Effect of olanzapine treatment on platelet glutamine synthetase-like protein and glutamate dehydrogenase immunoreactivity in schizophrenia.

According to contemporary views, the glutamatergic system is implicated in the pathogenesis of schizophrenia, and atypical neuroleptics exert their effects (at least partially) through the glutamatergic system. Immunoreactive glutamate-metabolising enzymes, such as glutamine synthetase-like protein (GSLP) and two glutamate dehydrogenase isoenzymes (GDH), have been discovered in human platelets. The amount of GSLP in the platelets of 40 chronic patients with schizophrenia was found to be significantly higher than in 33 controls (consistent with our previous finding of increased amounts of GSLP in the prefrontal cortex of chronic schizophrenia patients). Moreover, survival analysis of the group of patients treated with olanzapine for 28 weeks showed that the larger amount of GSLP measured in platelets before treatment, the shorter the treatment time needed to achieve a positive clinical response (defined a priori as > or = 20% reduction in PANSS total score from the initial level before the treatment). Hence, GSLP level may serve as a predictor of the treatment duration to achieve a positive outcome with olanzapine. Both GSLP and GDH were found significantly changed in the course of treatment; hence, treatment with olanzapine influences the amounts of glutamate-metabolising enzymes in the platelets of chronic schizophrenia patients.     

Low ERCC1 expression is associated with prolonged survival in patients with bladder cancer receiving platinum-based neoadjuvant chemotherapy

PurposeExcision repair cross-complementation group 1 enzyme (ERCC1) plays a key role in the removal of platinum induced DNA adducts and cisplatin resistance. Prognostic role of ERCC1 expression in the neoadjuvant setting in bladder cancer has not been reported before. We evaluated the prognostic role of ERCC1 expression in bladder cancer receiving platinum-based neoadjuvant chemotherapy.Materials and methodsThirty-eight patients with muscle invasive bladder cancer who received neoadjuvant platinum-based chemotherapy were included. Clinical and histopathologic parameters along with immunohistochemical ERCC1 staining were examined and correlated with response rates and survival.ResultsPathologic complete response rates were similar between patients with low and high ERCC1 expression. Median disease-free survival (DFS) was 9.3 vs. 20.5 months (P = 0.186) and median overall survival (OS) was 9.3 vs. 26.7 months (P = 0.058) in patients with high ERCC1 expression compared with those with low expression, respectively. In multivariate Cox regression analysis: pathological complete response (pCR) after chemotherapy (hazard ratio (HR) 0.1, 95% CI 0.012–0.842, P = 0.034) and high ERCC1 expression (HR 3.7, 95% CI 1.2–11.2, P = 0.019) were significantly associated with DFS. Patient age (>60 vs. ≤60 years) (HR 3.4, 95% CI 1.2–9.4, P = 0.018), the presence of pCR (HR 0.11, 95% CI 0.014–0.981, P = 0.048) and high ERCC expression (HR 6.1, 95 CI 1.9–19.9, P = 0.002) were significantly associated with OS.ConclusionsOur results showed that high ERCC1 expression was independently associated with shorter disease-free and overall survival in patients with bladder cancer who received neoadjuvant platinum-based chemotherapy. ERCC1 may represent a potential predictive marker for platinum-based treatment in bladder cancer.     

Analysis of YKL‐40 Acute‐Phase Protein and Interleukin‐6 Levels in Periodontal Disease

Background: YKL‐40, a new acute‐phase protein, is shown to be elevated in inflammatory diseases, such as rheumatoid arthritis, type 2 diabetes mellitus, and coronary artery diseases. However, there is no data indicating a relationship between YKL‐40 and periodontal disease. Interleukin‐6 (IL‐6) is the major regulator of acute‐phase protein synthesis and one of the most studied inflammatory markers in periodontal disease. The purpose of the present study is to evaluate YKL‐40 and IL‐6 levels in gingival crevicular fluid (GCF) and serum of patients with periodontal disease and healthy individuals. Methods: Periodontally healthy individuals (n = 15), patients with gingivitis (n = 15), and patients with severe chronic periodontitis (CP) (n = 15) without any systemic disease were included in the study. Clinical measurements were recorded; GCF and blood samples were obtained from each participant. GCF and serum YKL‐40 and IL‐6 levels were analyzed by enzyme‐linked immunosorbent assay. Statistical analysis was performed by parametric and non‐parametric tests. Results: Total amounts of YKL‐40 and IL‐6 in GCF as well as serum YKL‐40 and IL‐6 levels were significantly higher in patients with gingivitis and CP compared with healthy controls (P <0.01). YKL‐40 levels in GCF and serum as well as serum IL‐6 levels were significantly higher in patients with CP compared with patients with gingivitis (P <0.01). Conclusions: YKL‐40 levels in GCF as well as serum YKL‐40 and IL‐6 levels increased from gingivitis to periodontitis. Within the limits of the present study, the YKL‐40 molecule might be a potential novel inflammatory marker of periodontal disease.     

