Association between serum testosterone concentration and collagen degradation fragments in men with type 2 diabetes mellitus

The aim of the present study was to evaluate relationships between serum endogenous androgens and urinary concentration of cross-linked N-telopeptides of type I collagen (NTx), a bone resorption marker, in men with type 2 diabetes mellitus because low androgen concentrations are associated with both osteoporosis and cardiovascular disease. Relationships between serum free testosterone and urinary NTx concentrations were investigated in 246 consecutive men with type 2 diabetes mellitus. In addition, relationships between urinary NTx concentration and other variables including age, duration of diabetes, blood pressure, serum lipid concentration, hemoglobin A(1c), and body mass index were evaluated. Urinary NTx concentrations were 27.8 (26.4-29.3) nmol of bone collagen equivalent per millimole of creatinine, correlating inversely with serum free testosterone (r = -0.263, P < .0001). Multiple regression analysis identified serum free testosterone (beta = -.292, P < .0001), hemoglobin A(1c) (beta = .144, P = .0404), and smoking status (beta = .143, P = .0402) as independent determinants of urinary NTx. In conclusion, serum free testosterone concentration correlated inversely with urinary NTx concentration, which may partly account for an observed link between osteoporosis and cardiovascular disease in men with type 2 diabetes mellitus.     

Intrahepatic biliary epithelial cell damage and inflammation in portal tract in association with chronic colitis-harboring TCRalpha(-/-) mice.

BACKGROUND: Intrahepatic bile ducts are the target for inflammation in both primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). The mechanisms of biliary epithelial cell damage in both diseases are not clearly understood. Ulcerative colitis (UC) is one of the known complications in PSC. In this study, we assessed the possible influence of apoptosis inhibitor expressed by macrophages (AIM) on intrahepatic bile ducts in the chronic colitis-harboring condition by generating T cell receptor alpha-deficient (TCRalpha(-/-))xAIM-deficient (AIM(-/-)) double-knockout mice. METHODS: TCRalpha(-/-)xAIM(-/-) mice were generated by crossbreeding TCRalpha(-/-) mice with AIM(-/-) mice. At 24 weeks of age, mice were sacrificed to obtain liver tissues for pathological examinations, and blood was collected to study the serum levels of IgG, IgM and IgA. RESULTS: In female TCRalpha(-/-)xAIM(-/-) mouse livers, mixed cellular infiltration in the portal area and epithelial cell damage in bile ducts were observed, when compared with female TCRalpha(-/-)xAIM(+/-) and male TCRalpha(-/-)xAIM(-/-) mice. Inflammation in hepatic parenchyma was mild to none in all mice. In the female mouse group, the serum IgA level was relatively increased in TCRalpha(-/-)xAIM(-/-) mice compared to TCRalpha(-/-)xAIM(+/-) mice. CONCLUSION: The defect of AIM might be involved not only in colonic mucosal inflammation but also in portal inflammation, as well as in biliary epithelial cell damage in the livers of female TCRalpha(-/-)xAIM(-/-) mice.     

Idiopathic sudden hearing loss in patients with type 2 diabetes

The aim of the present study was to identify clinical and audiologic characteristics of idiopathic sudden hearing loss (ISHL) in patients with type 2 diabetes. We retrospectively investigated 148 cases of ISHL, whose age was more than 40 years, comparing clinical and audiologic valuables between diabetic and non-diabetic patients. Twenty-four patients (16.2%) had type 2 diabetes (16 male, 8 female). Prevalence of hypertension and hyperlipidemia were significantly greater in diabetic patients. Hearing in the affected ear was more impaired in diabetic than non-diabetic patients, although hearing in the unaffected ear and degree of recovery did not differ significantly. Mean BMI, duration of diabetes, HbA1c values, and ultrasonographically determined carotid intima-media thickness (IMT) and plaque scores in diabetic patients with ISHL were 24.0+/-3.7 kg/m(2), 9.8+/-7.8 years, 7.8+/-1.5%, 0.83+/-0.16 mm, and 3.8+/-2.8, respectively. Of 17 diabetic patients whose ISHL was treated with steroids, 12 required insulin for glycemic control during treatment. Compared with diabetic patients without ISHL, HbA1c value was significantly higher in diabetic patients with ISHL (7.2+/-1.2% versus 7.8+/-1.5%, P=0.0202). In conclusion, nearly 16% of our patients with ISHL had type 2 diabetes, and this subgroup was associated with more severe hearing loss. Further studies are needed to determine which subgroups of diabetic patients are most likely to develop ISHL, which patients are predisposed to more severe hearing loss, and how various factors and treatments influence outcome.     

