Is there any link between insulin resistance and inflammation in established preeclampsia?

Both insulin resistance and inflammation may contribute to the onset of preeclampsia. They also could be interrelated. We studied the relationship between inflammatory cytokines and markers of insulin resistance. During their third trimester, 22 proteinuric preeclamptic women and 16 normotensive controls underwent intravenous glucose tolerance test (minimal model). Preeclamptic women were more insulin-resistant (P = .009), and they had higher levels of serum soluble tumor necrosis alpha receptor II (TNFalpha RII) (P = .002), triglycerides (P = .006), uric acid (P = .001), and leptin (P = .002) than did the controls. However, the study groups did not differ in serum TNFalpha, C-reactive protein (CRP), interleukin-6 (IL-6), sex hormone-binding globulin (SHBG), and high-density lipoprotein-2 (HDL(2))-cholesterol. In multiple regression analysis only SHBG (P = .01) and triglycerides (P = .0036) were associated with insulin sensitivity independently of body mass index (BMI), weight gain, HDL(2)-cholesterol, CRP, TNFalpha, and TNFalpha RII, IL-6, and leptin. We conclude that insulin resistance and the inflammatory markers studied were not associated in established preeclampsia.     

Pleural effusion as the presenting feature of rheumatoid disease. The value of the level of complement in the pleural fluid. A propos of 2 cases

The authors report two cases of rheumatoid pleural effusion where the pleural syndrome preceded the joint manifestations. From a clinical standpoint, there was an effusion of moderate volume, pseudo-purulent in one case and straw coloured in the other. Signs of rheumatoid arthritis developed after a period of seven weeks in the first case and after a few days only in the second. Amongst the various characteristics of the pleural fluid which were analysed, the authors noted the value of a fall in glucose level, the lack of specificity of anti-gamma globulin factors, and the diagnostic value of the fall in pleural complement and its fractions. In view of the difficulty in obtaining specific histological proof by pleural biopsy, the reduced complement level is of valuable assistance in the aetiological diagnosis of rheumatoid pleural effusion, exceptional as a presenting feature.     

Sustained cardiomyocyte apoptosis and left ventricular remodelling after myocardial infarction in experimental diabetes

Aims/hypothesis Diabetes is known to reduce survival after myocardial infarction. Our aim was to examine whether diabetes is associated with enhanced cardiomyocyte apoptosis and thus interferes with the post-infarction remodelling process in myocardium in rat.Methods Four weeks after intravenous streptozotocin (diabetic groups) or citrate buffer (controls) injection, myocardial infarction was produced by ligation of left descending coronary artery. Level of cardiomyocyte apoptosis was quantified by TUNEL and caspase-3 methods. Collagen volume fraction and connective tissue growth factor were determined under microscope. Left ventricular dimensions were evaluated by echocardiography and planimetry.Results The number of apoptotic cardiomyocytes was equally high in diabetic and non-diabetic rats after 1 week from infarction. At 12 weeks after infarction the number of apoptotic cells was higher in the diabetic as compared to non-diabetic rats both in the border zone of infarction and in non-infarcted area. Correspondingly, left ventricular end diastolic diameter, relative cardiac weight, connective tissue growth factor-expression and fibrosis were increased in diabetic compared with non-diabetic rats with myocardial infarction.Conclusion/interpretation Sustained cardiomyocyte apoptosis, left ventricular enlargement, increased cardiac fibrosis and enhanced profibrogenic connective tissue growth factor expression were detected after myocardial infarction in experimental diabetes. Apoptotic myocyte loss could be an important mechanism contributing to progressive dilatation of the heart and poor prognosis after myocardial infarction in diabetes.Abbreviations STZ streptozotozin - MI myocardial infarction - CTGF connective tissue growth factor - LV left ventricular - LVEDD LV end-diastolic diameter - BNP B-type natriuretic peptide     

Renal and vascular effects of atrial natriuretic factor during cardiopulmonary bypass.

