Coffee has hepatoprotective benefits in Brazilian patients with chronic hepatitis C even in lower daily consumption than in American and European populations

The potential role of coffee as a hepatoprotective substance for chronic liver diseases has been widely discussed. Our main aim was to evaluate the effect of coffee intake regarding clinical, biochemical tests and liver biopsy data in treatment naïve patients with chronic hepatitis C. One hundred and thirty-six patients with chronic hepatitis C, diagnosed through liver biopsy, or by means of clinical, ultrasound or endoscopic signs of cirrhosis, were assessed by determination of biochemical tests, metabolic and morphological alterations. Food frequency was scrutinized by using a structured questionnaire. Coffee intake represented more than 90% of the total daily caffeine, and the 75th percentile was 4-Brazilian coffee-cup/day (≥255 mL/day or ≥123 mg caffeine/day). According to caffeine intake, patients were divided into two groups (< or ≥123 mg caffeine/day). Patients with higher ingestion of caffeine had lower serum levels of aspartate aminotransferase (× upper limit of normal) (1.8 ± 1.5 vs 2.3 ± 1.5, p = 0.04), lower frequencies of advanced (F3, F4) fibrosis (23.5% vs 54.5%, p < 0.001) and of histological activity grade (A3, A4) observed in liver biopsies (13.8% vs 36.9%, p < 0.001). By multivariate logistic regression, fibrosis was independently associated with caffeine intake (OR– 0.16; 95%CI – 0.03–0.80; p = 0.026), γ-glutamil transferase serum levels and morphological activity. But only fibrosis was associated with histological activity. In conclusion caffeine consumption greater than 123 mg/day was associated with reduced hepatic fibrosis. In addition, this study supports the assumption that coffee intake has hepatoprotective benefits for Brazilian patients with chronic hepatitis C, even in lower doses than that of American and European population intake.     

Telomere dysfunction in peripheral blood mononuclear cells from patients with primary biliary cirrhosis

BackgroundChromosomal instability in peripheral blood mononuclear cells has a role in the onset of primary biliary cirrhosis. We hypothesized that patients with primary biliary cirrhosis may harbour telomere dysfunction, with consequent chromosomal instability and cellular senescence.AimTo evaluate the clinical significance of telomerase activity and telomere length in peripheral blood mononuclear cells from patients with primary biliary cirrhosis.Study designIn this population-based case control study, 48 women with primary biliary cirrhosis (25 with cirrhosis), 12 with chronic hepatitis C matched by age and severity of disease, and 55 age-matched healthy women were identified. Mononuclear cells from the peripheral blood of patients and controls were isolated. Telomere length and telomerase activity were measured.ResultsTelomere length and telomerase activity did not differ between cases (5.9 ± 1.5 kb) and controls (6.2 ± 1.4 kb, p_c = 0.164). Telomere shortening and advanced-stage disease strongly correlated with telomerase activity. Patients with advanced disease retained significantly less telomerase activity than those with early-stage disease (0.6 ± 0.9 OD vs. 1.5 ± 3.7 OD, p = 0.03). Telomere loss correlated with age, suggesting premature cellular ageing in patients with primary biliary cirrhosis.ConclusionOur data strongly support the telomere hypothesis of human cirrhosis, indicating that telomere shortening and telomerase activity represent a molecular mechanism in the evolution of human cirrhosis in a selected population of patients.     

Blood levels of glucose and insulin and insulin resistance in patients with schizophrenia on clozapine monotherapy

ObjectiveWe tested the hypothesis that fasting blood glucose and insulin levels are higher in schizophrenic subjects on clozapine monotherapy compared with healthy controls and they correlate with anthropometric measurements, laboratory tests and body composition.MethodsData for 24 subjects with schizophrenia treated with clozapine and 24 age- and sex-matched healthy volunteers was analyzed.ResultsPatients taking clozapine had higher fasting levels of glucose (103.5 ± 31.6 vs. 87.8 ± 11.7 mg/dL, z = −2.03, p = 0.04), there was no difference for insulin concentrations and markers of insulin resistance. In the clozapine group glucose levels correlated with clozapine dose (R = −0.43, p = 0.03), while insulin levels correlated with weight (R = 0.66, p < 0.001), body mass index (R = 0.54, p = 0.007), abdominal (R = 0.53, p = 0.007) and waist (R = 0.43, p = 0.04) circumference, total body fat (R = 0.51, p = 0.01), and uric acid levels (R = 0.50, p = 0.01). In the clozapine group insulin levels were lower in subjects with body mass index <25 kg/m² (7.0 ± 3.3 vs. 13.4 ± 8.8 μU/mL, p = 0.04) and in subjects without abdominal obesity (6.3 ± 2.4 vs. 13.3 ± 8.6 μU/mL, p = 0.03).ConclusionsWe found higher blood glucose levels in subjects taking clozapine and no differences in blood insulin levels between subjects with schizophrenia and controls. Associations between blood insulin levels and abdominal/waist circumferences support the role of abdominal obesity as an important risk factor of insulin resistance.     

