Co-localization of iron binding on silica with p62/sequestosome1 (SQSTM1) in lung granulomas of mice with acute silicosis

The cellular mechanisms involved in the development of silicosis have not been fully elucidated. This study aimed to examine influence of silica-induced lung injury on autophagy. Suspensions of crystalline silica particles were administered transnasally to C57BL/6j mice. Immunohistochemical examination for Fas and p62 protein expression was performed using lung tissue specimens. Two-dimensional and quantitative analysis of silica deposits in the lungs were performed in situ using lung tissue sections by an in-air microparticle induced X-ray emission (in-air micro-PIXE) analysis system, which was based on irrradiation of specimens with a proton ion microbeam. Quantitative analysis showed a significant increase of iron levels on silica particles (assessed as the ratio of Fe relative to Si) on day 56 compared with day 7 (p<0.05). Fas and p62 were expressed by histiocytes in granulomas on day 7, and the expressions persisted for day 56. Fas- and p62-expressing histiocytes were co-localized in granulomas with silica particles that showed an increase of iron levels on silica particles in mouse lungs. Iron complexed with silica induces apoptosis, and may lead to dysregulations of autophagy in histiocytes of granulomas, and these mechanisms may contribute to granuloma development and progression in silicosis.     

Clinical significance of abnormal Q wave disappearance in acute transmural myocardial infarction

The clinical features of acute myocardial infarction patients in whom abnormal Q wave disappeared were analyzed. Of 201 patients, 40 (20%) (Group A) showed disappearance of Q wave in serial electrocardiograms. Regional ejection fraction of the infarcted portion improved significantly (from 24 +/- 2 to 34 +/- 4%, p less than 0.001) during chronic phase in Group A, but no such improvement was present in Group B patients who showed no change in the Q wave. Global ejection fraction was greater and percent akinetic segment was smaller in Group A than in Group B at chronic phase. Coronary occlusion occurred more often at segment 7 in Group A; in Group B, occlusion occurred more frequently upstream at segment 6, suggesting Group A had a smaller area of risk. Spontaneous recanalization was more often (57%) and complete occlusion was less frequent in Group A. These indicate that Group A is characterized by a smaller area of risk, smaller infarct size, earlier reperfusion, and greater improvement in wall motion. Twenty-eight patients (70%) of Group A lost Q wave within one month and 12 patients (30%), after 3 months or more. Electrical stunning of the myocardium may be a possible mechanism for the early disappearance of Q waves, and anatomical healing for the late disappearance of Q waves.     

Alfuzosin attenuates erectile dysfunction in rats with partial bladder outlet obstruction

OBJECTIVE

To determine how partial bladder outlet obstruction (PBOO) in a rat model affects erectile function, and whether an uroselective α1‐adrenoceptor antagonist, alfuzosin (Sanofi‐Aventis, Paris, France) attenuates any erectile dysfunction (ED).

MATERIALS AND METHODS

Adult male Sprague‐Dawley rats (120) were randomized into four groups: 1, sham‐operated; 2, alfuzosin‐treated; 3, PBOO; and 4, alfuzosin‐treated with PBOO. Groups 3 and 4 were subjected to PBOO for 6 weeks by ligation of the urethra, while groups 2 and 4 rats received daily oral alfuzosin (10 mg/day) for 6 weeks. In vivo erectile responses were monitored by evaluating ratios of intracavernosal pressure (ICP)/mean arterial pressure, and total ICP (area under the curve). Organ‐bath studies were performed on corpus cavernosum smooth muscle (CCSM) strips. Nitric oxide synthase (NOS) expression was determined immunohistochemically (IHC) for neuronal (n)NOS and by Western blot analysis for endothelial (e) and inducible (i) NOS protein.

