In vivo heat shock protects rat myocardial mitochondria

Heat shock (HS)/stress proteins (HSP) provide protection from a variety of stresses other than HS, including oxidative stress and mitochondria have been implicated as the target of HS-related protection in stressed cultured cells. Here we investigated whether mitochondria also are targets for the HS-mediated protection in vivo. Sprague Dawley rats were exposed, or not, to HS (41 degrees C, 15 min). After a 21 h recovery period, hearts were excised and perfused with or without H2O2 (0.15 mM). Myocardial mitochondria were then isolated, and their oxygen consumption was analyzed. HS prevented H2O2-induced alterations in state 3 respiration while increasing the expression of Hsp70 and heme oxygenase (HO). Thus, in vivo HS protects rat myocardial mitochondrial respiration against the deleterious effects of oxidative injury, a protection relating to Hsp70 and/or HO and targeting state 3 respiration.     

The influence of abutment surface roughness on plaque accumulation and peri-implant mucositis

Bacterial adhesion to intra-oral, hard surfaces is firmly influenced by the surface roughness to these structures. Previous studies showed a remarkable higher subgingival bacterial load on rough surfaces when compared to smooth sites. More recently, the additional effect of a further smoothening of intra-oral hard surfaces on clinical and microbiological parameters was examined in a short-term experiment. The results indicated that a reduction in surface roughness below R(a) = 0.2 microns, the so-called "thresholds R(a)", had no further effect on the quantitative/qualitative microbiological adhesion or colonisation, neither supra- nor subgingivally. This study aims to examine the long-term effects of smoothening intra-oral hard transgingival surfaces. In 6 patients expecting an overdenture in the lower jaw, supported by endosseus titanium implants, 2 different abutments (transmucosal part of the implant): a standard machined titanium (R(a) = 0.2 microns) and one highly polished and made of a ceramic material (R(a) = 0.06 microns) were randomly installed. After 3 months of intra-oral exposure, supra- and subgingival plaque samples from both abutments were compared with each other by means of differential phase-contrast microscopy (DPCM). Clinical periodontal parameters (probing depth, gingival recession, bleeding upon probing and Periotest-value) were recorded around each abutment. After 12 months, the supra- and subgingival samples were additionally cultured in aerobic, CO2-enriched and anaerobic conditions. The same clinical parameters as at the 3-month interval were recorded after 12 months. At 3 months, spirochetes and motile organisms were only detected subgingivally around the titanium abutments. After 12 months, however, both abutment-types harboured equal proportions of spirochetes and motile organisms, both supra- and subgingivally. The microbial culturing (month 12) failed to detect large inter-abutment differences. The differences in number of colony- forming units (aerobic and anaerobic) were within one division of a logarithmic scale. The aerobic culture data showed a higher proportion of Gram-negative organisms in the subgingival flora of the rougher abutments. From the group of potentially "pathogenic" bacteria, only Prevotella intermedia and Fusobacterium nucleatum were detected for anaerobic culturing and again the inter-abutment differences were negligible. Clinically, the smoothest abutment showed a slightly higher increase in probing depth between months 3 and 12, and more bleeding on probing. The present results confirm the findings of our previous short-term study, indicating that a further reduction of the surface roughness, below a certain "threshold R(a)" (0.2 microns), has no major impact on the supra- and subgingival microbial composition.     

Comparison of factor VIII-related antigen and erythrocyte sedimentation rate in outpatient management of vasculitis

Electroimmunodiffusion (Laurell rocket) determinations of factor VIII-related antigen in plasma were ordered to determine the cost/benefit ratio for factor VIII-related antigen as a putative test for endothelial damage in suspected vasculitis. Twenty-seven consecutive patients referred for vasculitis or suspected vasculitis were identified and followed up for an average of 9.1 +/- months (range: one to thirty-three months) in a prospective, unblinded study performed in a clinic, associated with a 1054-bed inner-city university hospital. There was no difference in Westergren erythrocyte sedimentation rate (WESR) in patients with final diagnosis of systemic vasculitis (SV) (38 +/- 12 mm/hour) compared to those without vasculitis (NV) (27 +/- 7) as the final diagnosis. The mean plasma concentration of factor VIII-related antigen was significantly elevated in SV (344 +/- 100%) when compared with NV (147 +/- 39%) (P < 0.016). The factor VIII-related antigen test in this study was 2.56 times more likely (crude odds ratio) than the WESR to contribute to a change in diagnosis or therapy (P = 0.016). Positive and negative predictive values (PPV and NPV) for factor VIII-related antigen (abnormal at greater than 220% of the normal value) were both 70%. PPV and NPV for WESR were 56% and 86%, respectively. The factor VIII-related test was less cost-effective than the WESR in the follow-up period unless it was important to define complete remission or differentiate vasculitis flare from infection. The authors conclude that factor VIII-related antigen is a useful test in the initial diagnosis of vasculitis.     

