Tumor necrosis factor alpha-mediated nitric oxide production enhances manganese superoxide dismutase nitration and mitochondrial dysfunction in primary neurons: an insight into the role of glial cells

Tumor necrosis factor-alpha (TNF-alpha), a ubiquitous pro-inflammatory cytokine, is an important mediator in the immune-neuroendocrine system that affects the CNS. The present study demonstrates that treatment with TNF-alpha activates microglia to increase TNF-alpha production in primary cultures of glial cells isolated from wild-type (WT) mice and mice deficient in the inducible form of nitric oxide synthase (iNOSKO). However, mitochondrial dysfunction in WT neurons occurs at lower concentrations of TNF-alpha when neurons are directly treated with TNF-alpha or co-cultured with TNF-alpha-treated microglia than iNOSKO neurons similarly treated. Immunofluorescent staining of primary neurons co-cultured with TNF-alpha-treated microglia reveals that the antioxidant enzyme in mitochondria, manganese superoxide dismutase (MnSOD), is co-localized with nitrotyrosine in WT but not in iNOSKO primary neuronal cells. Importantly, the percentage of surviving neurons is significantly reduced in WT neurons compared with iNOSKO neurons under identical treatment conditions. Together, the results suggest that TNF-alpha activates microglia to produce high levels of TNF-alpha and that production of nitric oxide (NO) in neurons is an important factor affecting MnSOD nitration and subsequent mitochondrial dysfunction.     

Anticarcinogenic effect of FTY720 in human prostate carcinoma DU145 cells: modulation of mitogenic signaling, FAK, cell-cycle entry and apoptosis

Despite the high frequency of prostate cancer, therapeutic options for advanced disease are limited to chemotherapy, radiation or hormonal therapy and eventually fail in all patients. Therefore, alternative approaches need to be developed. We previously reported that FTY720, a metabolite from Isaria sinclarii, is a unique antitumor agent for an androgen-independent prostate cancer cell line and requires caspase-3 activation in apoptosis. In our study, we have evaluated the effect of FTY720 on a family of mitogen-activated protein kinases (MAPKs), focal adhesion kinase (FAK), mitochondrial transmembrane potential, caspase-9 and caspase-8 and analyzed the expression of some cell-cycle regulator proteins in DU145 cells in order to understand the various antitumor effects of FTY720. Apoptosis was quantified by phosphatidylserine exposure. Activation of MAPKs, cleavage of caspase-9 and caspase-8, status of cyclin-dependent kinases (CDKs) and Cip1/p21, a cyclin-dependent kinase inhibitor, were evaluated by Western blot analysis, in addition to FAK and phospho-FAK immunoprecipitation and cell-cycle analysis by FACScan. We found that in DU145 cells, 40 microM FTY720 caused activation of p38 MAPK and the upstream kinase MKK3/MKK6 but not SAPK/JNK. Mitochondrial transmembrane potential, FAK and ERK1/2 were reduced while caspase-9 and caspase-8 were cleaved. The p38-specific inhibitor had no effect on apoptosis induced by FTY720, whereas z-VAD.FMK, a broad-spectrum caspase inhibitor, did not inhibit the p38 MAPK activation. An amount of 20 microM FTY720 resulted in G(1) arrest and a decrease of CDK2 as well as CDK4, whereas it induced Cip1/p21. FTY720 may exert anticarcinogenic effects against prostate cancer cells possibly involving modulation of mitogenic signaling, cell-cycle regulators, induction of G(1) arrest and apoptotic death in DU145 cells.     

Streptococcus mutans and dental caries in urban and rural schoolchildren in Thailand

Two groups of Thai schoolchildren aged 11-13 yr were examined for dental caries, dental fluorosis and Streptococcus mutans. One hundred children lived in an urban district, Bangkok, and 71 children in a rural district, Petchaboon. Saliva samples were analyzed for S. mutans by the spatula method. The fluoride content of the drinking waters was also determined. The prevalence of caries, diagnosed according to WHO, was 89% in Bangkok and 18% in the rural district. Mean DMFT was 3.46 and 0.38 respectively. S. mutans was found in 98% of the urban children and in 82% of the rural. The differences in distribution between S. mutans and DMFT classes were statistically significant for the total sample. Mild fluorosis was present in some of the rural children.     

Virosome and ISCOM vaccines against Newcastle disease: preparation, characterization and immunogenicity

The purpose of this study was to prepare and characterize virosomes and ISCOMs containing envelope proteins of Newcastle disease virus (NDV) and to evaluate their immunogenicity in target animals (chickens). Virosomes were prepared by solubilization of virus with either Triton X-100 or octyl glucoside (OG) followed by detergent removal. Biochemical analysis revealed that these virosomes contained both the haemagglutinin-neuraminidase protein (HN) and the fusion protein (F), with preserved biological activity. Acidic environment triggered the fusion between virosomes and chicken erythrocyte ghosts. Formation of ISCOMs was achieved by solubilizing phospholipids, cholesterol, envelope protein antigen and Quil A in Triton X-100. The ISCOM particles were formed by removal of the detergent. In each formulation the relative HN content correlated with the capability to agglutinate red blood cells. The immunogenicity of these lipid-based subunit vaccines was determined in chickens after subcutaneous immunization. The relative HN content of the subunit vaccines correlated with the haemagglutination-inhibition (HI) antibody titres. Virosomes prepared with Triton X-100 and ISCOMs offered high clinical protection (> 80%) upon challenge with virulent NDV. Virosomes prepared with OG yielded lower clinical protection despite high HI antibody titres. Virosomes with reduced antigen density showed poor immunogenicity and protection. In conclusion, ND virosomes and ISCOMs were found to be immunogenic and provided good protection.     