RESULTS

Rats with PBOO showed lower erectile responses than controls. Maximum electrical field stimulation‐mediated and endothelium‐dependent acetylcholine‐induced relaxations and contractile responses to phenylephrine were significantly reduced in CCSM strips from the PBOO group. The NO donor sodium nitroprusside completely relaxed CCSM from rats in all groups. IHC analyses showed decreased expression of nNOS in PBOO groups compared with controls; by contrast, protein expression of eNOS and iNOS was increased. Alfuzosin‐treatment partially attenuated functional and molecular changes in penises of PBOO rats.

CONCLUSION

Rats with PBOO show ED, most likely due to altered NOS expression and NO bioavailability. The α‐adrenoreceptor antagonist alfuzosin reversed this ED by altering sympathetic tone, increasing NO‐induced relaxation and augmenting blood flow in the penis. This study suggests a rationale for further clinical trials using combinations of α‐adrenoceptor antagonists and phosphodiesterase‐5 inhibitors in patients with ED and lower urinary tract symptoms.     

Repair of a milled cantilevered implant overdenture bar: a clinical report

This clinical report of a fractured cantilevered substructure bar describes an alternative treatment to the proposed refabrication of the substructure bar and overdenture prosthesis. This report outlines the clinical and laboratory procedures to repair the fractured bar, eliminating the time and expense of fabricating a new bar and prosthesis.     

Systemic assessments utilizing saliva: part 1 general considerations and current assessments

In this 2-part review series, the current uses of saliva as a diagnostic fluid are reviewed, first with a focus on known measurements of systemic conditions. In Part 2, the role of saliva to measure bone turnover with a special emphasis on osteoporosis will be discussed.     

Glimepiride increases high-density lipoprotein cholesterol via increasing adiponectin levels in type 2 diabetes mellitus

The aims of the present study are to investigate the effect of glimepiride 1 mg/d on plasma adiponectin and to assess the contribution of adiponectin in changing high-density lipoprotein cholesterol (HDL-c) levels after glimepiride treatment. Forty patients with type 2 diabetes mellitus were included. Plasma adiponectin, fasting plasma glucose, insulin, hemoglobin A_1c, and cholesterol were measured at study entry and after 3 months of treatment with glimepiride. Both plasma adiponectin level (7.5 ± 4.5 vs 8.3 ± 4.5 μg/mL, P = .040) and HDL-c level increased significantly (50 ± 11 vs 53 ± 10 mg/dL, P = .041) in the all-subjects group. In the low-adiponectin group (initial plasma adiponectin level <6 μg/mL), both plasma adiponectin level (4.5 ± 0.9 vs 5.9 ± 2.0 μg/mL, P = .004) and HDL-c level increased significantly (44 ± 8 vs 49 ± 9 mg/dL, P = .011). There was no significant change in the high-adiponectin group (initial plasma adiponectin level ≥6 μg/mL). Change in plasma adiponectin level was an independent factor for change in HDL-c level after adjustment for other factors (β = .574, P = .009, R² = 0.524, P = .036). In conclusion, glimepiride improved plasma adiponectin level, especially in the subjects with type 2 diabetes mellitus with low adiponectin level before treatment, and may directly contribute to improving HDL-c level.     

Effective knowledge management in translational medicine

Background  

The growing consensus that most valuable data source for biomedical discoveries is derived from human samples is clearly reflected in the growing number of translational medicine and translational sciences departments across pharma as well as academic and government supported initiatives such as Clinical and Translational Science Awards (CTSA) in the US and the Seventh Framework Programme (FP7) of EU with emphasis on translating research for human health.     

