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Patients suffering from type I diabetes mellitus have a descending expectancy of life, after developing diabetic nephropathy and undergoing haemodialysis. After 3 years of haemodialysis, approximately only 40% of the patients are still alive. The only remedy of this incurable metabolic disease is the simultaneous pancreas–kidney transplantation. After transplantation, fungal colonization and fungal infection is a serious threat for the patient's life. In this context, it is necessary to distinguish between colonization and invasive mycosis. In the case of unsuccessful antimycotic treatment, the removal of the transplanted organ, depending on the patient's condition, may be necessary to save the patient's life. [ABSTRACT FROM AUTHOR]

Continuos ambulatory peritoneal dialysis (CAPD) is a widespread method of treatment used in approximately 10% of all patients suffering from terminal renal insufficiency. The main problem of this procedure is the increased risk of peritoneal infection. The incidence of such a peritonitis is quoted at one episode per 13–18.4 months of treatment. Candidaperitonitis is a particularly severe form of CAPD peritonitis. This is a nosocomial infection with a high lethality rate of about 60%. The incidence ofCandidaperitonitis in CAPD patients amounts to approximately 5% of all intraabdominal infections and is on the increase. The authors describe a severe case ofCandidaperitonitis in a patient on CAPD. The therapeutic concept of this severe illness is illustrated. [ABSTRACT FROM AUTHOR]

Background: In a previous report we have demonstrated that the chymotryptic-like serine protease kallikrein 7 (KLK7/hK7) is overexpressed in pancreatic cancer. In normal skin, hK7 is thought to participate in skin desquamation by contributing in the degradation of desmosomal components, such as desmogleins. Thus, the ability of hK7 to degrade desmogleins was assessed and the effect of hK7 expression on desmoglein 2 was examined in cultured pancreatic cancer cells.Methods: The expression of Dsg1, Dsg2, and Dsg3 in pancreatic tissues was examined by immunohistochemistry and their expression in two pancreatic cancer cell lines, BxPC-3 and Panc-1, was determined by western blot analysis. The ability of hK7 to degrade Dsg1 and Dsg2 was investigated using in vitro degradation assays. BxPC-3 cells stably transfected to overexpress hK7 were used to examine the effect of hK7 on cell-surface resident Dsg2.Results: The levels of immunoreactive Dsg1 and Dsg2 were reduced in pancreatic adenocarcinomas compared with both normal pancreatic and chronic pancreatitis tissues. Among the desmosomal proteins examined, Dsg2 exhibited robust expression on the surface of BxPC-3 cells. When hK7 was overexpressed in this cell line, there was a significant increase in the amount of soluble Dsg2 released into the culture medium compared with vector-transfected control cells.Conclusion: A reduction in the amount of the cell adhesion components Dsg1 and Dsg2 in pancreatic tumors suggests that loss of these desmosomal proteins may play a role in pancreatic cancer invasion. Using in vitro degradation assays, both Dsg1 and Dsg2 could be readily proteolyzed by hK7, which is overexpressed in pancreatic adenocarcinomas. The enforced expression of hK7 in BxPC-3 cells that express significant amounts of Dsg2 resulted in a marked increase in the shedding of soluble Dsg2, which is consistent with the notion that aberrant expression of hK7 in pancreatic tumors may result in diminished cell-cell adhesion and facilitate tumor cell invasion. [ABSTRACT FROM AUTHOR]

To determine if dietary fat composition affects the progression of nonalcoholic fatty liver disease (NAFLD), we overfed male Sprague-Dawley rats low (5%) or high (70%) fat diets with different fat sources: olive oil (OO), corn oil (CO), or echium oil (EO), with total enteral nutrition (TEN) for 21 days. Overfeeding of the 5% CO or 5% EO diets resulted in less steatosis than 5% OO (P < 0.05). Affymetrix array analysis revealed significant differences in hepatic gene expression signatures associated with greater fatty acid synthesis, ChREBP, and SREBP-1c signaling and increased fatty acid transport (P < 0.05) in the 5% OO compared with 5% CO group. The OO groups had macrosteatosis, but no evidence of oxidative stress or necrosis. The 70% CO and 70% EO groups had a mixture of micro- and macrosteatosis or only microsteatosis, respectively; increased oxidative stress; and increased necrotic injury relative to their respective 5% groups (P < 0.05). Oxidative stress and necrosis correlated with increasing peroxidizability of the accumulated triglycerides. Affymetrix array analysis comparing the 70% OO and 70% CO groups revealed increased antioxidant pathways and lower expression of genes linked to inflammation and fibrosis in the 70% OO group. A second study in which 70% OO diet was overfed for 50 days produced no evidence of progression of injury beyond simple steatosis. These data suggest that dietary fat type strongly influences the progression of NAFLD and that a Mediterranean diet high in olive oil may reduce the risk of NAFLD progressing to nonalcoholic steatohepatitis. [ABSTRACT FROM AUTHOR]

