Oral lipid based drug delivery system (LBDDS): formulation, characterization and application: a review.

The major problem in oral drug formulations is low and erratic bioavailability, which mainly results from poor aqueous solubility. This may lead to high inter- and intra subject variability, lack of dose proportionality and therapeutic failure. The improvement of bio-availability of drugs with such properties presents one of the greatest challenges in drug formulations.

Left atrial reservoir function predicts atrial fibrillation recurrence after catheter ablation: a two-dimensional speckle strain study.

Background: Predictors of atrial fibrillation (AF) recurrence after catheter ablation (CA) are not fully defined. We hypothesized that 2D left atrial (LA) regional strain maps would help identify abnormal atrial substrate that increases susceptibility to AF recurrence post-CA.

Methods And Results: Sixty-three patients (63 ± 10 years, 60% male) underwent CA for symptomatic paroxysmal (75%) or persistent (25%) AF.

Rotavirus toxin NSP4 induces diarrhea by activation of TMEM16A and inhibition of Na+ absorption.

Rotavirus infection is the most frequent cause for severe diarrhea in infants, killing more than 600,000 every year. The nonstructural protein NSP4 acts as a rotavirus enterotoxin, inducing secretory diarrhea without any structural organ damage. Electrolyte transport was assessed in the colonic epithelium from pups and adult mice using Ussing chamber recordings.

Percutaneous ureteral elevation in laparoendoscopic single-site radical nephrectomy.

Background And Objectives: To describe our technique of suture-assisted ureteral retraction during Laparoendoscopic Single-Site (LESS) radical nephrectomy.

Materials And Methods: A healthy, 39-year-old woman with an incidental 5-cm enhancing left renal mass elected to undergo radical nephrectomy. A 2-cm skin incision was made in the left upper quadrant of the abdomen, and a Covidien SILS port was introduced using standard Hasson techniques.

Retrospective study of the impact of pharmacogenetic variants on paclitaxel toxicity and survival in patients with ovarian cancer.

Purpose: Paclitaxel has a broad spectrum of anti-tumor activity and is useful in the treatment of ovarian, breast, and lung cancer. Paclitaxel is metabolized in the liver by CYP2C8 and CYP3A4 and transported by P-glycoprotein. The dose-limiting toxicities are neuropathy and neutropenia, but the interindividual variability in toxicity and also survival is large.

A fuzzy logic-based system for anaesthesia monitoring.

In recent years there has been a rapid growth in patient monitoring and medical data analysis using a number of computer-aided systems based on expert systems, fuzzy logic and many other intelligent techniques. Fuzzy logic-based expert systems have shown potential to improve clinician performance by imitating human thought processes in complex circumstances and accurately executing repetitive tasks to which humans are ill-suited. The main goal of this study was to develop a clinically useful diagnostic alarm system for detecting critical events during anaesthesia administration.

The value of gynecologic cancer follow-up: evidence-based ignorance?

Introduction: To explore the extent of evidence-based data and cost-utility of follow-up after primary treatment of endometrial and ovarian cancer, addressing perspectives of technology, organization, economics, and patients.

Methods: Systematic literature searches according to the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions were conducted separately for each of the 4 perspectives. In addition, the organizational analysis included a nationwide questionnaire survey among all relevant hospital departments, and the operating costs were calculated.

Circulating fibroblast growth factor-23 is associated with fat mass and dyslipidemia in two independent cohorts of elderly individuals.

Objective: Disturbances in mineral metabolism define an increased cardiovascular risk in patients with chronic kidney disease. Fibroblast growth factor-23 (FGF23) is a circulating regulator of phosphate and vitamin D metabolism and has recently been implicated as a putative pathogenic factor in cardiovascular disease. Because other members of the FGF family play a role in lipid and glucose metabolism, we hypothesized that FGF23 would associate with metabolic factors that predispose to an increased cardiovascular risk.

Serum fibroblast growth factor-23 (FGF-23) and fracture risk in elderly men.

