Urease produced by Coccidioides posadasii contributes to the virulence of this respiratory pathogen

Urease activity during in vitro growth in the saprobic and parasitic phases of Coccidioides spp. is partly responsible for production of intracellular ammonia released into the culture media and contributes to alkalinity of the external microenvironment. Although the amino acid sequence of the urease of Coccidioides posadasii lacks a predicted signal peptide, the protein is transported from the cytosol into vesicles and the central vacuole of parasitic cells (spherules). Enzymatically active urease is released from the contents of mature spherules during the parasitic cycle endosporulation stage. The endospores, together with the urease and additional material which escape from the ruptured parasitic cells, elicit an intense host inflammatory response. Ammonia production by the spherules of C. posadasii is markedly increased by the availability of exogenous urea found in relatively high concentrations at sites of coccidioidal infection in the lungs of mice. Direct measurement of the pH at these infection sites revealed an alkaline microenvironment. Disruption of the urease gene of C. posadasii resulted in a marked reduction in the amount of ammonia secreted in vitro by the fungal cells. BALB/c mice challenged intranasally with the mutant strain showed increased survival, a well-organized granulomatous response to infection, and better clearance of the pathogen than animals challenged with either the parental or the reconstituted (revertant) strain. We conclude that ammonia and enzymatically active urease released from spherules during the parasitic cycle of C. posadasii contribute to host tissue damage, which exacerbates the severity of coccidioidal infection and enhances the virulence of this human respiratory pathogen.     

A pilot study on the early use of the vacuum erection device after radical retropubic prostatectomy

OBJECTIVE: To evaluate the effect of the early use of the vacuum erection device (VED) on erectile dysfunction (ED) and penile shortening after radical retropubic prostatectomy (RP), as these are important concerns for men choosing among treatment alternatives for localized prostate cancer. PATIENTS AND METHODS: Twenty-eight men undergoing RP were randomized to early intervention (1 month after RP, group 1) or a control group (6 months after RP, group 2) using a traditional VED protocol. An International Index of Erectile Function (IIEF) score of >11 (no, mild or mild to moderate ED) was required as a baseline criterion for inclusion in the study. Only patients in whom unilateral or bilateral nerves were spared were subsequently randomized. Patients in group 1 followed a daily rehabilitation protocol consisting of 10 min/day using the VED with no constriction ring, for 5 months. Patients were evaluated with the IIEF-5 questionnaire and measurements of penile flaccid length, stretched length, prepubic fat pad, and midshaft circumference before and at 1, 3, 6, 9 and 12 months after RP; the mean (range) last follow-up visit was 9.5 (6-12) months after RP. RESULTS: The mean (sd) baseline IIEF scores were similar in groups 1 and 2, at 21.1 (4.6) and 22.3 (3.3), respectively (P = 0.54). The IIEF scores were significantly higher in group 1 than group 2 at 3 months, at 11.5 (9.4) vs 1.8 (1.4) (P = 0.008) and at 6 months, at 12.4 (8.7) vs 3.0 (1.9) (P = 0.012) after RP. There were no significant changes in penile flaccid length, prepubic fat pad, or mid-shaft circumference in either group. Stretched penile length was significantly decreased at both 3 and 6 months, by approximately 2 cm (P = 0.013) in group 2. By contrast, stretched penile length was preserved in group 1 at all sample times. At the last follow-up, the proportion of men with a mean loss of penile length of >/= 2 cm was significantly lower in group 1 than group 2 (two/17, 12%, vs five/11, P = 0.044). CONCLUSIONS: Initiating the use of a VED protocol at 1 month after RP improves early sexual function and helps to preserve penile length.     

Evaluation of Safety and Efficacy of Rosiglitazone in the Treatment of HIV-Associated Lipodystrophy Syndrome

