Electron microscopy of neurosecretory nerve fibres in the neural lobe of the embryonic mouse

Summary Nerve fibres of the neurosecretory hypothalamo-hypophyseal tract were studied in embryonic C3H mouse neural lobes; at least four glands at each gestational day 15–19 were examined.Single axons and small bundles of fibres are visible at gestational days 15 and 16. By day 17 large fibre bundles penetrate between glial cells. They increase in number during the next two days.Electron-lucent and electron-dense vesicles are seen in the fibres of the 15th and 16th gestational days. In the 17–19 day-old embryos development is characterized by a successive rise in the number of the two types of vesicles. The mean diameter of the electron-lucent vesicles is approximately unchanged in all the stages examined (50 nm). The electron-dense vesicles increase in size from approximately 80–90 nm at days 15–16 to 140 nm at the 19th gestational day.By day 19 contacts between neurosecretory fibre terminals and the outer basement membrane of internal and peripheral capillaries are occasionally observed. The possibly adrenergic nature of a few terminals contacting peripheral vascular structures in 17 and 18 day-old embryos is suggested.This investigation was supported by grant No. 2180-020 from the Swedish Natural Science Research Council. The skilful technical assistance of Mrs. Ulla Wennerberg is gratefully acknowledged.     

The Role of Multiphosphorylated Peptides in Mineralized Tissue Regeneration

Several multiple phosphoseryl-containing proteins have been identified in mineralising tissue and body fluids where they have been proposed to act as nucleators and/or regulators of biomineralisation. In particular, the unique features of the multiphosphorylated caseins from milk and phosphophoryn from dentine enable them to have a role in mineralised tissue regeneration. In this review, three examples of therapeutic applications using multiphosphorylated peptides are described.     

Phenomic and genomic approaches to studying the inhibition of multiresistant Salmonella enterica by microcin J25

In livestock production, antibiotics are used to promote animal growth, control infections and thereby increase profitability. This practice has led to the emergence of multiresistant bacteria such as Salmonella, of which some serovars are disseminated in the environment. The objective of this study is to evaluate microcin J25 as an inhibitor of Salmonella enterica serovars of various origins including human, livestock and food. Among the 116 isolates tested, 37 (31.8%) were found resistant to at least one antibiotic, and 28 were multiresistant with 19 expressing the penta-resistant phenotype ACSSuT. Microcin J25 inhibited all isolates, with minimal inhibitory concentration values ranging from 0.06 μg/ml (28.4 nM) to 400 μg/ml (189 μM). Interestingly, no cross-resistance was found between microcin J25 and antibiotics. Multiple sequence alignments of genes encoding for the different proteins involved in the recognition and transport of microcin J25 showed that only ferric-hydroxamate uptake is an essential determinant for susceptibility of S. enterica to microcin J25. Examination of Salmonella strains exposed to microcin J25 by transmission electronic microscopy showed for the first-time involvement of a pore formation mechanism. Microcin J25 was a strong inhibitor of several multiresistant isolates of Salmonella and may have a great potential as an alternative to antibiotics.     

Gremlin in the pathogenesis of hepatocellular carcinoma complicating chronic hepatitis C: an immunohistochemical and PCR study of human liver biopsies

ABSTRACT: BACKGROUND: The possible role of secretory products of fibrous tissue in the development of hepatocellular carcinoma (HCC) complicating chronic hepatitis C was investigated. Our hypothesis was that gremlin, secreted by fibroblasts, inhibited bone morphogenic protein (BMP), which mediates stem cell maturation into adult functioning hepatocytes, and thus, arrest stem cell maturation and promoted their proliferation in an immature state possibly culminating into development of HCCs. RESULTS: Protein expression of cytokeratin 19 (CK19) and fibroblast growth factor 2 (FGF-2), and mRNA expression of gremlin and BMP-7 were studied in 35 cases of chronic hepatitis, cirrhosis and HCC complicating chronic hepatitis C. CK19 expression was higher in cases of cirrhosis (0.004), which correlated with the grade (r=0.64, p=0.009) and stage (r=0.71, p=0.001). All HCCs were negative for CK19. Stem cell niche activation (as indicated as a ductular reaction) was highest in cases of cirrhosis (p=0.001) and correlated with CK19 expression (r=0.42, p=0.012), the grade(r=0.56, p=0.024) and stage (0.66, p=0.006). FGF-2 expression was highest in HCCs and correlated with the grade (r=0.6, p=0.013), stage (0.72, p=0.002), CK19 expression (r=0.71, p=002) and ductular reaction (0.68, p=0.004) in hepatitis cases. Higher numbers of cirrhosis cases and HCCs (p=0.009) showed gremlin expression, which correlated with the stage (r=0.7, p=0.002). Gremlin expression correlated with that of CK19 (r=0.699, p=0.003) and FGF2 (r=0.75, p=0.001) in hepatitis cases. CONCLUSIONS: Fibrosis promotes carcinogenesis by fibroblast-secreted gremlin that blocks BMP function and promotes stem cell activation and proliferation as well as possibly HCC development.     

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.