The anatomical relationships between the serotonergic afferents and the neurons containing calcium-binding proteins in the rat claustrum

Claustrum is a telencephalic structure integrating information of various modalities. Proper functioning of this structure depends on the presence of a network of intrinsic connections. This includes GABA-ergic neuronal populations that also contain calcium-binding proteins (CaBPs). The goal of this study was to analyze qualitative and quantitative the 5-HT-containing fibers in the rat claustrum and to assess the relationships between these fibers and the populations of claustral neurons expressing CaBPs. We used the methods of immunocytochemistry and morphometry. The serotonergic fibers in the claustrum are heterogeneous, both with respect to their morphology and spatial distribution. Thin varicose fibers are more numerous and are homogeneously distributed within the claustrum. Remaining fibers were thicker and possessed larger varicosities. They were present mainly in the ventral part of the claustrum. Although the serotonergic fibers are found in the vicinity of claustral cells containing CaBPs, direct contacts between these fibers and cells are rare. Other mechanisms, including volume transmission, may possibly mediate serotonergic influences.     

Treatment of orthotopic malignant peripheral nerve sheath tumors with oncolytic herpes simplex virus

Backgrounds

Malignant peripheral nerve sheath tumors (MPNSTs) are an aggressive and often lethal sarcoma that frequently develops in patients with neurofibromatosis type 1 (NF1). We developed new preclinical MPNST models and tested the efficacy of oncolytic herpes simplex viruses (oHSVs), a promising cancer therapeutic that selectively replicates in and kills cancer cells.

Methods

Mouse NF1⁻ MPNST cell lines and human NF1⁻ MPNST stemlike cells (MSLCs) were implanted into the sciatic nerves of immunocompetent and athymic mice, respectively. Tumor growth was followed by external measurement and sciatic nerve deficit using a hind-limb scoring system. Oncolytic HSV G47Δ as well as “armed” G47Δ expressing platelet factor 4 (PF4) or interleukin (IL)-12 were injected intratumorally into established sciatic nerve tumors.

Results

Mouse MPNST cell lines formed tumors with varying growth kinetics. A single intratumoral injection of G47Δ in sciatic nerve tumors derived from human S462 MSLCs in athymic mice or mouse M2 (37-3-18-4) cells in immunocompetent mice significantly inhibited tumor growth and prolonged survival. Local IL-12 expression significantly improved the efficacy of G47Δ in syngeneic mice, while PF4 expression prolonged survival. Injection of G47Δ directly into the sciatic nerve of athymic mice resulted in only mild symptoms that did not differ from phosphate buffered saline control.

Conclusions

Two new orthotopic MPNST models are described, including in syngeneic mice, expanding the options for preclinical testing. Oncolytic HSV G47Δ exhibited robust efficacy in both immunodeficient and immunocompetent MPNST models while maintaining safety. Interleukin-12 expression improved efficacy. These studies support the clinical translation of G47Δ for patients with MPNST.     

Does the proper intravenous immunoglobulin substitution in primary immunodeficiency protect against HBV infections?: a description of a case series

There are no recommendations concerning preoperative management of primary immunodeficiency patients in cases of emergency or planned surgery in relation to risk of hepatitis type B virus infection. To assess if immunodeficient patients regularly supplemented with immunoglobulins are protected against hepatitis B. IgG, IgM and IgA total levels and anti-HBs level were estimated in adult patients with primary humoral immunodeficiency before and after immunoglobulins supplementation according to a standardized schedule. Serum IgG and anti-HBs level significantly increased after immunoglobulin supplementation. Anti-HBs titer increased in all cases over 100 IU/L regardless of initial total IgG serum value, reaching a highly protective level. There was no correlation between increase in concentration of IgG (DeltaIgG) versus Deltaanti-HBs in the studied patients. Patients with primary hypogammaglobulinemia supplemented with immunoglobulin are protected against hepatitis type B.     

Changing HCV genotypes distribution in Poland--relation to source and time of infection.

BACKGROUND: Understanding the distribution of HCV genotypes has implications for prognosis and therapy of hepatitis C. OBJECTIVES: To describe the distribution of HCV genotypes in Poland in relation to route of transmission and year of infection. STUDY DESIGN: Patients with chronic liver disease were evaluated at the Department of Infectious Diseases, Bialystok (Poland). HCV genotype was determined by means of 5'UTR sequencing and comparison with known sequences of particular genotypes. RESULTS: The genotypes mostly frequently detected were genotype 1 (57.5%); genotype 3 (31.3%); and genotype 4 (8.4%). Genotype 1 constituted the majority of HCV infections caused by blood transfusion (68.8%) and only 34.8% of HCV infections in the intravenous drug use (IVDU) group (p<0.05). In contrast genotype 3 constituted the majority of HCV infections in the IVDU group (56.5%). We observed a significant increase in the proportion of genotype 3 infections detected after 2000--from 19.1% to 38.9%. CONCLUSIONS: The relative proportion of genotype 1b in Poland has decreased and that of genotype 3a has increased, especially among IVDU.     

Thiamine antivitamins – an opportunity of therapy of fungal infections caused by Malassezia pachydermatis and Candida albicans

Severe skin diseases and systemic fungaemia are caused by Malassezia pachydermatis and Candida albicans respectively. Antifungal therapies are less effective because of chronic character of infections and high percentage of relapses. Therefore, there is a great need to develop new strategies of antifungal therapies. We previously found that oxythiamine decreases proliferation of yeast (Saccharomyces cerevisiae), therefore we suggest that thiamine antivitamins can be considered as antifungal agents. The aim of this study was the comparison of thiamine antivitamins (oxythiamine, amprolium, thiochrome, tetrahydrothiamine and tetrahydrooxythiamine) inhibitory effect on the growth rate and energetic metabolism efficiency in non‐pathogenic S. cerevisiae and two potentially pathogenic species M. pachydermatis and C. albicans. Investigated species were cultured on a Sabouraud medium supplemented with trace elements in the presence (40 mg l^?1) or absence of each tested antivitamins to estimate their influence on growth rate, enzyme activity and kinetic parameters of pyruvate decarboxylase and malate dehydrogenase of each tested species. Oxythiamine was the only antivitamin with antifungal potential. M. pachydermatis and S. cerevisiae were the most sensitive, whereas C. albicans was the least sensitive to oxythiamine action. Oxythiamine can be considered as supportive agent in superficial mycoses treatment, especially those caused by species from the genus Malassezia.     

The Effect of Ball Burnishing on Dry Fretting

Experiments were conducted under a dry gross fretting regime. Steel discs were put in contact with ceramic balls. Before tribological tests, discs were subjected to ball burnishing with different pressures. Due to ball burnishing, a decrease in surface amplitude and an increase in microhardness occurred. Ball burnishing caused decreases in the friction force and volumetric wear of up to 45% in comparison to sliding pairs containing milled discs. The friction force and volumetric wear were higher for a higher roughness of disc.