Aminoindoles, a novel scaffold with potent activity against Plasmodium falciparum.

This study characterizes aminoindole molecules that are analogs of Genz-644442. Genz-644442 was identified as a hit in a screen of ~70,000 compounds in the Broad Institute's small-molecule library and the ICCB-L compound collection at Harvard Medical School. Genz-644442 is a potent inhibitor of Plasmodium falciparum in vitro (50% inhibitory concentrations [IC₅₀s], 200 to 285 nM) and inhibits P.

Development of the piggyBac transposable system for Plasmodium berghei and its application for random mutagenesis in malaria parasites.

Background: The genome of a number of species of malaria parasites (Plasmodium spp.) has been sequenced in the hope of identifying new drug and vaccine targets. However, almost one-half of predicted Plasmodium genes are annotated as hypothetical and are difficult to analyse in bulk due to the inefficiency of current reverse genetic methodologies for Plasmodium.

Role of FDG PET/CT in staging of recurrent ovarian cancer.

Ovarian cancer is the fifth leading cause of cancer death among women in the United States and has a high likelihood of recurrence despite aggressive treatment strategies. Detection and exact localization of recurrent lesions are critical for guiding management and determining the proper therapeutic approach, which may prolong survival. Because of its high sensitivity and specificity compared with those of conventional techniques such as computed tomography (CT) and magnetic resonance (MR) imaging, fluorine 18 fluorodeoxyglucose positron emission tomography (PET) combined with CT is useful for detection of recurrent or residual ovarian cancer and for monitoring response to therapy.

Long-term effect on quality of life of repeat detrusor injections of botulinum neurotoxin-A for detrusor overactivity in patients with multiple sclerosis.

Purpose: We studied the effect of repeat detrusor botulinum neurotoxin type A injections on urinary symptoms, health and quality of life in patients with refractory neurogenic detrusor overactivity secondary to multiple sclerosis.

Materials And Methods: This was a prospective, open label, single center study in 137 patients with multiple sclerosis treated with detrusor injections of botulinum neurotoxin type A with observations made from 2002 to 2009. A minimally invasive outpatient technique was used for injection.

Urinary metabolic biomarkers of hepatocellular carcinoma in an Egyptian population: a validation study.

The advent of metabonomics has seen a proliferation of biofluid profiling studies of patients with hepatocellular carcinoma. The majority of these studies have been conducted in single indigenous populations making the widespread applicability of candidate metabolite biomarkers difficult. Presented here is a urinary proton nuclear magnetic resonance spectroscopy study of mainly hepatitis C virus infected Egyptian patients with hepatocellular carcinoma, which corroborates findings of a previous study from our group of mainly hepatitis B-infected Nigerian patients with hepatocellular carcinoma.

Upper gastrointestinal bleeding in a patient receiving selective serotonin reuptake inhibitor.

An older woman presented to the hospital with abdominal pain and subsequently had three episodes of melaena, requiring blood transfusions. She was known to suffer with severe depression and was on high-dose fluoxetine. Gastroscopy and colonoscopy failed to reveal an underlying cause for gastrointestinal (GI) bleeding.

Removal of heterologous sequences from Plasmodium falciparum mutants using FLPe-recombinase.

Genetically-modified mutants are now indispensable Plasmodium gene-function reagents, which are also being pursued as genetically attenuated parasite vaccines. Currently, the generation of transgenic malaria-parasites requires the use of drug-resistance markers. Here we present the development of an FRT/FLP-recombinase system that enables the generation of transgenic parasites free of resistance genes.

Hepatocellular carcinoma: diagnostics and screening.

Hepatocellular carcinoma (HCC) is the commonest primary hepatic malignancy and the third most common cause of cancer-related death worldwide. Incidence remains highest in the developing world and is steadily increasing across the developed world. The majority of HCC occurs on a background of cirrhosis, principally caused by two major risk factors, chronic hepatitis B and hepatitis C infection.

Investigating the evolution of apoptosis in malaria parasites: the importance of ecology.

Apoptosis is a precisely regulated process of cell death which occurs widely in multicellular organisms and is essential for normal development and immune defences. In recent years, interest has grown in the occurrence of apoptosis in unicellular organisms. In particular, as apoptosis has been reported in a wide range of species, including protozoan malaria parasites and trypanosomes, it may provide a novel target for intervention.

Comparison of the impact on health-related quality of life of repeated detrusor injections of botulinum toxin in patients with idiopathic or neurogenic detrusor overactivity.

Study Type: Therapy (case series).

Level Of Evidence: 4. What's known on the subject? and What does the study add? We know that repeated injections of botulinum toxin A are effective in treating refractory detrusor overactivity particularly in NDO.

Sequestration and tissue accumulation of human malaria parasites: can we learn anything from rodent models of malaria?

The sequestration of Plasmodium falciparum-infected red blood cells (irbcs) in the microvasculature of organs is associated with severe disease; correspondingly, the molecular basis of irbc adherence is an active area of study. In contrast to P. falciparum, much less is known about sequestration in other Plasmodium parasites, including those species that are used as models to study severe malaria.

Novel inhibitors of Plasmodium falciparum dihydroorotate dehydrogenase with anti-malarial activity in the mouse model.