Strong correlation by ultrasonography of hepatomegaly and the presence of co-infection in HIV/HCV cirrhotic patients

ObjectivesProgression of hepatic fibrosis is accelerated in patients co-infected with human immunodeficiency virus and hepatitis C virus compared to hepatitis C virus mono-infected patients. This study aimed to compare ultrasound features and selected clinical and biochemical variables between patients with human immunodeficiency virus/hepatitis C virus co-infection (n = 16) versus hepatitis C virus mono-infection (n = 16).MethodsEach patient underwent abdominal ultrasound, and a specific evaluation was performed in order to detect findings consistent with chronic liver disease. Characterization of spleen size, liver structural pattern, diameter of the portal, spleen, and mesenteric veins was based on classical ultrasound parameters. Propensity score was used for control of selection bias and performed using binary logistic regression to generate a score for each patient. The Fisher and Mann–Whitney tests were used to evaluate categorical variables and continuous variables, respectively.ResultsOn univariate analysis right hepatic lobe size was larger in human immunodeficiency virus/hepatitis C virus patients (157.06 ± 17.56 mm) compared to hepatitis C virus mono-infected patients (134.94 ± 16.95 mm) (p = 0.0011). The left hepatic lobe was also significantly larger in human immunodeficiency virus/hepatitis C virus patients (115.88 ± 22.69 mm) versus hepatitis C virus mono-infected patients (95.06 ± 24.18 mm) (p = 0.0177). Also, there was a strong correlation between hepatomegaly and co-infection (p = 0.005).ConclusionHuman immunodeficiency virus infection was the primary variable influencing liver enlargement in this population. Hepatomegaly on ultrasound was more common among cirrhotic human immunodeficiency virus/hepatitis C virus co-infected patients than among cirrhotic hepatitis C virus mono-infected patients. This aspect is very important in the management of human immunodeficiency virus/hepatitis C virus co-infected patients, because screening for hepatocellular carcinoma is necessary in this population.     

Pre-diabetes in overweight youth and early atherogenic risk

PurposeTo compare atherogenic lipoprotein particles and vascular smooth muscle biomarkers in overweight youth with pre-diabetes (PD) vs. normal glucose tolerance (NGT).Methods144 adolescents (60 black, 84 white; 102 female; PD = 45, NGT = 99) aged 10–19 years underwent a fasting blood draw and 2-h OGTT. Lipoprotein particle size and subclass concentration and vascular smooth muscle biomarkers (ICAM-1, VCAM-1 and E-selectin) were compared between youth with PD and NGT.ResultsCompared with NGT, PD adolescents had smaller LDL (mean ± SE: 20.5 ± 0.1 vs. 21.0 ± 0.1 nm; P = 0.002) and HDL (8.62 ± 0.05 vs. 8.85 ± 0.04 nm; P = 0.013) size and elevated medium small (159.2 ± 10.3 vs. 123.8 ± 6.4 nmol/L; P = 0.037) and very small (626.3 ± 45.4 vs. 458.5 ± 26.4 nmol/L; P = 0.032) LDL particle concentrations, after adjustment for race and BMI. Further adjusting for fasting insulin or visceral adiposity obviated these differences between the groups except for LDL size. ICAM-1 and E-selectin did not differ in youth with PD but correlated with LDL and HDL size, and small LDL particle concentrations.ConclusionsOverweight adolescents with PD have an atherogenic lipoprotein profile of small LDL and HDL size and increased concentrations of small LDL, moderated by insulin resistance and visceral adiposity, but independently driven by dysglycemia for LDL size. Associations between smooth muscle biomarkers and lipoproteins could be an early signal heralding the atherogenic process. It remains to be determined if correction of dysglycemia and associated lipoprotein abnormalities in obese youth could prove effective in halting this process.     

