Serum neopterin as a prognostic indicator in patients with breast carcinoma

Neopterin is a useful indicator of the activation state of the cellular immune system, and an elevated level predicts prognosis in different types of tumors. The aim of this study was to evaluate serum neopterin levels if it is viable predictor for prognosis in breast carcinoma patients. Serum neopterin was investigated in 56 breast carcinoma patients, 16 patients with benign breast lesions and 16 healthy women as controls. Neopterin was measured by ELISA (Enzyme-linked immunosorbent assay). The clinicopathological parameters were determined by reviewing both medical charts and pathological records. All patients had been followed-up until September 2009 or death.The mean serum neopterin concentrations were 8.5 ± 5.2 nmol/L in patients with breast carcinoma, 6.5±3.1 nmol/L in patients with benign breast lesion and 8.1 ± 1.9 nmol/L in healthy volunteers (p>0.05). Elevated neopterin levels were significantly correlated with age, elevated serum CRP level, advanced stage and presence of the distant metastases (p<0.05). Overall survival was significantly shorter in patients with a serum neopterin level >10 nmol/L than patients with neopterin <10 nmol/L level (56 months vs. 76 months, p=0.011). Increased preoperative serum neopterin concentrations are associated with a poor prognosis in patients with breast carcinoma.     

NK cells and gamma interferon coordinate the formation and function of hepatic granulomas in mice infected with the Francisella tularensis live vaccine strain

Host innate immune responses to many intracellular pathogens include the formation of inflammatory granulomas that are thought to provide a physical barrier between the microbe and host. Because two common features of infections with the live vaccine strain (LVS) of Francisella tularensis within the mouse liver are the formation of granulomas and the production of gamma interferon (IFN-gamma), we have asked what role IFN-gamma plays in hepatic granuloma formation and function. Francisella antigens were predominantly localized within granulomas of the livers of mice infected with F. tularensis LVS 4 days postinfection. Hepatic granulomas also contained large numbers of dying cells, some of which coexpressed the F4/80 macrophage antigen and activated caspase-3. IFN-gamma-deficient mice did not form normal numbers of hepatic granulomas and showed widely disseminated Francisella antigens within the liver. The incidence of cell death within hepatic granulomas also decreased significantly in the absence of IFN-gamma. Inducible NO synthase (iNOS) expression was restricted to the granulomas of wild-type mice but was not seen for IFN-gamma-deficient mice. Cell death within granulomas was also significantly decreased for iNOS-deficient mice. The predominant IFN-gamma-expressing cells in the liver were NK cells. Depleting NK cells resulted in the expression of bacterial antigens and iNOS outside the granulomas and the appearance of extensive hepatic focal necrosis. These findings indicate that IFN-gamma and hepatic NK cells that are activated during F. tularensis LVS infections regulate hepatic granuloma formation, the spatial containment of infection, the expression of iNOS, and the induction of cell death within the liver.     

Rat primary hepatocytes show enhanced performance and sensitivity to acetaminophen during three-dimensional culture on a polystyrene scaffold designed for routine use

The in vitro evaluation of hepatotoxicity is an essential stage in the research and development of new pharmaceuticals as the liver is one of the most commonly impacted organs during preclinical toxicity studies. Fresh primary hepatocytes in monolayer culture are the most commonly used in vitro model of the liver but often exhibit limited viability and/or reduction or loss of important liver-specific functions. These limitations could potentially be overcome using three-dimensional (3D) culture systems, but their experimental nature and limited use in liver toxicity screening and drug metabolism has impaired their uptake into commercial screening programs. In this study we use a commercially available polystyrene scaffold developed for routine 3D cell culture to maintain primary rat hepatocytes for use in metabolism and toxicity studies over 72?h. We show that primary hepatocytes retain their natural cuboidal morphology with significantly higher viability (>74%) than cells grown in monolayer culture (maximum of 57%). Hepatocytes in the 3D scaffolds exhibit differential expression of genes associated with phase I, II, and III drug metabolism under basal conditions compared with monolayer culture and can be induced to stably express significantly higher levels of the cytochrome-P450 enzymes 1A2, 2B1, and 3A2 over 48?h. In toxicity studies the hepatocytes in the 3D scaffolds also show increased sensitivity to the model toxicant acetaminophen. These improvements over monolayer culture and the availability of this new easy to use 3D scaffold system could facilitate the uptake of 3D technologies into routine drug screening programs.     

Morphine Potentiates Neuropathogenesis of SIV Infection in Rhesus Macaques

Despite the advent of antiretroviral therapy, complications of HIV-1 infection with concurrent drug abuse are an emerging problem. Opiates are well known to modulate immune responses by preventing the development of cell-mediated immune responses. Their effect on the pathogenesis of HIV-1 infection however remains controversial. Using the simian immunodeficiency virus/macaque model of HIV pathogenesis, we sought to explore the impact of morphine on disease progression and pathogenesis. Sixteen rhesus macaques were divided into two groups; four were administered saline and 12 others morphine routinely. Both groups of animals were then inoculated with SIVmacR71/17E and followed longitudinally for disease pathogenesis. The morphine group (M+V) exhibited a trend towards higher mortality rates and retardation in weight gain compared to the virus-alone group. Interestingly, a subset of M+V animals succumbed to disease within weeks post-infection. These rapid progressors also exhibited a higher incidence of other end-organ pathologies. Despite the higher numbers of circulating CD4+ and CD8+ T cells in the M+V group, CD4/CD8 ratios between the groups remained unchanged. Plasma and CSF viral load in the M+V group was at least a log higher than the control group. Similarly, there was a trend toward increased virus build-up in the brains of M+V animals compared with controls. A novel finding of this study was the increased influx of infected monocyte/macrophages in the brains of M+V animals.     

Evaluation of Erythropoiesis by Serum Transferrin Receptor and Ferritin in Infants Aged 0–6 Months

The aim of this study was to evaluate erythropoiesis in 198 healthy babies aged 0–6 months by determination of their blood count, serum transferrin receptor (STfR), and ferritin levels. Anemia and microcytosis were present in 9% and 13% of the sample, respectively. Microcytosis rate was as high as 45% in 6-month-old babies. In infants with normal blood counts, the values of sTfR/ferritin and sTfR-F index were increasing with the increase of sTfR and decrease of ferritin beginning from 2 months of age. In the 5- to 6-month-old group, sTfR concentrations, sTfR/ferritin ratio, and sTfR-F index were higher in infants with anemia and microcytosis. This research showed a high frequency of iron deficiency detected in otherwise healthy babies. Only problems with early weaning practices were found to be significantly more common in babies with iron deficiency.