Thrombocytopenia in HIV infection: impairment of platelet formation and loss correlates with increased c-Mpl and ligand thrombopoietin expression

Thrombocytopenia is a common hematologic disorder in patients infected with the human immunodeficiency virus (HIV) and represents a risk for bleeding which is further deleterious during surgery. The major causes of the thrombocytopenia include accelerated peripheral platelet destruction by antiplatelet antibodies and insufficient production of platelets from the infected megakaryocytes. Additionally, at an earlier stage of platelet development, HIV may inhibit megakaryopoiesis at multiple stages of pluripotent CD34+ progenitor stem cell differentiation possibly contributing to decreased levels of platelets in circulation. In HIV infected patients, both the serum thrombopoietin (TPO) levels and theTPO-c-Mpl complexes on the platelet surface were significantly elevated. Therapeutic infusion of HIV infected patients with pegylated recombinant human megakaryocyte growth development factor (PEG-rHu-MGDF) restores platelet counts to normal levels and reduces the c-Mpl expression per platelet. In vitro aggregation of platelets treated with TPO and agonist, adenosine diphosphate (ADP), decrease the dose of ADP that is required for half-maximum aggregation. In vivo dosing does not effect platelet aggregation showing that the metabolism of TPO following its internalization through TPO-c-Mpl complex is rapid and that dosing within the therapeutic range does not constitute increased risk of thrombotic disease.     

Lung growth after reduced size transplantation in a sheep model

BACKGROUND: The growth of mature allografts is a critical issue in pediatric lung transplantation. This study explores the architectural changes of mature sheep lung when submitted to two different compensatory growth forces: either transplantation into a neonatal host or expansion in an otherwise empty adult hemithorax. METHODS: Right upper lobes (RUL) (mean+/-SEM, 66.7+/-1.9 kg) from 4- to 5-year old (adult sheep) were transplanted into newborn (n=6) lambs (5.4+/-0.3 kg, 5+/-2 days old) that were then allowed to survive for 45 days. Changes in pulmonary volume and architecture were measured before and after transplantation. Allografts were compared with both normal adult RUL (n=10) and adult (65.8+/-2.2 kg and 4 to 5 year old) RUL that remained in situ for 45 days after resection of the corresponding middle and lower lobes (n=6). Statistical differences were analyzed using two-sample and paired t tests. RESULTS: In adult animals, RUL remaining in the otherwise empty hemithorax compensated by an 85% increase in volume (251.5+/-18.7 ml vs. 466+/-32.8 ml) (P<0.0001). Concomitant increases in total internal alveolar surface area (48%) and alveolar size were prominent. The number of alveoli per volume decreased proportionately to the increases in volume (P<0.0001). There was no significant change in the calculated number of alveoli (345.6+/-40.5 x 10(6)) compared with the normal adult RUL (402.4+/-40.7x10(6)) (P=0.37). Transplant recipients received a reduced-size normal adult RUL (49%) in volume (125.3+/-21.5 ml). Allografts 45 days after transplantation showed a 73% increase in volume (216.4+/-21.3 ml) (P<0.0001) with a parallel (83%) increase in total internal alveolar surface area (P=0.008). The number of alveoli per volume remained constant (P=0.21) despite the increase in volume. There was therefore a significant increase in the calculated number of alveoli from before transplantation (172.5+/-35.9x 106) compared with that observed 45 days after transplantation (389.7+/-77.7x10(6)) (P=0.012). CONCLUSIONS: We conclude that mature sheep RUL parenchyma compensates with dilation of the respiratory structures in the adult animal, whereas there is alveolar multiplication when transplanted into newborn recipients.     

The tourniquet in total knee arthroplasty. A prospective, randomised study

We assessed the influence of the use of a tourniquet in total knee arthroplasty in a prospective, randomised study. After satisfying exclusion criteria, we divided 77 patients into two groups, one to undergo surgery with a tourniquet and one without. Both groups were well matched. The mean change in knee flexion in the group that had surgery without a tourniquet was significantly better at one week (p = 0.03) than in the other group, but movement was similar at six weeks and at four months. There was no significant difference in the surgical time, postoperative pain, need for analgesia, the volume collected in the drains, postoperative swelling, and the incidence of wound complications or of deep-venous thrombosis. We conclude that the use of a tourniquet is safe and that current practice can be continued.