STUDY OBJECTIVE: To evaluate renal and vasodilator effects of synthetic atrial natriuretic factor (ANF) in patients undergoing cardiopulmonary bypass (CPB) with special reference to the applicability of ANF as a diuretic and natriuretic. DESIGN: The study consisted of two parts. The first 15 consecutive patients in a university hospital received a pharmacologically effective bolus dose of 100 micrograms ANF, as demonstrated previously in other studies, or placebo. After analysis of the bolus data (see "Results" section below), the 12 subsequent patients were administered ANF 50 micrograms as a constant 30-min infusion at a rate of 1.67 micrograms/min or placebo. PATIENTS: The patients were scheduled for elective coronary artery bypass grafting operation. There was no evidence of congestive heart failure in any patient, and no one had an endocrine or renal disorder. INTERVENTIONS: After achievement of hypothermia (29 to 30 degrees C of rectal temperature) during CPB, a bolus dose of ANF 100 micrograms was given or an infusion of ANF 1.67 micrograms/min for 30 min, ie, a total dose of 50 micrograms was started. The control patients received placebo correspondingly. Intravenous fluids were administered according to a predetermined scheme. MEASUREMENTS AND MAIN RESULTS: For the pharmacologic effects of ANF urine volume, urinary sodium excretion and mean arterial pressure (MAP) were measured. Only three of the eight patients receiving the bolus dose of ANF had a diuretic and natriuretic response to the drug, and the responses were significantly related (r = 0.91, p less than 0.05 and r = 0.98, p less than 0.001, respectively) to the prevailing MAP at the time of the bolus administration. The bolus dose of ANF decreased MAP significantly (p less than 0.001 vs placebo) from 65 +/- 6 (mean +/- SEM) to 55 +/- 6 mm Hg within 5 min. The infusion of ANF did not affect MAP, but it increased urine output (16.1 +/- 5.0 ml/min, when the data obtained during the 30-min infusion and a 30-min period after the infusion were combined) and urinary sodium excretion (1,651 +/- 514 microEq/min) significantly (p less than 0.05 and p less than 0.01, respectively) as compared with the corresponding values of 3.3 +/- 1.1 ml/min and 386 +/- 141 microEq/min after placebo. CONCLUSIONS: Prevailing arterial pressure is an important determinant of the diuretic and natriuretic activity of synthetic ANF in patients undergoing CPB. A low-dose infusion of ANF (50 micrograms within 30 min) provides diuresis and natriuresis without significant changes in MAP in these patients.     

Enhanced discrimination between threatening and safe contexts in high-anxious individuals

Trait anxiety, a stable personality trait associated with increased fear responses to threat, is regarded as a risk factor for the development and maintenance of anxiety disorders. Although the effect of trait anxiety has been examined with regard to explicit threat cues, little is known about the effect of trait anxiety on contextual threat learning. To assess this issue, extreme groups of low and high trait anxiety underwent a contextual fear conditioning protocol using virtual reality. Two virtual office rooms served as the conditioned contexts. One virtual office room (CXT+) was paired with unpredictable electrical stimuli. In the other virtual office room, no electrical stimuli were delivered (CXT−). High-anxious participants tended to show faster acquisition of startle potentiation in the CXT+ versus the CXT− than low-anxious participants. This enhanced contextual fear learning might function as a risk factor for anxiety disorders that are characterized by sustained anxiety.     

Microbiology of parapharyngeal abscesses in adults: in search of the significant pathogens

European Journal of Clinical Microbiology & Infectious Diseases - We aimed to describe the microbiology of parapharyngeal abscess (PPA) and point out the likely pathogens using the following...     

Low total haemoglobin mass, blood volume and aerobic capacity in men with type 1 diabetes

Blood O₂ carrying capacity affects aerobic capacity (VO_2max). Patients with type 1 diabetes have a risk for anaemia along with renal impairment, and they often have low VO_2max. We investigated whether total haemoglobin mass (tHb-mass) and blood volume (BV) differ in men with type 1 diabetes (T1D, n = 12) presently without complications and in healthy men (CON, n = 23) (age-, anthropometry-, physical activity-matched), to seek an explanation for low VO_2max. We determined tHb-mass, BV, haemoglobin concentration ([Hb]), and VO_2max in T1D and CON. With similar (mean ± SD) [Hb] (144 vs. 145 g l^?1), T1D had lower tHb-mass (10.1 ± 1.4 vs. 11.0 ± 1.1 g kg^?1, P < 0.05), BV (76.8 ± 9.5 vs. 83.5 ± 8.3 ml kg^?1, P < 0.05) and VO_2max (35.4 ± 4.8 vs. 44.9 ± 7.5 ml kg^?1 min^?1, P < 0.001) than CON. VO_2max correlated with tHb-mass and BV both in T1D (r = 0.71, P < 0.01 and 0.67, P < 0.05, respectively) and CON (r = 0.54, P < 0.01 and 0.66, P < 0.001, respectively), but not with [Hb]. Linear regression slopes were shallower in T1D than CON both between VO_2max and tHb-mass (2.4 and 3.6 ml kg^?1 min^?1 vs. g kg^?1, respectively) and VO_2max and BV (0.3 and 0.6 ml kg^?1 min^?1 vs. g kg^?1, respectively), indicating that T1D were unable to reach similar VO_2max than CON at a given tHb-mass and BV. In conclusion, low tHb-mass and BV partly explained low VO_2max in T1D and may provide early and more sensitive markers of blood O₂ carrying capacity than [Hb] alone.     

