The use of cortisone-treated mice in the screening of soil for pathogenic fungi

Summary Fifty-seven samples of desert soils were screened for pathogenic fungi by injection into cortisone-treated and non-treated mice. Four samples yielded pathogenic fungi in the cortisone-treated mice only.Nocardia asteroides was isolated from the cortisone-treated mice and from the controls. All of the cortisone-treated and the control mice injected with soil from the root zone of a dead century plant became critically ill very shortly after injection and cultures from all of the animals showed a variety of fungi. Seven species were isolated from the cortisone-treated animals and 5 species from the controls.The yeast,Torulopsis glabrata, was found in 69 of the 225 control mice and in 115 of the 213 cortisone-treated animals that came to autopsy. This organism was not considered to have been derived from the soil.The results appear to justify the conclusion that this method of soil screening deserves further consideration and study.     

Anti-Arthritic Activity of Schistosoma mansoni and Trichinella spiralis Derived-Antigens in Adjuvant Arthritis in Rats: Role of FOXP3+ Treg Cells

A growing body of evidence supports the concept of helminths therapy in a variety of autoimmune diseases. Here, we aimed to investigate the protective effects of autoclaved Schistosoma mansoni antigen (ASMA) and Trichinella spiralis antigen (ATSA) on the clinical and immunopathological features of rheumatoid arthritis (RA). Adjuvant arthritis was induced by subcutaneous and intradermal injections of complete Freund’s adjuvant into the plantar surface of the right hind paw and the root of the tail, respectively. Rats were randomly assigned to serve as normal control, untreated arthritis, ASMA or ATSA-treated arthritis groups. Antigens were given by intradermal injection in two doses, two weeks apart. The development, progression of arthritic features, and the impact on animals’ gait and body weight were followed up for 4 weeks. The associated changes in serum cytokines (IL-17, IFN-γ and IL-10), joints’ histopathology and immunohistochemistry of Foxp3⁺ T regulatory cells (Tregs) were evaluated at the end of the study. Treatment with either ASMA or ATSA attenuated the progression of clinical features of polyarthritis, improved gait and body weight gain, reduced the elevated serum IL-17 and further increased both IFN-γ and IL-10. Histopathologically, this was associated with a remarkable regression of paws’ inflammation that was limited only to the subcutaneous tissue, and a significant increase in the number of Foxp 3+ cells versus the untreated arthritis group. In conclusion, both Schistosoma mansoni and Trichinella spiralis derived antigens exerted protective effect against adjuvant arthritis with better effect achieved by ASMA treatment. This anti-arthritic activity is attributed to upregulation of the Foxp3⁺ Tregs, with subsequent favorable modulation of both pro- and anti-inflammatory cytokines. The use of autoclaved parasitic antigens excludes the deleterious effects of imposing helminthic infection by using live parasites, which may pave the way to a new therapeutic modality in treating RA.     

Sediment accumulation in Lakes Lilla Ullfjärden and Stora Ullfjärden,Sweden

X-ray radiography is a superior method of showing structures in recently deposited sediments. Annually laminated sediments have been proved to exist in Lakes Lilla Ullfjärden and Stora Ullfjärden using this method.From X-ray radiographs of laminated sediment cores sampled nearly every year since 1977 in Lake Lilla Ullfjärden and since 1978 in Lake Stora Ullfjärden, it is possible to distinguish the seasonal variation in sediment deposition in the lakes. The variation in time and space in sediment accumulation is possible to estimate. The rate of sediment accumulation has been calculated to be 320 g solids/m² · y^–1 for the deepest part of Lake Lilla Ullfjärden and 920 g solids/m² · y^–1 for the central part of Lake Stora Ullfjärden for the period 1978 to 1983. It is also possible to trace the effect of eutrophication in time and space. An estimation of the appearance of the oxygen deficit in Lilla Ullfjärden gives a time around 1885.     

