Protective effect of aminoguanidine against nephrotoxicity induced by cisplatin in normal rats

The effect of aminoguanidine (AG) on nephrotoxicity induced by cisplatin (CDDP) was investigated. A single dose of CDDP (7.5 mg/kg i.p.) induced nephrotoxicity, manifested biochemically by a significant elevation in serum urea, creatinine and a severe decrease in serum albumin. Moreover, marked increases in kidney weight, urine volume and urinary excretion of albumin were observed. Nephrotoxicity was further confirmed by a significant decrease in glutathione-S-transferase (GST, E.C. 2.5.1.18), glutathione peroxidase (GSH-Px, E.C. 1.11.1.9) and catalase (E.C. 1.11.1.6) and a significant increase in lipid peroxides measured as malondialdhyde (MDA) in kidney homogenates. Administration of AG (100 mg/kg per day p.o.) in drinking water 5 days before and 5 days after CDDP injection produced a significant protection against nephrotoxicity induced by CDDP. The amelioration of nephrotoxicity was evidenced by significant reductions in serum urea and creatinine concentrations. In addition, AG tended to normalize decreased levels of serum albumin. Urine volume, urinary excretions of albumin and GST and kidney weight were significantly decreased. Moreover, AG prevented the rise of MDA and the reduction of GST and GSH-Px activities in the kidney. These results suggest that AG has a protective effect on nephrotoxicity induced by CDDP and it may therefore improve the therapeutic index of CDDP.     

Efficacité et innocuité du prélèvement percutané de sperme testiculaire dans la prise en charge de l’infertilité masculine

Objective

To assess the efficacy and safety of percutaneous testicular biopsy to provide sperm cells for ICSI in male patients with azoospermia not amenable to surgical treatment.

Materials and methods

From October 1995 to December 2001, 175 biopsies were performed in men with azoospermia to provide material for intracytoplasmic sperm injection. Azoospermia was obstructive (OA) in 41 cases and non-obstructive (NOA) in 134 cases. Open biopsy was performed in the first 15 patients in the series and percutaneous biopsy was performed on an outpatient basis, under local anesthesia, with a Biopty Gun® (14G needle), in the subsequent patients as the first step in management. Open surgical biopsies were performed in another 15 patients following a sperm cell-negative percutaneous biopsy.

Results

All biopsies performed for OA were positive, but only 51/134 biopsies (38%) were positive in the NOA group. The material provided by percutaneous biopsy, when positive for sperm cells, was always sufficient to perform ICSI. When percutaneous biopsy was negative, open surgical biopsy failed to give better results. Five men developed minor complications (acute hematocele) following percutaneous biopsies requiring reoperation for hemostasis (3.12%). No major complications were observed. Results were comparable in terms of fertilization and pregnancy rates whether fresh or frozen-thawed sperm was used.

Conclusion

Percutaneous testicular sperm extraction is a safe, well-tolerated and cost-effective procedure in the management of male-factor infertility related to azoospermia.     

Synthesis and anti-HBV activity of thiouracils linked via S and N-1 to the 5-position of methyl beta-D-ribofuranoside

Reverse nucleoside derivatives of 2-(methylsulfanyl)uracils 6a-d were prepared by treating of the sodium salt of 2-(methylsulfanyl)uracils (5a-d) with methyl 2,3-O-isopropylidene-5-O-p-toluenesulfonyl-beta-D-ribofuranoside (2). The alkylation of 2-thiouracils 4a-d with methyl 5-deoxy-5-iodo-2,3-O-isopropylidene-D-ribofuranoside (3) afforded the corresponding S-ribofuranoside derivatives 8a-d. Deisopropylidenation of 6a-d and 8a-d afforded the corresponding deprotected derivatives 7a-d and 9a-d, respectively. The Anti-HBV activity of selected compounds was studied.     

Non-peptide alphavbeta3 antagonists. Part 6: design and synthesis of alphavbeta3 antagonists containing a pyridone or pyrazinone central scaffold

Two novel series of small-molecule RGD mimetics containing either a substituted pyridone or pyrazinone central constraint were prepared. Modification of the beta-alanine 3-substituent produced compounds that are potent and selective alpha(v)beta(3) antagonists and exhibit a range of physicochemical properties.     

Ultrastructural changes in the muscles,midgut, hemopoietic organ,imaginal discs and Malpighian tubules of the mosquito Aedes aegypti larvae infected by the fungus Coelomomyces stegomyiae

Fungi belonging to the genus Coelomomyces can infect mosquito larvae and develop within the larval hemocoel. To examine fungal development, Aedesaegypti larvae infected with Coelomomyces stegomyiae Keilin were fixed, embedded and sectioned for both light and electron microscopy. While fungal hyphae of C. stegomyiae did not invade cells other than the cuticular epithelial cells, they did penetrate a number of tissues including muscles, midgut, hemopoietic organ, imaginal discs, and Malpighian tubules. This revised version was published online in July 2006 with corrections to the Cover Date.     

