistically significant, P < 0.001). Conclusion: Alcohol is the most common etiology of cirrhosis of liver in north-east India. Socio-cultural milieu in our part may play a role with alcohol contributing to a major but preventable heath burden. Anti-HAV vaccination in our setting is not indicated routinely to cirrhosis of liver patients as it will not be cost-effective. However, young cirrhotics should be screened for anti-HAV antibody and if negative, may be offered vaccination. Screening should target young chronic liver disease patients in view of reports of decreasing seroprevalence across Asia as compared to one or two decades back.

Profile of systemic sclerosis and associated renal involvement

Background: Systemic sclerosis (SSc) patients are encountered in all parts of the world. Few Indian studies are found in the literature on this connective tissue disorder of unknown etiology. The spectrum of sclerodermatous diseases comprises a wide variety of clinical entities. Renal involvement is not common in Indian patients when compared to western patient′s in spite of the kidney being commonly affected in scleroderma due to vascular changes. Aim and Objective: To primarily study the prevalence of renal involvement in SSc and to correlate it with high-sensitivity C-reactive protein (hsCRP) over a period of 1 year in a tertiary care hospital in North-East India. Materials and Methods: A total of 38 consecutive scleroderma patients of both sexes, diagnosed by established criteria, were examined, and hsCRP was estimated in all. Evaluation for nephropathy by biochemical tests and sonography were carried out. Relevant clinical/biochemical examinations were carried out. Results: SSc was 3 times more common in mostly in middle aged females. About 50% presented within 1 year of disease onset. Renal involvement was uncommon (18%) and hsCRP was detected in 26%. Conclusion: SSc with nephropathy, not renal crisis, presents early and hsCRP is a good marker for the same.

Profile of acute severe malaria with hepatopathy

Background: The single most dreaded complication in severe malaria is cerebral malaria, but extracerebral serious complications are becoming frequent in endemic areas, which include hepatic dysfunctions with jaundice. Materials and Methods: This prospective case series study was undertaken to observe the clinical profile in 81cases of complicated malaria presenting with jaundice out of 344 hospitalized patients diagnosed with acute severe malaria. Liver function tests were assessed and the patients were followed up to 4 weeks. Results: 85% cases with jaundice had Plasmodium falciparum ( Pf ) infection. Significant findings included a predominantly hemolytic jaundice (mean bilirubin 7.6 mg%, unconjugated 4.83 mg%, conjugated 2.79 mg%), raised ALT > AST (mean 101.2 vs.74.7 iu) and a mean prothrombin time of 3 sec > control. Acute renal failure was common (77%). No residual hepatic dysfunctions were detected in survivors on follow-up. Mortality was 10%, mostly due to delayed diagnosis and associated serious co-morbid conditions. Conclusion: Differentiating fulminant viral hepatitis with multi-organ failure and early treatment of associated complications are crucial to reduce mortality in malaria presenting with jaundice. Hemolytic jaundice with mild and relatively early reversibility of hepatocellular dysfunction usually points towards complicated Pf malaria. Histologically, there is mild hepatic derangement. Acute renal failure is commonly associated. Vivax malaria can also cause hepatic dysfunctions. Mere presence of jaundice does not increase mortality compared to those without jaundice

Portal vein thrombosis in a young patient of previously asymptomatic hepatocellular carcinoma with Hepatitis-B related cirrhosis

Portal vein thrombosis (PVT) is a rare condition whose exact prevalence is unknown. In developing countries like India it is most often due to umbilical or intra-abodominal sepsis in young patients. In South-East Asia, PVT is usually seen in middle age and above commonly when due to hepatitis-B related chronic liver disease or HCC, and other malignancies, being extremely rare in those below 30 years. We report a case of abrupt onset PVT with incidentally detected hepatitis-B associated cirrhosis of liver and HCC in a previously healthy young man, presenting with acute hepatic decompensation and some unusual features in the involvement of the portal vein.