Role of granulocyte colony-stimulating factor in the treatment of mucormycosis

Several problems in the management of life-threatening mucormycosis remain unresolved, necessitating new methods of management. Four patients with histopathologically proven rhinocerebral mucormycosis were treated with high cumulative doses of granulocyte colony-stimulating factor (G-CSF). All had multiple predisposing factors for mucormycosis, particularly leukemia and neutropenia. Two patients refractory to fluconazole therapy were treated with liposomal amphotericin B. The improvement in clinical manifestations was closely related to neutrophil recovery, and all patients were alive at the end of therapy. In addition to surgical debridement and antifungal therapy, G-CSF seems to have played a role in their survival.     

Is there any correlation between restriction fragment length polymorphism of the L-MYC gene and metastasis of human nonsmall cell lung cancer?

A potential molecular marker associated with cancer susceptibility as well as metastasis, prognosis and adverse survival, is the L-myc gene. The studies of lung cancer patients from different populations have yielded controversial results. We studied 64 nonsmall cell lung cancer (NSCLC) patients and 37 healthy controls of Turkish origin for L-myc gene polymorphism. Our aim was to test the hypothesis that there was association between L-myc S allele in NSCLC and predisposition to the disease and TNM stage indicating tumor size, node classification and metastasis. Polymerase chain reaction restriction fragment length polymorphism and agarose gel electrophoresis were used to determine the L-myc oncogene genotypes. We found no significant difference, both in the distribution of the LL, LS and SS genotypes and in the allelic frequencies, between the patient group and the control group; that is, the frequencies of L-myc alleles were, L and S, 0.59 and 0.41, 0.60 and 0.40, respectively. Our data between the patient group and the control group; that is, the frequencies of L-myc alleles were, L and S, 0.59 and 0.41, 0.60 and 0.40, respectively. Our data concerning age, sex, size of tumors, histological type of tumors showed no significant association with L-myc genotype. However, a higher frequency of L-myc S allele in the squamous cell carcinoma compared to other histological groups was found, although this difference was not statistically significant. No association was found between the L-myc RFLP and increased risk of metastasis either to the lymph nodes or to other organs. Our results suggested that L-myc gene polymorphism was not a suitable prognostic marker of metastatic development in Turkish NSCLC patients.     

Enhancing effect of chitosan on peptide drug delivery across buccal mucosa

The buccal mucosa represents a potentially important topical route for delivery of peptide or protein drugs with some unique advantages such as the avoidance of hepatic first-pass metabolism and the acidity and protease activity encountered in the gastrointestinal tract. However, the bioavailabilities or relative potencies of intraorally administered peptides are usually quite low, unless permeabilizers are employed. Chitosan, a mucopolysaccharide of marine origin, has been claimed to act both as a bioadhesive and permeabilizer, making it a candidate system for mucosal drug delivery. In this study, the enhancement effect of chitosan in gel form for oral mucosa was investigated with a large bioactive peptide, transforming growth factor-beta (TGF-beta). Chitosan gel was prepared at 2% concentration in dilute lactic acid and TGF-beta was incorporated into the gel. The effect of chitosan as a permeabilizer was determined by measuring the flux of TGF-beta across porcine oral mucosa in an in vitro system. The localization of TGF-beta within the oral mucosa was determined by horizontal sectioning and counting. Chitosan was found to exert a marked permeabilizing effect on buccal mucosa for peptide drug.     