Evaluation of the Pharmacokinetic Interaction between Repeated Doses of Rifapentine or Rifampin and a Single Dose of Bedaquiline in Healthy Adult Subjects

This study assessed the effects of rifapentine or rifampin on the pharmacokinetics of a single dose of bedaquiline and its M2 metabolite in healthy subjects using a two-period single-sequence design. In period 1, subjects received a single dose of bedaquiline (400 mg), followed by a 28-day washout. In period 2, subjects received either rifapentine (600 mg) or rifampin (600 mg) from day 20 to day 41, as well as a single bedaquiline dose (400 mg) on day 29. The pharmacokinetic profiles of bedaquiline and M2 were compared over 336 h after the administration of bedaquiline alone and in combination with steady-state rifapentine or rifampin. Coadministration of bedaquiline with rifapentine or rifampin resulted in lower bedaquiline exposures. The geometric mean ratios (GMRs) and 90% confidence intervals (CIs) for the maximum observed concentration (C_max), area under the concentration-time curve to the last available concentration time point (AUC_0–t), and AUC extrapolated to infinity (AUC_0–inf) of bedaquiline were 62.19% (53.37 to 72.47), 42.79% (37.77 to 48.49), and 44.52% (40.12 to 49.39), respectively, when coadministered with rifapentine. Similarly, the GMRs and 90% CIs for the C_max, AUC_0–t, and AUC_0–inf of bedaquiline were 60.24% (51.96 to 69.84), 41.36% (37.70 to 45.36), and 47.32% (41.49 to 53.97), respectively, when coadministered with rifampin. The C_max, AUC_0–t, and AUC_0–inf of M2 were also altered when bedaquiline was coadministered with rifapentine or rifampin. Single doses of bedaquiline, administered alone or with multiple doses of rifapentine or rifampin, were well tolerated, with no safety concerns related to coadministration. Daily administration of rifapentine to patients with tuberculosis presents the same drug interaction challenges as rifampin and other rifamycins. Strong inducers of the cytochrome P450 isoenzyme CYP3A4 should be avoided when considering the use of bedaquiline. (This study is registered at clinicaltrials.gov under identifier {"type":"clinical-trial","attrs":{"text":"NCT02216331","term_id":"NCT02216331"}}NCT02216331.)     

The Cyclic Peptide Ecumicin Targeting ClpC1 Is Active against Mycobacterium tuberculosis In Vivo

Drug-resistant tuberculosis (TB) has lent urgency to finding new drug leads with novel modes of action. A high-throughput screening campaign of >65,000 actinomycete extracts for inhibition of Mycobacterium tuberculosis viability identified ecumicin, a macrocyclic tridecapeptide that exerts potent, selective bactericidal activity against M. tuberculosis in vitro, including nonreplicating cells. Ecumicin retains activity against isolated multiple-drug-resistant (MDR) and extensively drug-resistant (XDR) strains of M. tuberculosis. The subcutaneous administration to mice of ecumicin in a micellar formulation at 20 mg/kg body weight resulted in plasma and lung exposures exceeding the MIC. Complete inhibition of M. tuberculosis growth in the lungs of mice was achieved following 12 doses at 20 or 32 mg/kg. Genome mining of lab-generated, spontaneous ecumicin-resistant M. tuberculosis strains identified the ClpC1 ATPase complex as the putative target, and this was confirmed by a drug affinity response test. ClpC1 functions in protein breakdown with the ClpP1P2 protease complex. Ecumicin markedly enhanced the ATPase activity of wild-type (WT) ClpC1 but prevented activation of proteolysis by ClpC1. Less stimulation was observed with ClpC1 from ecumicin-resistant mutants. Thus, ClpC1 is a valid drug target against M. tuberculosis, and ecumicin may serve as a lead compound for anti-TB drug development.