Diet induced insulin resistance is due to induction of PTEN expression.

Type 2 Diabetes (T2D) is a condition that is often associated with obesity and defined by reduced sensitivity of PI3K signaling to insulin (insulin resistance), hyperinsulinemia and hyperglycemia. Molecular causes and early signaling events underlying insulin resistance are not well understood. Insulin activation of PI3K signaling causes mTOR dependent induction of PTEN translation, a negative regulator of PI3K signaling.

Influence of iontophoresis on delivery of NSAID-loaded deformable liposomal dispersions: and evaluation.

Negatively charged deformable liposomes (DL) of ketoprofen were formulated to enhance transdermal delivery of ketoprofen (KP) under the influence of iontophoresis for intraarticular delivery. Conventional and deformable KP liposomes were prepared using thin film hydration, characterized and intraarticular delivery of KP was evaluated using Sprague-Dawley rats. Vesicles displayed entrapment efficiency (>71%); zeta potential <-25 mV; size between 152.

Signal amplification in growth cone gradient sensing by a double negative feedback loop among PTEN, PI(3,4,5)P and actomyosin.

Axon guidance during neural wiring involves a series of precisely controlled chemotactic events by the motile axonal tip, the growth cone. A fundamental question is how neuronal growth cones make directional decisions in response to extremely shallow gradients of guidance cues with exquisite sensitivity. Here we report that nerve growth cones possess a signal amplification mechanism during gradient sensing process.

Regulation of PTEN translation by PI3K signaling maintains pathway homeostasis.

The PI3K pathway regulates cell metabolism, proliferation, and migration, and its dysregulation is common in cancer. We now show that both physiologic and oncogenic activation of PI3K signaling increase the expression of its negative regulator PTEN. This limits the duration of the signal and output of the pathway.

Iontophoretic Mediated Intraarticular Delivery of Deformable Liposomes of Diclofenac Sodium.

Background And Objective: Topical therapy is ineffective in the case of Musculoskeletal Disorders (MSD) as it is not able to maintain therapeutic levels of the drug in the affected joint due to its inability to surpass the dermal circulation and penetrate into deeper tissues. One of the approaches to enhance deep tissue penetration of drugs is to increase drug delivery much above the dermal clearance. The objective of the present work was to formulate negatively charged Deformable Liposomes (DL) of Diclofenac Sodium (DS) using biosurfactants and target the same to the synovial fluid by application of iontophoresis.

Thermosensitive liposomal gels loaded with antimicrobial agent for oral care in critically ill patients.

A novel thermosensitive gel loaded with meropenem (MP) liposomes was designed to improve retention in the oral cavity as a prophylactic measure to prevent ventilator-acquired pneumonia in critically ill patients. Meropenem liposomes were incorporated into poloxamer 407 gels and gamma irradiated. Mean size of liposome was 247 nm, polydispersity index < 0.

Systems Biology of Cancer Metastasis.

Cancer metastasis is no longer viewed as a linear cascade of events but rather as a series of concurrent, partially overlapping processes, as successfully metastasizing cells assume new phenotypes while jettisoning older behaviors. The lack of a systemic understanding of this complex phenomenon has limited progress in developing treatments for metastatic disease. Because metastasis has traditionally been investigated in distinct physiological compartments, the integration of these complex and interlinked aspects remains a challenge for both systems-level experimental and computational modeling of metastasis.

A Loss of Epigenetic Control Can Promote Cell Death through Reversing the Balance of Pathways in a Signaling Network.

Epigenetic control of regulatory networks is only partially understood. Expression of Insulin-like growth factor-II (IGF2) is controlled by genomic imprinting, mediated by silencing of the maternal allele. Loss of imprinting of IGF2 (LOI) is linked to intestinal and colorectal cancers, causally in murine models and epidemiologically in humans.

Development and evaluation of an oral fast disintegrating anti-allergic film using hot-melt extrusion technology.

The main objective of this novel study was to develop chlorpheniramine maleate orally disintegrating films (ODF) using hot-melt extrusion technology and evaluate the characteristics of the formulation using in vitro and in vivo methods. Modified starch with glycerol was used as a polymer matrix for melt extrusion. Sweetening and saliva-simulating agents were incorporated to improve palatability and lower the disintegration time of film formulations.

A study on knowledge and awareness about tuberculosis in senior school children in Bangalore, India.

Background: Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (M. tuberculosis), commonly affecting the lungs. All health care professionals including the pharmacists provide a valuable public health role in promoting community awareness of TB particularly in reducing stigma attached to TB.

Two interferon-independent double-stranded RNA-induced host defense strategies suppress the common cold virus at warm temperature.

Most strains of rhinovirus (RV), the common cold virus, replicate better at cool temperatures found in the nasal cavity (33-35 °C) than at lung temperature (37 °C). Recent studies found that although 37 °C temperature suppressed RV growth largely by engaging the type 1 IFN response in infected epithelial cells, a significant temperature dependence to viral replication remained in cells devoid of IFN induction or signaling. To gain insight into IFN-independent mechanisms limiting RV replication at 37 °C, we studied RV infection in human bronchial epithelial cells and H1-HeLa cells.

Development of taste masked caffeine citrate formulations utilizing hot melt extrusion technology and in vitro-in vivo evaluations.

The objective of this study was to develop caffeine citrate orally disintegrating tablet (ODT) formulations utilizing hot-melt extrusion technology and evaluate the ability of the formulation composition to mask the unpleasant bitter taste of the drug using in vitro and in vivo methods. Ethylcellulose, along with a suitable plasticizer, was used as a polymeric carrier. Pore forming agents were incorporated into the extruded matrix to enhance drug release.

