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Background Diabetes increases the risk of infections as well as coronary heart disease (CHD). Whether infections increase the risk of CHD and how this applies to individuals with diabetes is unclear. Objectives To investigate the association between bacterial infections and the risk of CHD in type 1 diabetes. Methods Individuals with type 1 diabetes (n = 3781) were recruited from the Finnish Diabetic Nephropathy Study (FinnDiane), a prospective follow-up study. CHD was defined as incident events: fatal or non-fatal myocardial infarction, coronary artery bypass surgery or percutaneous coronary intervention, identified through national hospital discharge register data. Infections were identified through national register data on all antibiotic purchases from outpatient care. Register data were available from 1.1.1995-31.12.2015. Bacterial lipopolysaccharide (LPS) activity was measured from serum samples at baseline. Data on traditional risk factors for CHD were collected during baseline and consecutive visits. Results Individuals with an incident CHD event (n = 370) had a higher mean number of antibiotic purchases per follow-up year compared to those without incident CHD (1.34 [95% CI: 1.16-1.52], versus 0.79 [0.76-0.82],P

The aim of this study was to examine the changes in hemostasis parameters in endocarditis and thromboembolic events in nonfatal methicillin-sensitive Staphylococcus aureus bacteremia (MS-SAB) - a topic not evaluated previously. In total, 155 patients were recruited and were categorized according to the presence of endocarditis or thromboembolic events with gender-age adjusted controls. Patients who deceased within 90 days or patients not chosen as controls were excluded. SAB management was supervised by an infectious disease specialist. Patients with endocarditis (N = 21), compared to controls (N = 21), presented lower antithrombin III at day 4 (p

The action of central and peripheral type benzodiazepine ligands on growth hormone, luteinizing hormone and follicle stimulating hormone levels in serum were studied in male rats. Graded doses of Ro 5-4864, that binds to the peripheral type benzodiazepine receptors, clonazepam, a fairly pure central type agonist and diazepam, a mixed-type agonist, were given intraperitoneally. Also a benzodiazepine partial inverse agonist, FG 7142, was investigated. Clonazepam increased growth hormone levels at 0.2 mg/kg while higher doses were not active. Diazepam (5-25 mg/kg) was not effective. FG 7142 (15 mg/kg) and Ro 5-4864 (25 mg/kg) decreased growth hormone levels. Flumazenil, a central-type antagonist, reversed at least partially the effects of clonazepam and FG 7142, suggesting an effect through GABA-benzodiazepine complex. Elevation of growth hormone could be associated with anxiolysis and decrease of growth hormone with enhanced anxiety. Clonazepam (0.2-5 mg/kg) and diazepam (5-25 mg/kg) increased luteinizing hormone concentrations, but only the effects of 1 mg/kg of clonazepam and 5 mg/kg of diazepam reached statistical significance. Even FG 7142 caused a modest increase of luteinizing hormone at 5 mg/kg, but Ro 5-4864 rather decreased luteinizing hormone, although not significantly. Flumazenil (25 mg/kg) antagonized partially the effects of diazepam and clonazepam. Effects of Ro 5-4864 and FG 7142 were not modified by flumazenil or PK 11195, a peripheral-type mixed antagonist/agonist. Luteinizing hormone stimulation by benzodiazepine ligands may be a pituitary action while inhibition could be caused by the activation of the central GABAergic system. Serum follicle stimulating hormone levels were not significantly altered by central or peripheral type benzodiazepine agonists or antagonists.

The mechanism of action of the TRH induced inhibition of contractions of the transmurally stimulated rat duodenum has been studied. The effect of TRH was not antagonized by atropine, pentolinium, phenoxybenzamine, sotalol, methysergide, domperidone, diphenhydramine, cimetidine, aminophylline, antazolin, indomethacin, morphine, naloxone or tetrodotoxin. In contrast, the adrenergic α2-antagonist atipamezole, the benzodiazepines chlordiaxepoxide and midazolam or GABA-A-antagonist bicucullin but not picrotoxin or SR-95531 attenuated the response to TRH. An opioid-kappa-receptor agonist having benzodiazepine structure, tifluadom, but not MR 2034 also diminished the response to TRH. However, these actions were not modified by the α2-agonist medetomidine, benzodiazepine antagonist flumazenil, GABA-agonists muscimol or baclofen or naloxone, respectively. While the binding of [3H][3-Me-His2]TRH to the rat anterior pituitary, hypothalamus, cortex and brainstem homogenates was saturable and of high affinity, no saturable binding was observed in the duodenal smooth muscle. Agents that were effective in the duodenal preparation displaced [3H][3-Me-His2]TRH from its binding sites in brain homogenates and the inhibitory constants (Ki) were (in μM): 0.038-0.107 (TRH), 0.19-5.8 (chlordiazepoxide), 0.021-8.9 (midazolam), 1.5-17 (tifluadom), 60-210 (bicucullin) and 150-530 (atipamezole). Atipamezole, bicucullin and chlordiazepoxide caused competitive displacement indicated by the increased KD of the labelled ligand but no change in the Bmax while tifluadom increased KD and decreased Bmax. It is concluded that the inhibitory effect of TRH on the contractions of the duodenal smooth muscle is mediated directly by the smooth muscle and it is apparently specific for TRH. The competitive displacement of [3H][3-Me-His2]TRH binding in brain homogenates by benzodiazepines, bicucullin and atipamezole suggest a similar mechanism for their antagonistic effect of the TRH-induced inhibition of duodenal contractions.

The development of tachyphylaxis to the pressor, tachycardiac, ventilatory and smooth muscle effects of thyrotropin-releasing hormone (TRH) was studied. Subsequent administrations of increasing doses of TRH (0.1-1000 nmol/kg intracerebroventicularly), at 20 min. intervals in urethane-anesthetized rats dose-dependently increased the mean arterial blood pressure, heart rate and minute ventilation volume. At all doses the effect on mean arterial blood pressure was apparent at least 20 min. after each injection whereas at low doses (0.1-1 nmol/kg) the duration of the effects on heart rate or minute ventilation volume were shorter. The cardiorespiratory effects of TRH 10 nmol/kg intracerebroventricularly did not subside completely within an observation period of 1 hr. However, a repeated administration of TRH at 1 hr resulted in the levels of mean arterial blood pressure, heart rate and minute ventilation volume not statistically different from the peak levels of the first injection. While the cardiorespiratory effects of TRH were long-lasting, the TRH induced inhibition of the contractions of the rat duodenal smooth muscle lasted only 12-18 sec. The TRH-treated duodenal preparation responded normally to noradrenaline but remained unresponsive to further administrations of TRH until washed extensively. When the medium after cessation of the TRH response was transferred into another chamber with an untreated preparation, a full response was resulted. Inhibitors of TRH metabolism, bacitracin, EDTA and iodoacetamide, did not prolong nor enhance the response. Likewise, a stable TRH-analogue MK-771 did not produce any longer response than TRH. It is concluded that no tachyphylaxis was produced to the neurally mediated pressor, tachycardiac or ventilatory effects of TRH. However, the duodenal smooth muscle effect of TRH was attenuated due to rapid homologous tachyphylaxis not related to breakdown of TRH.