Clinicopathologic evaluation of CDw75 antigen expression in patients with gastric carcinoma

Situated on mature B lymphocytes, CDw75 antigen is a sialylated carbohydrate epitope generated by the enzyme beta-galactosyl alpha-2,6-sialyltransferase. Although CDw75 antigen expression was found to be correlated with aggressive behaviour of tumour cells in gastric adenocarcinomas, its prognostic role still remains unknown. The objective of this study was to determine the value of CDw75 antigen expression as a marker of the metastatic potential and prognosis of gastric adenocarcinomas. CDw75 antigen expression was evaluated immunohistochemically in 64 tumours and their nodal metastases. The correlation was analysed between CDw75 antigen expression and selected clinicopathological variables, including survival. Positive staining was detected in 31 cases. Non-neoplastic gastric mucosa was consistently negative. CDw75 expression was correlated with larger tumour size (p<0.006), infiltrative growth pattern (p<0.044), advanced stage (p<0.0006), and positive lymph nodes (p<0.0003).The overall survival rate of patients with CDw75 expression was 28%, which was significantly worse than that of patients without CDw75 expression (53%) (p<0.0005). Multivariate analysis showed that CDw75 expression was an independent prognostic indicator, together with the growth pattern of the tumour. These results indicate that immunohistochemical detection of CDw75 antigen expression may be a good indicator of metastatic potential and of prognosis in patients with gastric carcinomas.     

Transfection of human macrophages by lipoplexes via the combined use of transferrin and pH-sensitive peptides

The crucial function of macrophages in a variety of biological processes and pathologies render these cells important targets for gene therapeutic interventions. Commonly used synthetic gene delivery vectors have not been successful in transfecting these non-dividing cells. A combination strategy involving cationic liposomes to condense and carry DNA, transferrin to facilitate cellular uptake, and the pH-sensitive peptide GALA to promote endosome destabilization, resulted in significant expression of a luciferase gene. Transfection of macrophages was dependent on the degree of differentiation of the cells. The quaternary complexes of cationic liposomes, DNA, transferrin, and GALA exhibited a net negative charge, which may obviate a limitation of cationic synthetic vectors in vivo. The lack of cytotoxicity and the expected lack of immunogenicity of these complexes may render them useful for gene delivery to macrophages in vivo.     

Factor V gene (1691A and 4070G) and prothrombin gene 20210A mutations in patients with Behçet's disease

OBJECTIVES: Beh?et's disease (BD) is a chronic inflammatory disorder of still unknown etiology, characterized by endothelial cell injury/dysfunction and thrombosis and/or aneurysm of large blood vessels. Thrombophilia may play a role in the pathogenesis of thrombosis in BD. The common inherited gene defects, factor V (FV) 1691A (Leiden) and prothrombin (PT) 20210A, are known risk factors for thrombosis. The FV 4070G polymorphism was shown to influence circulating FV levels and to contribute to the activated protein C resistance phenotype. The aim of the study was to evaluate the role of FV 1691A, FV 4070G and PT 20210A gene mutations in Turkish BD patients with and without venous thrombosis. METHODS: Seventy-one patients with BD (27 with venous thrombosis) and 91 healthy subjects were included in the study. FV 1691A, FV 4070G, and PT 20210A mutations were determined by a method based on PCR-RFLP. RESULTS: The frequency of FV 1691A heterozygous mutation in BD patients with venous thrombosis (25.9%) was significantly higher than that in healthy subjects (8.8%; OR = 3.63; 95% CI 1.18-11.2). Although the frequency of this mutation in patients with venous thrombosis was higher than that in the patients without venous thrombosis (11.4%), the difference did not reach a statistically significant level (OR = 2.73; 95% CI 0.77-9.70). In BD patients with thrombosis, the frequencies of FV 4070G and PT 20210A were not significantly different compared to the BD patients without venous thrombosis and healthy subjects. CONCLUSIONS: Our results suggest that the FV 1691A, FV 4070G, and PT 20210A mutations are unlikely to play an important role in the pathogenesis of thrombosis in patients with BD.     

Protective effects of moderate exercise with dietary vitamin C and E on blood antioxidative defense mechanism in rats with streptozotocin-induced diabetes.