Levels of plasma cell-free DNA and its correlation with disease activity in rheumatoid arthritis and systemic lupus erythematosus patients

BackgroundCell free deoxyribonucleic acid (cf-DNA) is now emerging as a useful tool for non-invasive diagnostic methods related to a wide range of clinical conditions including autoimmune diseases.Aim of the workTo estimate the concentration of plasma cf-DNA in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) patients compared with healthy subjects and to correlate the results with clinical and laboratory parameters of disease activity.Patients and methodsThe study included 30 RA patients, 35 SLE patients and 25 matched control. Plasma cf-DNA was estimated by real-time quantitative PCR. Disease activity parameters for each disease were assessed; Disease Activity Score-28 (DAS28) was used for RA and SLE disease activity index 2000 (SLEDAI-2K) for SLE patients.ResultsThe RA patients (F:M 4:1) had a mean age of 36.8 ± 9.6 years and disease duration of 8.3 ± 1.1 years while the SLE patients (F:M 7.75:1) had a mean age of 35.6 ± 8.8 years and disease duration of 8.1 ± 0.87 years. There was a highly significant increase in the cf-DNA level in SLE patients (17.33 ± 2.4 ng/ml) and RA patients (11.15 ± 2.3 ng/ml) compared to the level in the control (4.15 ± 1.4 ng/ml) (p = 0.0005). The cf-DNA significantly correlated with the erythrocyte sedimentation rate (ESR) (p = 0.04), C-reactive protein (p = 0.04) and the DAS28 (p = 0.005) in the RA patients and with the ESR (p = 0.03), anti-ds-DNA (p = 0.008), complement-4 (p = 0.04) and SLEDAI-2K (p = 0.002).ConclusionThe increased cf-DNA implicates a possible role in the pathogenesis of both RA and SLE and appears to be a useful marker of disease activity in addition to other laboratory tests.     

Pilot trial of diabetes self-management education in the hospital setting

AimsDiabetes self-management education (DSME) is recommended for all patients with diabetes. Current estimates indicate that <50% of patients receive DSME, increasing risk for hospitalization which occurs more frequently with diabetes. Hospitalization presents opportunities to provide DSME, potentially decreasing readmissions. To address this, we investigated the feasibility of providing DSME to inpatients with diabetes.MethodsPatients hospitalized on four medicine units were randomized to receive DSME (Education Group) (n = 9) prescribed by a certified diabetes educator and delivered by a registered nurse, or Usual Care (n = 12). Participants completed Diabetes Knowledge Tests (DKT), Medical Outcomes Short Form (SF-36), Diabetes Treatment Satisfaction Questionnaire (DTSQ), and the DTSQ-inpatient (DTSQ-IP). Bedside capillary blood glucoses (CBG) on day of admission, randomization and discharge were compared.ResultsThere were no group differences in demographics, diabetes treatment, admission CBG (186 ± 93 mg/dL vs. 219 ± 84 mg/dL, p = 0.40), DKT scores (Education vs. Usual Care 48 ± 25 vs. 68 ± 19, p = 0.09), SF-36, and DTSQ scores (28 ± 6 vs. 25 ± 7, p = 0.41). Patients receiving education reported more satisfaction with inpatient treatment (83 ± 13 vs. 65 ± 19, p = 0.03), less hyperglycemia prior to (2.7 ± 4.5 vs. 4.5 ± 1.4, p = 0.03) and during hospitalization (3.9 ± 1.9 vs. 5.5 ± 1.2, p = 0.04); and had lower mean discharge CBG (159 ± 38 mg/dL vs. 211 ± 67 mg/dL, p = 0.02).ConclusionsInpatient diabetes education has potential to improve treatment satisfaction, and reduce CBG.     

No impact of interleukin-28B polymorphisms on spontaneous or drug-induced hepatitis delta virus clearance

Backgroundrs12979860 and rs8099917 interleukin-28B polymorphisms are associated with spontaneous or interferon-alpha induced hepatitis C clearance, “CC” and “TT” genotypes (respectively) being the most favourable. There are no data on the influence of interleukin-28B polymorphisms on hepatitis delta clearance in hepatitis B/D co-infected patients.AimsThe present study explores the potential influence of both rs12979860 and rs8099917 polymorphisms on delta infection outcome.MethodsRetrospective-longitudinal study on 55 European patients observed for at least 4 years, selected from a cohort of 439 subjects positive for hepatitis delta antibodies and hepatitis B core antibodies.The rate of spontaneous and interferon induced delta-RNA clearance was compared in interleukin-28B rs12979860 “CC” vs “non CC”, and in rs8099917 “TT” vs “non TT” genotypes.ResultsPrevalence of rs12979860 C allele was 60%, consistent with the reported prevalence in Italy (67%, p = 0.128). No significant differences in spontaneous clearance rate were observed between rs12979860 “CC” and “non CC” genotypes (13.3% vs 7.5%, respectively, p = 0.60), and between rs8099917 “TT” and “non-TT” genotypes (11.1 vs 7.1%, respectively, p = 0.67). No differences were observed for interferon-induced delta-RNA clearance either.ConclusionsOur data suggest that interleukin-28B polymorphisms might not influence hepatitis delta clearance rate in either natural history or interferon-alpha response.     

