Differential regulation of the superoxide dismutase family in experimental aortic aneurysms and rat aortic explants

OBJECTIVE: Oxidative stress has been implicated in abdominal aortic aneurysm pathogenesis. This study sought to characterize the relevance of superoxide dismutases (SOD), a family of reactive oxygen catalyzing metalloenzymes, including manganese SOD (MnSOD), copper-zinc SOD (CuZnSOD), and extracellular SOD (EcSOD), in a rodent aortic aneurysm model. METHODS: Male rat infrarenal abdominal aortas were perfused with either saline (control) or porcine pancreatic elastase (6 U/mL). Aortic diameter was measured and aortas harvested on post-operation days 1, 2, and 7 (N=5-6 per treatment group per day). MnSOD, CuZnSOD, EcSOD, catalase, MMP-2, MMP-9, and beta-actin expression in aortic tissue was determined by quantitative real-time PCR. MnSOD protein levels were measured using western immunoblotting and immunohistochemistry. In subsequent experiments, aimed at understanding the mechanism by which SOD is involved in AAA pathogenesis, rat aortic explants (RAEs) were incubated in media for 24 h in the presence of interleukin-1beta (IL-1beta, 2 ng/mL) and TEMPOL (SOD mimetic), catalase, or a combined SOD and catalase mimetic. Media MMP-2 and MMP-9 activity was determined by zymography. Data were analyzed by Student's t-tests and ANOVA. RESULTS: Elastase-perfused aortic diameters were significantly increased compared to control aortas by post-perfusion day 7 (P=0.016). MnSOD mRNA levels in elastase perfused aortas were 6.0 (P=0.05) and 7.5 times (P<0.01) greater than control aortas at post-perfusion days 1 and 2, respectively. EcSOD, CuZnSOD, catalase, and MMP-2 mRNA expression did not statistically vary between the two groups. MMP-9 expression was 3.5-fold higher in the elastase group on post-perfusion day 2 (P=0.04). Western immunoblotting confirmed MnSOD protein was up-regulated on day 4 in the elastase-perfused group compared to controls (P=0.02). Immunohistrochemistry demonstrated increased MnSOD staining in the elastase group on day 4. In RAE experiments, TEMPOL increased both MMP-9 and MMP-2 activity 2 (P=0.09) and 3-fold (P=0.05), respectively, whereas catalase and the combined SOD/catalase mimetic failed to increase MMP-2 or MMP-9 activity. CONCLUSION: Experimental abdominal aortic aneurysm formation is associated with early increases in MnSOD expression and an increase in MMP-9 activity. Strategies aimed at inhibiting oxidative stress during AAA formation should focus on MnSOD.     

Effect of menstrual cycle phase on dopamine D2 receptor availability in female cynomolgus monkeys

Sex differences have been reported in a variety of affective and neurodegenerative disorders that involve dysfunctional dopamine (DA) neurotransmission. In addition, there is evidence for differences in sensitivity to the abuse-related effects of psychostimulants across the menstrual cycle which may result from effects of ovarian hormones on DA function. The goal of the present study was to extend previous work examining menstrual cycle-related changes in DA D2 receptor availability in humans to drug-naive female cynomolgus monkeys (n=7) using the selective D2-like receptor ligand [(18)F]fluoroclebopride (FCP) and a high-resolution microPET P4 scanner. Menstrual cycle phase was characterized by daily vaginal swabs and measurements of serum progesterone levels. PET studies were conducted once during the luteal phase and once during the follicular phase. Regions of interest in the caudate nucleus, putamen, and cerebellum were defined on coregistered MRIs. Distribution volumes were calculated for FCP in each structure and the distribution volume ratio (DVR) for both brain regions relative to the cerebellum was used as a measure of D2 receptor availability. FCP DVRs were significantly higher in the luteal phase compared to the follicular phase in both the caudate nucleus (11.7% difference, p=0.02) and putamen (11.6% difference, p=0.03). These findings extend earlier work in humans and suggest that changes in DA receptor availability may be involved in the variation in symptoms of various neuropsychiatric disorders across the menstrual cycle, including differences in sensitivity to the abuse-related effects of stimulants.     

Frequency of GCH1 deletions in Dopa-responsive dystonia

We performed a systematic study on the frequency of point mutations and deletions of the gene GCH1 in dopa-responsive dystonia (DRD). A total of 136 dystonia patients were studied. Fifty of these had a sustained response to oral L-Dopa therapy (group 1: definite diagnosis of DRD), whereas the response to L-Dopa was incomplete or not tested in 86 patients (group 2: possible diagnosis of DRD). We found a GCH1 point mutation in 27 patients of group 1 (54%) and in four patients of group 2 (5%). Of these, nine single and one double mutation have not been described before. GCH1 deletions were detected in four patients of group 1 (8%) and in one patient of group 2 (1%). Among GCH1 point-mutation-negative patients with a definite diagnosis of DRD (group 1), the frequency of GCH1 deletions was 17% (4/23). We conclude that GCH1 deletion analysis should be incorporated into the routine molecular diagnosis of all patients with DRD with a sustained response to L-Dopa.     

Transfusion Transmitted Infections in Armed Forces: Prevalence and Trends

Background

This study presents data on the prevalence rate of infectious markers among voluntary and replacement donors in the blood transfusion service in Armed Forces from 2000 to 2004.

Methods

39,646 units of blood were collected from donors during the period from 2000 to 2004. All the samples were screened for hepatitis B surface antigen (HBsAg), human immunodeficiency virus (HIV) 1&2, hepatitis C virus (HCV), and by venereal disease research laboratory test (VDRL).

