Antitumor activity and antioxidant role of Bauhinia racemosa against Ehrlich ascites carcinoma in Swiss albino mice [corrected]

AIM: To study the antitumor effect and antioxidant role of Bauhinia racemosa. METHODS: Antitumor activity and antioxidant status of methanol extract (50, 100, and 200 mg/kg) of Bauhinia racemosa stem bark was evaluated against Ehrlich ascites carcinoma (EAC) tumor in mice. Acute and short-term toxicity studies were performed initially in order to ascertain the safety of methanol extract of Bauhinia racemosa (MEBR). After 24 h of tumor inoculation, the extract was administered daily for 14 d. After administration of the last dose followed by 18 h fasting, mice were then sacrificed for observation of antitumor activity. The effect of MEBR on the growth of transplantable murine tumor, life span of EAC bearing hosts and simultaneous alterations in the hematological profile and liver biochemical parameters (lipid peroxidation, antioxidant enzymes) were estimated. RESULTS: The MEBR showed decrease in tumor volume, packed cell volume and viable cell count, and increased the nonviable cell count and mean survival time thereby increasing life span of EAC tumor bearing mice. Hematological profile reverted to more or less normal levels in extract treated mice. Treatment with MEBR decreased the levels of lipid peroxidation and increased the levels of glutathione, superoxide dismutase and catalase. CONCLUSION: The methanol extract of Bauhinia racemosa stem bark exhibited antitumor effect by modulating lipid peroxidation and augmenting antioxidant defense system in EAC bearing mice.     

A Hybrid Markov Chain–von Mises Density Model for the Drug-Dosing Interval and Drug Holiday Distributions

Lack of adherence is a frequent cause of hospitalizations, but its effects on dosing patterns have not been extensively investigated. The purpose of this work was to critically evaluate a novel pharmacometric model for deriving the relationships of adherence to dosing patterns and the dosing interval distribution. The hybrid, stochastic model combines a Markov chain process with the von Mises distribution. The model was challenged with electronic medication monitoring data from 207 hypertension patients and against 5-year persistence data. The model estimates distributions of dosing runs, drug holidays, and dosing intervals. Drug holidays, which can vary between individuals with the same adherence, were characterized by the patient cooperativity index parameter. The drug holiday and dosing run distributions deviate markedly from normality. The dosing interval distribution exhibits complex patterns of multimodality and can be long-tailed. Dosing patterns are an important but under recognized covariate for explaining within-individual variance in drug concentrations.

Electronic supplementary material

The online version of this article (doi:10.1208/s12248-014-9713-5) contains supplementary material, which is available to authorized users.KEY WORDS: adherence, circular distribution, compliance, dosing patterns, runs     

Case Report: Cystic Adventitial Disease of the External Iliac Artery with Imaging Features of a Complicating Proximal Dissection

IntroductionCystic adventitial disease (CAD) is a rare cause of claudication. We report a case of CAD involving the external iliac artery, with possible cyst rupture intramurally causing significant long segment stenosis of the external iliac artery.Case reportA 52-year-old female presented with sudden onset (over 1 day) lifestyle-limiting claudication affecting the left calf and thigh. CT angiography of the lower limbs revealed an eccentric low density wall thickening of the left external iliac artery (EIA) producing a 70% stenosis and a cystic lesion just distal to the stenosis.DiscussionA diagnosis of cystic adventitial disease was made and the patient proceeded to iliofemoral bypass.     

Presence of calcitonin-like peptide in rat milk: possible physiological role in regulation of neonatal prolactin secretion

Previous results have shown that salmon calcitonin (sCT), a peptide in rat brain and pituitary gland, inhibits basal and TRH-stimulated PRL release and reduces PRL mRNA levels in isolated anterior pituitary cells of adult rats in culture. Rat milk contains a variety of neuropeptides and hormones, some of which are absorbed in bioactive form to exert endocrine influences in the developing offspring. The present studies were undertaken to investigate whether a CT-like peptide is present in rat milk. Circulating PRL levels in neonatal rats are low, and there is an abrupt increase in the basal secretion of this hormone at weaning. A second objective was to examine whether CT plays a role in the regulation of PRL secretion in neonatal animals. A sensitive and specific RIA for sCT was developed and used to assay rat milk on various days of lactation for sCT-like immunoreactivity. sCT-like activity was present in the water-soluble (infranatant) fraction of milk throughout lactation in concentrations as high as 1589 pg/ml. There were no statistically significant differences in immunoreactive levels of the peptide in milk samples from different days of lactation. sCT-like immunoreactivity in rat milk infranatant coeluted with synthetic sCT on reverse phase HPLC, and these HPLC fractions inhibited basal PRL release when added to cultures of anterior pituitary cells. This inhibition of PRL release by the sCT-immunoreactive HPLC fractions was comparable to that exerted by equivalent concentrations of synthetic sCT. Newborn rats were injected sc with 10 microliters normal rabbit serum or anti-sCT serum from the day of birth until postpartum day 10. The rats were killed on day 11, and their sera were analyzed for PRL. Anti-sCT-injected rats showed a significant increase in serum PRL levels compared to those in untreated or normal serum-treated rats. These results demonstrate that a CT-like peptide, which is a potent inhibitor of PRL release, is present in rat milk throughout lactation, and that passive immunization with a highly specific anti-sCT serum leads to an increase in serum PRL levels in neonatal rats. CT, possibly of milk origin, may be a physiologically relevant PRL-inhibiting factor during the neonatal period.     

New norms for a new generation: cognitive performance in the framingham offspring cohort

A previous publication presented normative data on neuropsychological tests stratified by age, gender, and education based on the Original Cohort of the Framingham Heart Study. Many contemporary investigations include subject samples with higher levels of education, a factor known to affect cognitive performance. Secular change in education prompted the reexamination of norms in the children of the Original Cohort. The study population consisted of 853 men and 988 women from the Offspring Study, free of clinical neurological disease, who underwent a neuropsychological examination, which included tests given to their parents in 1974 to 1976 as well as additional newer tests to provide a more comprehensive battery. The Offspring population overall was more evenly distributed by gender and better educated. Their performance on cognitive tests was superior to that of the Original Cohort. Multivariable analyses revealed that more years of education explained only a part of the cohort differences. These findings suggest that continued surveillance of each generation is necessary to document the impact that unique social and economic variables have on cognitive function. Here, the authors provide updated normative data.