Paraoxonase 1 gene (Gln192–Arg) polymorphism and the risk of coronary artery disease in type 2 diabetes mellitus

BackgroundParaoxonase 1 (PON1) is reported to have antioxidant and cardioprotective properties. Recently, an association of glutamine (Gln) or type A/arginine (Arg) or type B polymorphism at position 192 of PON1 gene has been suggested with coronary artery disease (CAD) among patients with diabetes mellitus (DM). However, conflicting results have also been reported.ObjectivesTo investigate the relationship between PON1 gene (Gln¹⁹²–Arg) polymorphism and the presence, extent and severity of CAD in type 2 DM.MethodsThe study comprised 180 patients recruited from those undergoing coronary angiography for suspected CAD, who were divided according to the presence or absence of CAD and DM into four groups: Group I (n = 40 patients) nondiabetic subjects without CAD, Group II (n = 45 patients) diabetic patients without CAD, Group III (n = 47 patients) nondiabetic patients with CAD and Group IV (n = 48 patients) diabetic patients with CAD. PON1(Gln¹⁹²–Arg) genotype was assessed using polymerase chain reaction (PCR) followed by AlwI digestion.ResultsThe frequency of Gln allele (type A) was significantly higher in Group I and Group II compared to Group III and Group IV (62.5%, 60% vs. 38.3%, 31.25%, respectively, p < 0.001) while the frequency of Arg allele (type B + type AB) was significantly higher in ischemic groups (III and IV) compared to nonischemic groups (I and II) (61.7%, 68.75% vs. 37.5%, 40%, respectively, p < 0.001). Patients with CAD and DM (Group IV) have significantly higher severity score and vessel score than those with CAD only (Group III) (9.7 ± 2.97, 2.44 ± 0.56 vs. 6.99 ± 3.71, 1.67 ± 0.89, respectively, p < 0.001) Patients with vessel score 3 had significantly higher severity score and higher Arg allele frequency than patients with vessel score 2, the latter group had also significantly higher severity score and Arg allele frequency than patients with vessel score 1 (8.9 ± 2.79 vs. 5.21 ± 2.13 and 80.49% vs. 67.86%), (5.21 ± 2.13 vs. 3.11 ± 0.89 and 67.86% vs. 53.85%), p < 0.001 for all. In multivariate logistic regression analysis of different variables for prediction of CAD, age [OR 2.99, CI (1.11–10.5), p < 0.01], smoking [OR 4.13, CI (1.37–11.7), p < 0.001], low-density lipoprotein (LDL) cholesterol > 100 mg/dL [OR 4.31, CI (1.25–12.5), p < 0.001], high-density lipoprotein (HDL) cholesterol < 40 mg/dL [OR 5.11, CI (1.79–16.33), p < 0.001] and PON1 192 Arg allele [OR 4.62, CI (1.67–13.57), p < 0.001] were significantly independent predictors of CAD.ConclusionArg allele of PON1 192 gene polymorphism is an independent risk factor for CAD and is associated not only with the presence of CAD but also with its extent and severity and its impact is clearly more pronounced in diabetic patients.     

Metabolic disturbances after acute vascular events: A comparative study of acute coronary syndrome and ischaemic atherothrombotic stroke

ObjectiveThis pilot study aimed to compare metabolic disturbances, particularly insulin resistance (IR) and cardiovascular risk factors (CRFs), following two types of acute vascular atherothrombotic disease events: ischaemic atherothrombotic stroke (AS); and acute coronary syndrome (ACS).Design and methodsA total of 110 non-diabetic patients presenting with either AS (n = 55) or ACS (n = 55) were included in our prospective comparative study, and matched for age and gender. IR was determined using the homoeostasis model assessment of insulin resistance (HOMA-IR) method, and each patient's personal and family history were also recorded.ResultsIR was significantly higher in the ACS vs AS group (HOMA-IR index 2.17 ± 1.90 vs 1.50 ± 0.81, respectively; P = 0.03). The AS group had a significantly higher prevalence of personal history of hypertension (51% vs 31%; P = 0.03), while current smoking was more prevalent in the ACS group (30% vs 18%; P = 0.04). There were no significant differences between the two groups as regards any other CRFs.ConclusionThe distribution of CRFs varied depending on the vascular event, and metabolic disturbances differed according to the atherothrombotic disease. IR was greater after ACS than AS.     