Results

24,527 (61.9%) were voluntary donations and 15,119 (38.1%) replacement donations. Prevalence of HBsAg had decreased, amongst voluntary donors from 1.67% to 0.77% but the positivity rate has not showed significant change. Seropositivity of HIV had decreased both in voluntary and replacement donors to 0.22% and 0.86% respectively. The seropositivity for anti-HCV showed steady decrease amongst voluntary donors from 0.46% to 0.20% in 2004, but in replacement donors, there was an increase in reactivity rate from 0.43% to 0.65%.

Conclusion

The increased seropositivity for HCV, HIV and HBsAg could be decreased by introduction of nucleic acid amplification testing (NAT) in minipools for HCV and HIV and introduction of anti-HBcAg (IgM) for hepatitis B virus (HBV) infection. But this may not be possible in near future in developing countries due to financial constraints. At present implementation of strict donor criteria and with use of sensitive laboratory screening tests it is possible to reduce the incidence of transfusion transmitted infections (TTI) in Indian scenario.Key Words: Transfusion transmitted infections, Human immunodeficiency virus, Hepatitis C virus, Hepatitis B virus     

Effect of parenterally administered gold therapy on the course of adult rheumatoid arthritis.

OBJECTIVE: To describe the course of rheumatoid arthritis over 5 years in adults and to evaluate the effect of parenterally administered gold salts on that course. DESIGN: A prospective observational study of adults with rheumatoid arthritis. Data derived from annual interviews with patients from 1983 to 1988 and from physician surveys in 1983 and 1987. SETTING: Rheumatology practices in the community. PATIENTS: The study began in 1982 with 822 adults who had rheumatoid arthritis and were under the care of rheumatologists. INTERVENTIONS: Those selected by rheumatologists in the management of their patients. MEASUREMENTS: Information describing sociodemographic and clinical characteristics, course, and therapy was collected from patients and verified by physician reports. Functional status, measured by the Health Assessment Questionnaire, and the number of painful joints were used as outcome variables. Outcome variables were adjusted for age, sex, disease duration, baseline values of the outcome variable, and the use of four disease-remittive agents other than gold. MAIN RESULTS: Multivariate repeated-measures analysis of variance showed no change in the course of rheumatoid arthritis over 5 years. The use of parenteral gold for at least 2 consecutive years at the start of the observation period produced, on average, no change in the course over 5 years in the two outcome variables. CONCLUSION: In our study of a community-based population of adults with rheumatoid arthritis who were under the care of community rheumatologists, we found that there was, on average, no statistically significant change in function or number of painful joints between 1983 and 1988. Patients receiving parenteral gold therapy for at least 2 consecutive years did not show a statistically significant difference in outcome when compared with those not receiving such therapy.     

Per-implant care of ailing implants with the carbon dioxide laser.

One of the many applications for which lasers have been proposed in implant dentistry is for the decontamination process. The purposes of this study were to assess possible alterations in titanium implants in vitro and in vivo by use of the carbon dioxide (CO2) laser and to determine whether new bone formation can occur on previously contaminated implants. In vitro, temperature changes at the bone-titanium implant interface were recorded during use of a CO2 laser-scanning system (Swiftlase). Additionally, the effects of laser irradiation on titanium implants at various power settings were examined. In 6 beagle dogs, a total of 60 implants and bony defects resulting from plaque accumulation were treated by air-powder abrasive (the conventional treatment), laser irradiation, or both. Depending on the parameters chosen, melting and other surface alterations were seen in vitro, especially in the superpulse mode. Otherwise, no alterations were found, even at high power settings in the continuous mode. In vivo, corresponding histologic examination of 4-month sections showed evidence of new direct bone-to-implant contact after laser-assisted therapy, especially when the implants had been treated concomitantly with submerged membranes. These results support the hypothesis that peri-implant defects can be treated successfully by laser decontamination without damaging the surrounding tissues in the dog model. Nevertheless, further investigations will be required to determine the clinical efficacy of the treatment.     

The economic cost of illness in the Federal Republic of Germany in the year 1980.

This paper provides an empirical investigation of the economic cost of illness, disability and premature death in the Federal Republic of Germany in the year 1980. Direct and indirect cost of morbidity and mortality are estimated and allocated to the disease categories of the ICD-International Classification of Diseases. Against the background of increasingly scarce resources in health care, the findings of cost of illness studies obtain special significance for the setting of priorities for the allocation of these resources. In comparison to the status quo, a disease-oriented approach may provide a more differentiated and national basis for the ex-ante macro-allocation of health care resources as well as for the identification of areas for increased efforts in prevention.     

Surgical considerations for ‘intrinsic＇ brainstem gliomas： proposal of a modification in classification

BACKGROUND： Brainstem gliomas are highly heterogeneous tumors both in their clinical manifestation and in their pathology. Despite significant advances in the surgery for brainstem gliomas many aspects of this pathology are still unelear. OBJECTIVE： To evaluate the clinical, radiological and surgical outcome of 40 focal ＂intrinsic＂ brainstem gliomas and propose a surgical strategyoriented classification. MATERIALS AND METHODS： A total of 40 focal ‘intrinsie’ （＂expanding variety＂） tumors have been operated over a period of 8.5-years （January 1998-June 2007）. Our criteria included patients with （1） well-defined gadolinium enhancing tumor, （2） relatively long duration of symptoms （〉 six months） and （3） good neurological functional status and independent for all activities of davy living. The cutoff size of 2 cm was not rigidly adhered to. RESULTS： The ＂intrinsic＂ brainstem tumors were classified into three types： Expanding, diffuse infiltrative and pure ventral varieties.