Ultrasonographic evaluation of the calf muscle mass and architecture in elderly patients with and without sarcopenia

Background/objectivesTo sonographically assess the muscle mass and architecture of sarcopenic elderly subjects, and to explore the utility of ultrasound (US) measurements in predicting sarcopenia.MethodsOne hundred elderly subjects were enrolled in this cross-sectional study. Mean age value of our study population was 73.08 ± 6.18 years. The diagnosis of sarcopenia was confirmed by measuring fat-free mass index (using bioelectrical impedance analysis) and handgrip strength. Calf circumference was measured and US evaluations comprised bilateral gastrocnemius muscle (MG) thickness, fascicle length and pennate angles; subcutaneous fat and dermis thicknesses in the calf.ResultsBilateral muscle thickness and fascicle length values were significantly lower in patients with sarcopenia (both p < 0.05). Sarcopenic and nonsarcopenic subjects had similar pennate angles, subcutaneous fat and dermis thicknesses. Median thickness ratio (100 × t (MG)/[t (subcutaneous tissue) + t (dermis) + t (MG)]) values were 64% (40–88%) in the right and 64% (38–86%) in the left calf. Bilateral MG thickness and fascicle length values showed high sensitivity in predicting sarcopenia (all values > 76.92%).ConclusionsGastrocnemius muscle thickness and fascicle length values are lower in sarcopenic elderly and these two parameters can serve as alternative measurements for predicting/quantifying sarcopenia. Calf circumference measurements alone may not be appropriate for assessing sarcopenia. Instead, US imaging can conveniently be used to evaluate different compartments of the musculoskelal system in (sarcopenic) elderly.     

Association of nutrition and immune-endocrine dysfunction with muscle mass and performance in cognitively impaired older adults

BackgroundWith lean mass declining early in Alzheimer’s disease, muscle quality beyond quantity is relevant to physical performance. We sought to identify potentially modifiable factors for the differential loss of muscle mass (pre-sarcopenia) and its performance (sarcopenia) in older adults with mild cognitive impairment (MCI) and mild-to-moderate Alzheimer’s disease (AD).MethodsThis is a cross-sectional study of 108 community-dwelling older adults with MCI and mild-to-moderate AD. Participants were categorized as: (i) No sarcopenia (normal muscle mass), (ii) Pre-sarcopenia (low muscle mass without weakness or slowness), (iii) Sarcopenia (low muscle mass AND weak grip strength and/or slow gait speed) using Asian cut-offs. Muscle quality was defined as the ratio of grip and knee extension strength to average arm and leg lean mass respectively. We measured cognitive, functional and physical (Short Physical Performance Battery, SPPB) performance; physical activity level; nutritional status; and blood biomarkers of inflammation and endocrine dysfunction.ResultsSPPB (p = 0.033) and activity level (p = 0.010) were highest in the pre-sarcopenic group. Pre-sarcopenic group had highest arm muscle quality [10.6 (7.7–12.2) vs 13.9 (12.6–15.7) vs 11.3 (9.7–12.8), p < 0.001], despite significantly lower appendicular lean mass than non-sarcopenic group. In multi-nomial logistic regression reference to non-sarcopenic group, malnutrition independently increased risk for both pre-sarcopenia (Relative risk = 7.53, 95% C.I 1.20–47.51, p = 0.032) and sarcopenia (Relative risk = 11.91, 95% C.I 2.85–49.77, p = 0.001). A combined pro-inflammatory and endocrine deficient state significantly increased the risk of sarcopenia (Relative risk = 5.17, 95% C.I 1.31–20.37, p = 0.019).ConclusionMalnutrition is a precursor for progressive loss of muscle mass, but a pro-inflammatory and endocrine deficient state may potentially aggravate decline in muscle quality to culminate in frank sarcopenia.     