Effects of adipose tissue distribution on maximum lipid oxidation rate during exercise in normal-weight women

AimFat mass localization affects lipid metabolism differently at rest and during exercise in overweight and normal-weight subjects. The aim of this study was to investigate the impact of a low vs high ratio of abdominal to lower-body fat mass (index of adipose tissue distribution) on the exercise intensity (Lipox_max) that elicits the maximum lipid oxidation rate in normal-weight women.MethodsTwenty-one normal-weight women (22.0 ± 0.6 years, 22.3 ± 0.1 kg.m⁻²) were separated into two groups of either a low or high abdominal to lower-body fat mass ratio [L-A/LB (n = 11) or H-A/LB (n = 10), respectively]. Lipox_max and maximum lipid oxidation rate (MLOR) were determined during a submaximum incremental exercise test. Abdominal and lower-body fat mass were determined from DXA scans.ResultsThe two groups did not differ in aerobic fitness, total fat mass, or total and localized fat-free mass. Lipox_max and MLOR were significantly lower in H-A/LB vs L-A/LB women (43 ± 3% VO_2max vs 54 ± 4% VO_2max, and 4.8 ± 0.6 mg min⁻¹ kg FFM⁻¹ vs 8.4 ± 0.9 mg min⁻¹ kg FFM⁻¹, respectively; P < 0.001). Total and abdominal fat mass measurements were negatively associated with Lipox_max (r = –0.57 and r = –0.64, respectively; P < 0.01) and MLOR [r = –0.63 (P < 0.01) and r = –0.76 (P < 0.001), respectively].ConclusionThese findings indicate that, in normal-weight women, a predominantly abdominal fat mass distribution compared with a predominantly peripheral fat mass distribution is associated with a lower capacity to maximize lipid oxidation during exercise, as evidenced by their lower Lipoxmax and MLOR.     

Hyoscine N-butylbromide for adenoma detection during colonoscopy: A randomized,double-blind,placebo-controlled study

BackgroundHyoscine N-butylbromide (HBB), commonly used during colonoscopy to facilitate cecal intubation, has been proposed to increase the adenoma detection rate (ADR).AimsTo evaluate whether HBB administration increases the adenoma detection rate and influences patients’ tolerance.MethodsConsecutive colonoscopy outpatients were randomized after cecal intubation to receive either 20 mg HBB or placebo i.v. The number, size, histology and location of polyps were recorded. The air retained in the abdomen was either indirectly estimated by ΔAC (difference in the abdominal circumference measured before and after colonoscopy) or directly evaluated by patients’ perception (visual analogic scale, range 0–100).Results402 patients (44% male; mean age 57.7 ± 12.5 years) received either HBB or placebo. No differences in ADR (31.7% vs. 28%, p = 0.48), advanced-ADR (7.4% vs. 10.5%, p = 0.35) were observed between HBB and placebo group, respectively. A significantly lower detection rate of flat/depressed lesions was observed in the HBB group (0.5% vs. 5.5%, p = 0.003). The ΔAC and the bloating perception were comparable between the two groups (p = 0.22 and p = 0.48, respectively).ConclusionsHBB administered before colonoscope withdrawal does not increase adenoma detection rate and seems to hamper the visualization of flat/depressed lesions. This finding raises concerns on the indiscriminate use of HBB during colonoscopy.     

Angiopoietin-2 as a biomarker for metabolic syndrome and disease activity in rheumatoid arthritis patients

BackgroundThe incidence of metabolic syndrome (MetS) increases in rheumatoid arthritis (RA) patients which increases the risk of cardiovascular disease (CVD). Angiopoietin-2 levels increase in RA and were reported to predict CVD.Aim of the workTo assess the level of angiopoietin-2 in RA patients and study its relation to disease activity and its role in those with MetS.Patients and methodsThe study included 80 RA patients (67 females and 13 males) and 20 healthy age and sex matched controls. The patients were divided into Group 1 (n = 40) with MetS and Group 2 (n = 40) without. Data were collected throughout history, basic clinical examination and investigation. Disease activity score (DAS-28) was assessed in all patients. Enzyme linked immunosorbent assay was used for the estimation of angiopoietin-2.ResultsThe age and disease duration of those with MetS (40.7 ± 7.23 years and 9.63 ± 6.73 years respectively) and those without (38.6 ± 9.2 and 8.65 ± 5.52 years respectively) were comparable (p = 0.26 and p = 0.48 respectively). The disease activity (DAS-28) was also similar in both groups (5.12 ± 0.77 and 5.01 ± 0.96 respectively; p = 0.56). There was a significant increase in the angiopoietin-2 levels in RA patients with MetS (5.31 ± 0.56 ng/ml) than those without (4.93 ± 0.44 ng/ml) (p < 0.001). The levels were significantly higher than those of the control (4.44 ± 0.29 ng/ml) (p < 0.001). The angiopoietin-2 level significantly correlated with the DAS-28 (r = 0.23, p = 0.045), systolic (r = 0.36, p = 0.001) and diastolic blood pressure (r = 0.35, p = 0.001), fasting blood sugar (r = 0.29, p = 0.009) and triglycerides (r = 0.24, p = 0.03).ConclusionsAngiopoietin-2 can be used as a biomarker of MetS and disease activity in RA patients. This could point to those RA patients at risk of developing CVDs.     