Synthesis and antiplatelet, antiinflammatory, and antiallergic activities of substituted 3-chloro-5,8-dimethoxy-1,4-naphthoquinone and related compounds

2-Amino (6), 2-alkylamino (7-8), 2-methoxy (9), 2-acetamido (10), and 5,8-diacetoxy (11) derivatives of the lead compound 2,3-dichloro-5,8-dimethoxy-1,4-naphthoquinone (4) were synthesized, together with 6,7-dichloro-5,8dimethoxy-1,4-naphthoquinone (5), a positional isomer of 4. Antiplatelet, antiinflammatory, and antiallergic activities were evaluated, and most compounds were quite potent in all assays. Compounds 5 and 9-11 were especially active; however, 5 was ineffective against neutrophil superoxide formation, and 10 was ineffective against mast cell degranulation.     

Argon laser punctal therapy versus thermal cautery for the treatment of aqueous deficiency dry eye syndrome

1. Pregnant Wistar rats were treated orally with a single dose of 100 microg 3,3',4,4'-tetrachlorobiphenyl (PCB 77)/kg b.w. or 10 microg 3,3',4,4',5 pentachlorobiphenyl (PCB 126)/kg b.w. on day 15 of pregnancy. The control rats received peanut oil at the same day. Developmental landmarks were assessed in all offspring rats and reproductive effects of PCB 77 and PCB 126 on male offspring were studied on postnatal day 65 (at puberty) and on postnatal day 140 (at adulthood). 2. The ano-genital distance as well as the ratio ano-genital distance to body length was reduced in male pups of the PCB 126 group and the age at vaginal opening was significantly delayed in the female pups. 3. Testis, brain weights and daily sperm production were permanently increased and seminal vesicle weights were decreased in male offspring of the PCB 77 group. In male rats of PCB 126 group, the brain weights were permanently increased and ventral prostate weights permanently reduced. In both PCB groups, however, serum testosterone concentration was reduced only at adulthood. Additionally, the male rats of the PCB 126 group showed alterations in sexual behavior. In these rats the number of mounts with intromissions was significantly increased. 4. The results of this study show that PCB 126 elicits some TCDD-like reproductive effects after in utero exposure, while the reproductive effects of in utero exposure to PCB 77 on male offspring may be attributed to the neonatal hypothyroidism induced by the substance during early fetal development. Further studies using multiple doses and providing thyroid hormone data will be necessary to support this hypothesis.     

Open-heart correction of tetralogy of Fallot in an acyanotic dog

Tetralogy of Fallot was diagnosed in an acyanotic 11-month-old dog. Predicted pressure gradient across the pulmonic valve, as assessed by use of continuous wave Doppler echocardiography, was 94.5 mm Hg. Bidirectional shunting was identified by means of selective angiography. Open-heart correction was performed, using a transatrial approach with limited ventriculotomy and cardiopulmonary bypass. The hypertrophied infundibulum was resected, the ventricular septal defect was closed primarily, and a transannular pericardial patch graft was applied. Pressure gradients across the pulmonic valve were 52.9 and 22.8 mm Hg 2 weeks and 4 months after surgery, respectively. Advances in cardiopulmonary bypass, anesthetic management, and use of the transatrial approach may improve the success of open-heart correction of tetralogy of Fallot in dogs.     

Evidence for genetic anticipation in nodal osteoarthritis

OBJECTIVE: Evidence was sought for genetic anticipation (disease occurring at an earlier age in subsequent generations, with increasing severity) in nodal osteoarthritis (NOA). METHODS: Age at symptom onset and disease severity was compared within 30 parent/offspring pairs with NOA. Correlation between the offspring age of disease onset and the parental age at conception was also assessed. RESULTS: The age at onset of nodal symptoms was earlier in the offspring (43 years (95% confidence intervals (CI) 38 to 47) v 61 (CI 58 to 65); mean difference 18 years (CI 13 to 22): p < 0.001) as was larger joint symptom onset (48 years (CI 41 to 55) v 67 (CI 61 to 73); mean difference 20 years (CI 13 to 27): p < 0.01). A negative correlation existed between age of offspring symptom onset and parental age at conception. Fifteen (50%) offspring had similar or more extensive disease than their parents. CONCLUSIONS: These results suggest genetic anticipation occurs in NOA and if confirmed a search for trinucleotide repeats is warranted.     

Expression of the Evi-1 gene in haemopoietic cells of children with juvenile myelomonocytic leukaemia and normal donors

Activation of the Evi-1 gene was first described to be associated with the transformation of murine myeloid leukaemias and has previously been detected in cases of human acute myeloid leukaemia (AML) and chronic myeloid leukaemia (CML) in blast crises and in myelodysplastic syndromes. In this study we determined the frequency and the level of Evi-1 expression in juvenile myelomonocytic leukaemia (JMML) and in normal haemopoiesis. Using RT-PCR and Southern blot hybridization mRNA of Evi-1 could be detected in bone marrow (BM) and peripheral blood (PB) mononuclear cells (MNC) of normal donors. In JMML 12/20 patients examined expressed elevated levels of Evi-1 compared to normal controls. In these samples over-expression of the gene was correlated with a higher percentage of blasts (P = 0.02). Expression levels in BFU-E and CFU-GM derived colonies from BM of JMML patients were lower than those in the corresponding MNC samples. Analysis of CD34+ and CD34- cells demonstrated that Evi-1 is primarily expressed in the CD34+ cell population of both JMML and normal donors. These findings suggest that Evi-1 expression is linked to the early stages of haemopoiesis. Studies on the regulation of Evi-1 expression in CD34+ cells will elucidate its function in progenitor cells and clarify its possible role in the pathogenesis of JMML.