Antitumor and Radiosensitizing Effects of Withaferin a on Mouse Ehrlich Ascites Carcinoma in vivo

The antitumor and radiosensitizing effects of withaferin A (WA), a steroidal lactone from Withania somnifera, was studied on Ehrlich ascites carcinoma in vivo. The acute LD₅₀₍₁₄₎ for WA in Swiss mice was ∼ 80 mg/kg. Twenty-four hours after i.p. inoculation of 10⁶ tumor cells, WA was injected i.p. at different dose fractions (5 or 7.5 mg/kg × 8, 10 mg/kg × 5, 20 or 30 mg/kg × 2) with or without abdominal gamma irradiation (RT, 7.5 Gy) after the first drug dose. Increase in life span and tumor-free survival were studied up to 120 days. The drug inhibited tumor growth and increased survival, which was dependent on the WA dose per fraction rather than the total dose. Combination of RT with all the drug schedules increased tumor cure and tumor-free survival, the best effect seen after 2 fractions of 30 mg/kg each. In another experiment WA was given as 2 (40 mg/kg × 2), 3 (30 mg/ kg × 3) or 4 (20 mg/kg × 4) fractions at 5, 7 or 10 days after tumor inoculation with or without RT after the first drug dose. At 7 and 10 days after inoculation the drug was effective only at 40 mg/kg × 2, but with RT 30 mg/kg × 3 produced an equal effect (20% survival) on 7 day old tumors.     

Isolation and evaluation of diagnostic value of two major secreted proteins of Mycobacterium tuberculosis

Two secreted antigens of Mycobacterium tuberculosis, namely the antigen 85 complex (30/31) and 38kDa antigens, were purified from the whole culture filtrate by using two dimensional preparative electrophoresis and anion exchange chromatography, respectively. Individual components of the antigen 85 complex namely, antigen 85A, 85B and 85C, were separated using hydrophobic interaction chromatography. The humoral antibody activity to these antigens in sputum positive cases of active pulmonary tuberculosis and normal healthy volunteers was determined by enzyme linked immunosorbent assay (ELISA) and immunoblot. Recombinant 38kDa and antigen 6 were used as reference antigens for the assay. None of the healthy volunteers reacted with the 38kDa antigen, while 52% of the TB sera reacted with it. Of the three components of the antigen 85 complex, 85B gave the highest positivity of 40 per cent. The results of combination of 38kDa with antigen 6 offered better results with 76% positivity.     

Insulin-like growth factor binding protein-3 induces early apoptosis in malignant prostate cancer cells and inhibits tumor formation in vivo

BACKGROUND: Insulin-like growth factor binding protein (IGFBP-3) levels are significantly reduced in malignant prostate epithelial cells. In this study, we evaluated the role of endogenous IGFBP-3 on prostate cancer cell growth and tumorigenesis. METHODS: IGFBP-3 was re-expressed by stable transfection of human IGFBP-3 cDNA in a model of human prostate cancer, M12, a malignant subline in which IGFBP-3 levels are undetectable in comparison to the parent epithelial cell, P69. Effect of IGFBP-3 re-expression (M12-BP-3) on growth kinetics, morphology, propensity to apoptosis, and in vivo tumor formation were studied. RESULTS: M12-BP-3 cells secreted IGFBP-3 and growth arrested at a cell density that was threefold lower than control cells and this was associated with marked alteration in cell morphology. Control cells when grown in conditioned media secreted by M12-BP-3 also showed altered morphology compared to when cultured in IGFBP-3-immunodepleted conditioned media. The M12-BP-3 clones showed altered mitochondrial membrane potential, increased PARP cleavage, increase in sub-G1 peak, decreased levels of neuron specific enolase, and decreased tumor formation in athymic, nude mice. CONCLUSIONS: These data suggest that IGFBP-3 induces early apoptosis and has potential tumor suppressive effect in prostate cancer. Prostate 51: 141-152, 2002.     

Hyperhomocysteinemia,and low intakes of folic acid and vitamin B12 in urban North India