Hyperdynamic circulatory syndrome in a mouse model transgenic for SerpinB3

Introduction and objectivesSerpinB3 is a cysteine protease inhibitor involved in several biological activities. It is progressively expressed in chronic liver disease, but not in normal liver. The role in vascular reactivity of this serpin, belonging to the same family of Angiotensin II, is still unknown. Our aim was to evaluate the in vivo and in vitro effects of SerpinB3 on systemic and splanchnic hemodynamics.Material and methodsDifferent hemodynamic parameters were evaluated by ultrasonography in two colonies of mice (transgenic for human SerpinB3 and C57BL/6J controls) at baseline and after chronic carbon tetrachloride (CCl₄) treatment. In vitro SerpinB3 effect on mesenteric microvessels of 5 Wistar-Kyoto rats was analyzed measuring its direct action on: (a) preconstricted arteries, (b) dose–response curves to phenylephrine, before and after inhibition of angiotensin II type 1 receptors with irbesartan. Hearts of SerpinB3 transgenic mice and of the corresponding controls were also analyzed by morphometric assessment.ResultsIn SerpinB3 transgenic mice, cardiac output (51.6 ± 21.5 vs 30.1 ± 10.8 ml/min, p = 0.003), hepatic artery pulsatility index (0.85 ± 0.13 vs 0.65 ± 0.11, p < 0.001) and portal vein blood flow (5.3 ± 3.2 vs 3.1 ± 1.8 ml/min, p = 0.03) were significantly increased, compared to controls. In vitro, recombinant SerpinB3 had no direct hemodynamic effect on mesenteric arteries, but it increased their sensitivity to phenylephrine-mediated vasoconstriction (p < 0.01). This effect was suppressed by inhibiting angiotensin II type-1 receptors.ConclusionsIn transgenic mice, SerpinB3 is associated with a hyperdynamic circulatory syndrome-like pattern, possibly mediated by angiotensin receptors.     

Assessment of the acute impact of normobaric hypoxia as a part of an intermittent hypoxic training on heart rate variability

AimTo assess the dynamics of ANS by means of heart rate variability (HRV) during and after acute exposure to normobaric hypoxia, representing a single session of an intermittent hypoxic training protocol.Material and methodsTwenty four healthy males aged 28.0 ± 7.2 (mean ± SD) breathed hypoxic air (FIO2 = 12.3 ± 1.5%) for one hour delivered via hypoxicator (AltiPro 8850 Summit+, Altitude Tech, Canada). Pulse oximetry and HRV were measured before, during and after the hypoxic exposure.ResultsAt the end of the hypoxic session all of the tested subjects had higher low frequency (lnLF) (6.9 ± 1.1 ms² vs. 7.5 ± 1.1 ms²; p = 0.042), LF/HF (1.5 ± 0.8 vs. 3.3 ± 2.8; p = 0.007) and standard deviation 2 of the Poincaré plot (SD2) (92.8 ± 140.0 ms vs. 120.2 ± 54.2 ms; p = 0.005) as well as increase in the Total power (7.7 ± 1.1 ms² vs. 8.1 ± 1.2 ms²; p = 0.032) and the Standard deviation of normal-to-normal interbeat intervals (SDNN) (57.3 ± 31.0 ms vs. 72.3 ± 41.1 ms; p = 0.024) but lower Sample entropy (SampEn) (1.6 ± 0.2 vs. 1.4 ± 0.2; p = 0.010). Immediately after the hypoxic exposure LF/HF lowered (3.3 ± 2.8 vs. 2.2 ± 1.8; p = 0.001) but lnHF significantly increased (6.6 ± 1.4 ms² vs. 7.1 ± 1.3 ms²; p = 0.020).ConclusionAcute normobaric hypoxia as a part of a single session of an intermittent hypoxic training protocol leads to changes in the activity of the ANS. The sympathetic tone prevails during hypoxic exposure and parasympathetic tone increases immediately after the hypoxic factor is withdrawn.     

