Prolyl hydroxylase 3 (PHD3) is essential for hypoxic regulation of neutrophilic inflammation in humans and mice.

The regulation of neutrophil lifespan by induction of apoptosis is critical for maintaining an effective host response and preventing excessive inflammation. The hypoxia-inducible factor (HIF) oxygen-sensing pathway has a major effect on the susceptibility of neutrophils to apoptosis, with a marked delay in cell death observed under hypoxic conditions. HIF expression and transcriptional activity are regulated by the oxygen-sensitive prolyl hydroxylases (PHD1-3), but the role of PHDs in neutrophil survival is unclear.

Novel transplant strategies for generating graft-versus-leukemia effect in acute myeloid leukemia.

Purpose Of Review: This review summarizes the recent developments in the clinical research and therapeutic applications for prevention and treatment of postallogeneic stem cell transplant (SCT) relapse. Specifically, we address various maneuvers to optimize the graft-versus-leukemia (GVL) effect while preventing graft-versus-host-disease (GVHD).

Recent Findings: Alloreactive natural killer (NK) cells can be recruited to mediate GVL effect by careful mismatching on the killer-cell immunoglobulin-like receptors (KIRs) ligand.

Oral carcinoma cuniculatum in a young child.

From the Department of Dental Specialties, Birmingham Children's Hospital. This case study describes a rare case of oral carcinoma cuniculatum in a 7-year-old female. She presented with an enlarged mass of the anterior maxilla arising from the gingiva.

Novel bioluminescent quantitative detection of nucleic acid amplification in real-time.

Background: The real-time monitoring of polynucleotide amplification is at the core of most molecular assays. This conventionally relies on fluorescent detection of the amplicon produced, requiring complex and costly hardware, often restricting it to specialised laboratories.

Principal Findings: Here we report the first real-time, closed-tube luminescent reporter system for nucleic acid amplification technologies (NAATs) enabling the progress of amplification to be continuously monitored using simple light measuring equipment.

Prophylaxis of graft-versus-host disease in unrelated donor transplantation with pentostatin, tacrolimus, and mini-methotrexate: a phase I/II controlled, adaptively randomized study.

Purpose: Acute graft-versus-host disease (aGVHD) is a major cause of morbidity and mortality after matched unrelated, related, or mismatched related donor hematopoietic stem-cell transplantation (HSCT). Improved GVHD prevention methods are needed. Pentostatin, an adenosine deaminase inhibitor, leads to lymphocyte depletion with low risk of myelosuppression.

Anticonvulsant activity of solasodine isolated from Solanum sisymbriifolium fruits in rodents.

Context: Solanum sisymbriifolium Lam. (Solanaceae), commonly known as sticky nightshade, is traditionally used for central nervous system (CNS) disorders. Although solasodine has been isolated from this plant, little is known about its anticonvulsant and CNS depressant actions.

Genetic variants of the insulin receptor substrate-1 are influencing the therapeutic efficacy of oral antidiabetics.

Aim: The therapeutic efficacy of oral hypoglycaemic drugs varies between individuals, and pharmacogenetic factors contribute to this variability. The Gly972Arg polymorphism in the insulin receptor substrate-1 (IRS-1) has been shown to play a role in insulin signal transduction and therapeutic failure to sulphonylurea drugs.

Methods: We studied the association between the IRS-1 polymorphism and the haemoglobin A1c (HbA1c) level in diabetic patients treated with insulinotropic versus non-insulinotropic hypoglycaemic drugs as a marker for the efficacy of an antidiabetic treatment.

Hypofractionated accelerated radiotherapy with concurrent carboplatin for locally advanced squamous cell carcinoma of the head and neck.

Aims: Hypofractionated accelerated radiotherapy with concurrent carboplatin utilises both advantages of altered fractionation and synchronous chemotherapy to maximise local control in locally advanced head and neck cancer. Such fractionation schedules are increasingly used in the intensity-modulated radiotherapy era and the aim of this study was to determine the outcome of hypofractionated accelerated radiotherapy with carboplatin.

Materials And Methods: One hundred and fifty consecutive patients with squamous cell carcinoma of the larynx, oropharynx, oral cavity and hypopharynx (International Union Against Cancer [IUAC] stage II-IV) treated with 55Gy in 20 fractions over 25 days with concurrent carboplatin were analysed.

Impact of CYP2D6*4 genotype on progression free survival in tamoxifen breast cancer treatment.

Objective: The cytochrome P450 2D6 (CYP2D6) polymorphism was reported to have a significant impact on outcome of tamoxifen treatment in estrogen receptor positive breast cancer patients. The objective of this study was to explore the effect of the CYP2D6*4 polymorphism on tamoxifen treatment outcome in a cohort of patients from a single clinical trial which included women with a history of previous chemotherapy.

Research Design And Methods: A total of 493 patients of the Austrian TIGER study receiving adjuvant tamoxifen therapy were studied for this pharmacogenetic interaction.

Ex vivo expansion of umbilical cord blood for transplantation.

Umbilical cord blood (UCB) has become an important source of hematopoietic stem cell transplant (HSCT) for hematologic malignancies in adults. Its ready availability, allowance of higher HLA disparity and lower incidence of graft-versus-host disease (GVHD) makes it a very attractive source especially for minority populations. The major limitation to a wider use of this source of HSCT is the relative low number of progenitor cells in the graft.

Neuropharmacological activity of hydroalcoholic extract of leaves of Colocasia esculenta.

