Recent advances and novel strategies in pre-clinical formulation development: an overview.

Preclinical profiling for a New Chemical Entity (NCE), if carried out carefully, can be a good predictor of human clinical outcome. Along with the pre-clinical study design a thorough understanding of the physico-chemical properties of the drug candidate and a careful selection of the formulation development strategy are of high importance. The study scientist can experience various challenges in executing a pre-clinical study.

Developmental profile and regulation of the glycolytic enzyme hexokinase 2 in normal brain and glioblastoma multiforme.

Highly proliferating cells, normal or transformed, undergo aerobic glycolysis whereby glucose is metabolized to lactate rather than by oxidative metabolism, even in the presence of oxygen. This metabolic adaptation provides a survival advantage and facilitates synthesis of biosynthetic precursors required for continued cellular proliferation. An important mediator of aerobic glycolysis is our demonstration that in malignant gliomas there is over-expression of the glycolytic enzyme hexokinase 2 (HK2), phosphorylating glucose as the first step of the glycolytic pathway.

Antimicrobial activity of essential oil and various extracts of fruits of greater cardamom.

Greater cardamom (Amomum subulatum Roxb. Zingiberaceae) commonly known as "Bari ilaichi" is a well known plant used in Ayurvedic and Unani medicine. It has been used for the treatment of various diseases and disorders like gastric ulcer.

A GATA4-regulated tumor suppressor network represses formation of malignant human astrocytomas.

Glioblastoma Multiforme (GBM), the most common and lethal primary human brain tumor, exhibits multiple molecular aberrations. We report that loss of the transcription factor GATA4, a negative regulator of normal astrocyte proliferation, is a driver in glioma formation and fulfills the hallmarks of a tumor suppressor gene (TSG). Although GATA4 was expressed in normal brain, loss of GATA4 was observed in 94/163 GBM operative samples and was a negative survival prognostic marker.

Targeting metabolic remodeling in glioblastoma multiforme.

A key aberrant biological difference between tumor cells and normal differentiated cells is altered metabolism, whereby cancer cells acquire a number of stable genetic and epigenetic alterations to retain proliferation, survive under unfavorable microenvironments and invade into surrounding tissues. A classic biochemical adaptation is the metabolic shift to aerobic glycolysis rather than mitochondrial oxidative phosphorylation, regardless of oxygen availability, a phenomenon termed the "Warburg Effect". Aerobic glycolysis, characterized by high glucose uptake, low oxygen consumption and elevated production of lactate, is associated with a survival advantage as well as the generation of substrates such as fatty acids, amino acids and nucleotides necessary in rapidly proliferating cells.

An investigation of the effects of sports-related concussion in youth using functional magnetic resonance imaging and the head impact telemetry system.

One of the most commonly reported injuries in children who participate in sports is concussion or mild traumatic brain injury (mTBI). Children and youth involved in organized sports such as competitive hockey are nearly six times more likely to suffer a severe concussion compared to children involved in other leisure physical activities. While the most common cognitive sequelae of mTBI appear similar for children and adults, the recovery profile and breadth of consequences in children remains largely unknown, as does the influence of pre-injury characteristics (e.

Hexokinase 2 is a key mediator of aerobic glycolysis and promotes tumor growth in human glioblastoma multiforme.

Proliferating embryonic and cancer cells preferentially use aerobic glycolysis to support growth, a metabolic alteration commonly referred to as the "Warburg effect." Here, we show that the glycolytic enzyme hexokinase 2 (HK2) is crucial for the Warburg effect in human glioblastoma multiforme (GBM), the most common malignant brain tumor. In contrast to normal brain and low-grade gliomas, which express predominantly HK1, GBMs show increased HK2 expression.

From health care to home community: an Aboriginal community-based ABI transition strategy.

Primary Objective: To explore the barriers and enablers surrounding the transition from health care to home community settings for Aboriginal clients recovering from acquired brain injuries (ABI) in northwestern Ontario.

Research Design: Participatory research design using qualitative methods.

Methods: Focus groups conducted with clients with ABI, their caregivers and hospital and community health-care workers.

Preparation of liposomal vancomycin and intracellular killing of meticillin-resistant Staphylococcus aureus (MRSA).

Meticillin-resistant Staphylococcus aureus (MRSA) can persist in alveolar macrophages and contribute to clinical failure of intravenous vancomycin to cure pneumonia. In this study, it was shown that vancomycin in standard solution is unable to kill intracellular MRSA within macrophages. The intracellular viability of MRSA inside macrophages treated with two different formulations of encapsulated liposomal vancomycin prepared using a hydration-dehydration method was then determined.

Epigenetic regulation of glial fibrillary acidic protein by DNA methylation in human malignant gliomas.

Glial fibrillary acidic protein (GFAP) is an intermediate filament expressed in glial cells that stabilizes and maintains the cytoskeleton of normal astrocytes. In glial tumors, GFAP expression is frequently lost with increasing grade of malignancy, suggesting that GFAP is important for maintaining glial cell morphology or regulating astrocytoma cell growth. Most permanent human glioma cell lines are GFAP negative by immunocytochemistry.

Community integration interventions for youth with acquired brain injuries: a review.

Objective: To identify and summarize published literature that examined the effectiveness of social and community integration interventions for children and adolescents with ABI in order to provide recommendations regarding future research on this topic.

Methods: A literature review was conducted to identify studies that focused on social and community integration interventions for youth with ABI. Further manual searching of relevant journals with a paediatric rehabilitation focus was also carried out.

Sensory processing and adaptive behavior deficits of children across the fetal alcohol spectrum disorder continuum.