Evaluation of microalbuminuria in patients with systemic sclerosis as an indicator of early renal damage and increased morbidity

IntroductionRenal involvement and systemic vascular damage have been shown to be significantly affecting prognosis in systemic sclerosis.Aim of workMicroalbuminuria detection in SSc patients as an indicator of early renal involvement and its correlation with various SSc clinical, laboratory parameters and severity of organ systems’ damage assessed by Scleroderma Assessment Questionnaire.Patients and methodsForty SSc patients (33 females and 7 males) with mean age of 27.48 ± 12.56 years and mean disease duration of 6.2 ± 4.14 years were included. Twenty-four (60%) had lSSc; 13 (32.5%) had dSSc and 3 (7.5%) patients had SSc sine scleroderma.ResultsEight (20%) had microalbuminuria and 9 (22.5%) patients had decreased creatinine clearance. Albumin/creatinine ratio was significantly higher among dSSc patients compared to those with lSSc and SSc sine scleroderma (X² = 9.077; p = 0.01). Albumin/creatinine ratio showed significant positive correlations with telangiectasia (r = 0.322; p = 0.04) and mRodnan’s skin score (r = 0.352; p = 0.026) and negative correlations with inter-incisor distance (r = ?0.525; p = 0.001) and pleurisy (r = ?0.446; p = 0.004). Albumin/creatinine ratio correlated significantly and positively with IMSS and IDS indices of SAQ (r = 0.378, 0.32; p = 0.016, 0.044, respectively). SSc patients with microalbuminuria showed significantly higher mean IDS than those without (1.058 vs. 0.631, p = 0.04). No statistically significant correlations were found between creatinine clearance and the different demographic, clinical features and the indices of SAQ.ConclusionMicroalbuminuria compared to creatinine clearance may be a more sensitive indicator of early renal affection and predictor of increased morbidity.     

Association between C-reactive protein level and echocardiography assessed left ventricular function in first ST-segment elevation myocardial infarction patients who underwent primary coronary intervention

BackgroundAn elevated C-reactive protein (CRP) level is associated with adverse outcomes in patients with acute myocardial infarction (AMI). Although CRP levels have been shown to be associated with left ventricular (LV) systolic function and remodeling in AMI, little is known about their relation to early LV diastolic function.MethodsWe retrospectively studied 173 consecutive patients <75 years of age with first ST-segment elevation MI (STEMI) that was treated by primary percutaneous coronary intervention (PPCI). They had presented within 24 h of chest pain onset and their CRP levels were determined within 6 h of hospital admission. They all underwent echocardiography within 3 days of admission and were stratified by CRP tertiles.ResultsThe cut-off points for the CRP tertiles were <2.6 mg/L, 2.6–7.9 mg/L, and >7.9 mg/L. Patients with higher CRP levels had a significantly higher mean mitral inflow E wave velocity (68 ± 16 cm/s vs 77 ± 19 cm/s vs 76 ± 17 cm/s; p = 0.02), a higher E/average e′ (8.9 ± 1.9 vs 9.8 ± 2.8 vs 10.4 ± 3.2; p = 0.02), and a higher systolic pulmonary artery pressure (27 ± 6 mmHg vs 30 ± 8 mmHg vs 32 ± 10 mmHg; p = 0.04). Elevated CRP levels were associated with more advanced diastolic dysfunction than normal CRP levels (p = 0.04). The admission CRP level was an independent predictor of average E/e′ ratio (multivariate analysis).ConclusionAdmission CRP levels are associated with echocardiographic parameters of elevated LV filling pressure in patients with STEMI treated with PPCI.     

Switching fibrate to statin in type 2 diabetic patients: Consequences on lipid profile