Plasmodium falciparum, the causative agent of the most deadly form of human malaria, is unable to salvage pyrimidines and must rely on de novo biosynthesis for survival. Dihydroorotate dehydrogenase (DHODH) catalyzes the rate-limiting step in the pyrimidine biosynthetic pathway and represents a potential target for anti-malarial therapy. A high throughput screen and subsequent medicinal chemistry program identified a series of N-alkyl-5-(1H-benzimidazol-1-yl)thiophene-2-carboxamides with low nanomolar in vitro potency against DHODH from P.

A genotype and phenotype database of genetically modified malaria-parasites.

The RMgm database, www.pberghei.eu, is a web-based, manually curated, repository containing information on genetically modified rodent-malaria parasites.

Risk of urinary tract infection after detrusor botulinum toxin A injections for refractory neurogenic detrusor overactivity in patients with no antibiotic treatment.

Objective: To determine if antibiotic prophylaxis is required for intradetrusor botulinum toxin A (BoNT-A) injections.

Patients And Methods: This was a prospective non-randomized study. Inclusion criteria were adult patients with neurogenic detrusor overactivity who failed anticholinergic-based first-line treatment and had sterile urine culture 7 days before injections, a negative dipstick test on the day of the injections, and were performing clean intermittent self-catheterization.

Factors affecting accessibility and acceptability of voluntary counselling and testing among high risk group (HRG) for human immunodeficiency virus (HIV) in NWFP Pakistan.

Objective: To identify the factors that affect the accessibility and acceptability of Voluntary Counselling and Testing (VCT) services among High Risk Groups for HIV in NWFP.

Methods: A cross sectional study was conducted in two districts of N.W.

Three members of the 6-cys protein family of Plasmodium play a role in gamete fertility.

The process of fertilization is critically dependent on the mutual recognition of gametes and in Plasmodium, the male gamete surface protein P48/45 is vital to this process. This protein belongs to a family of 10 structurally related proteins, the so called 6-cys family. To identify the role of additional members of this family in Plasmodium fertilisation, we performed genetic and functional analysis on the five members of the 6-cys family that are transcribed during the gametocyte stage of P.

Functional identification of the Plasmodium centromere and generation of a Plasmodium artificial chromosome.

The artificial chromosome represents a useful tool for gene transfer, both as cloning vectors and in chromosome biology research. To generate a Plasmodium artificial chromosome (PAC), we had to first functionally identify and characterize the parasite's centromere. A putative centromere (pbcen5) was cloned from chromosome 5 of the rodent parasite P.

Targeted capture and next-generation sequencing identifies C9orf75, encoding taperin, as the mutated gene in nonsyndromic deafness DFNB79.

Targeted genome capture combined with next-generation sequencing was used to analyze 2.9 Mb of the DFNB79 interval on chromosome 9q34.3, which includes 108 candidate genes.

Screening for metabolic syndrome and testosterone deficiency in patients with erectile dysfunction: results from the first UK prospective study.

Objective: To screen patients with erectile dysfunction (ED) for the presence of metabolic syndrome (MetS), testosterone deficiency and cardiovascular (CV) risk factors, in a secondary referral centre in the UK, as men with ED have a high incidence of CV risk factors that might amount to MetS, with obesity, increased risk of coronary heart disease and type II diabetes; testosterone deficiency has also been associated with both ED and MetS.

Patients And Methods: We assessed 124 men presenting with ED between March 2007 and August 2008. Data were collected prospectively for patient demographics, risk factors associated with MetS, and hypogonadism.

Characterization of urinary biomarkers of hepatocellular carcinoma using magnetic resonance spectroscopy in a Nigerian population.

Hepatocellular carcinoma (HCC) is the commonest primary hepatic malignancy worldwide. Current serum diagnostic biomarkers, such as alpha-fetoprotein, are expensive and insensitive in early tumor diagnosis. Urinary biomarkers differentiating HCC from chronic liver disease would be practical and widely applicable.

Myosin motors drive long range alignment of actin filaments.

The bulk alignment of actin filament sliding movement, powered by randomly oriented myosin molecules, has been observed and studied using an in vitro motility assay. The well established, actin filament gliding assay is a minimal experimental system for studying actomyosin motility. Here, we show that when the assay is performed at densities of actin filaments approaching those found in living cells, filament gliding takes up a preferred orientation.

Liver transplantation for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the commonest primary malignancy of the liver. It usually occurs in the setting of chronic liver disease and has a poor prognosis if untreated. Orthotopic liver transplantation (OLT) is a suitable therapeutic option for early, unresectable HCC particularly in the setting of chronic liver disease.

Visualisation and quantitative analysis of the rodent malaria liver stage by real time imaging.

The quantitative analysis of Plasmodium development in the liver in laboratory animals in cultured cells is hampered by low parasite infection rates and the complicated methods required to monitor intracellular development. As a consequence, this important phase of the parasite's life cycle has been poorly studied compared to blood stages, for example in screening anti-malarial drugs. Here we report the use of a transgenic P.

Helicobacter urease: niche construction at the single molecule level.

The urease of the human pathogen, Helicobacter pylori, is essential for pathogenesis. The ammonia produced by the enzyme neutralizes stomach acid; thereby modifying its environment. The dodecameric enzyme complex has high affinity for its substrate, urea.