Expression of proliferative and preapoptotic molecules in human myometrium and leiomyoma throughout the menstrual cycle

The pathogenesis of leiomyoma may be related to an imbalance in the interaction of sex steroids with paracrine growth factors that may control the modulation of mitogenesis and local immunity. The authors investigate the temporal and spatial expression of proliferative and preapoptotic molecules that may participate in the modulation of myometrial function and leiomyoma pathogenesis. Immunohistochemistry and Western blot analysis are used to investigate Fas ligand (FasL), phosphatase and tensin homolog deletion on chromosome 10 (PTEN), and proliferating cell nuclear antigen (PCNA) expression in myometrium and leiomyoma. Western blot results show that in the secretory phase, FasL expression is 1.8-fold and 2.3-fold higher compared with the proliferative phase in the myometrium and leiomyoma, respectively (P = .022 and .047, respectively). A paired comparison between myometrium and leiomyoma reveals higher FasL expression in the leiomyoma (P = .003). On the contrary, when compared with the secretory phase, PCNA expression during the proliferative phase is 4.6-fold and 3.7-fold higher in the myometrium and leiomyoma, respectively (P = .041 and .034, respectively). A paired comparison between myometrium and leiomyoma reveals higher PCNA expression in the leiomyoma. Furthermore, lower PTEN expression is detected in the leiomyoma compared with the myometrium (P < .032). Immunohistochemistry results reveal that FasL, PTEN, and PCNA are expressed in the myometrium and leiomyoma, consistent with the results from the Western blot analysis. The results suggest that FasL, PTEN, and PCNA may be involved in the pathophysiology of leiomyoma. A higher FasL level in the leiomyoma is likely to correspond to suppression of local immunity by inducing apoptosis of immune cells, while a higher level of PCNA and a lower level of PTEN may be related to increased mitogenesis and decreased apoptosis in leiomyoma.     

The effects of selective nitric oxide synthase blocker on survival, mesenteric blood flow and multiple organ failure induced by zymosan

BACKGROUND: Circulatory failure in multiple organ dysfunction syndromes (MODS) is characterized with systemic vasodilation, diminished blood flow to various vascular beds. The aim of this study was to investigate the effects of selective inhibition of nitric oxide on the mesenteric arterial blood flow (MABF), survival and organ injury of the liver, kidney, lung and spleen in zymosan-induced MODS. MATERIALS AND METHODS: Forty Swiss albino mice (20-40 g), 7 to 9 weeks old, were obtained. Animals were randomly divided into four groups. The first group were treated intraperitoneally (i.p) with vehicle (saline) and served as a sham group for aminoguanidine (AG) (n=10). The second group was treated with zymosan (500 mg/kg, suspended in saline solution, i.p). The mice in the third and fourth group received AG (15 mg/kg) 1 h and 6 h after zymosan or saline administration, respectively. Eighteen hours after the administration of zymosan, animals were assessed for MODS described subsequently. The signals from the flowmeter were also recorded on mesenteric arterial blood flow values. RESULTS: In zymosan-treated animals, the MABF was significantly lower than that of solvent (saline)-treated controls (ml min(-1), controls: 4.6 +/- 0.6; zymosan: 1.6 +/- 0.9, P <0.05). When animals were treated with AG, there were no significant differences in MABF values between AG group and solvent (saline)-treated control group. However AG prevented zymosan-induced mesenteric MABF decrease. Treatment with aminoguanidine also decreased mortality. CONCLUSION: AG is capable of inhibiting both the induction and the activity of the already iNOS; it remains a potential therapeutic agent in patients with MODS.