Inhibitory effect of inositol phosphates on parathyroid hormone-induced bone resorption in organ cultures

This study investigates the ability of phytic acid, its inositol phosphate derivatives (inositol penta-, tetra-, tri-, di-, and monophosphate), and inorganic phosphate to inhibit parathyroid hormone (PTH)-induced resorption of fetal rat long bones in organ culture. Pregnant rats injected with 45Ca on the 18th day of gestation were killed the next day and their fetuses removed. Half of each pair of dissected long bones was incubated in a chemically defined control medium, while the contralateral half was incubated in medium containing PTH or PTH plus the phosphate compound to be tested. 45Ca released into the medium was indicative of the amount of bone resorption. All phosphate compounds tested inhibited resorption. The inositol phosphates should be studied further to assess their suitability as therapeutic agents for treatment of metabolic bone diseases involving increased turnover.     

Baseline Results from Hawaii's Nā Mikimiki Project: A Physical Activity Intervention Tailored to Multiethnic Postpartum Women

During the postpartum period, ethnic minority women have higher rates of inactivity/under-activity than white women. The Nā Mikimiki (“the active ones”) Project is designed to increase moderate-to-vigorous physical activity over 18 months among multiethnic women with infants 2–12 months old. The study was designed to test, via a randomized controlled trial, the effectiveness of a tailored telephone counseling of moderate-to-vigorous physical activity intervention compared to a print/website materials-only condition. Healthy, underactive women (mean age = 32 ± 5.6 years) with a baby (mean age = 5.7 ± 2.8 months) were enrolled from 2008–2009 (N = 278). Of the total sample, 84% were ethnic minority women, predominantly Asian–American and Native Hawaiian. Mean self-reported baseline level of moderate-to-vigorous physical activity was 40 minutes/week with no significant differences by study condition, ethnicity, infant's age, maternal body mass index, or maternal employment. Women had high scores on perceived benefits, self-efficacy, and environmental support for exercise but low scores on social support for exercise. This multiethnic sample's demographic and psychosocial characteristics and their perceived barriers to exercise were comparable to previous physical activity studies conducted largely with white postpartum women. The Nā Mikimiki Project's innovative tailored technology-based intervention and unique population are significant contributions to the literature on moderate-to-vigorous physical activity in postpartum women.     

Persistent Enhancement on Contrast-Enhanced Ultrasound Studies of Severe Crohn's Disease: Stuck Bubbles?

A small population of patients with severe Crohn's disease (CD) exhibit atypical lack of intensity decline on intestinal contrast-enhanced ultrasound. From a retrospective CD cohort examined with contrast-enhanced ultrasound, 104 patients were identified. Twenty study patients with severe active disease exhibited high peak enhancement (>23 dB) and minimal decline. From the same cohort, 84 control patients also exhibited high peak enhancement >23dB, but with typical intensity decline. Patient outcomes were assessed. Time–intensity curve analysis revealed a significantly higher (p < 0.0001) area under the curve (44.7 ± 1.5 dB·s), washout time and intensities at 60s and 120s in the study population compared with controls (40.0 ± 1.1 dB·s). Study patients had a worse overall outcome with surgery in 30% versus 10% (p?=?0.027) during follow-up. Heightened enhancement with lack of decline on contrast-enhanced ultrasound suggests microbubbles are stuck within the inflamed bowel wall for an extended period. This observation occurs in patients with severe disease and a bad outcome.     

Metallic crown-induced occlusal trauma as a protocol to evaluate inflammatory response in temporomandibular joint and periodontal tissues of rats

Clinical Oral Investigations - The goal of this study is to propose a standard protocol of experimental occlusal trauma to evaluate the inflammatory hyperalgesia induced by metallic crowns on...     

Boosting of SIV-specific T cell responses in rhesus macaques that resist repeated intravaginal challenge with SIVmac251

Despite repeated high-risk exposure to infectious HIV-1, some individuals remain HIV-1 seronegative and apparently uninfected. The use of nonhuman primate model systems to study SIVmac transmission may help to elucidate the factors responsible for protection in exposed, seronegative (ESN) humans. In an earlier vaccination study, three control rhesus macaques that were exposed to three sequential intravaginal challenges with pathogenic SIVmac251 failed to show evidence of infection after 5 years of observation. 51Cr release assay results suggested that these animals had low-level cytotoxic T lymphocyte responses to SIVmac proteins. We hypothesized that these responses might be an important component of protection from mucosal challenge. We performed an additional intravaginal challenge of all three macaques and monitored SIV-specific T cell responses in peripheral blood, using the sensitive enzyme-linked immunospot (ELISpot) assay. After the fourth challenge, one animal became infected; this animal did not mount a strong SIV-specific T cell response. Two other macaques remained uninfected as determined by peripheral blood mononuclear cell (PBMC) coculture, polymerase chain reaction (PCR), and branched DNA (bDNA) analysis of peripheral blood and lymphoid tissues, but demonstrated boosting of SIV-specific T cell responses after challenge. These results support a protective role for SIVmac-specific T cells in repeatedly exposed, persistently seronegative rhesus macaques.     

