POLR3A-related spastic ataxia: new mutations and a look into the phenotype

Journal of Neurology - Adolescent-onset spastic ataxia is a proposed novel phenotype in compound heterozygous carriers of an intronic mutation (c.1909 + 22G > A) in...     

Insulin-like growth factor-binding protein 5 (Igfbp5) compromises survival, growth, muscle development, and fertility in mice

The insulin-like growth factors (IGFs) are essential for development; bioavailable IGF is tightly regulated by six related IGF-binding proteins (IGFBPs). Igfbp5 is the most conserved and is developmentally up-regulated in key lineages and pathologies; in vitro studies suggest that IGFBP-5 functions independently of IGF interaction. Genetic ablation of individual Igfbps has yielded limited phenotypes because of substantial compensation by remaining family members. Therefore, to reveal Igfbp5 actions in vivo, we generated lines of transgenic mice that ubiquitously overexpressed Igfbp5 from early development. Significantly increased neonatal mortality, reduced female fertility, whole-body growth inhibition, and retarded muscle development were observed in Igfbp5-overexpressing mice. The magnitude of the response in individual transgenic lines was positively correlated with Igfbp5 expression. Circulating IGFBP-5 concentrations increased a maximum of only 4-fold, total and free IGF-I concentrations increased up to 2-fold, and IGFBP-5 was detected in high M(r) complexes; however, no detectable decrease in the proportion of free IGF-I was observed. Thus, despite only modest changes in IGF and IGFBP concentrations, the Igfbp5-overexpressing mice displayed a phenotype more extreme than that observed for other Igfbp genetic models. Although growth retardation was obvious prenatally, maximal inhibition occurred postnatally before the onset of growth hormone-dependent growth, regardless of Igfbp5 expression level, revealing a period of sensitivity to IGFBP-5 during this important stage of tissue programming.     

Accelerated evolution of SIV env within the cerebral compartment in the setting of morphine-dependent rapid disease progression

Human immunodeficiency virus-1 (HIV-1) and simian immunodeficiency virus (SIV) have been shown to compartmentalize within various tissues, including the brain. However, the evolution of viral quasispecies in the setting of drug abuse has not been characterized. The goal of this study was to examine viral evolution in the cerebral compartment of morphine-dependent and control macaques to determine its role in rapid disease progression. To address this issue, we analyzed the envelope (env) gene from proviral DNA in our SIV/SHIV macaque model of morphine dependence and AIDS. Analyses of proviral DNA revealed a direct correlation between total genetic changes and survival time. However, the rate of evolution during disease progression was higher in morphine-dependent and rapid-progressor macaques than was the rate of evolution in the control animals. This study provides additional insight into SIV envelope variation in the CNS of morphine-dependent macaques and genotypes that may have evolved in the brain and contributed to disease progression.     

Robot‐assisted vs pure laparoscopic radical prostatectomy: are there any differences?

OBJECTIVE: To compare our experience of pure laparoscopic radical prostatectomy (LRP) with robot-assisted radical prostatectomy (RAP). PATIENTS AND METHODS: The two techniques were compared retrospectively in 100 patients with localized prostate cancer who had LRP or RAP (50 each). Both groups were similar in age, serum prostate-specific antigen level, Gleason score and clinical stage. Their charts were reviewed, collating intraoperative data and early functional outcome. RESULTS: The mean surgical time for LRP and RAP was 235 and 202 min (P > 0.05) and mean (95% confidence interval) blood loss 299 (40) and 206 (63) mL (P = 0.014), with no transfusions in either group. The positive margin rate did not differ significantly (14% LRP and 12% RAP) and there was no biochemical recurrence in either group. Early functional outcomes were similar. CONCLUSIONS: Both LRP and RAP are technically demanding, but feasible, with the patient clearly benefiting. There were no major surgical differences between the techniques, but RAP is more costly.     

Antimicrobial Activity of Neotropical Wood and Bark Extracts

A total of 203 wood and bark extracts obtained from a Neotropical lowland rainforest in French Guiana were tested for antimicrobial activity against a panel of four human pathogens. Inhibitory activity against Staphylococcus aureus was regularly observed. Significant growth inhibition against Enterococcus faecilis was found in species belonging to the plant genus Sloanea (Elaeocarpaceae) and various Sapotaceae. The plant genera Eschweilera, Gustavia and Couratari (Lecythidaceae) showed notable growth inhibitory activity against both Escherichia coli and Enterococcus faecilis. Fractionation of the active extracts showed that the activities against Gram-positive and Gram-negative bacteria appear to be associated with different compounds. In some cases several replicates were sampled, showing that intraspecific activity levels may vary. The results of the screening experiments are compared to eth nomedicinal information available from northern South America and adjacent areas.     

Determination of methyl and ethyl esters of methanesulfonic, benzenesulfonic and p-toluenesulfonic acids in active pharmaceutical ingredients by solid-phase microextraction (SPME) coupled to GC/SIM-MS

The development, optimization and validation of an extraction method for methyl and ethyl esters of various sulfonic acids is presented. The extraction and determination of these esters in active pharmaceutical ingredients (APIs) was accomplished using solid-phase microextraction coupled to GC/MS in the SIM mode. The factors affecting the extraction efficiency are discussed. This method was validated as a limits test and allows the determination of the sulfonic esters at the 5 ppm level in APIs. The method proved to be reproducible (%R.S.D.s less than 6%) and suitable for use with external standard quantitation, and also met basic validation requirements. This method offers numerous advantages over liquid-liquid extraction methods and was also compared to other extraction techniques such as solid-phase extraction (SPE) and liquid-phase microextraction (LPME) also being developed in our laboratories.     

Laparoscopic radical prostatectomy following laparoscopic bilateral mesh hernia repair.

Laparoscopic mesh hernia repair is an effective form of management of inguinal hernias. Polypropylene mesh is generally placed at the internal rings extending across the midline resulting in an intense fibrotic reaction that can make subsequent radical retropubic prostatectomy and lymphadenectomy difficult. We report the first case of laparoscopic radical prostatectomy following laparoscopic bilateral mesh hernia repair.