A Novel NCI-H69AR Drug-Resistant Small-Cell Lung Cancer Mini-Tumor Model for Anti-Cancer Treatment Screening.

Small-cell lung cancer is a fast-growing carcinoma with a poor prognosis and a high level of relapse due to multi-drug resistance (MDR). Genetic mutations that lead to the overexpression of efflux transporter proteins can contribute to MDR. In vitro cancer models play a tremendous role in chemotherapy development and the screening of possible anti-cancer molecules.

Comparison of RPMI 2650 cell layers and excised sheep nasal epithelial tissues in terms of nasal drug delivery and immunocytochemistry properties.

Nasal drug administration has been identified as a potential alternative to oral drug administration, especially for systemic delivery of large molecular weight compounds. Major advantages of nasal drug delivery include high vascularity and permeability of the epithelial membranes as well as circumvention of first-pass metabolism. RPMI 2650 cell layers (in vitro cell model) and excised sheep nasal mucosal tissues (ex vivo sheep model) were evaluated with regard to epithelial thickness, selected tight junction protein expression (i.

The Role of Functional Excipients in Solid Oral Dosage Forms to Overcome Poor Drug Dissolution and Bioavailability.

Many active pharmaceutical ingredients (APIs) exhibit poor solubility and low dissolution rates in aqueous environments such as the luminal fluids of the gastrointestinal tract. The oral bioavailability of these compounds is usually very low as a result of their poor solubility properties. In order to improve the bioavailability of these poorly soluble drugs, formulation strategies have been applied as a means to improve their aqueous solubility and dissolution rates.

Capsaicin and Piperine as Functional Excipients for Improved Drug Delivery across Nasal Epithelial Models.

The fruit from various pepper plants has been employed for the seasoning of food, as perfuming agents, and also as traditional medicines. Phytochemicals isolated from different pepper species have been found to modulate the pharmacokinetics of orally administered drugs. This study investigated the possibility to apply capsaicin and piperine (extracted alkaloids) as modulators for drug delivery across the nasal epithelium.

Antihypertensive drug therapy for mild to moderate hypertension during pregnancy.

Background: Antihypertensive drugs are often used in the belief that lowering blood pressure will prevent progression to more severe disease, and thereby improve pregnancy outcome. This Cochrane Review is an updated review, first published in 2001 and subsequently updated in 2007 and 2014.

Objectives: To assess the effects of antihypertensive drug treatments for women with mild to moderate hypertension during pregnancy.

The In Vitro and In Vivo Effects of Hypoxis hemerocallidea on Indinavir Pharmacokinetics: Modulation of Efflux.

(African potato) is a popular medicinal plant that has been used traditionally for the treatment of various disorders. Some HIV/AIDS patients use this traditional medicine together with their antiretroviral therapy. This study aimed to determine the impact of selected materials (i.

Evaluation of Isolated Fractions of Aloe vera Gel Materials on Indinavir Pharmacokinetics: In vitro and in vivo Studies.

Aloe vera is a plant with a long history of traditional medicinal use and is consumed in different products, sometimes in conjunction with prescribed medicines. A. vera gel has shown the ability to modulate drug absorption in vitro.

Treatments for breast abscesses in breastfeeding women.

Background: The benefits of breastfeeding are well known, and the World Health Organization recommends exclusive breastfeeding for the first six months of life and continuing breastfeeding to age two. However, many women stop breastfeeding due to lactational breast abscesses. A breast abscess is a localised accumulation of infected fluid in breast tissue.

Herbal hepatotoxicity: current status, examples, and challenges.

Introduction: Herbal medicines have commonly been considered safe by the general public due to their natural origin and long history of traditional uses. In contrast to this belief, many plants produce toxic substances as secondary metabolites that are sometimes not easily distinguishable from the pharmacological active compounds. Some herbal medicines have been associated with adverse effects and toxic effects, including hepatotoxicity, which have been reversed upon discontinuation of the herbal medicine by the patient.

Novel non-invasive protein and peptide drug delivery approaches.

Protein and peptide based therapeutics are typically administered by injection due to their poor uptake when administered via enteral routes of drug administration. Unfortunately, chronic administration of these drugs through multiple injections presents certain patient related problems and it is difficult to mimic the normal physiological release patterns via this mode of drug administration. A need therefore exists to non-invasively deliver these drugs by means of alternative ways such as via the oral, pulmonary, nasal, transdermal and buccal administration routes.

