Gram-negative bacterial endotoxin- induced infertility: a birds eye view

Alleviation of infertility on the one hand and development of improved methods of contraception on the other are global concerns to woman's health. The molecular signals that regulate implantation are of clinical relevance since understanding the nature of these signals may lead to strategies to correct implantation failure and to develop novel contraceptive approaches. The other pressing concern is the poor pregnancy rate resulting from in vitro fertilization (IVF). The pregnancy rate in IVF programs remains about 20-30% in spite of the high rate of successful fertilization. This has led to the proposition that additional uterine factors, critical for the implantation process, must be limiting. Identification of such parameters could help in determining the appropriate physiological state of the uterus for embryo transfer. Several factors are known to have a direct or indirect impact on the ability of the uterus to develop to a functionally receptive state. This would disrupt the normal coordination between embryonic and uterine development even though all molecular players may seem otherwise normal.     

Comprehending the role of LPS in Gram-negative bacterial vaginosis: ogling into the causes of unfulfilled child-wish

Introduction Intrauterine infection is frequently associated with pregnancy loss in pregnant women.Discussion This article reviews the role of Gram-negative bacterial infection in various complications related to early pregnancy and subsequent pregnancy loss. Here we discus the pathways of ascending intrauterine infection, microbiology and the pathophysiology of such infections. The clinical impact, therapy, consequences, prevention and implications of Gram-negative bacterial infections in women during their reproductive life span is also discussed. This article also makes an attempt to discuss our studies and findings, related to the effect of the LPS component of the Gram-negative bacterial endotoxin on preimplantation stage embryonic development and implantation. This early phase of pregnancy remains mostly unnoticed by the mother as well as the health care provider, and therefore holds more threat to the life of the fetus and the mother. The molecular mechanisms of LPS-induced pregnancy losses through abnormal embryonic development, implantation failure, and preterm labor and birth with specific references to the role of proinflammatory cytokines like IL-1 and TNF are discussed.Conclusion Once these inflammatory mediators have increased in the feto-maternal tissues, it may be too late or harmful to try and prevent the adverse outcomes of pregnancy.     

Bile salt exposure causes phosphatidyl-inositol-3-kinase-mediated proliferation in a Barrett's adenocarcinoma cell line

BACKGROUND: The mechanisms by which gastroesophageal reflux promotes malignant progression in Barrett's esophagus are poorly understood. The phosphatidylinositol-3-kinase (PI3 kinase)/Akt pathway regulates proliferation and apoptosis. We hypothesized that the PI3 kinase/Akt pathway mediates the pro-proliferative and antiapoptotic effects of bile. METHODS: The Barrett's adenocarcinoma cell line, SEG-1, was exposed to the conjugated bile salt, glycochenodeoxycholic acid (GCDA). Cell number was measured by the MTT incorporation assay and by Coulter counter. PI3 kinase/Akt activity was inferred from Western blots of phosphorylated and total Akt. Proliferation and apoptosis were determined by BrdU incorporation and cell death ELISA. RESULTS: A dose-dependent cell number increase was seen with a 20-minute exposure to GCDA. On Western blot, 200 micromol/L GCDA caused a 3-fold increase in Akt phosphorylation within 20 minutes, which was inhibited by 90% with the addition of PI3 kinase inhibitor, LY294002. LY294002 produced dose-dependent inhibition of GCDA-induced cell number increases. 200 micromol/L GCDA decreased apoptosis by 25%. Addition of LY294002 did not completely inhibit the antiapoptotic effect of bile. CONCLUSIONS: Bile salts activate the PI3 kinase/Akt signaling pathway and stimulate cell growth in SEG-1. The majority of this PI3 kinase-mediated effect is secondary to increases in proliferation rather than to decreases in apoptosis.     

Evaluation of seizure-like episodes in survivors of moderate and severe traumatic brain injury

BACKGROUND: Transient paroxysmal alterations of consciousness or behavior are common sequelae of moderate and severe traumatic brain injury (TBI). Clinicians caring for patients with such episodes often diagnose them as epileptic seizures, a frequent and well-studied complication of TBI. As it is difficult to confirm this diagnosis, antiepileptic drugs are often used empirically. However, as such therapy is frequently ineffective, we studied the usefulness of prolonged video electroencephalogram (VEEG) monitoring in the clinical management of paroxysmal behaviors in TBI survivors. METHODS: Records of patients referred evaluation in an epilepsy monitoring unit for management of medically intractable epilepsy were retrospectively reviewed. Patients with a documented history of moderate-to-severe brain injury preceding the onset of epilepsy were identified. These patients were studied by simultaneous videotape and scalp electroencephalographic recordings, and the majority also underwent magnetic resonance imaging and neuropsychologic studies. RESULTS: Of the 1858 consecutive admissions over a 66-month period, 127 (7%) fulfilled enrollment criteria. VEEG monitoring was conducted for an average of 4.6 days. Monitoring was successful in establishing a diagnosis in 82% of the cases referred: 62% had focal seizures, 6% had generalized seizures, and 33% had psychogenic nonepileptic seizures. Of those with temporal lobe epilepsy, 53% had mesial temporal sclerosis, as shown by magnetic resonance imaging. CONCLUSIONS: VEEG is a useful procedure in the evaluation of TBI survivors with spells. The yield of diagnoses that may alter treatment is substantial. Additionally, mesial temporal sclerosis is associated with TBI. Given the variety of seizure types found in survivors of moderate-to-severe TBI, obtaining specific diagnosis of seizure type by VEEG monitoring impacts treatment options.     

Apocrine carcinoma of the breast presenting as a solitary cyst: cytological and histopathological study of a case

Apocrine carcinoma is a rare, unique and morphologically distinct type of invasive breast carcinoma. This tumor has predilection for elderly females (6th and 7th decade). This report is of apocrine carcinoma of the breast arising in a 27 year old female, a rare occurrence in this age group, with only a few cases on record.     

Steady-state pharmacokinetics of fluvastatin in healthy subjects following a new extended release fluvastatin tablet, Lescol XL

This was an open-label, randomized, three-period, three-treatment, multiple dose, crossover study in 12 healthy male and female subjects. This study evaluated single dose and steady-state pharmacokinetics of fluvastatin following single and multiple dose administrations of a new extended release fluvastatin 8 h matrix tablet, Lescol XL 80 mg and 160 mg doses once a day. The study also included a twice a day administration of an immediate release (IR) form of fluvastatin capsule, Lescol, for comparative purposes. All doses were administered for 7 days. The safety and tolerability were also assessed. The pharmacokinetics of fluvastatin were evaluated on days 1 and 7 following each treatment. Fluvastatin systemic exposure was 50% less when administered as Lescol XL 80 mg qd compared with Lescol IR 40 mg bid. Conversely, fluvastatin systemic exposure was 22% higher when administered as Lescol XL 160 mg qd compared with Lescol IR 40 mg bid. Single doses of Lescol XL 80 mg and 160 mg were dose proportional but, deviation (30%) from dose proportionality was observed for the Lescol XL 160 mg at steady-state. There appeared to be moderate (20%-40%) accumulation of serum fluvastatin maximal concentrations and exposure after multiple doses of Lescol XL tablets. Both Lescol XL 80 mg and 160 mg showed delayed absorption and longer apparent elimination half-life compared with fluvastatin IR capsule. Single and multiple doses of fluvastatin were generally well tolerated in this healthy volunteer population. Adverse event profiles were consistent with the published safety profile of the marketed formulations. Aside from one incidence of creatine phosphokinase (CPK) elevation (following Lescol XL 160 mg qd treatment), there were no safety concerns with any of the treatments when administered acutely (7 days).