Assessment ofall-trans retinoic acid (ATRA) efficacy as a single agent in primary lymphoid neoplasia

All-trans retinoic acid (ATRA) is currently widely used in the therapy of acute promyelocytic leukemia and is being tested in vitro and in vivo on several other malignancies. Previously ATRA has been shown to inhibit the growth in vitro, of established human myeloma cell lines as well as cultured primary myeloma cells from patients. ATRA acts by down-regulating IL-6-receptor-alpha or gp130 on the surface of the myeloma cells. However, despite its in vitro effects on myeloma cells, ATRA therapy on advanced stage multiple myeloma (MM) patients has so far largely been ineffective. In current studies, we have assessed the efficacy of ATRA therapy against primary murine plasma cell tumors, which are an animal model for human MM. These tumors are induced at about 50% incidence in pristane-primed BALB/c mice by injection of v-raf/v-myc- containing retroviruses and are IL-6 dependent. Using this animal model, we assessed the effect of ATRA as a therapeutic agent against primary tumors at two early time points in disease development. ATRA was administered in liposomal vesicles (ATRAGEN), since liposomal-ATRA has been shown to circumvent clearance mechanisms by hepatic microsomes, which normally occur with free ATRA. In addition, ATRAGEN was previously shown to be less toxic in mice than free ATRA. ATRAGEN was administered beginning on day 25 or day 45 after virus injection and continued twice weekly for 8-11 weeks. ATRAGEN administration begun at either time point did not alter the incidence or the latency of plasma cell tumors compared with control animals. These results suggest that ATRA may not be an effective sole therapy against early MM.     

Exposure to CSF from sporadic amyotrophic lateral sclerosis patients induces morphological transformation of astroglia and enhances GFAP and S100β expression

We have earlier shown that cerebrospinal fluid (CSF) of amyotrophic lateral sclerosis (ALS) patients’ produces selective degeneration of motor neurons, both in vitro as well as in vivo. The present study further evaluates the effect of ALS–CSF on the astrocytes in embryonic rat spinal cord cultures. We quantified the number of flat and process-bearing astrocytes in spinal cord cultures exposed to ALS–CSF and compared them against controls. In addition, GFAP and S100β expression were quantified by Western blot and measurement of immunofluorescence intensity respectively. We found higher number of process-bearing astrocytes in the cultures exposed to ALS–CSF. Both these proteins increased significantly in cultures exposed to ALS–CSF. Our results provide evidence that astroglia respond to toxic factor(s) present in ALS–CSF by undergoing morphological transformation from flat to process bearing which is further confirmed by elevated expression of GFAP and S100β. The above changes could possibly alter the microenvironment hastening the motor neuron degeneration.     

Intermittent fasting during Ramadan causes a transient increase in total,LDL, and HDL cholesterols and hs-CRP in ethnic obese adolescents

The radical change of lifestyle during Ramadan fast has shown to affect cardiometabolic risk variables in adults. In youth, however, no studies are available. We aimed to evaluate the effect of Ramadan fast on Body Mass Index (BMI) and the cardiometabolic profile of obese adolescents. A prospective cohort study was conducted. We measured weight, height, body composition, blood pressure, heart rate, glucose, insulin, total cholesterol, low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol, triglycerides, and high sensitivity C-reactive protein (hs-CRP) levels before, during the last week of and at 6 weeks after Ramadan. Twenty-five obese adolescents were included. BMI and glucose metabolism did not change after Ramadan or at 6 week after cessation of Ramadan. At the end of Ramadan, a significant decrease in body fat percentage was observed, while significant increases in heart rate, total cholesterol, LDL cholesterol, HDL cholesterol, and hs-CRP were found (all P?<?0.05). Six weeks after Ramadan, all parameters returned to baseline levels. Conclusion: In this sample of 25 ethnic obese adolescents transient cardiometabolic changes were observed during Ramadan fasting. Since most of these changes were reversible within 6 weeks, there seems no harm or benefit for obese adolescents to participate in Ramadan.     