High density ozone monitoring using gas sensitive semi-conductor sensors in the Lower Fraser Valley, British Columbia.

A cost-efficient technology for accurate surface ozone monitoring using gas-sensitive semiconducting oxide (GSS) technology, solar power, and automated cell-phone communications was deployed and validated in a 50 sensor test-bed in the Lower Fraser Valley of British Columbia, over 3 months from May-September 2012. Before field deployment, the entire set of instruments was colocated with reference instruments for at least 48 h, comparing hourly averaged data. The standard error of estimate over a typical range 0-50 ppb for the set was 3 ± 2 ppb.

Antihypertensive drug therapy for mild to moderate hypertension during pregnancy.

Background: Mild to moderate hypertension during pregnancy is common. Antihypertensive drugs are often used in the belief that lowering blood pressure will prevent progression to more severe disease, and thereby improve the outcome.

Objectives: To assess the effects of antihypertensive drug treatments for women with mild to moderate hypertension during pregnancy.

A risk prediction model for the assessment and triage of women with hypertensive disorders of pregnancy in low-resourced settings: the miniPIERS (Pre-eclampsia Integrated Estimate of RiSk) multi-country prospective cohort study.

Background: Pre-eclampsia/eclampsia are leading causes of maternal mortality and morbidity, particularly in low- and middle- income countries (LMICs). We developed the miniPIERS risk prediction model to provide a simple, evidence-based tool to identify pregnant women in LMICs at increased risk of death or major hypertensive-related complications.

Methods And Findings: From 1 July 2008 to 31 March 2012, in five LMICs, data were collected prospectively on 2,081 women with any hypertensive disorder of pregnancy admitted to a participating centre.

Global deposition of airborne dioxin.

We present a global dioxin model that simulates one year of atmospheric emissions, transport processes, and depositions to the earth's terrestrial and marine habitats. We map starting emission levels for each land area, and we also map the resulting deposits to terrestrial and marine environments. This model confirms that 'hot spots' of deposition are likely to be in northern Europe, eastern North America, and in parts of Asia with the highest marine dioxin depositions being the northeast and northwest Atlantic, western Pacific, northern Indian Ocean and the Mediterranean.

Co-operative additive effects between HLA alleles in control of HIV-1.

Background: HLA class I genotype is a major determinant of the outcome of HIV infection, and the impact of certain alleles on HIV disease outcome is well studied. Recent studies have demonstrated that certain HLA class I alleles that are in linkage disequilibrium, such as HLA-A*74 and HLA-B*57, appear to function co-operatively to result in greater immune control of HIV than mediated by either single allele alone. We here investigate the extent to which HLA alleles--irrespective of linkage disequilibrium--function co-operatively.

Task shifting of antiretroviral treatment from doctors to primary-care nurses in South Africa (STRETCH): a pragmatic, parallel, cluster-randomised trial.

Background: Robust evidence of the effectiveness of task shifting of antiretroviral therapy (ART) from doctors to other health workers is scarce. We aimed to assess the effects on mortality, viral suppression, and other health outcomes and quality indicators of the Streamlining Tasks and Roles to Expand Treatment and Care for HIV (STRETCH) programme, which provides educational outreach training of nurses to initiate and represcribe ART, and to decentralise care.

Methods: We undertook a pragmatic, parallel, cluster-randomised trial in South Africa between Jan 28, 2008, and June 30, 2010.

HIV control through a single nucleotide on the HLA-B locus.

Genetic variation within the HLA-B locus has the strongest impact on HIV disease progression of any polymorphisms within the human genome. However, identifying the exact mechanism involved is complicated by several factors. HLA-Bw4 alleles provide ligands for NK cells and for CD8 T cells, and strong linkage disequilibrium between HLA class I alleles complicates the discrimination of individual HLA allelic effects from those of other HLA and non-HLA alleles on the same haplotype.

Fallopian tube reanastomosis by laparotomy versus laparoscopy: a meta-analysis.

Objective: To compare efficacy of sterilization reversals by laparotomy versus laparoscopy.

Design: Meta-analysis.

Search Strategy: Electronic searches were carried out for randomized controlled trials and retrospective and prospective clinical studies.

