Immune responses of a meningococcal A + W outer membrane vesicle (OMV) vaccine with and without aluminium hydroxide adjuvant in two different mouse strains

Meningococci (Neisseria meningiditis) of serogroups A and W have caused large epidemics of meningitis in sub‐Saharan Africa for decades, and affordable and multivalent vaccines, effective in all age groups, are needed. A bivalent serogroup A and W (A + W) meningococcal vaccine candidate consisting of deoxycholate‐extracted outer membrane vesicles (OMV) from representative African disease isolates was previously found to be highly immunogenic in outbred mice when formulated with the adjuvant aluminium hydroxide (AH). OMV has been shown to have inherent adjuvant properties. In order to study the importance of AH and genetical differences between mice strains on immune responses, we compared the immunogenicity of the A + W OMV vaccine when formulated with or without AH in inbred C57BL/6J and BALB/cJ mice (Th1 and Th2 dominant strains, respectively). The immunogenicity of the vaccine was found to be comparable in the two mice strains despite their different immune profiles. Adsorption to AH increased anti‐OMV IgG levels and serum bactericidal activity (SBA). The immune responses were increased by each dose for the adsorbed vaccine, but the third dose did not significantly improve the immunogenicity further. Thus, a vaccine formulation with the A and W OMV will likely benefit from including AH as adjuvant.     

Aortic function is compromised in a rat model of polycystic ovary syndrome

BACKGROUND: Arterial mechanical parameters are modified in women with polycystic ovary syndrome (PCOS), before and during pregnancy. This study tested the hypothesis that aortic mechanics and endothelial function are modified in the mifepristone-treated rat model of PCOS. METHODS: Female rats injected daily with mifepristone or vehicle for 7-9 days were assessed by ultrasound to allow estimation of aortic stiffness index and compliance. The influence of acetylcholine (ACh) and sodium nitroprusside (SNP) on dissected phenylephrine-contracted aortic rings was assessed. RESULTS: Aortic compliance was reduced by 67% in mifepristone-treated rats versus controls (P<0.05), while stiffness index was increased 2.3-fold (P<0.02). ACh-induced dilation was less in aortic rings from mifepristone-treated rats (P=0.022) and was less sensitive to the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) (P<0.001), while SNP-induced dilation was greater (P=0.001). CONCLUSIONS: Aortic mechanics in vivo and endothelial function in vitro were consistently perturbed in mifepristone-treated rats. Aortic ring behaviour suggested that NO release was depressed or degradation elevated, with a compensatory increase in NO sensitivity and/or activation of a non-NO-mediated relaxation mechanism. The mifepristone-treated rat is a valid model for investigation of the vascular deficits seen in PCOS.     

Thiamine responsive megaloblastic anemia syndrome

Thiamine responsive megaloblastic anemia syndrome (TRMA) is a clinical triad characterized by thiamine-responsive anemia, diabetes mellitus and sensorineural deafness. We report a 4-year-old girl with TRMA whose anemia improved following administration of thiamine and this case report sensitizes the early diagnosis and treatment with thiamine in children presenting with anemia, diabetes and deafness.     

Fibrodysplasia ossificans progressiva

A 2-year-old boy presented with low-grade fever and multiple progressive painful swellings over upper dorsal trunk and supraclavicular region with progressive stiffening of skin for the last 2 months. Examination revealed dysmorphic face, proximally placed thumb and bilateral hallux valgus. Hence, a diagnosis of Fibrodysplasia Ossificans Progressiva was entertained     

Trends in prescribing beta-lactam antibiotics for treatment of community-associated methicillin-resistant Staphylococcus aureus infections

Rates of prescribing of beta-lactam antibiotics as initial empirical therapy for patients with skin and soft tissue infections (SSTIs) caused by molecularly and epidemiologically characterized community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) isolates were assessed over a 3-year period. A prospectively developed database was used to calculate the prevalence of CA-MRSA SSTIs from 2004 to 2006. Molecular characterization of the MRSA isolate and medical record review for assessment of initial antimicrobial therapy were performed on a subset of patients. Among 2,636 patients with S. aureus SSTIs, the prevalence of CA-MRSA was 9% in 2004, 16% in 2005, and 21% in 2006 (P < 0.0001, chi-square test for trend). Seventy-five percent of CA-MRSA isolates tested were of the USA 300 or 400 clone type. Ninety-two percent of CA-MRSA isolates tested were positive for Panton-Valentine leukocidin, of which 90% carried staphylococcal chromosomal cassette mec type IV. The rate of use of a beta-lactam antibiotic as initial empirical therapy for patients with CA-MRSA SSTIs was 86%, 77%, and 60% in 2004, 2005, and 2006, respectively (P = 0.04, chi-square test for trend). Thirty percent of beta-lactam-treated patients had a documented risk factor for CA-MRSA infection. The use of a beta-lactam antibiotic as initial empirical therapy for CA-MRSA SSTIs has decreased significantly over the past 3 years. However, even as the prevalence of CA-MRSA SSTIs approaches 25%, the majority of patients are still receiving inactive antimicrobial therapy. Further evaluation of the outcomes associated with discordant therapy for CA-MRSA SSTIs is needed.     

Bone nodules on chitosan-polygalacturonic acid-hydroxyapatite nanocomposite films mimic hierarchy of natural bone

The ultimate goal of bone tissue engineering is to develop bony tissues on tissue engineered constructs that mimic the native bone. Nanoscale characterization of in vitro generated bony tissues on engineered scaffolds is essential to understanding both the physical and mechanical characteristics of the engineered bone. Bone nodule formation, a typical early indicator of bone formation was observed on chitosan-polygalacturonic acid-hydroxyapatite (Chi-PgA-HAP) nanocomposite films without the use of differentiating media. Thus, the Chi-PgA-HAP substrates designed are osteoinductive and provide an appropriate microenvironment for cell organization and tissue regeneration. Imaging using atomic force microscopy revealed several levels of hierarchical structures of bone in the bone nodules, consisting of mineralized collagen fibers, fibrils and mineral deposits in extrafibrillar spaces. The nanoscale elastic properties of the collagen and mineral crystals were found to be in close agreement with the experimental and simulations results on natural bone reported in the literature. Fourier transform infrared spectroscopy experiments indicate the presence of collagen and biological apatite in bone nodules exhibiting the characteristics of newly precipitated, immature bone. Collectively, our structural, chemical, and mechanical analyses support the conclusion that synthetic bone nodules mimic the hierarchy of natural bone.     

Mycosis fungoides: A case report

Mycosis fungoides is the commonest cutaneous T cell lymphoma. Clinically it is characterized by patch, plaque, tumor nodules; erythrodermic and poikoilodermous stages which may overlap. Extracutaneous spread takes place in late stages where any organ may be involved. The majority of reported cases are in adult males. A rare case of mycosis fungoides in a 38-year-old female is described. She presented in advance stage of disease with nodules all over the body.