A normal mineral metabolism is integral for skeletal development and preservation of bone integrity. Fibroblast growth factor 23 (FGF-23) is a bone-derived circulating factor that decreases serum concentrations of inorganic phosphorous (P(i)) and 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)]. Increased FGF-23 expression is a direct or indirect culprit in several skeletal disorders; however, the relation between FGF-23 and fracture risk remains undetermined.

Role of humic acid on oral drug delivery of an antiepileptic drug.

Context: Humic acid (HA) is omnipresent in natural organic matter that is a macromolecular, negatively charged polyelectrolyte that contains a hydrophobic core. It is also present in a significant amount in Shilajit (used frequently in traditional medicines), which is used in this study as a source of extraction. HA is evaluated for the oral drug delivery of carbamazepine (CBZ).

Kruppel-like factor-4 transcriptionally regulates VE-cadherin expression and endothelial barrier function.

Rationale: Vascular endothelial (VE)-cadherin localized at adherens junctions (AJs) regulates endothelial barrier function. Because WNT (wingless) signaling-induced activation of the transcription factor Krüppel-like factor (KLF)4 may have an important role in mediating the expression of VE-cadherin and AJ integrity, we studied the function of KLF4 in regulating VE-cadherin expression and the control of endothelial barrier function.

Objective: The goal of this study was to determine the transcriptional role of KLF4 in regulating VE-cadherin expression and endothelial barrier function.

Does race affect outcomes in triple negative breast cancer?

Background: There is discordance among studies assessing the impact of race on outcome of patients with Triple Negative Breast Cancer (TNBC). We assessed survival outcomes for African American (AA) versus Caucasian (CA) women with TNBC treated at an urban cancer center in Memphis, TN with a predominant AA patient population.

Methods: Patients with Stage I-III TNBC were identified from our breast database.

Parathyroid Klotho and FGF-receptor 1 expression decline with renal function in hyperparathyroid patients with chronic kidney disease and kidney transplant recipients.

Current studies suggest that short-term exposure of parathyroid glands to fibroblast growth factor 23 (FGF23) reduces parathyroid hormone secretion. However, patients with chronic kidney disease (CKD) develop secondary hyperparathyroidism despite high levels of serum FGF23, indicating a parathyroid FGF23 'resistance'. Here we analyzed the expression of the FGF23 receptors Klotho and FGF receptor 1 (FGFR1) in 88 hyperplastic parathyroid glands from 31 patients with CKD (including 21 renal allograft recipients), and their regulation in isolated bovine and human hyperplastic parathyroid cells.

FoxM1 regulates re-annealing of endothelial adherens junctions through transcriptional control of beta-catenin expression.

Repair of the injured vascular intima requires a series of coordinated events that mediate both endothelial regeneration and reannealing of adherens junctions (AJs) to form a restrictive endothelial barrier. The forkhead transcription factor FoxM1 is essential for endothelial proliferation after vascular injury. However, little is known about mechanisms by which FoxM1 regulates endothelial barrier reannealing.

Iatrogenic gall bladder perforations in laparoscopic cholecystectomy: an audit of 200 cases.

This study was done to evaluate the frequency of iatrogenic gall bladder perforation (IGBP) in laparoscopic cholecystectomy and to determine its association with gender, adhesions in right upper quadrant and types of gall bladder. This retrospective descriptive study included 200 patients who underwent laparoscopic cholecystectomy for symptomatic cholelithiasis at Jamal Noor Hospital and Hamdard University Hospital, Karachi from January 2007 to January 2009. Video recording of all 200 laparoscopic cholecystectomies were analyzed for the IGBP.

A phase II study of combination chemotherapy in early relapsed epithelial ovarian cancer using gemcitabine and pegylated liposomal doxorubicin.

Objective: Treatment of epithelial ovarian cancer patients relapsing with a short treatment-free interval (TFI) after prior chemotherapy is unsatisfactory. This phase II trial evaluated the activity and feasibility of pegylated liposomal doxorubicin (PLD) plus gemcitabine in this setting.

Methods: Patients who had received prior platinum and paclitaxel with a TFI 0-12 months received PLD 25 mg/m(2)day 1 plus gemcitabine 800 mg/m(2)day 1, 8 every 21 days.

