Prevalence of hepatitis A, B and C serological markers in children from western Mexico

Introduction. Viral hepatitis in children is a major public health problem worldwide.Aim. To evaluate the prevalence of serological markers for hepatitis A, B and C infections in Mexican children diagnosed with hepatitis during a five-year period.Material and methods. A total of 31,818 children admitted to a tertiary level hospital in Mexico from 2005 to 2009 were evaluated for hepatitis.Results. Hepatitis was found in 215 (0.7%) of the children. Serum samples from hepatitis-positive children were screened for anti-HAV IgM, HBsAg, total anti-HBc and anti-HCV. HAV was the leading cause of viral hepatitis (81%), followed by HBV and HCV (3.1 and 2%, respectively), whereas no serological marker was observed in 13.9% of the analyzed samples. Furthermore, when children were categorized by age, a significant increase in anti-HAV detection was observed in school-aged children (7-11 years old) (p < 0.001) and a reduction in adolescents (12-15 years old).Conclusion. In conclusion, hepatitis A is the most prevalent viral hepatitis infection detected in children, followed by HBV and HCV. In addition, the high percentage of hepatitis infections without a known etiological agent and the serological test limitations require the detection of occult HBV, HCV and hepatitis E infections. The age-dependent vulnerability of groups with HAV infections emphasizes the importance of HAV vaccination in young children in Mexico.     

Inflammatory myofibroblastic tumor of the liver

Hepatic inflammatory myofibroblastic tumors are uncommon low grade malignant neoplasms. They can be confused clinically and by imaging studies with abscess.     

Optimization of the position of the acetabulum in a ganz periacetabular osteotomy by finite element analysis

Periacetabular osteotomy (PAO) is a surgical procedure to correct acetabular orientation in developmental dysplasia of the hip (DDH). It changes the position of the acetabulum to increase femoral head coverage and distribute the contact pressure over the cartilage surface. The success of PAO depends significantly on the surgeon's experience. Using computed tomography data from patients with DDH, we developed a 3D finite element (FE) model to investigate the optimal position of the acetabulum following PAO. A virtual PAO was performed with the acetabulum rotated in increments from the original center edge (CE) angle. Contact area, contact pressure, and Von Mises stress in the femoral and pelvic cartilage were analyzed. Five dysplastic hips from four patients were modeled. Contact area, contact pressure, and Von Mises stress in the cartilage all varied according to the change of CE angle through virtual PAO. An optimal position could be achieved for the acetabulum that maximizes the contact area while minimizing the contact pressure and von Mises stress in the pelvic and femoral cartilage. The optimal position of the acetabulum was patient dependent and did not always correspond to what would be considered a “normal” CE angle. We demonstrated for the first time the interrelation of correction angle, contact area, and contact pressure between the pelvic and femoral cartilage in PAO surgery. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 472–479, 2013     

Efficient radiosynthesis and preclinical evaluation of [18F]FOMPyD as a positron emission tomography tracer candidate for TrkB/C receptor imaging

Herein we report an efficient radiolabeling of a ¹⁸F-fluorinated derivative of dual inhibitor GW2580, with its subsequent evaluation as a positron emission tomography (PET) tracer candidate for imaging of two neuroreceptor targets implicated in the pathophysiology of neurodegeneration: tropomyosin receptor kinases (TrkB/C) and colony stimulating factor receptor (CSF-1R). [¹⁸F]FOMPyD was synthesized from a boronic acid pinacolate precursor via copper-mediated ¹⁸F-fluorination concerted with thermal deprotection of the four Boc groups on a diaminopyrimidine moiety in an 8.7±2.8% radiochemical yield, a radiochemical purity >99%, and an effective molar activity of 187±93 GBq/μmol. [¹⁸F]FOMPyD showed moderate brain permeability in wild-type rats (SUV_max = 0.75) and a slow washout rate. The brain uptake was partially reduced (ΔAUC_40–90 = 11.6%) by administration of the nonradioactive FOMPyD (up to 30 μg/kg). In autoradiography, [¹⁸F]FOMPyD exhibits ubiquitous distribution in rat and human brain tissues with relatively high nonspecific binding revealed by self-blocking experiment. The binding was blocked by TrkB/C inhibitors, but not with a CSF-1R inhibitor, suggesting selective binding to the former receptor. Although an unfavorable pharmacokinetic profile will likely preclude application of [¹⁸F]FOMPyD as a PET tracer for brain imaging, the concomitant one-pot copper-mediated ¹⁸F-fluorination/Boc-deprotection is a practical technique for the automated radiosynthesis of acid-sensitive PET tracers.     

Intermittent fasting favored the resolution of <Emphasis Type="Italic">Salmonella typhimurium</Emphasis> infection in middle-aged BALB/c mice

Intermittent fasting (IF) reportedly increases resistance and intestinal IgA response to Salmonella typhimurium infection in mature mice. The aim of this study was to explore the effect of aging on the aforementioned improved immune response found with IF. Middle-aged male BALB/c mice were submitted to IF or ad libitum (AL) feeding for 40 weeks and then orally infected with S. typhimurium. Thereafter, infected animals were all fed AL (to maximize their viability) until sacrifice on day 7 or 14 post-infection. We evaluated body weight, bacterial load (in feces, Peyer’s patches, spleen and liver), total and specific intestinal IgA, lamina propria IgA+ plasma cells, plasma corticosterone, and messenger RNA (mRNA) expression of α-chain, J-chain, and the polymeric immunoglobulin receptor (pIgR) in liver and intestinal mucosa. In comparison with the infected AL counterpart, the infected IF group (long-term IF followed by post-infection AL feeding) generally had lower intestinal and systemic bacterial loads as well as higher total IgA on both post-infection days. Both infected groups showed no differences in corticosterone levels, body weight, or food and caloric intake. The increase in intestinal IgA was associated with enhanced pIgR mRNA expression in the intestine (day 7) and liver. Thus, to maintain body weight and caloric intake, IF elicited metabolic signals that possibly induced the increased hepatic and intestinal pIgR mRNA expression found. The increase in IgA probably resulted from intestinal IgA transcytosis via pIgR. This IgA response along with phagocyte-induced killing of bacteria in systemic organs (not measured) may explain the resolution of the S. typhimurium infection.     

Shigella flexneri phagosomal escape is independent of invasion

Infections with Salmonella enterica serovar Typhimurium and Shigella flexneri result in mucosal inflammation in response to epithelial cell invasion and macrophage cytotoxicity. These processes are mediated by type III secretion systems encoded in homologous virulence loci in the two species, namely, Salmonella pathogenicity island 1 (SPI-1), carried in the genome, and the Shigella entry region (SER), carried in a large virulence plasmid. Here we show that SPI-1 can functionally complement a deletion of SER in S. flexneri, restoring invasion of epithelial cells, macrophage cytotoxicity, and phagosomal escape. Furthermore, S. flexneri phagosomal escape requires the SER and another gene(s) carried on the large virulence plasmid. We demonstrate that the processes of invasion and phagosomal escape can be uncoupled in S. flexneri.