Ultrafast-charging and long cycle-life anode materials of TiO2-bronze/nitrogen-doped graphene nanocomposites for high-performance lithium-ion batteries

Emerging technologies demand a new generation of lithium-ion batteries that are high in power density, fast-charging, safe to use, and have long cycle lives. This work reports charging rates and specific capacities of TiO₂(B)/N-doped graphene (TNG) composites. The TNG composites were prepared by the hydrothermal method in various reaction times (3, 6, 9, 12, and 24 h), while the N-doped graphene was synthesized using the modified Hummer''s method followed by a heat-treatment process. The different morphologies of TiO₂ dispersed on the N-doped graphene sheet were confirmed as anatase-nanoparticles (3, 6 h), TiO₂(B)-nanotubes (9 h), and TiO₂(B)-nanorods (12, 24 h) by XRD, TEM, and EELS. In electrochemical studies, the best battery performance was obtained with the nanorods TiO₂(B)/N-doped graphene (TNG-24h) electrode, with a relatively high specific capacity of 500 mA h g⁻¹ at 1C (539.5 mA g⁻¹). In long-term cycling, excellent stability was observed. The capacity retention of 150 mA h g⁻¹ was observed after 7000 cycles, at an ultrahigh current of 50C (27.0 A g⁻¹). The synthesized composites have the potential for fast-charging and have high stability, showing potential as an anode material in advanced power batteries for next-generation applications.

The TiO₂-bronze/nitrogen-doped graphene nanocomposites have the potential for fast-charging and have high stability, showing potential as an anode material in advanced power batteries for next-generation applications.     

Sphingosylphosphorylcholine is a novel messenger for Rho-kinase-mediated Ca2+ sensitization in the bovine cerebral artery: unimportant role for protein kinase C

Although recent investigations have suggested that a Rho-kinase-mediated Ca2+ sensitization of vascular smooth muscle contraction plays a critical role in the pathogenesis of cerebral and coronary vasospasm, the upstream of this signal transduction has not been elucidated. In addition, the involvement of protein kinase C (PKC) may also be related to cerebral vasospasm. We recently reported that sphingosylphosphorylcholine (SPC), a sphingolipid, induces Rho-kinase-mediated Ca2+ sensitization in pig coronary arteries. The purpose of this present study was to examine the possible mediation of SPC in Ca2+ sensitization of the bovine middle cerebral artery (MCA) and the relation to signal transduction pathways mediated by Rho-kinase and PKC. In intact MCA, SPC induced a concentration-dependent (EC50=3.0 micromol/L) contraction, without [Ca2+]i elevation. In membrane-permeabilized MCA, SPC induced Ca2+ sensitization even in the absence of added GTP, which is required for activation of G-proteins coupled to membrane receptors. The SPC-induced Ca2+ sensitization was blocked by a Rho-kinase inhibitor (Y-27632) and a dominant-negative Rho-kinase, but not by a pseudosubstrate peptide for conventional PKC, which abolished the Ca2+-independent contraction induced by phorbol ester. In contrast, phorbol ester-induced Ca2+ sensitization was resistant to a Rho-kinase inhibitor and a dominant-negative Rho-kinase. In primary cultured vascular smooth muscle cells, SPC induced the translocation of cytosolic Rho-kinase to the cell membrane. We propose that SPC is a novel messenger for Rho-kinase-mediated Ca2+ sensitization of cerebral arterial smooth muscle and, therefore, may play a pivotal role in the pathogenesis of abnormal contraction of the cerebral artery such as vasospasm. The SPC/Rho-kinase pathway functions independently of the PKC pathway.     

Pediatric bacterial meningitis prognosis and antibiotic treatment

An evaluation committee studied the relationship between initial treatment drug and prognosis in 339 of 466 subjects with bacterial meningitis treated at 108 institutions between April 2004 and January 2007, after excluding those with uncertain diagnosis or non-assessable records. Prognosis was considered unfavorable if meningitis sequelae such as quadriplegia, deafness, or epilepsy were present in 3- month follow-up; Based on this definition, 43 (12.7%) had a poor prognosis. No significant relationship was seen between unfavorable prognosis and age or causative pathogen. More had an unfavorable prognosis if treatment was initiated 4 days or later after onset. The percentage with an unfavorable prognosis was 6.4% (4/64) in the group administered combined panipenem/betamipron (PAPM/BP) plus ceftriaxone (CTRX), 10.5% (6/57) administered MEPM plus cefotaxime (CTX), 14.0% (7/50) administered meropenem (MEPM) plus CTRX, and none of the 23 administered CTRX alone. The percentage with an unfavorable prognosis was 26.2% (11/42) in those administered MEPM, significantly higher than that in those administered PAPM/BP plus CTRX, MEPM plus CTX, or CTRX alone (p < 0.05). We concluded that in initial treatment, it would be more desirable to use MEPM combined with another drug than alone.     