Poliomyelitis trends in Pondicherry, south India, 1989-91.

STUDY OBJECTIVES: To assess the poliomyelitis trend, including study of the epidemiological features, and to correlate this with the immunisation coverage of infants. DESIGN: Three annual lameness surveys in children aged 0-60 months employing cluster sampling methods and a series of five cross sectional surveys of immunisation coverage in children aged 12-23 months of age were undertaken. SETTING: Pondicherry, India, 1988-92. SUBJECTS: More than 10,000 children in the age group of 0-60 months took part in the three annual lameness surveys and samples of 210 children aged 12-23 months were covered each year in immunisation coverage surveys. MEASUREMENTS AND MAIN RESULTS: Altogether 50 of 11,461, 24 of 10,093, and 17 of 11,218 children surveyed during 1989, 1990, and 1991 respectively had become lame as a result of poliomyelitis, giving prevalences of 4.4, 2.4, and 1.5 per 1000 children for the three surveys. The corrected prevalences of poliomyelitis were 5.9, 3.2, and 2.0 per 1000 children during 1989, 1990, and 1991 respectively. The proportion of cases aged up to 36 months fell from 48% in 1989 to 12.5% in 1990 and 6% in 1991. The age at onset was less than 1 year in most. The median age at onset was 10.7 months. About 54% of the affected children had received three doses of oral poliomyelitis vaccine (OPV) before the onset of paralysis. In 1988 immunisation coverage for the third dose of OPV was 91% and in 1992 it was 97.6%. The drop out rate for the first versus the third dose of OPV fell from 6.3 in 1988 to 1.9% in 1992. CONCLUSION: Three successive annual lameness surveys showed that poliomyelitis was declining between 1989 and 1991. Five immunisation coverage surveys conducted from 1988 to 1992 showed high initial coverage followed by an improvement in the form of almost universal coverage for OPV.     

Clinicopathological Profile of Myelomatous Pleural Effusion: Single-center Real-world Experience and Review of Literature

Background

Multiple myeloma (MM) is a hematologic malignancy of plasma cell origin. MM primarily affects bone marrow, but extramedullary sites can also be involved. Myelomatous pleural effusion (MPE) is an atypical and rare complication of MM. We aimed to systematically study the incidence and clinicopathologic profile of patients with MPE in a real-world setting.

Chemopreventive efficacy of gallic acid,an antioxidant and anticarcinogenic polyphenol,against 1,2-dimethyl hydrazine induced rat colon carcinogenesis

Colon cancer is a major cause of morbidity and mortality in developed and developing countries and its etiology is known to be a combination of hereditary, environmental, dietary factors and lack of physical activity. Chemoprevention offers a novel approach to control the incidence of colon cancer. Gallic acid (GA) is a polyphenol widely present in tea and other plants which is popularly used in the traditional medicine of China. The present study was to evaluate the efficacy of GA supplementation on tissue lipid peroxidation and antioxidant defense system in 1,2-dimethyhydrazine (DMH) induced colon carcinogenesis in male Wistar rats. The rats were assorted into six groups, viz., group1 control rats received modified pellet diet; group 2 rats received GA (50 mg/kg body weight) orally along with modified pellet diet; group 3 rats received DMH (20 mg/kg body weight) subcutaneously once a week for the first 15 weeks; groups 4, 5 and 6 rats received GA along with DMH during the initiation, post- initiation stages and the entire period of study respectively. All the rats were sacrificed at the end of 30 weeks and the tissues were evaluated biochemically. We observed decreased lipid peroxidation (LPO) products such as thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (LOOH) and conjugated dienes (CD) and diminished levels of antioxidants such as superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), glutathione reductase (GR) and glutathione peroxidase (GPx) in the tissues of DMH treated rats, which were elevated significantly on GA supplementation. Moreover, enhanced activity of ascorbic acid and α-tocopherol levels were also observed in DMH alone treated rats which were significantly reduced on GA supplementation. Our results suggest that GA could exert a significant chemopreventive effect on DMH induced colon carcinogenesis.