Combination therapy of Western drugs and herbal medicines: recent advances in understanding interactions involving metabolism and efflux.

Introduction: While complementary and alternative medicine markets prosper with an increasing number of consumers of herbal medicines, there is an associated likelihood for herb-drug interactions to occur. Modulation of the activity of metabolic enzymes and/or active transporters by chemical constituents of herbal medicines may influence the therapeutic outcomes of coadministered allopathic medicines due to changes in their pharmacokinetic profiles. Although valuable information on herb-drug interactions is obtained by in vitro studies, such as the mechanisms of interaction, clinical significance of interactions is ultimately demonstrated by in vivo data.

Is metformin indicated as primary ovulation induction agent in women with PCOS? A systematic review and meta-analysis.

Background: A recent meta-analysis has proven that metformin (M) is highly effective for ovulation induction in the clomiphene citrate (CC)-resistant patient. There is uncertainty whether M should be introduced as a primary ovulation induction agent in polycystic ovarian syndrome (PCOS).

Methods: We conducted a systematic review and meta-analysis to establish if M is better when given alone or in combination with CC (CC+M) when compared with CC alone.

PIERS proteinuria: relationship with adverse maternal and perinatal outcome.

Objective: To examine the ability of three different proteinuria assessment methods (urinary dipstick, spot urine protein:creatinine ratio [Pr/Cr], and 24-hour urine collection) to predict adverse pregnancy outcomes.

Methods: We performed a prospective multicentre cohort study, PIERS (Preeclampsia Integrated Estimate of RiSk), in seven academic tertiary maternity centres practising expectant management of preeclampsia remote from term in Canada, New Zealand, and Australia. Eligible women were those admitted with preeclampsia who had at least one antenatal proteinuria assessment by urinary dipstick, spot urine Pr/Cr ratio, and/or 24-hour urine collection.

Progression to AIDS in South Africa is associated with both reverting and compensatory viral mutations.

We lack the understanding of why HIV-infected individuals in South Africa progress to AIDS. We hypothesised that in end-stage disease there is a shifting dynamic between T cell imposed immunity and viral immune escape, which, through both compensatory and reverting viral mutations, results in increased viral fitness, elevated plasma viral loads and disease progression. We explored how T cell responses, viral adaptation and viral fitness inter-relate in South African cohorts recruited from Bloemfontein, the Free State (n = 278) and Durban, KwaZulu-Natal (n = 775).

HLA-A*7401-mediated control of HIV viremia is independent of its linkage disequilibrium with HLA-B*5703.

The potential contribution of HLA-A alleles to viremic control in chronic HIV type 1 (HIV-1) infection has been relatively understudied compared with HLA-B. In these studies, we show that HLA-A*7401 is associated with favorable viremic control in extended southern African cohorts of >2100 C-clade-infected subjects. We present evidence that HLA-A*7401 operates an effect that is independent of HLA-B*5703, with which it is in linkage disequilibrium in some populations, to mediate lowered viremia.

Estimation of southern resident killer whale exposure to exhaust emissions from whale-watching vessels and potential adverse health effects and toxicity thresholds.

Southern resident killer whales in British Columbia and Washington are exposed to heavy vessel traffic. This study investigates their exposure to exhaust gases from whale-watching vessels by using a simple dispersion model incorporating data on whale and vessel behavior, atmospheric conditions, and output of airborne pollutants from the whale-watching fleet based on emissions data from regulatory agencies. Our findings suggest that current whale-watching guidelines are usually effective in limiting pollutant exposure to levels at or just below those at which measurable adverse health effects would be expected in killer whales.

Nasal delivery of recombinant human growth hormone: in vivo evaluation with Pheroid technology and N-trimethyl chitosan chloride.

Purpose: It was the aim of this study to investigate the possible enhancement of the absorption of recombinant human growth hormone (rhGH) in the nasal cavity, in the presence of a polymeric absorption enhancer, N-trimethyl chitosan chloride (TMC) and a fatty acid-based delivery system, Pheroid.

Methods: Two types of Pheroid formulations, Pheroid vesicles and Pheroid microsponges were characterized and evaluated with regard to particle size and morphology. In vivo bioavailability studies in rats were performed and the nasal bioavailability of Pheroid vesicles and Pheroid microsponges were compared relative to subcutaneous administration.