Summary Background and Aim An adverse coronary risk profile has been reported amongst rural-to-urban migrant population living in urban slums undergoing stressful socio-economic transition. These individuals are likely to have low intakes of folic acid and vitamin B12, which may have an adverse impact on serum levels of homocysteine (Hcy). To test this hypothesis, we studied serum levels of Hcy in subjects living in an urban slum of North India and healthy subjects from urban non-slum area. Methods Group I consisted of 46 subjects (22 males and 24 females) living in an urban slum, while group II consisted of healthy subjects (n = 26, 13 males and 13 females) living in the adjacent non-slum area. Anthropometric measurements, biochemical profile (fasting blood glucose, total cholesterol, serum triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol) and fasting serum levels of Hcy were measured. Dietary intakes of folic acid, vitamin B12, vitamin B1, and iron were calculated by the 24-hour dietary recall method. Serum levels of Hcy were correlated with dietary intakes of nutrients, anthropometry, and metabolic variables. Results Sex-adjusted serum levels of Hcy in mmol/L (Mean ± SD) were high, though statistically comparable, in both the groups (group I: 20.8 ± 5.9 and group II: 23.2 ± 5.9). Overall, higher than normal serum levels of Hcy (> 15 μmol/L) were recorded in 84 % of the subjects. A substantial proportion of subjects in both groups had daily nutrient intakes below that recommended for the Asian Indian population (folic acid: 93.4 % in group I and 96.7 % in group II, vitamin B12: 76.1 % in group I and 88.4 % in group II). However, between the two groups, average daily dietary intakes of both the nutrients were statistically comparable. As compared to non-vegetarians, vegetarians showed lower intakes of folic acid (p < 0.01) and vitamin B12 (p < 0.01) in both groups. On multivariate linear regression analysis with serum Hcy as the response variable and vegetarian/non-vegetarian status and sex (male/female) as predictor variables, higher serum levels of Hcy were observed in vegetarians vs non-vegetarians (β = 4.6, p < 0.05) and males vs females (β = 5.3, p < 0.01). Conclusions Low intakes of folic acid and vitamin B12, and hyperhomocysteinemia, in both the healthy population living in urban slums and adjacent urban non-slum areas, are important observations for the prevention of nutritional and cardiovascular diseases in the Indian subcontinent. Received: 30 October 2001, Accepted: 14 January 2002     

Solitary pulmonary metastasis from intracranial meningiothelial meningioma

Although known, histologically proven pulmonary metastasis from a benign intracranial meningioma is exceedingly rare. We report a case of meningiothelial meningioma producing a solitary pulmonary deposit.     

Tuberculoma en plaque: a case report

A 14 year old girl presented with a 6-month history of headaches and visual blurring. CT showed a right tentorial enhancing lesion. Angiogram showed no enhancement. Histopathological examination of the excised material was consistent with tuberculoma. The presentation of such unusual intracranial tuberculoma is reported and the literature reviewed on the subject.     

Unusual cervical mass — A surgical dilemma and unfortunate sequelae

The differential diagnosis of a neck mass encompasses a broad range of possibilities including congenital cysts, inflammatory masses and both primary and metastatic neoplasms. A clear understanding of the normal anatomy of the neck and a high index of suspicion with a detailed history elicitation, proper physical examination and adjunctive test reports all lead to an accurate diagnosis. This is a case report of a thirty three year old lady who presented with a mass in the posterior triangle of neck with paraesthesia and mild weakness of the upper limb of the same side. The diagnostic evaluation revealed possibility of Schwannoma of the Brachial plexus and the surgical management posed a great surgical dilemma and led to cervical 5^th and 6^th trunk paralysis. We performed a second stage Sural nerve grafting.     

Effect of irradiation at the early foetal stage on adult brain function of mouse: learning and memory

PURPOSE: To study the long-term effect of early foetal irradiation on the learning and memory in the adult mouse. MATERIALS AND METHODS: The abdominal area of pregnant Swiss albino mice was exposed to a single dose of 0.25-1.5Gy gamma-radiation on the 14th day of gestation and the mice were left to deliver their offspring. At 6 months of age, the learning and memory functions of the F(1) mice were tested by hole-board activity, conditioned avoidance response and radial arm maze performance. The animals were again subjected to the radial arm maze test at 12 and 18 months of age. RESULTS: There was a significant dose-dependent decrease in the learning ability and memory retention of 6-month-old mice at doses > 0.25Gy. The significant changes persisted to 18 months of age in mice exposed to >or= 0.5Gy. All changes showed a linear dose-response at doses < 1Gy. CONCLUSIONS: The gestational day 14 of Swiss albino mice is a sensitive stage in brain development to gamma-ray-induced impairment of learning and memory during the adult life. Permanent deficits in these functions can be induced by a dose of approximately 0.5Gy at this stage, when the developmental activity of the cerebral cortex is at its peak.     

Protective effect of leaf extract of Ficus hispida Linn. against paracetamol-induced hepatotoxicity in rats

The methanol extract of the leaves of Ficus hispida Linn. (Moraceae) was evaluated for hepatoprotective activity in rats by inducing acute liver damage by paracetamol (750 mg/kg, p.o.). The extract at an oral dose of 400 mg/kg exhibited a significant protective effect by lowering the serum levels of transaminase (SGOT and SGPT), bilirubin and alkaline phosphatase (ALP). These biochemical observations were supplemented by histopathological examination of liver sections. The activity of extract was also comparable to that of Liv-52 a known hepatoprotective formulation.     

Transforming Orphanage Care: A Case Example in Zimbabwe

The author presents the voices of boys from an orphanage in Zimbabwe that he himself grew up in over a period of 10 years. After gaining professional child and youth care training in Canada, he has returned to the orphanage seeking to be an advocate and a catalyst for change in order to assist the Director and Board of Governors in the transformation of the residence.