Association between visceral,cardiac and sensorimotor polyneuropathies in diabetes mellitus

AimsGastrointestinal complaints are common in diabetes mellitus. However, its association to peripheral sensorimotor and autonomic neuropathies is not well investigated. The aim was to assess skin, muscle, bone and visceral sensitivity in diabetes patients with sensorimotor neuropathy, and correlate these with gastrointestinal symptoms and degree of cardiac autonomic neuropathy.MethodsTwenty patients with sensorimotor neuropathy (65% type 2 diabetes, aged 58.3 ± 12.0 years, diabetes duration 15.8 ± 10.0 years) and 16 healthy controls were recruited. Cutaneous sensitivity to von Frey filaments, mechanical allodynia, muscle/bone/rectosigmoid sensitivities, and heart rate variability were examined. Gastrointestinal symptom scores (PAGI-SYM) and health-related quality of life (SF-36) were also recorded.ResultsPatients displayed hypesthesia to von Frey filaments (p = 0.028), but no difference to muscle and bone pain sensitivities. Also, patients were hyposensitive to multimodal rectal stimulations (all p < 0.05), although they suffered more gastrointestinal complaints. Heart rate variability was reduced in the patient cohort. Rectal mechanical and cutaneous sensitivities correlated (p < 0.001), and both were associated with heart rate variability as well as PAGI-SYM and SF-36 scores (p < 0.01).ConclusionsIn diabetic sensorimotor neuropathy there is substantial evidence of concomitant cutaneous, cardiac and visceral autonomic neuropathies. The neuropathy may reduce quality of life and explain the higher prevalence of gastrointestinal complaints.     

Whey protein supplementation in nursing home residents. A randomized controlled trial

PurposeThe effects of supplementation with whey proteins high in leucine content were tested in older nursing home residents.Materials and methodsResident of a municipal nursing home (n = 106) were recruited to this 6-month randomized controlled trial. Both the test (n = 49) and control group (n = 57) received 1.5 deciliters of juice three times a day. The test juice was fortified with whey protein fractions (20 g/d: 75% β-lactoglobulin, 25% α-lactalbumin). The responses of muscle mass (bioimpedance spectroscopy), strength (hand grip, knee extension) and physical performance (walking, toileting) were measured. In addition to blood samples, data from comprehensive geriatric assessment were collected.ResultsWhey supplementation resulted in 2.1% increase in body weight, in contrast to 1.9% weight loss in the control group (P = 0.001). The skeletal muscle index decreased in the control group (P = 0.028), resulting in mean difference of 10.3% between groups (P = 0.039) during the first 3 months, but this difference leveled off at 6 months. The responses in muscle strength were similar, but patients on whey protein needed less physical assistance after 6 months. Insulin like growth factor 1 (IGF-1) and insulin increased in the test group, in which patients experienced less often infections, skin ulcers, and worsening of discomfort behavior.ConclusionSupplementation with whey protein fractions increases body weight and activates the IGF-1 axis in typical nursing home residents in Finland. Supplementation seems to also associate with maintenance of skeletal muscle mass, reduction in required physical assistance and general well being. However, larger well-designed trials are needed to confirm these associations.     

Association of adiponectin with peripheral muscle status in elderly patients with heart failure

BackgroundReduced peripheral muscle mass was demonstrated in patients with chronic heart failure (HF). Adipokines may have potent metabolic effects on skeletal muscle. The associations between adipokines, peripheral muscle mass, and muscle function have been poorly investigated in patients with HF.MethodsWe measured markers of fat and bone metabolism (adiponectin, leptin, 25-hydroxy vitamin D, parathyroid hormone, osteoprotegerin, RANKL), N-terminal pro B-type natriuretic peptide (NT-pro-BNP) in 73 non-cachectic, non-diabetic, male patients with chronic HF (age: 68 ± 7 years, New York Heart Association class II/III: 76/26%, left ventricular ejection fraction 29 ± 8%) and 20 healthy controls of similar age. Lean mass as a measure of skeletal muscle mass was measured by dual energy X-ray absorptiometry (DEXA), while muscle strength was assessed by hand grip strength measured by Jamar dynamometer.ResultsSerum levels of adiponectin, parathyroid hormone, osteoprotegerin, RANKL, and NT-pro-BNP were elevated in patients with chronic HF compared to healthy controls (all p < 0.0001), while no difference in serum levels of leptin, testosterone or SHBG was noted. Levels of 25-hydroxy vitamin D were reduced (p = 0.002) in HF group. Peripheral lean mass and hand grip strength were reduced in patients with HF compared to healthy subjects (p = 0.006 and p < 0.0001, respectively). Using backward selection multivariable regression, serum levels of increased adiponectin remained significantly associated with reduced arm lean mass and muscle strength.ConclusionsOur findings may indicate a cross-sectional metabolic association of increased serum adiponectin with reduced peripheral muscle mass and muscle strength in non-cachectic, non-diabetic, elderly HF patients.     