Trends in the operative management of renal tumors over a 14-year period

OBJECTIVE: To review the trends in the operative management of renal tumours over a 14-year period at a university hospital, as the therapeutic options available for treating renal tumours have increased over the past decade. PATIENTS AND METHODS: The study was a retrospective chart review of 1621 consecutive patients undergoing treatment for renal tumours from January 1991 to March 2005. The characteristics assessed included patient demographics, tumour size, operative duration and treatment. RESULTS: During the study period, 624 (38.6%) open, 883 (54.6%) laparoscopic and 111 (6.7%) percutaneous approaches were performed. The number of renal tumours treated increased annually, as did the use of minimally invasive techniques (93.4% in 2005). Conversely, the number of open surgical treatments used declined both absolutely and proportionally. Over the study period, for tumours of 7 cm, open radical nephrectomy (ORN) was the most common method of treatment over all years. However, since 2002, laparoscopic radical nephrectomy (LRN) surgery has been increasingly used over ORN for treating this tumour group (73% LRN vs 19.2% ORN in 2004). CONCLUSION: The available treatment options for renal tumours have increased significantly since the early 1990s. At a university hospital in which there are physicians with a specific interest in minimally invasive surgery and ablative treatments, minimally invasive approaches have become the standard treatment.     

Percutaneous computerized tomography guided cryoablation for localized renal cell carcinoma: factors influencing success

PURPOSE: We evaluated the factors that influenced the initial success rate and complication rate of percutaneous computerized tomography guided cryoablation of localized renal cell carcinoma of clinical stage T1N0M0. MATERIALS AND METHODS: A total of 21 patients with a mean age of 71.5 years and a pathological diagnosis of renal cell carcinoma were treated with percutaneous computerized tomography guided cryoablation under conscious sedation on an outpatient basis. We retrospectively reviewed clinical data, tumor characteristics, techniques and results. Tumors with complete loss of contrast enhancement were considered successfully treated. RESULTS: A total of 21 patients with 23 tumors underwent 25 cryoablation sessions. The mean intraoperative computerized tomography scan tumor size was 2.1 cm (range 0.5 to 4.3) and the mean ice ball size was 4.1 cm (range 2.2 to 7.2). Of the patients 82.6% (19 of 23) had a single treatment. Patients were followed with postoperative scans of 4.6 to 18.3 months (mean 12.3). There were 2 recurrences. The rate of successful complete tumor ablation was influenced by various factors. Tumor location and size were the major determinants for achieving tumor eradication. CONCLUSIONS: Percutaneous renal cryoablation using computerized tomography imaging proved to be a successful technique for guiding probe placement and monitoring ice ball formation. Patient selection based on tumor size and location may aid in improved outcomes. Further study and followup are necessary to determine long-term oncological efficacy.     

Laparoscopic versus open partial nephrectomy for the treatment of pathological T1N0M0 renal cell carcinoma: a 5-year survival rate

PURPOSE: We retrospectively compared the oncological adequacy of laparoscopic partial nephrectomy to that of open partial nephrectomy in the treatment of patients with pathological stage T1N0M0 renal cell carcinoma. MATERIALS AND METHODS: A total of 143 patients with stage T1N0M0 renal tumors confirmed by pathological examination of the surgical specimen underwent partial nephrectomy between January 1996 and June 2004 with a followup of at least 1.5 years. Of these patients 85 were treated laparoscopically and the remaining 58 underwent open surgery. Medical and operative records were retrospectively reviewed with emphasis on tumor recurrence and survival. Statistical analysis was performed using Kaplan-Meier analysis. RESULTS: The mean followup for the laparoscopy group was 40.4 +/- 18.0 months. A total of 83 patients survived. Of these patients 2 patients experienced disease recurrence within 18 to 46.2 months, 1 patient died of cancer metastasis to brain within 29.7 months and 1 died of an unrelated cause. Seeding of the port sites did not develop in any of the patients. The 5-year disease-free and actuarial survival rates for this group were 91.4%, and 93.8%, respectively. The 58 patients who underwent open surgery had a mean followup of 49.68 +/- 28.84 months. A total of 53 patients survived without any disease recurrence, 1 survived with recurrence within 8 months, 1 survived with metastasis within 49 months and 3 died of unrelated causes. The 5-year disease-free and patient survival rates for this group were 97.6% and 95.8%, respectively. Kaplan-Meier disease-free survival and patient survival analysis revealed no significant differences between the laparoscopic and open partial nephrectomy groups. CONCLUSIONS: Laparoscopic partial nephrectomy is an alternative technique with mid-range oncological results comparable to open partial nephrectomy in patients with localized pathological stage T1N0M0 renal cell carcinoma.     

Thai men's health and sexual attitude

Men's health awareness, including the research and study of quality of life, sexual desires and risk factors, has increased worldwide. In Thailand, this advancement is made possible by cooperation, research and sponsorship from the local Thai community. This article aims to illustrate the sexual attitudes of Thai people, to determine the degree of erectile dysfunction (ED) and to investigate how to manage and cope with ED in a Thai community. We reviewed the relevant literature from Thai-based articles and surveys in regard to men's health, sexual attitudes, the prevalence of ED and common risk factors in the Thai community. The primary risk factor for ED in Thai men was age-related health decline and the presence of vascular disease. Most Thai men will seek consultation from their partner in regard to ED. The main presentation of metabolic disease in Thai patients was dyslipidemia. New selective serotonin reuptake inhibitors are not available for premature ejaculation in Thai communities. The debate in regard to malpractice compensation is an issue that should be closely monitored. There is currently a shortage of home care for the elderly in Thailand. The insights provided by the articles helped recruit the study patients and in turn, helped us gain knowledge that can be translated into improved men's health care in Thailand.