To determine if dietary fat composition affects the progression of nonalcoholic fatty liver disease (NAFLD), we overfed male Sprague-Dawley rats low (5%) or high (70%) fat diets with different fat sources: olive oil (OO), corn oil (CO), or echium oil (EO), with total enteral nutrition (TEN) for 21 days. Overfeeding of the 5% CO or 5% EO diets resulted in less steatosis than 5% OO (P< 0.05). Affymetrix array analysis revealed significant differences in hepatic gene expression signatures associated with greater fatty acid synthesis, ChREBP, and SREBP-1c signaling and increased fatty acid transport (P< 0.05) in the 5% OO compared with 5% CO group. The OO groups had macrosteatosis, but no evidence of oxidative stress or necrosis. The 70% CO and 70% EO groups had a mixture of micro- and macrosteatosis or only microsteatosis, respectively; increased oxidative stress; and increased necrotic injury relative to their respective 5% groups (P< 0.05). Oxidative stress and necrosis correlated with increasing peroxidizability of the accumulated triglycerides. Affymetrix array analysis comparing the 70% OO and 70% CO groups revealed increased antioxidant pathways and lower expression of genes linked to inflammation and fibrosis in the 70% OO group. A second study in which 70% OO diet was overfed for 50 days produced no evidence of progression of injury beyond simple steatosis. These data suggest that dietary fat type strongly influences the progression of NAFLD and that a Mediterranean diet high in olive oil may reduce the risk of NAFLD progressing to nonalcoholic steatohepatitis. [ABSTRACT FROM AUTHOR]

Vascular endothelial growth factor (VEGF) is a central mediator of angiogenesis in breast cancer. We have conducted a clinical trial using bevacizumab (B) in breast cancer in the neoadjuvant setting and showed improved pathologic complete response (pCR) when B was added to chemotherapy (CT). 41% of patients (Pts) who received B+CT achieved pCR. Blood and tumor samples were collected at baseline and serially on treatment from 39 patients who participated in the study. The correlative study was approved by the IRB and consent forms were obtained at the time of enrollment. Since patients do not equally benefit from B, it has become necessary to define the profile of patients who will benefit and those who are more likely to have major side effects from the drug. This study was conducted to evaluate for the presence of specific SNPs and CNV in the germ line and a serum protein profile that might be predictive of pCR in the neoadjuvant setting in breast cancer patients receiving B and CT. Methods: To test for the presence of functional germ line SNPs and CNVs that may influence pCR, DNA was extracted from buffy coats of study participants and SNPs/CNVs were determined using Illumina technology. To test the hypothesis that individuals who achieved pCR were those with differential expression of selected proteins in their blood, custom multiplex was performed for the following serum proteins: ANG-1, ANG-2, bFGF, IL -1a, MMP-9, PDGF-BB, PECAM-1, Tie-2, VEGF, and VEGFR2. Statistical test: The association between genotype and CNV of each SNP vs. pCR status were analyzed using Cochran-Armitage Trend Test. Differences in serum protein levels between pCR and non-pCR groups were examined by Wilcoxon rank sum test. Significance of association was evaluated in two settings of α (I) α=0.05 (ii) α=0.00001. Results: Genotype and CNV vs. pCR (n = 38). In genotype vs. pCR status by SNPs tests, 131618 (-13%) SNPs with allele frequency <0.05 were excluded from the analysis. In CNV vs. pCR status by SNPs tests, only 46891 (4.6%) SNPs were analyzed. Many SNPs were excluded because there was no variability in their CNVs. Though no SNPs found significant at genome-wide level of significance (<10-5), a number of SNPs were significant at the level of individual tests in these comparisons. Four SNPs at a p value <0.0001 were identified. A SNP in the promoter region of H(+)-myo-inositol co-transporter gene was most frequently associated with pCR. Analysis of baseline serum protein data (n = 34). The results of pCR vs. serum protein data analysis suggest that there is a statistically significant difference between the concentration of bFGF and Tie-2 in the pCR group (higher baseline values) and those in the non-pCR group (p-values <0.05). The difference of concentrations of VEGF trended toward significance between these two groups. Conclusion: Elevated serum baseline Tie-2 and bFGF and special SNP in the promoter of H(+)-myo-inositol co-transporter gene are candidate predictors for pCR in response to B/CT and need to be validated in a larger clinical study. [ABSTRACT FROM AUTHOR]