Delving into disability in Crohn's disease: Dysregulation of molecular pathways may explain skeletal muscle loss in Crohn's disease

Background/aimsIn Crohn's disease (CD), skeletal muscle mass and function are reduced compared to healthy controls, potentially resulting in disability. Mechanisms contributing to muscle impairment, and thus potential therapeutic targets, are poorly understood. This study aimed to measure and compare skeletal muscle size and molecular targets involved in skeletal muscle growth, in CD subjects and healthy controls.MethodsCD (n = 27) and healthy (n = 22) subjects were recruited from the IBD outpatient clinic and via local advertisement respectively. Demographics and clinical data were collected via survey and interview. Quadriceps muscle cross-sectional area was measured using peripheral quantitative CT scanning. Levels of muscle hypertrophy and atrophy signalling targets using quantitative PCR and western blotting were measured in muscle biopsies.ResultsMuscle size was 14% lower (p = 0.055) and a 54% lower phosphorylated:total (p:t) Akt ratio was measured in the muscle samples (p < 0.05), indicating an attenuated muscle hypertrophy pathway in CD compared with controls. In those with CD, a lower p:t Akt ratio (< 0.97) was associated with lower serum vitamin D3, lower physical activity indices (49 vs 64 mmol/L, 1.7 vs 2.2 × 10⁶ accelerometer counts respectively, each p < 0.05) and a trend towards lower serum ferritin levels (128 vs 322 mg/L, p = 0.07), compared with CD subjects with normal/high p:t Akt ratios.ConclusionThe reduced muscle mass in CD may be explained, in part, by impaired activation of muscle protein synthesis pathways, notably the IGF1–Akt pathway. Normal vitamin D levels and regular exercise may be protective in CD against this trend, though confirmatory longitudinal studies are needed.     

Efficacy and Safety of Oral Conivaptan,a Vasopressin-Receptor Antagonist,Evaluated in a Randomized,Controlled Trial in Patients With Euvolemic or Hypervolemic Hyponatremia

BackgroundIn most cases of hyponatremia, arginine vasopressin secretion is inappropriately high. This placebo-controlled, randomized, double-blind multicenter study evaluated the efficacy and safety of oral conivaptan, a V_1A/V₂-receptor antagonist, in patients with euvolemic or hypervolemic hyponatremia.MethodsEighty-three patients with serum [Na⁺] less than 130 mEq/L were stratified by volume status and randomly assigned to placebo or conivaptan 40 or 80 mg/d for 5 days.ResultsConivaptan increased the baseline-adjusted area under the serum [Na⁺]-time curve significantly more than placebo (P = 0.0001). Patients given either dose of conivaptan demonstrated a serum [Na⁺] of 4 mEq/L or greater above baseline significantly faster than those given placebo (P < 0.001) and maintained that increase for a greater total time (P = 0.0001). The least squares mean change in serum [Na⁺] from baseline to end of treatment was also significantly greater with conivaptan 40 and 80 mg/d (6.8 and 8.8 mEq/L, respectively) (P = 0.0001) than that with placebo (1.2 mEq/L). The percentage of patients who obtained an increase from baseline in serum [Na⁺] of 6 mEq/L or greater or normal serum [Na⁺] was significantly higher among patients given conivaptan 40 and 80 mg/d (67% and 88%, respectively) than among those given placebo (20%; P < 0.001). Conivaptan was well tolerated; the most frequent adverse events were urinary tract infection, anemia, pyrexia, cardiac failure, hypotension, and hypokalemia.ConclusionOral conivaptan was effective in increasing serum [Na⁺] in patients with euvolemic or hypervolemic hyponatremia and had a favorable safety profile.     

