The combination of oral-recombinant methioninase and azacitidine arrests a chemotherapy-resistant osteosarcoma patient-derived orthotopic xenograft mouse model

Cancer Chemotherapy and Pharmacology - Cancers are methionine (MET) and methylation addicted, causing them to be highly sensitive to MET restriction. The present study determined the efficacy of...     

The effects of nicotine on the alpha-7 and beta-2 nicotinic acetycholine receptor subunits in the developing piglet brainstem

Exposure to cigarette smoke is a major risk factor for sudden infant death syndrome (SIDS). We tested the hypothesis that nicotine increases expression of the nicotinic acetylcholine receptor (nAChR) subunits α7 and β2 in a piglet model. Piglets exposed to 2 mg/kg/day nicotine for 14 days postnatally (n = 14) were compared to non-exposed controls (n = 14), (equal gender proportions). Immunohistochemistry was performed to identify and quantify changes in, α7 and β2 nAChR subunits in 8 nuclei of the medulla at both the rostral and caudal levels. Compared to controls, nicotine exposed piglets had decreased α7 in the rostral dorsal motor nucleus of the vagus (rDMNV) (p = 0.01), and increased β2 in the caudal DMNV (cDMNV) (p = 0.05), caudal nucleus of the spinal trigeminal tract (cNSTT) (p = 0.03) and caudal nucleus of the solitary tract (cNTS) (p = 0.04). Analysis by gender showed that in the control group, compared to males, females had higher β2 in the caudal hypoglossal (cXII) (p < 0.01) and caudal inferior olivary (p = 0.04) nuclei, while in the nicotine group females had higher β2 in the cDMNV (p = 0.02). Compared to control males, nicotine exposed males had lower β2 in the cXII (p < 0.01). Overall, changes in α7 were specific to nicotine exposure with no gender differentiation. Changes in β2 were more widespread but showed gender-specific effects. These findings provide evidence that early postnatal exposure to nicotine significantly affects nAChR subunit expressions in the developing brainstem.     

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     

Thrombotic thrombocytopenic purpura without schistocytes on the peripheral blood smear

A hallmark of the clinical syndrome of thrombotic thrombocytopenic purpura (TTP) is evidence of microangiopathic hemolytic anemia. The presence of schistocytes on the peripheral blood smear, elevated plasma lactic dehydrogenase, and decreased haptoglobin concentration are used as evidence of microangiopathic hemolytic anemia to make a diagnosis of TTP. This report describes a case of recurrence of TTP in the absence of schistocytes in the peripheral blood smear during the recurrent episode. Although careful attention should be paid to microscopic examination of a blood smear in any patient presenting with acute renal failure and thrombocytopenia, this case emphasizes the need to consider TTP-hemolytic uremic syndrome in the differential diagnosis, even in the absence of peripheral schistocytosis.     

Cardiac angiography and conversion disorder

BACKGROUND: Somatoform disorders are disorders in which "psychic energy" is transferred to somatic symptoms secondary to stressors. The concept of somatoform disorders and their associations among patients with cardiac disease is a relatively unfamiliar area. OBJECTIVE: The authors present a case that illustrates how conversion disorder, a specific type of somatoform disorder, may be associated with the psychologic stressor involved with cardiac angiography. The authors will discuss the literature concerning the identification and treatment of this disorder. METHODS: The relevant literature in the area of conversion disorder and cardiac angiography was reviewed. RESULTS: This report is the first documented case of a woman who developed conversion disorder after coronary catheterization. Using the case, a summary of diagnostic and treatment modalities used in this disorder is provided. CONCLUSIONS: The case highlights how conversion disorder can occur as a sequelae of coronary catheterization. The principles involved in the diagnosis and treatment of conversion disorder were successful in managing this patient. It is hoped that the case can aid cardiologists in becoming cognizant of this uncommon psychiatric disorder.     

Accumbal neural responses during the initiation and maintenance of intravenous cocaine self-administration

During a chronic extracellular recording session, animals with a history of cocaine self-administration were allowed to initiate drug seeking under drug-free conditions. Later, in the same recording session, animals engaged in intravenous cocaine self-administration. During the drug-free period, 31% of 70 accumbal neurons showed a significant increase in average firing rate in association with either or both the exposure to cues that signaled the onset of cocaine availability and the subsequent onset of drug-seeking behavior. The neurons that showed an average excitatory response during the drug-free period were the only group of neurons that showed an average excitatory phasic response to cocaine-reinforced lever presses during the drug self-administration session. A majority of the neurons that were activated during the drug-free period, like the majority of other neurons, showed decreases in average firing in response to self-administered cocaine. However, the neurons that were activated during the drug-free period maintained a higher rate of firing throughout the self-administration session than did other accumbal neurons. The data of the present study are consistent with the conclusion that accumbal neurons contribute to, or otherwise process, initiation of drug seeking under drug-free conditions and that they do so via primarily excitatory responses. Furthermore, there is continuity between the drug-free and -exposed conditions in neural responses associated with drug seeking. Finally, the data have potential implications for understanding mechanisms that transduce accumbal-mediated drug effects that contribute to drug addiction.     

C-reactive proteins as an indicator of sub-clinical infection in cases of premature rupture of membranes

The present study was conducted on 25 cases of preterm, premature rupture of membranes and 25 patients preterm with intact membranes, between 28-36 weeks of gestation, admitted in the maternity ward of Obstetrics and Gynecology, PGIMS, Rohtak. The sensitivity and specificity of CRP determination was found to be 80% each as an early predictor of subclinical chorioamnionitis. TLC had a low sensitivity of 20% and specificity of 60% in detecting histopathological chorioamnionitis. So CRP estimation is a reliable marker for detection of early choriamnionitis, at the same time, it is quite affordable and reasonably simple.