Daily moderate exercise and supplementation of vitamins C and E (VCE) can be beneficial in diabetes by ameliorating the effects of free radical production. The present study sought to analyze the effect of moderate exercise accompanying VCE supplementation on lipid peroxidation (LP) and antioxidative systems in the blood of streptozotocin-induced diabetic rats. Forty female Wistar rats were randomly divided 4 groups. The 1st and 2nd groups served as the control and diabetic groups, respectively. The 3rd group was the diabetic-exercise group. The 4th group, also diabetic-exercise rats, received VCE-supplemented feed. Animals in the exercised groups were moderately exercised on a treadmill 5 days a week for 3 weeks. Diabetes was induced on Day 0 of the exercise. Plasma and red blood cell (RBC) samples were taken from all animals on Day 20. Glutathione peroxidase, catalase, and reduced glutathione levels in plasma and RBCs, and vitamins A, E, and beta-carotene in plasma were lower in diabetic rats than in control animals, whereas there was a significant increase in platelet counts in both plasma and RBC LP levels. The decreased antioxidant enzymes and vitamins, and the increased LP levels and WBC counts, did improve through exercise only, although their levels were mostly increased by exercise + VCE supplementation. There were no significant changes in the hemoglobin and hematocrit values in the 4 groups. In conclusion, these data demonstrate an increase in LP in the blood of diabetic animals whereas there was a decrease in the antioxidant vitamins and enzymes. However, dietary VCE with moderate exercise may strengthen the antioxidant defense system by decreasing reactive oxygen species.     

Molecular epidemiology of penicillin-resistant Streptococcus pneumoniae in a university hospital, Ankara, Turkey

Penicillin-resistant Streptococcus pneumoniae isolates (n = 76) from clinical samples of patients admitted to Hacettepe University Hospital between January 1997 and December 2001 were included in the study. MICs of penicillin G, erythromycin A, clindamycin, cefaclor, cefotaxime, vancomycin, chloramphenicol, tetracycline, ciprofloxacin and rifampicin were determined by agar dilution. The isolates were serogrouped on the basis of the Neufeld Quellung reaction and were typed by BOX-PCR. Genetic polymorphism of the penicillin resistance genes pbp2b and pbp2x was investigated by restriction fragment length polymorphism (RFLP) analysis. Of the 76 isolates tested, 64 (84.2%) showed intermediate resistance to penicillin, while 12 (15.8%) were resistant to higher levels of penicillin (MIC > or = 2 mg/L). The resistance patterns of the isolates revealed six different resistance profiles. There were 22 different serotypes, with c. 55% of the isolates belonging to serotypes 23B, 19A, 19F, 14, 6 A and 9V. Five distinct patterns for pbp2b and 12 distinct patterns for pbp2x were obtained by RFLP analysis of penicillin-binding protein genes. The combination of these patterns allowed isolates to be classified into 22 fingerprint subgroups. BOX-PCR analysis showed that the isolates fell into 14 distinct BOX genotypes, with 33 subtypes. Serotype 9V isolates with pbp genotype 2-6 and BOX-PCR type 4, 4.1 or 4.2 were related to the pandemic clone Spain(9V)-3. No relatedness to other international clones was detected among the other study strains, but genetic relatedness was observed among some of the serotype 19A and 23B isolates. Overall, the results demonstrated that most of the penicillin-resistant pneumococcal isolates in Turkey, other than those belonging to serotypes 9V, 19A and 23B, were derived from several independent clones, possibly resulting from multiple importation of strains originating from outside the country. Differences in pbp patterns, serotypes and resistance profiles among isolates that showed similar BOX-PCR patterns supported the hypothesis that horizontal transfer of capsular genes, pbp genes and other genetic determinants between S. pneumoniae and viridans group streptococci may have occurred.     

微乳液反应法制备磺胺嘧啶银均匀微晶及其最佳处方评价

目的：应用微乳液反应法制备磺胺嘧啶银均匀微晶,均匀制得的微晶的粒径大小约为2～4um,均匀微晶的结晶性好,纯度高。用均匀设计方法优化条件,制备的均匀的微晶平均粒径大小为2.09um,实验结果达到预测结果要求。结论：用微乳液反应法能获得磺胺嘧啶银均匀微晶。