Brain modulation of the immune system: association between lymphocyte responsiveness and paw preference in mice

An association between handedness and immune disorders has been described in man, left-handers being more susceptible to autoimmune or allergic diseases. However, this correlation was established between handedness and clinical signs of immune disorders without studying immune functions. Using an animal model, we demonstrated for the first time an association between handedness and lymphocyte reactivity. Left-handed mice were shown to exhibit higher mitogen-induced T lymphocyte proliferation than right-handed animals.     

Studies with pre-treatment of milk with calcium acetata to reduce the phosphate content

European Journal of Pediatrics -     

Expression of the c-raf protooncogene, gamma-glutamyltranspeptidase, and gap junction protein in rat liver neoplasms

Female Harlan Sprague-Dawley and F-344 rats were subjected to a 70% hepatectomy and 18 h later given one dose of 30 mg diethylnitrosamine/kg body weight. Beginning 1 week later, the animals were fed a diet containing 0.05% phenobarbital. Groups of rats were sacrificed 6 and 15 months later, and the livers were either frozen for cryostat sectioning or used to isolate RNA. Primary liver tumors present in these animals were used for RNA isolation, and a portion was taken for histopathological analysis. Eleven of 13 primary lesions, consisting of either neoplastic nodules or hepatocellular carcinomas, showed elevated levels of mRNA for the c-raf protooncogene. Increased c-raf mRNA in these tumors appeared to be unrelated to their cellular proliferative status inasmuch as the levels of c-raf mRNA did not correlate with levels of H4 histone mRNA. Decreased expression of the major rat liver gap junction protein mRNA was observed in all of the primary tumors. Immunocytochemical analysis using an anti-gap junction antibody revealed a decrease in gap junction immunoreactivity in some but not all preneoplastic focal lesions. All preneoplastic foci having positive gamma-glutamyltranspeptidase enzyme staining also exhibited a marked increase in gamma-glutamyltranspeptidase mRNA as determined by in situ hybridization. The possible relation of alterations of the mRNA levels of c-raf and the gap junction protein to the further development of preneoplastic foci is discussed.     

Are There Differences between Women who Choose Elective Repeat Caesarean Versus Trial of Labour in St. John's,NL?

Objectives

To compare the demographic and clinical characteristics between women who chose elective repeat Caesarean section (ERCS) versus trial of labour after Caesarean section (TOLAC) in St. John's, Newfoundland and Labrador (NL).

Iron deficiency impairs contractility of human cardiomyocytes through decreased mitochondrial function

Aims

Iron deficiency is common in patients with heart failure and associated with a poor cardiac function and higher mortality. How iron deficiency impairs cardiac function on a cellular level in the human setting is unknown. This study aims to determine the direct effects of iron deficiency and iron repletion on human cardiomyocytes.

Methods and results

Human embryonic stem cell‐derived cardiomyocytes were depleted of iron by incubation with the iron chelator deferoxamine (DFO). Mitochondrial respiration was determined by Seahorse Mito Stress test, and contractility was directly quantified using video analyses according to the BASiC method. The activity of the mitochondrial respiratory chain complexes was examined using spectrophotometric enzyme assays. Four days of iron depletion resulted in an 84% decrease in ferritin (P < 0.0001) and significantly increased gene expression of transferrin receptor 1 and divalent metal transporter 1 (both P < 0.001). Mitochondrial function was reduced in iron‐deficient cardiomyocytes, in particular ATP‐linked respiration and respiratory reserve were impaired (both P < 0.0001). Iron depletion affected mitochondrial function through reduced activity of the iron–sulfur cluster containing complexes I, II and III, but not complexes IV and V. Iron deficiency reduced cellular ATP levels by 74% (P < 0.0001) and reduced contractile force by 43% (P < 0.05). The maximum velocities during both systole and diastole were reduced by 64% and 85%, respectively (both P < 0.001). Supplementation of transferrin‐bound iron recovered functional and morphological abnormalities within 3 days.

Conclusion

Iron deficiency directly affects human cardiomyocyte function, impairing mitochondrial respiration, and reducing contractility and relaxation. Restoration of intracellular iron levels can reverse these effects.     

Diagnosis of Cytomegalovirus Anterior Uveitis in Two European Referral Centers

Purpose: To evaluate diagnostic methods and clinical signs of CMV anterior uveitis (AU), a rarely described entity in Europe.

Methods: We included patients with clinical characteristics of CMV AU and positive PCR and/or Goldmann-Witmer coefficient (GWc) for CMV.

Results: We report 21 patients with unilateral uveitis (100%) and signs of Posner-Schlossman syndrome (PSS) (n = 20, 95.2%), Fuchs uveitis syndrome (FUS) (n = 1, 4.7%), and endotheliitis (n = 4, 19,04%). PCR was positive in 15/21 (71.4%) and GWc in 8/9 patients (88.9%) in aqueous for CMV. GWc was the only positive test in 6/9 patients (66,6%). When PCR alone was performed (without GWc) in the first tap, repeated aqueous taps were needed, twice in five cases and thrice in one case.

Conclusion: Combining PCR and GWc were very helpful to confirm the clinical diagnosis of CMV AU. In case of very high clinical suspicion and negative results, repeated tap seems to be recommended.     

HLA class II polymorphism influences onset and severity of pathology in Schistosoma mansoni-infected transgenic mice

Genetic factors that might influence susceptibility or resistance in naive individuals and early-stage pathology in schistosomiasis are difficult to study in clinical trials, since in areas where the disease is endemic the first contact with the parasite occurs most often at very early ages. Therefore, four strains (DR1.Abeta degrees, DR2.Abeta degrees, DQ8.Abeta degrees, and DQ6.Abeta degrees ) of major histocompatibility complex class II-deficient mice (Abeta degrees ), transgenic for different HLA alleles, have been used to evaluate the potential role of HLA class II polymorphism in the onset of the infection by Schistosoma mansoni. The survival rates and parasitological and immunological parameters after infection were evaluated and compared against the control values obtained with Abeta degrees mice. All four mouse strains used in this study were able to generate a specific immune response against S. mansoni antigens (cytokine production and antibody production). However, only mice expressing DR alleles survived until the chronic stage of the infection and were able to mount protective granulomatous response avoiding hepatic damage, presenting predominant gamma interferon production. In contrast, strains expressing DQ alleles revealed an impairment in generating effective granulomas, resulting in earlier death, which was associated with an impaired hepatic granulomatous response and liquefactic necrosis, reflecting the influence of HLA polymorphism in the establishment of protective response in the early stage of infection.