Background: Prenatal alcohol exposure can have detrimental effects on a child's development of adaptive behaviors necessary for success in the areas of academic achievement, socialization, and self-care. Sensory processing abilities have been found to affect a child's ability to successfully perform adaptive behaviors. The current study explored whether significant differences in sensory processing abilities, adaptive behavior, and neurocognitive functioning are observed between children diagnosed with partial Fetal Alcohol Syndrome (pFAS), Alcohol-Related Neurodevelopmental Disorder (ARND), or children who were prenatally exposed to alcohol (PEA), but did not meet criteria for an FASD diagnosis.

A molecular simulation study of propane and propylene adsorption onto single-walled carbon nanotube bundles.

We have carried out configurational-bias Grand Canonical Monte Carlo simulations of propane and propylene adsorption onto homogeneous bundles of single-walled carbon nanotubes, at ambient temperature (T = 298.15 K) and over a pressure range of 0.1 bar < or = p < 10.

Controlled release application of multilamellar vesicles: a novel drug delivery approach.

A novel multilamellar vesicular delivery system was developed for the controlled release application. Multilamellar vesicles were prepared by thin film hydration and converted into proliposomes by freeze-drying. A model drug metoclopramide, a highly hydrophilic drug, was successfully encapsulated into proliposomes.

Laparoscopic repair of spontaneous vaginal evisceration of small bowel: report of a case.

Spontaneous vaginal evisceration of the small bowel is a rare event. It is precipitated in the postmenopausal woman commonly by hysterectomy and in the premenopausal woman by vaginal trauma. We report a case of a 75-year-old woman presenting with a protruding mass in her vagina and associated abdominal pain.

Drug loaded poly[Lac(Glc-Leu)] microparticles: formulation and release characteristics.

Valdecoxib has been entrapped in sub-5 microm particles of poly[Lac(Glc-Leu)] copolymer using a oil-in-water (o/w) emulsification-solvent evaporation technique. To achieve monodispersed sized particles, a microfluidizer was used as ultrasonication device. Formulation parameters such as effect of polymer load, ultrasonication time, stabilizer concentration and stirring rate have a profound effect on particle size, and polydispersity.

Aging of nanocarbons in ambient conditions: probable metastability of carbon nanotubes.

We studied the physicochemical properties of several commercially available single- and multi-walled carbon nanotubes (SWNTs and MWNTs) and fullerenes stored in normal ambient conditions for 24 months. We found that SWNTs exhibit a trend of decreasing surface area and pore volume up to 7-15 months but then stabilized, no longer being impacted by sample age or outgassing temperatures. Using X-ray Photoelectron Spectroscopy, we also observed a trend of decreasing surface oxygen in all samples from the beginning with much lower % oxygen observed after 12-15 months of aging under ambient conditions.

Multicystic nephroma: a rare entity.

Multicystic nephroma is a rare renal pathology, which is characterized usually by a unilateral renal mass with multiple thin-walled cysts divided by septa. We report the case of a boy aged 2 years, who was diagnosed in utero with an abdominal cystic lesion during routine antenatal ultrasonography examination. The patient underwent a nephrectomy, and diagnosis of cystic nephroma was confirmed by histology.

GATA4 is a regulator of astrocyte cell proliferation and apoptosis in the human and murine central nervous system.

The GATA transcription factors consist of six family members, which bind to the consensus DNA-binding element, W-GATA-R, and are poorly characterized in the central nervous system (CNS). Using retroviral gene trapping on transgenic mouse glioma models, we identified GATA6 to be a novel tumor suppressor gene in glioblastoma multiforme. We now show GATA4, a family member of GATA6, to be expressed in the neurons and glia of normal murine and human embryonic and adult CNS.

Extensively drug resistance (XDR) tb is not always fatal.

The chance of incidence of XDR TB is on the rise due to improper use of second line anti-tubercular drugs. XDR-TB is very difficult to treat successfully and is often referred to as "virtually untreatable form of TB". We herein report a case of XDR TB confirmed by bacteriological examination in a WHO recognised laboratory who after 12 months of regular treatment improved both clinically and radiologically with sputum smear conversion.

Electrophoretic mobility of colloidal gold particles in electrolyte solutions.

The electrophoretic mobility of five different-sized spherical colloidal gold particles has been measured in aqueous potassium chloride (KCl) and sodium phosphate electrolyte solutions over the concentration range 0.005-0.154 M solutions.

Pharmacokinetics of intramuscular microparticle depot of valdecoxib in an experimental model.

Aim: We did a prospective study to investigate pharmacokinetics of a single intramuscularly (i.m.) administered Valdecoxib (VC) polymeric microparticles in New Zealand white rabbits.

Prediction of stature using hand dimensions.

In this study, an attempt was made to find out possible correlations between hand dimensions and stature using linear and curvilinear regression models for both genders. The study was conducted amongst 250 medical students (125 male and 125 female) aged 18-30 years. Each student has been studied for measurements of stature, hand length and hand breadth.

Diclofenac-loaded biopolymeric nanosuspensions for ophthalmic application.

Polymeric nanoparticle suspensions (NS) were prepared from poly(lactide-co-glycolide) and poly(lactide-co-glycolide-leucine) {poly[Lac(Glc-Leu)]} biodegradable polymers and loaded with diclofenac sodium (DS), with the aim of improving the ocular availability of the drug. NS were prepared by emulsion and solvent evaporation technique and characterized on the basis of physicochemical properties, stability, and drug release features. The nanoparticle system showed an interesting size distribution suitable for ophthalmic application.