Interest of statins in terms of morbid-mortality reduction in primary and secondary prevention in type 2 diabetic patients has broadly been proven in recent studies, while evidence for fibrates preventive effect is considerably weaker. HMGCoA reductase inhibitors are known to decrease low density lipoprotein cholesterol (LDL C) in a greater extension than triglycerides (TG). In type 2 diabetic patients, the dyslipidemic profile is commonly associated with reduced high-density lipoproteins (HDL C), increased TG and normal or mildly elevated LDL C.Patients and methodsType 2 diabetic outpatients (n = 45) treated with fibrate with or without history of cardiovascular disease were included. Mean age was 57.7 ± 13.2 yr, sex ratio was 16/39 (F/M), and BMI was 29.3 ± 4.4 kg/m². Non-inclusion criteria were TG ≥ 3.5 g/L and intolerance to statins or a combined lowering lipid therapy. Serum lipid profile, HbA_1c and creatin kinase (CK) were assessed under treatment with fibrate, then after a 3-month wash-out period, and after a 6-month treatment with a low dose of atorvastatin (10 mg/day).ResultsAfter a 3-month wash-out period, total cholesterol (TC) was 1.98 ± 0.31 g/L (m ± SD), TG 1.63 ± 1.09 g/L, HDL C 0.46 ± 0.12 g/L, and LDL C 1.22 ± 0.31 g/L. Comparing lipid profile with atorvastatin vs fibrate, we observed a significant decrease in TC and LDL C (1.56 vs 1.79 g/L P = 0.001, and 0.84 vs 1.09 g/L, P = 0.001, respectively). No significant difference between treatments was observed for TG (1.35 vs 1.17 g/L, P = 0.06), and HDL C (0.44 vs 0.48 g/L, P = 0.15). When treated with atorvastatin, 90% of patients achieved a LDL C < 1 g/L, compared to 51% when treated with fibrate (P = 0.001). HbA_1c remained about 7.6 ± 1.5%, and CK in the normal range.ConclusionIn well-controlled type 2 diabetic patients previously treated with fibrate, short-term (6 months) treatment with low-dose atorvastatin (10 mg/day) improves TC and LDL C levels, without any alteration in TG and HDL C levels.     

Sexual dimorphism in growth and insulin-like growth factor-I in children with type 1 diabetes mellitus

ObjectiveImpaired linear growth and reduced IGF-I levels in children with type 1 diabetes (T1DM) have been related to poor metabolic control. The aim of this study was to identify additional factors which may negatively affect growth and IGF system in patients with T1DM.DesignNinety-one T1DM children (54 males, age = : 11.73 ± 3 years, disease duration = 5.6 ± 2.1 years) were studied. All children were on intensive insulin therapy: 62 children were on multiple injection therapy (MI) and 29 children on continuous subcutaneous insulin infusion (CSII).ResultsHeight velocity (HV) SDS and IGF-I levels were higher in females and in pubertal children [HV SDS: females = 0.6 ± 2.4 vs males = − 0.45 ± 2.3 (p = 0.04); IGF-I SDS: females = − 1.09 ± 0.58 vs males = − 1.4 ± 0.6 (p = 0.02); IGF-I/IGFBP-3 molar ratio: females = 0.25 ± 0.1 vs males = 0.21 ± 0.08 (p = 0.04); IGF-I SDS: pre-pubertal = − 1.58 ± 0.46 vs pubertal = − 1.15 ± 0.65 (p < 0.001); IGF-I/IGFBP-3 molar ratio: pre-pubertal = 0.16 ± 0.08 vs pubertal = 0.26 ± 0.09 (p < 0.001)]. No differences between children on CSII or MI therapy were found. IGF-I SDS was positively related to C peptide level (p < 0.001), puberty (p < 0.001) and female gender (p = 0.02) and negatively related to HbA1c (p = 0.04). IGF-I/IGFBP-3 molar ratio was positively affected by C peptide level (p < 0.001), puberty (p < 0.001) and daily insulin dose (p < 0.001).ConclusionsOur results indicate that despite intensive insulin therapy, T1DM still negatively affects IGF-I secretion and linear growth. Growth impairment is more severe in males and primarily related to poor glycemic control and loss of the residual beta cell mass.     

Interleukin-27 and its relation to disease parameters in SLE patients

IntroductionIL-27 exerts profound anti-inflammatory effects in several experimental autoimmune models, suggesting that it may be therapeutically relevant in SLE.Aim of the workTo evaluate IL-27 level in SLE patients and its association to clinical manifestations, disease activity parameters and management strategy.Patients and methodsWe studied 80 SLE patients and 50 controls in a cross sectional study. Demographic, clinical and serological data were evaluated. Systemic lupus erythematosus disease activity index (SLEDAI) and Systemic Lupus International Collaboration Clinics/ACR damage index (SLICC) were assessed. Serum IL-27 was measured by ELISA.ResultsThere was statistically significant difference in IL-27 level in SLE patients and healthy controls (9.7 ± 21.9 pg/ml vs 20.2 ± 47.3 pg/ml in SLE vs controls, respectively) (p = 0.04), also it was found that IL-27 level was statistically significantly lower in SLE patients with lupus nephritis (p = 0.02) and cerebritis (p = 0.03). Interleukin 27 level had a statistically significant negative correlation with the cumulative dose of hydroxychloroquine and azathioprine (r = ?0.3, p = 0.03 and r = ?0.3 and p = 0.04, respectively).ConclusionIL-27 has anti-inflammatory effect in SLE patients especially those without nephritis or cerebritis and can be therapeutically relevant in SLE. To confirm our results we propose larger scale, multicentre studies with longer evaluation periods.