Liposomes as carriers of the lipid soluble antioxidant resveratrol: evaluation of amelioration of oxidative stress by additional antioxidant vitamin.

Aim: Resveratrol (RES) is a well-known antioxidant, yet in combination with other antioxidant vitamins, it was found to be more effective than any of these antioxidants alone. Present work aims to compare the antioxidant actions of resveratrol with and without vitamin C following delivery as liposomes tested using chemical and cellular antioxidative test systems.

Main Methods: Liposomes were prepared by the thin film hydration method and characterised for percent drug entrapment (PDE), Z-average mean size (nm), polydispersity index (PDI) and zeta potential.

Newer diagnostic tools in tuberculosis.

Tuberculosis (TB) is a global health problem. Multi Drug Resistant TB (MDR-TB) and Extensively Drug Resistant TB (XDR-TB) cause high mortality. There are obstacles to the diagnosis of TB due to lack of accurate, cost effective and rapid diagnostic tools.

Stem cell differentiation as a renewal-reward process: predictions and validation in the colonic crypt.

Stem cells serve as persistent reservoirs for replenishment of rapidly renewing tissues, frequently also ensuring that the correct tissue morphology is maintained. This process is inherently stochastic due to the small number and stochastic division patterns within the stem cell compartments, as well as the essentially stochastic differentiation events that follow the initial stem cell expansion. Here we propose a new formalism to describe this process, by employing the approach known in statistics as the renewal-reward process.

Drug-drug interactions of anti-infective drugs: utility of fluorescence cyp inhibition assays in drug discovery.

Drug interactions are often a result of induction or inhibition of cytochrome P450 (CYP) enzymes by co-administered drugs. A high throughput fluorescence assay using cDNA-expressed human CYP isozymes and fluorogenic substrates has been reported for the study of CYP inhibition. We used this assay to evaluate CYP inhibition profiles of 21 marketed anti-infective drugs.

Nuclear quadrupole resonance studies of transparent conducting oxides.

We report (63,65)Cu spin-lattice relaxation rates measured by nuclear quadrupole resonance (NQR) in the delafossite compound CuYO(2) and CuYO(2):Ca over a temperature range from 200 to 450K. CuYO(2):Ca is a prototype transparent oxide exhibiting p-type electrical conductivity. Relaxation rates in CuYO(2):Ca are enhanced by one to two orders of magnitude relative to undoped material, exhibit much stronger temperature dependence, and contain contributions from magnetic and quadrupolar relaxation mechanisms with roughly equal strengths.

Membrane sweeping in conjunction with labor induction.

Objective: To determine whether cervical membrane sweeping (stripping) during induction of labor is beneficial.

Methods: We compared outcomes of labor after induction in pregnant women at term in a randomized trial. Women were assigned to having their membranes swept or not during induction.

Correlation of change in uterine activity to blood loss in the third stage of labour.

In 47 women, the change in the uterine activity after the administration of a uterotonic agent was correlated with the amount of blood loss during the same period of time. Uterine activity was measured by a Gaeltec catheter-tipped pressure transducer inserted transcervically within 5 min of delivery of the placenta. A uterotonic agent (either intravenous syntocinon, intramuscular syntometrine or oral misoprostol) was given after the insertion of the intrauterine pressure catheter and pressure recorded for another 90 min.

Validation of a laboratory method of measuring postpartum blood loss.

Laboratory methods give more accurate measurement of blood loss in the postpartum period than visual estimation. In order to evaluate a laboratory method used to quantify blood loss postpartum, blood lost at gynecological operations was collected in a measuring bottle. The measured amount of blood (50-1,000 ml) was then poured onto absorbent paper towels and sanitary pads, in order to mimic conditions when measuring blood loss in clinical trials in the postpartum period.

The reliability of catheter-tip transducers for the measurement of intrauterine pressure in the third stage of labour.

In order to assess the reliability of intrauterine pressure measurements in the third stage of labour, catheter-tip transducers were used in 20 women randomly allocated into two groups of 10. In each case in the first group two catheters were tied together and introduced transcervically into the uterine cavity after delivery of the placenta. In each case in the second group two catheters were inserted independently into the same uterine cavity.

Preinduction cervical ripening: prostaglandin E2 gel vs hygroscopic mechanical dilator.

Objectives: To evaluate the efficacy and safety of hygroscopic mechanical dilators (Dilapan) for ripening the pregnant cervix prior to induction of labour at or near term and to compare it with an intracervical PGE2 gel (Prepidil).

Methods: One hundred and eighty-five women (69 nulliparae, 116 multiparae) at term with singleton pregnancies in cephalic presentation, who were scheduled for induction of labour in the labour ward at the National University Hospital, but had an unfavourable cervical score were randomized into 2 groups by random number table. In group 1 (Prepidil), 0.

The role of transvaginal ultrasonography and colour Doppler imaging in the detection of ectopic pregnancy.

Objective: To assess the use of transvaginal ultrasound and colour Doppler imaging in the detection of ectopic pregnancy.

Materials And Methods: Seventy-one patients with suspected ectopic pregnancies had transvaginal sonography and colour Doppler imaging performed and 61 ectopic pregnancies were confirmed at surgery. Various ultrasound features on transvaginal B mode scanning were noted and the resistance index of peritrophoblastic flow in the adnexal masses computed.

Beliefs and practices of urban mothers regarding "hot" and "cold" foods in childhood illnesses.

Beliefs and practices of 100 urban mothers regarding "hot" and "cold" foods during four common childhood illnesses were determined by using a pretested, partly structured interview schedule. Egg, by 60% of mothers, mango by 52%, lentils by 49%, jaggery by 46% were considered "hot" properties. "Hot" foods were preferred and "cold" foods restricted in the treatment of cough and cold and illnesses with rash.