Surface-retained tPA is essential for effective fibrinolysis on vascular endothelial cells

In a previous study, we demonstrated unique secretory dynamics of tissue plasminogen activator (tPA) in which tPA was retained on the cell surface in a heavy chain-dependent manner after exocytosis from secretory granules in vascular endothelial cells. Here, we examined how retained tPA expresses its enzymatic activity. Retained tPA effectively increased the lysine binding site-dependent binding of plasminogen on the cell surface and pericellular area; this was abolished by inhibition of enzymatic activity of either tPA or plasmin, which suggests that de novo generation of carboxyl-terminal lysine as a consequence of degradation of surface/pericellular proteins by plasmin is essential. Retained tPA initiated zonal clot lysis of a fibrin network that had been formed on vascular endothelial cells, which was preceded by the binding of plasminogen to the lysis front. Our results provide evidence that secreted and retained tPA is essential for maintaining both high fibrinolytic activity and effective clot lysis on the vascular endothelial cell surface.     

Plasminogen activator inhibitor type 1 promotes fibrosarcoma cell migration by modifying cellular attachment to vitronectin via alpha(v)beta(5) integrin

Both urokinase plasminogen activator (u-PA) and plasminogen activator inhibitor type 1 (PAI-1) are associated with a poor prognosis in cancer patients. We demonstrate that PAI-1 inhibits human fibrosarcoma cell (HT-1080) adhesion to vitronectin (Vn) via alpha (v)beta (5) integrin, and stimulates cell migration from Vn toward collagen type IV (Col). The cells attached more strongly to Vn and Col than to fibronectin (Fn), whereas PAI-1 interfered with cell attachment to Vn only. An integrin antagonist, RGD peptide, and anti-alpha (v)beta (5) integrin antibodies, which similarly inhibited cell attachment to Vn, also stimulated cell migration from Vn toward Col. u-PA did not modify cell attachment directly, but reversed the PAI-1-mediated inhibitory effect on cell adhesion to Vn, and its stimulatory effect on cell migration from Vn toward Col. Thus HT-1080 cell migration appears to be modified by u-PA and PAI-1, altering cell adhesion to Vn via alpha (v)beta (5) integrin. This may be related to their tumor-promoting effect.     

Pulmonary function testing and chest tomography in patients with acromegaly

Background

Despite the gradual improvement in treatment procedures and cure rates of acromegaly, a steady increase in the mortality rate due to respiratory disease has been documented in recent decades. In this study, our objectives were to describe the abnormalities in lung structure and function that occur in acromegalic patients and to correlate these changes with hormonal levels.

Methods

This cross-sectional study included 20 acromegalic patients and 20 age-and height-matched control subjects, all non-smokers. All subjects underwent spirometry, whole body plethysmography, carbon monoxide diffusing capacity, and respiratory muscle strength. Acromegalic patients also performed high-resolution computed tomography (HRCT).

Results

Most patients were female (65%), with a mean age of 52.5?±?13 years. Acromegalic patients showed lower values of maximum expiratory pressure (55.9?±?17.1 vs. 103.7?±?19.2%; p < 0.001) and maximum inspiratory pressure (71.4?±?27.8 vs. 85.3?±?24.1%; p = 0.005) compared to control subjects. The values of forced vital capacity (107.1?±?15.9 vs. 98.9?±?21.4%; p = 0.028), total lung capacity – TLC (107.3?±?12.9 vs. 93.7?±?7.60%; p = 0.002), residual volume (114.1?±?22.7 vs. 90.0?±?14.6%; p < 0.001), and airways’ resistance (3.82 vs. 2.31 cmH₂O/L/s; p = 0.039) were greater in acromegalic patients than in control subjects. The difference between the TLC measured by plethysmography and the V_A (alveolar volume) measured during the DL_CO maneuver was higher in acromegalic patients than in control subjects (0.69?±?0.46 vs. 0.19?±?0.61 L; p = 0.021). The main findings in HRCT in acromegalic patients were air trapping, airway calcification and bronchiectasis, which were observed in 60%, 40% and 35% of cases, respectively. There was no significant correlation between the levels of growth hormone and insulin-like growth factor I, the lung function and the air trapping.

Conclusions

Acromegalic patients show changes consistent with the involvement of the small airways and ventilation inhomogeneity, both in terms of lung function and structure. However, air trapping cannot be explained either by hormone levels or changes in lung function.