TGFβ restricts expansion,survival, and function of T cells within the tuberculous granuloma

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Cimetidine a promising radio-protective agent through modulating Bax/Bcl2 ratio: An in vivo study in male rats

Radiotherapy is one of the most effective modalities for treatment of neoplastic diseases. Radiation damage is to a large extent caused by overproduction of reactive oxygen species. To improve the therapeutic index, identifying effective substances for prevention or treatment of postirradiation intestinal and bone marrow injury should be prompted. This study was designed to evaluate the protective effects of cimetidine on the in rats exposed to γ-irradiation (5 Gy) and exploring the B-cell lymphoma 2 (Bcl2)/Bcl2 associated X (bax) pathway as a probable underlying mechanism. Eighteen adult male rats were randomly grouped into three: control, untreated irradiated rats, and irradiated rats pretreated with cimetidine. Seven days postirradiation the rats were culled, the bone marrow (BM) and jejunum tissue samples were collected for biochemical, histological, and immunohistological evaluation of BM cell count (BMCs), intestinal fibrosis, oxidative stress, tumor necrosis factor-α, Bcl2, and Bax. Cimetidine pretreatment significantly reversed the loss of BMCs, intestinal lining destruction, and fibrosis seen in the untreated irradiated rats and significantly decreased the underlying oxidative stress, inflammation, and Bax/Bcl2 ratio. There was a significant differential correlation between Bax/Bcl2 ratio, tissue oxidative stress level, and tissue injury. Cimetidine represents a very promising radioprotective agent with a potential differential beneficial effect on both cancer cells (inducing apoptosis) as previously proved through different studies and adjacent healthy cells (providing radioprotection via inhibiting apoptosis) as clearly demonstrated through this study, via its antioxidant effect and subsequent regulation of type 2 apoptotic pathway through modulation of Bax/Bcl2 ratio.     

Antibiotic resistance and molecular typing among cockle (Anadara granosa) strains of Vibrio parahaemolyticus by polymerase chain reaction (PCR)-based analysis

Genomic DNA of Vibrio parahaemolyticus were characterized by antibiotic resistance, enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR) and random amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR) analysis. These isolates originated from 3 distantly locations of Selangor, Negeri Sembilan and Melaka (East coastal areas), Malaysia. A total of 44 (n = 44) of tentatively V. parahaemolyticus were also examined for the presence of toxR, tdh and trh gene. Of 44 isolates, 37 were positive towards toxR gene; while, none were positive to tdh and trh gene. Antibiotic resistance analysis showed the V. parahaemolyticus isolates were highly resistant to bacitracin (92 %, 34/37) and penicillin (89 %, 33/37) followed by resistance towards ampicillin (68 %, 25/37), cefuroxime (38 %, 14/37), amikacin (6 %, 2/37) and ceftazidime (14 %, 5/37). None of the V. parahaemolyticus isolates were resistant towards chloramphenicol, ciprofloxacin, ceftriaxone, enrofloxacin, norfloxacin, streptomycin and vancomycin. Antibiogram patterns exhibited, 9 patterns and phenotypically less heterogenous when compared to PCR-based techniques using ERIC- and RAPD-PCR. The results of the ERIC- and RAPD-PCR were analyzed using GelCompare software. ERIC-PCR with primers ERIC1R and ERIC2 discriminated the V. parahaemolyticus isolates into 6 clusters and 21 single isolates at a similarity level of 80 %. While, RAPD-PCR with primer Gen8 discriminated the V. parahaemolyticus isolates into 11 clusters and 10 single isolates and Gen9 into 8 clusters and 16 single isolates at the same similarity level examined. Results in the presence study demonstrated combination of phenotypically and genotypically methods show a wide heterogeneity among cockle isolates of V. parahaemolyticus.     

On the estimation of average treatment effects with right-censored time to event outcome and competing risks

We are interested in the estimation of average treatment effects based on right-censored data of an observational study. We focus on causal inference of differences between t-year absolute event risks in a situation with competing risks. We derive doubly robust estimation equations and implement estimators for the nuisance parameters based on working regression models for the outcome, censoring, and treatment distribution conditional on auxiliary baseline covariates. We use the functional delta method to show that these estimators are regular asymptotically linear estimators and estimate their variances based on estimates of their influence functions. In empirical studies, we assess the robustness of the estimators and the coverage of confidence intervals. The methods are further illustrated using data from a Danish registry study.