Flow cytometric estimation of cytotoxic activity of rhodexin A isolated from Rhodea japonica in human leukemia K562 cells

We have examined the cytotoxic effect of rhodexin A isolated from the extract of Rhodea japonica on human leukemia K562 cells using a flow cytometer and compared it with that of ouabain. Rhodexin A at 30 nM started to attenuate growth without affecting viability and further increases in the concentration of rhodexin A (100 nM or more) completely inhibited growth with decreasing viability. Rhodexin A at 30-100 nM increased the G(2)M population, but decreased the G(0)G(1) population, suggesting cell cycle arrest in the G(2)M phase. Rhodexin A at 100 nM increased the number of cells with hypodiploid DNA, indicating that rhodexin A induced apoptosis. The potency of rhodexin A to inhibit growth was greater than that of ouabain. The results indicate that rhodexin A exerts a potent inhibitory action on the growth of human leukemia K562 cells by inducing cell cycle arrest and apoptosis. Rhodexin A may also be a candidate for cancer treatment because there have been clinical reports of tumor regression in patients taking cardiac glycosides.     

Use of Plan-Do-Study-Act cycles to decrease incidence of neonatal hypothermia in the labor room

Background

Body temperature of a neonate continues to be under-documented, under-recognized, and under-managed, even though studies have shown that neonatal hypothermia increases mortality and morbidity. We aimed to reduce neonatal hypothermia (body temperature <36.5 °C) at 1 h following normal vaginal delivery in term and late preterm neonates in delivery room from 50% at baseline to less than 10% by 6 weeks.

Gamma-hydroxybutyric acid, a metabolite of UFT, shows anti-angiogenic activities and antitumor effect

We investigated the antitumor vasculogenesis and antitumor activity of gamma-hydroxybutyric acid (GHB), a metabolite of UFT. In a mouse dorsal air sac (DAS) assay, UFT demonstrated a wide spectrum of anti-tumor vasculogenesis except for AZ-521 tumor. Although the expression of vascular endothelial growth factor (VEGF) was detected in almost all tumor cell lines used in the DAS assays, expression of basic fibroblast growth factor (bFGF) was only detected in the AZ-521 tumor. GHB inhibited the chemotactic migration and morphological changes of human umbilical vein endothelial cells (HUVECs) induced by VEGF at IC50 values of 2.8 and 0.31 microM respectively. In addition to these in vitro assays, GHB blocked tumor growth of MC-5, a human breast cancer, in a xenograft model at inhibition rate of 37%. Moreover, GHB showed an additive effect in combination with 5-FU in this model. These results indicate that the anti-tumor vasculogenesis activity of GHB is involved in part in the antitumor effect of UFT.     

Oral pyogenic granuloma—a review of 215 cases in a South Indian Teaching Hospital, Karnataka, over a period of 20?years

Introduction

Pyogenic granuloma (PG) is a solitary, benign vascular growth. The precise cause for the development of pyogenic granuloma is unknown. It is believed, however, to be an exuberant tissue response to local irritation or trauma. Up to date, few studies have been carried out among Asians, particularly on the Indian subcontinent.

Materials and methods

Biopsy services were researched from 1989 to 2009. Two hundred-fifteen histologically confirmed PGs were retrieved and retrospectively analyzed for incidence, age, gender, site distribution, clinical presentation and histopathology. These cases were also evaluated for recurrence.

Results and discussion

Pyogenic granuloma accounted for 50.35% among reactive lesions in this study with a mean age of 34.27?years and a peak incidence in the third decade of life. PG was more common in females with a greater predilection for the maxillary gingivae (50.23%). Eighteen cases occurred in pregnant women. Clinically, PG occurred more frequently as pedunculated lesions (103). Gingival irritation and inflammation due to poor oral hygiene were the major precipitating factors. Histologically, PG presented a greater number of vascular channels of varied sizes, lined with plump endothelial cells, capillary budding, and chronic inflammatory cells, namely lymphocytes and plasma cells. Recurrence was seen in 14.88% of patients, predominantly in females, especially in the maxillary anterior region.

Conclusion

Among the reactive lesions, PG had the highest incidence. The frequency of pyogenic granuloma in the southern part of India was much higher compared to other studies. Additional epidemiological research is required to understand the frequency.     

Pharmacogenetic evaluation of ABCB1, Cyp2C9, Cyp2C19 and methylene tetrahydrofolate reductase polymorphisms in teratogenicity of anti-epileptic drugs in women with epilepsy

Aim:

Pregnancy in women with epilepsy (WWE) who are on anti-epileptic drugs (AEDs) has two- to three-fold increased risk of fetal malformations. AEDs are mostly metabolized by Cyp2C9, Cyp2C19 and Cyp3A4 and transported by ABCB1. Patients on AED therapy can have folate deficiency. We hypothesize that the polymorphisms in ABCB1, Cyp2C9, Cyp2C19 and methylene tetrahydrofolate reductase (MTHFR) might result in differential expression resulting in differential drug transport, drug metabolism and folate metabolism, which in turn may contribute to the teratogenic impact of AEDs.

Materials and Methods:

The ABCB1, Cyp2C9, Cyp2C19 and MTHFR polymorphisms were genotyped for their role in teratogenic potential and the nature of teratogenecity in response to AED treatment in WWE. The allelic, genotypic associations were tested in 266 WWE comprising of 143 WWE who had given birth to babies with WWE-malformation (WWE-M) and 123 WWE who had normal offsprings (WWE-N).

Results:

In WWE-M, CC genotype of Ex07 + 139C/T was overrepresented (P = 0.0032) whereas the poor metabolizer allele *2 and *2 *2 genotype of CYP2C219 was significantly higher in comparison to WWE-N group (P = 0.007 and P = 0.005, respectively). All these observations were independent of the nature of malformation (cardiac vs. non cardiac malformations).

Conclusion:

Our study indicates the possibility that ABCB1 and Cyp2C19 may play a pivotal role in the AED induced teratogenesis, which is independent of nature of malformation. This is one of the first reports indicating the pharmacogenetic role of Cyp2C19 and ABCB1 in teratogenesis of AED in pregnant WWE.     

Essential hypertension as a result of neurochemical changes at the rostral ventrolateral medulla

Acute ischemia of the brainstem has been known to produce hypertension. After an initial review of central nervous system mechanisms contributing to systemic hypertension and the impact of the rostral ventrolateral medulla (RVLM) on arterial pressure, the authors propose that essential hypertension involves neurochemical changes at the level of the RVLM which are triggered by cerebral ischemia. Experimental and clinical data are presented to show that there is a link between ischemia of the brainstem and chronic hypertension. Atherosclerosis of the cerebral circulation leads to ischemia of the RVLM and other regions with autonomic function. This ischemic process results in increased availability of angiotensin II in the RVLM, which maintains the chronic hypertensive state via either direct stimulation of the RVLM or exacerbation of brainstem ischemia due to increased vasoconstriction.