Abstract Background: HIV-associated lipodystrophy syndrome (LDS) as a long-term side effect of HAART is becoming increasingly important and negatively affects adherence to medication. Currently, an effective therapy is not available. There is some evidence that the drug class of thiazolidindiones might be effective in the treatment of LDS. Patients and Methods: Prospective open-label study with 20 HIV-infected patients suffering from severe LDS. Patients received 4 mg rosiglitazone once daily for a 24-week study period. Efficacy was assessed by measurement of metabolic and anthropometric parameters, total body DXA scan, CT scan of the abdomen, photo documentation and self-assessment. Results: Rosiglitazone treatment was well tolerated. DXA scans demonstrated a highly significant increase in adipose tissue of the limbs (2644 ± 1334 g vs 3380 ± 1614 g, p ≤ 0.001) without any change in total fat mass. Abdominal CT-scans revealed a significant increase in subcutaneous adipose tissue (113.7 ± 82.4cm² vs 125.3 ± 83.7 cm², p = 0.04). Abdominal circumference decreased significantly (94.7 ± 8.7 cm vs 92.2 ± 8.45 cm, p = 0.03) without any relevant change of body weight or BMI. We observed an increase in serum cholesterol (248 vs 281 mg/dl, p = 0.006) and serum triglycerides (301 vs 351 mg/dl, p = 0.1). Furthermore, no side effects of clinical relevance were observed. The insulin sensitivity index improved without reaching statistical significance. Thirteen patients (65%) reported general improvement of LDS symptoms. Evaluation of photo documentation by five HIV-experts revealed poor concordance and no relevant change of LDS. Conclusions: The results of this study suggest that rosiglitazone is safe in the treatment of HAART-associated lipodystrophy and has moderate clinical efficacy. We found a trend towards improved insulin sensitivity and as a possible limiting factor an unfavorable increase in serum cholesterol and triglycerides.     

Interferon‐α–inducible proteins are novel autoantigens in murine lupus

Objective

To investigate the spectrum of B cell autoimmunity in the recently described anti‐CD1–autoreactive T cell receptor (TCR)–transgenic murine lupus‐like (CD1 lupus‐like) model.

Methods

Lethally irradiated BALB/c/nu/nu mice were injected intravenously with donor BALB/c bone marrow and spleen cells expressing TCRα and TCRβ transgenes that recognize CD1d. Sera from adoptive host animals that developed lupus (i.e., CD1 lupus mice) were collected at serial time points and analyzed by Western blotting and immunoprecipitation, using protein extracts prepared from NIH3T3 mouse fibroblasts and EL‐4 lymphocytes, respectively. Sera obtained from older animals in several models of spontaneous lupus (NZB/NZW, MRL++, and MRL/lpr mice), unmanipulated BALB/c/nu/nu mice, and normal BALB/c mice were used as controls.

Results

Analyses demonstrated that the prominent targets of autoantibodies in the CD1 lupus‐like model are interferon‐α (IFNα)–inducible antigens. Biochemical and serologic characterizations identified one antigen as belonging to the interferon‐inducible 202 (Ifi202) subfamily of proteins within the Ifi200 family, and a second antigen as a member of the 70‐kd heat‐shock protein family. Autoantibodies directed against these antigens were rapidly produced at an early stage of disease. Anti‐p50 autoantibodies were present in sera from 7 (78%) of 9 CD1 lupus mice that developed severe kidney disease.

Conclusion

IFNα‐inducible proteins represent a novel class of autoantigens in murine lupus, and the findings suggest additional roles for IFNα in this disease. Since Ifi202 autoantigens are encoded by the murine non–major histocompatibility complex lupus‐susceptibility gene locus Ifi202, these data provide a link between recent advances in lupus genetics and the formation of autoantibodies.

     

Population genetic analysis of 12 X-chromosomal STRs in a Swiss sample

International Journal of Legal Medicine - X-chromosomal STRs are a powerful tool to assess a broad variety of complex kinship scenarios. We introduce herewith the first Swiss X-STR dataset based on...     

Microstructure analysis of dental castings used in fixed dental prostheses—a simple method for quality control

The aim of this study was to evaluate the microstructural quality of noble alloy castings from commercial dental laboratories using the wiping–etching method as a simple method for quality control. In total, 240 castings from two noble alloys (AuAgCuPt and AuPtZn) were taken from a day's production of five different dental laboratories. The casting quality was evaluated by determining the grain size and by assessing the number and size of shrinkage cavities after acidic etching of the alloy surfaces. The AuAgCuPt alloy castings showed an acceptable quality in the microstructural analysis. The results of AuPtZn castings, however, were not satisfactory because 50.8% of the samples showed a remarkably poorer quality compared to the specifications made by the manufacturer. The proportion of the employed reclaimed alloy had no influence on the casting quality when AuAgCuPt alloy was used, but was influential when casting restorations with AuPtZn alloy. When determining the quantity and size of shrinkage cavities, none of the evaluated castings was of such a poor quality that a replacement of the castings had to be considered. The differences in grain size and quantity of shrinkage cavities were reflecting the individual laboratory process rather than the admixture of new/reclaimed alloy. The presented analysis can be used as a simple method for quality control of dental castings.