Lung epithelial barrier function and wound healing are decreased by IL-4 and IL-13 and enhanced by IFN-gamma

To understand theeffects of cytokines on epithelial cells in asthma, we haveinvestigated the effects of interleukin (IL)-4, IL-13, and interferon(IFN)- on barrier function and wound healing in Calu-3 human lungepithelial cells. IL-4 and IL-13 treatment of Calu-3 cells grown onTranswell filters resulted in a 70-75% decrease in barrierfunction as assessed by electrophysiological and[¹⁴C]mannitol flux measurements. In contrast, IFN-enhanced barrier function threefold using these same parameters. Cellstreated concurrently with IFN- and IL-4 or IL-13 showed an initialdecline in barrier function that was reversed within 2 days, resulting in barrier levels comparable to control cells. Analysis of the tightjunction-associated proteins ZO-1 and occludin showed that IL-4 andIL-13 significantly reduced ZO-1 expression and modestly decreasedoccludin expression compared with controls. IFN-, quite unexpectedlygiven its enhancing effect on barrier function, reduced expression ofZO-1 and occludin to almost undetectable levels compared with controls.In wound-healing assays of cells grown on collagen I, IL-4 and IL-13decreased migration, whereas IFN- treatment enhanced migration,compared with control cells. Addition of IFN-, in combination withIL-4 or IL-13, restored migration of cells to control levels. Migrationdifferences observed between the various cytokine treatments wascorrelated with expression of the collagen I-binding₂₁-integrin at the leading edge of cellsat the wound front; ₂₁-integrinexpression was decreased in IFN--treated cells compared withcontrols, whereas it was highest in IL-4- and IL-13-treated cells.These results demonstrate that IL-4 and IL-13 diminish the capacity ofCalu-3 cells to maintain barrier function and repair wounds, whereasIFN- promotes epithelial restitution by enhancing barrier functionand wound healing.

     

High Prevalence of Severe Food Insecurity and Malnutrition among HIV-Infected Adults in Senegal,West Africa

Background

Malnutrition and food insecurity are associated with increased mortality and poor clinical outcomes among people living with HIV/AIDS; however, the prevalence of malnutrition and food insecurity among people living with HIV/AIDS in Senegal, West Africa is unknown. The objective of this study was to determine the prevalence and severity of food insecurity and malnutrition among HIV-infected adults in Senegal, and to identify associations between food insecurity, malnutrition, and HIV outcomes.

Methods

We conducted a cross-sectional study at outpatient clinics in Dakar and Ziguinchor, Senegal. Data were collected using participant interviews, anthropometry, the Household Food Insecurity Access Scale, the Individual Dietary Diversity Scale, and chart review.

Results

One hundred and nine HIV-1 and/or HIV-2 participants were enrolled. The prevalence of food insecurity was 84.6% in Dakar and 89.5% in Ziguinchor. The prevalence of severe food insecurity was 59.6% in Dakar and 75.4% in Ziguinchor. The prevalence of malnutrition (BMI <18.5) was 19.2% in Dakar and 26.3% in Ziguinchor. Severe food insecurity was associated with missing clinic appointments (p = 0.01) and not taking antiretroviral therapy due to hunger (p = 0.02). Malnutrition was associated with lower CD4 cell counts (p = 0.01).

Conclusions

Severe food insecurity and malnutrition are highly prevalent among HIV-infected adults in both Dakar and Ziguinchor, and are associated with poor HIV outcomes. Our findings warrant further studies to determine the root causes of malnutrition and food insecurity in Senegal, and the short- and long-term impacts of malnutrition and food insecurity on HIV care. Urgent interventions are needed to address the unacceptably high rates of malnutrition and food insecurity in this population.     

A Bioeconomic Model of a Multi-site Fishery with Nonlinear Demand Function: Number of Sites Optimizing the Total Catch

We present a mathematical model of a fishery on several sites with a variable price. The model takes into account the evolution during the time of the resource, fish and boat movement between the different sites, fishing effort and price that varies with respect to supply and demand. We suppose that the movements of the boats and resource as well as the variation of the price go on at a fast time scale. We use methods of aggregation of variables in order to reduce the number of variables and we derive a reduced model governing two global variables, respectively the biomass of the resource and the fishing effort of the whole fishery. We look for the existence of equilibria of the aggregated model and perform local stability analysis. Two main cases can occur. The first one corresponds to over-exploitation leading to fish extinction. At extinction, the fishing effort tends to a positive value. The second case corresponds to a durable fishery equilibrium which is globally asymptotically stable. In the later case, we show that there exists a number of fishing sites that optimizes the total catch of the fishery.     

A Mathematical Model of a Fishery with Variable Market Price: Sustainable Fishery/Over-exploitation

We present a mathematical bioeconomic model of a fishery with a variable price. The model describes the time evolution of the resource, the fishing effort and the price which is assumed to vary with respect to supply and demand. The supply is the instantaneous catch while the demand function is assumed to be a monotone decreasing function of price. We show that a generic market price equation (MPE) can be derived and has to be solved to calculate non trivial equilibria of the model. This MPE can have 1, 2 or 3 equilibria. We perform the analysis of local and global stability of equilibria. The MPE is extended to two cases: an age-structured fish population and a fishery with storage of the resource.