Structure of dimeric mitochondrial ATP synthase: novel F0 bridging features and the structural basis of mitochondrial cristae biogenesis

The F1F0-ATP synthase exists as a dimer in mitochondria, where it is essential for the biogenesis of the inner membrane cristae. How two ATP synthase complexes dimerize to promote cristae formation is unknown. Here we resolved the structure of the dimeric F1F0 ATP synthase complex isolated from bovine heart mitochondria by transmission electron microscopy. The structure of the ATP synthase dimer has an overall conic appearance that is consistent with the proposed role of the dimeric enzyme in mitochondrial cristae biogenesis. The ATP synthase dimer interface is formed by contacts on both the F0 and F1 domains. A cross-bridging protein density was resolved which connects the two F0 domains on the intermembrane space side of the membrane. On the matrix side of the complex, the two F1 moieties are connected by a protein bridge, which is attributable to the IF1 inhibitor protein.     

Inhaled iloprost to treat severe pulmonary hypertension. An uncontrolled trial. German PPH Study Group

BACKGROUND: Inhaled aerosolized iloprost, a stable prostacyclin analogue, has been considered a selective pulmonary vasodilator in the management of pulmonary hypertension. OBJECTIVE: To assess the efficacy of inhaled iloprost in the treatment of life-threatening pulmonary hypertension. DESIGN: Open, uncontrolled, multicenter study. SETTING: Intensive care units and pulmonary hypertension clinics at six university hospitals in Germany. PATIENTS: 19 patients who had progressive right-heart failure despite receiving maximum conventional therapy (12 with primary pulmonary hypertension, 3 with pulmonary hypertension related to collagen vascular disease without lung fibrosis, and 4 with secondary pulmonary hypertension). INTERVENTION: Inhaled iloprost, 6 to 12 times daily (50 to 200 microg/d). MEASUREMENTS: Right-heart catheterization and distance walked in 6 minutes at baseline and after 3 months of therapy. RESULTS: During the first 3 months of therapy, New York Heart Association functional class improved in 8 patients and was unchanged in 7 patients. Four patients died, 3 of right-heart failure and 1 of sepsis. The acute hemodynamic response to inhaled iloprost was predominant pulmonary vasodilatation with little systemic effect at baseline and at 3 months (data available for 12 patients). Hemodynamic variables were improved at 3 months, and the distance walked in 6 minutes improved by 148 m (95% CI, 4.5 to 282 m; P = 0.048). Of the 15 patients who continued to use inhaled iloprost, 8 stopped: Four had lung transplantation, 1 switched to intravenous prostacyclin therapy, and 3 died. Seven patients are still receiving inhaled iloprost (mean +/-SD) duration of therapy, 536 +/- 309 days; mean dosage, 164 +/- 38 microg/d). CONCLUSIONS: Inhaled iloprost may offer a new therapeutic option for improvement of hemodynamics and physical function in patients with life-threatening pulmonary hypertension and progressive right-heart failure that is refractory to conventional therapy.     

Unsuspected vascular disease: A potential limitation to the use of the intra-aortic balloon

Since vascular tortuosity or stenosis may preclude placement of the Intra-aortic balloon, 63 consecutive patients (37 men) having routine Judkins' cardiac catheterization had an aortogram prior to withdrawal of the last catheter. No patient had a history of claudication, palpable aneurysms, pulse deficit, or bruit. No complications occurred. Significant peripheral vascular disease was found in ten patients: three had aortic, one had iliac, and six had femoral stenosis or tortuosity. All were men. The age of patients with peripheral vascular disease was 61.4 ± 7.7 years, while those without were 56.9 ± 9.3 years (P = NS). No difficulty was encountered entering the femoral artery in any patient; there was difficulty advancing the catheter in five of ten (50%) patients with peripheral vascular disease and in three of 54 (6%) patients without (P < 0.002). Fifteen patients without peripheral vascular disease had normal coronary arteries, while none with peripheral vascular disease was normal. In patients with coronary disease, the number of vessels involved was the same in both groups. Peripheral vascular disease that might preclude placement of the Intra-aortic balloon occurs in 14% of patients undergoing cardiac catheterization and 18% of patients with coronary artery disease. Aortography may be safely performed and should be considered during routine cardiac catheterization in patients who may require Intra-aortic balloon placement.