A radiofrequency transseptal needle: initial animal studies.

Objectives: The objective of this study was to demonstrate the safety and efficacy of a new transseptal needle design with a radiofrequency (RF) tip combined with the ease of use of the needle configuration.

Background: RF transseptal puncture to enter the left heart, with a RF wire-catheter system is a successful technique in patients with complex access using a standard transseptal needle.

Methods: The RF transseptal needle (NRG™ Transseptal Needle; Baylis Medical, Montreal, Canada) was designed for RF percutaneous transseptal access to the left heart.

Subregional hippocampal deformations in major depressive disorder.

Background: Hippocampal atrophy is a well reported feature of major depressive disorder, although the evidence has been mixed. The present study sought to examine hippocampal volume and subregional morphology in patients with major depressive disorder, who were all medication-free and in an acute depressive episode of moderate severity.

Methods: Structural magnetic resonance imaging scans were acquired in 37 patients (mean age 42 years) and 37 age, gender and IQ-matched healthy individuals.

Impact of CYP2C8*3 on paclitaxel clearance: a population pharmacokinetic and pharmacogenomic study in 93 patients with ovarian cancer.

The primary purpose of this study was to evaluate the effect of CYP2C8*3 and three genetic ABCB1 variants on the elimination of paclitaxel. We studied 93 Caucasian women with ovarian cancer treated with paclitaxel and carboplatin. Using sparse sampling and nonlinear mixed effects modeling, the individual clearance of unbound paclitaxel was estimated from total plasma paclitaxel and Cremophor EL.

Caveolin-1 deficiency dampens Toll-like receptor 4 signaling through eNOS activation.

Caveolin-1 (Cav1), the scaffolding protein of caveolae, has been shown to play an important role in host defense and inflammation. However, the underlying molecular basis for these actions remains elusive. Here, using double mutant mice with genetic deletions of Cav1 and NOS3, we show that chronic endothelial nitric oxide synthase (eNOS) activation secondary to loss of Cav1 serves a crucial immunomodulatory function through tyrosine nitration-mediated impairment of interleukin-1 receptor associated kinase (IRAK)4, a signaling component required for nuclear factor-kappaB activation and innate immunity.

Multiple common variants for celiac disease influencing immune gene expression.

We performed a second-generation genome-wide association study of 4,533 individuals with celiac disease (cases) and 10,750 control subjects. We genotyped 113 selected SNPs with P(GWAS) < 10(-4) and 18 SNPs from 14 known loci in a further 4,918 cases and 5,684 controls. Variants from 13 new regions reached genome-wide significance (P(combined) < 5 x 10(-8)); most contain genes with immune functions (BACH2, CCR4, CD80, CIITA-SOCS1-CLEC16A, ICOSLG and ZMIZ1), with ETS1, RUNX3, THEMIS and TNFRSF14 having key roles in thymic T-cell selection.

Effects of Azospirillum brasilense with genetically modified auxin biosynthesis gene ipdC upon the diversity of the indigenous microbiota of the wheat rhizosphere.

The phytostimulatory properties of Azospirillum inoculants, which entail production of the phytohormone indole-3-acetic acid (IAA), can be enhanced by genetic means. However, it is not known whether this could affect their interactions with indigenous soil microbes. Here, wheat seeds were inoculated with the wild-type strain Azospirillum brasilense Sp245 or one of three genetically modified (GM) derivatives and grown for one month.

Expression and function of epithelial anoctamins.

The calcium-activated chloride channel anoctamin1 (ANO1; TMEM16A) is fundamental for the function of epithelial organs. Mice lacking ANO1 expression exhibit transport defects and a pathology similar to cystic fibrosis. They also show a general defect of epithelial electrolyte transport.

Solitary plexiform neurofibroma, a pitfall in diagnosis of lipoma.

Plexiform neurofibromatosis is almost invariably associated with neurofibromatosis type I. A case of an isolated back plexiform neurofibroma, initially thought to be a lipoma, is presented, with emphasis on the importance of eliciting family history in reaching a diagnosis of neurofibromatosis. Currently, surgical resection is still the treatment of choice though a management plan is not well defined.