Context: Although Colocasia esculenta Linn. (Araceae), commonly known as elephant ear (English), possesses diverse pharmacological activities in animals, little is known about its neuropharmacological activity.

Objective: The present study evaluated the neuropharmacological activities of hydroalcoholic extract of leaves of Colocasia esculenta (HECE) using several experimental models.

Nucleic acid dipstick test for molecular diagnosis of pandemic H1N1.

A new nucleic acid amplification-based rapid test for diagnosis of pandemic influenza (H1N1) 2009 virus was developed. The molecular test for pandemic H1N1, SAMBA (simple amplification-based assay), is based on isothermal amplification and visual detection on a dipstick characterized by high sensitivity, high specificity, a short turnaround time, and minimal technical requirements. The amplification step is monitored with an internal control to ensure correct interpretation of test results.

Clinical strategies in the management of complex maxillofacial injuries sustained by British military personnel.

The maxillofacial injuries sustained by British troops requiring aeromedical evacuation to the United Kingdom are almost exclusively treated at The Royal Centre for Defence Medicine in Birmingham. As a result the Maxillofacial Department has collectively gained extensive experience in the management of ballistic injuries. In many cases the most successful outcomes have been achieved by using traditional strategies combined with contemporary techniques.

Oculohypotensive effect of perindopril in acute and chronic models of glaucoma in rabbits.

We studied the effect of perindopril (1%) on intraocular pressure (IOP) and compared it with the effect of pilocarpine, a therapeutic agent used in experimentally induced acute and chronic models of glaucoma in rabbits. Acute glaucoma was induced by intravenous administration of 5% glucose. Pretreatment with topical perindopril (1%) and pilocarpine (1%) prevented acute rise in IOP induced by intravenous administration of 5% glucose.

Community pharmacy contribution to weight management: identifying opportunities.

Objectives: The aim of the study was to determine the public's views on weight-management services, including pharmacies as a potential venue, and the extent of current pharmacy involvement in weight management.

Methods: Two questionnaires were developed for face-to-face interview in one Primary Care Trust area: one for the general public and one for community pharmacists.

Key Findings: Interviews were conducted with 177 members of the public, 75% of whom had tried to lose weight.

Influence of sulfur deficiency on the expression of specific sulfate transporters and the distribution of sulfur, selenium, and molybdenum in wheat.

Interactions between sulfur (S) nutritional status and sulfate transporter expression in field-grown wheat (Triticum aestivum) were investigated using Broadbalk +S and -S treatments (S fertilizer withheld) at Rothamsted, United Kingdom. In 2008, S, sulfate, selenium (Se), and molybdenum (Mo) concentrations and sulfate transporter gene expression were analyzed throughout development. Total S concentrations were lower in all tissues of -S plants, principally as a result of decreased sulfate pools.

The use of a T-shaped contoured unilocking titanium radial plate for prophylactic internal fixation of the radial osteocutaneous donor site.

The radial osteocutaneous flap retains a limited role in reconstructive maxillofacial surgery The application of prophylactic internal fixation, using straight 3.5 mm plates, has become established to substantially reduce the incidence of fracture at the radial donor site. New lower profile T-shaped 2.

Overcoming the barriers to umbilical cord blood transplantation.

Umbilical cord blood (UCB) transplantation (UCBT) has seen a marked increase in utilization in recent years, especially in the pediatric population; however, graft failure, delayed engraftment and profound delay in immune reconstitution leads to significant morbidity and mortality in adults. The lack of cells available for post-transplant therapies, such as donor lymphocyte infusions, has also been considered a disadvantage. To overcome the cell-dose barrier, the combination of two UCB units is becoming commonplace in adolescent and adult populations, and is currently being studied in pediatrics as well.

Anti-prostate-specific membrane antigen-based radioimmunotherapy for prostate cancer.

Despite recent advances, advanced prostate cancer is suboptimally responsive to current chemotherapeutic agents. Radiolabeled monoclonal antibody therapy that targets prostate-specific membrane antigen (PSMA) shows promise and is an area of active investigation. J591 is a deimmunized IgG monoclonal antibody developed to target the extracellular domain of PSMA.

The sulfate transporter family in wheat: tissue-specific gene expression in relation to nutrition.

Sulfate uptake and distribution in plants are managed by the differential expression of a family of transporters, developmentally, spatially, and in response to sulfur nutrition. Elucidation of the signaling pathways involved requires a knowledge of the component parts and their interactions. Here, the expression patterns of the full complement of sulfate transporters in wheat, as influenced by development and sulfur nutrition, are described.

Copper exposure interferes with the regulation of the uptake, distribution and metabolism of sulfate in Chinese cabbage.

Exposure of Chinese cabbage (Brassica pekinensis) to enhanced Cu(2+) concentrations (1-10 microM) resulted in leaf chlorosis, a loss of photosynthetic capacity and lower biomass production at > or = 5 microM. The decrease in pigment content was likely not the consequence of degradation, but due to hindered chloroplast development upon Cu exposure. The Cu content of the root increased with the Cu(2+) concentration (up to 40-fold), though only a minor proportion (4%) was transferred to the shoot.

Can statin be a novel pharmacophore for antidiabetic activity?

Currently, statins are in lime light due to their pleiotropic effects. One of their pleiotropic effects is on glucose metabolism. Various clinical and preclinical studies were designed to evaluate statins' effect on glucose metabolism.