Effects of l-arginine supplementation associated with continuous or interval aerobic training on chronic heart failure rats

ObjectiveChronic heart failure (CHF) is related with exercise intolerance and impaired nitric oxide (NO) production, which can lead to several functional capacity alterations. Considering the possible superiority of aerobic interval training compared to continuous training and the capacity of l-arginine to restore the NO pathway, the aim of the present study was to investigate whether these treatments are beneficial to exercise capacity, muscle mass preservation and hemodynamic, inflammatory and oxidative stress parameters in CHF rats.MethodsThirty-eight male Wistar rats post 6 weeks of myocardial infarction (MI) surgery were randomly assigned into 6 CHF groups: sedentary (SED, n = 6); SED + Arg (n = 7); ACT (n = 8); ACT + Arg (n = 5); AIT (n = 7); AIT + Arg (n = 5). Exercise test capacity (ETC) was performed pre and post 8 weeks of intervention. Supplemented rats received Arg (1 g/kg) by oral gavage (7 ×/week). Exercise training was performed on a rat treadmill (5 ×/week). Hemodynamic variables, tissue collection, congestion, inflammatory cytokines, and oxidative parameters were evaluated at the end of protocols.ResultsAll trained groups showed a superior exercise capacity compared to SED groups on the post-intervention test (p < 0.0001). Pulmonary congestion was attenuated in AIT and AIT + Arg compared with the SED group (p < 0.05). Left ventricular end-diastolic pressure (LVEDP) was lower in ACT + Arg, AIT, and AIT + Arg groups than SED group (p < 0.05). Association of AIT with Arg supplementation was able to improve hemodynamic responses (left ventricular systolic pressure (LVSP), systolic blood pressure (SBP), + dP/dt_max, and − dP/dt_max (p < 0.05), likewise, decrease muscular and renal lipid peroxidation and tumor necrosis factor (TNF)-α, and increase interleukin (IL)-10/TNF-α plasmatic levels (p < 0.01). Groups that associated aerobic exercise with Arg supplementation (ACT + Arg and AIT + Arg) revealed higher gastrocnemius mass compared to the SED group (p < 0.01).ConclusionsBoth aerobic training protocols were capable to improve aerobic capacity, and the association with Arg supplementation was important to attenuate muscle loss. Moreover, interval training associated with Arg supplementation elicits greater improvements in hemodynamic parameters, contributing to reduction in pulmonary congestion, and demonstrated particular responses in the inflammatory profile and in the antioxidant status.     

Differences in skeletal and non-skeletal factors in a diverse sample of men with and without type 2 diabetes mellitus

AimsPatients with type 2 diabetes mellitus (T2DM) have increased fracture risk yet higher bone mineral density (BMD), but data are inconsistent in men. We compared skeletal and non-skeletal (e.g., muscle mass, strength) factors in men with/without T2DM.MethodsCross-sectional study of 1137 Boston men 30–79 years in the Boston Area Community Health/Bone Survey. Diabetes status was self-reported, and BMD and body composition were measured by DXA, and grip strength by hand dynamometer. Physical function was assessed by walking speed and chair stands. Multivariable linear regressions examined associations of T2DM with skeletal/non-skeletal factors.ResultsMean age was 48 years. The population was 24.6% Black, 13.0% Hispanic, and 62.4% White. Prevalence of T2DM was 12.5%; average disease duration was 7.4 years. While subjects with T2DM did not differ in skeletal factors (e.g., BMD), they had significantly lower appendicular lean mass [mean difference (MD) = − 1.04 kg; standard error (SE) = 0.50; p = 0.04], arms lean mass (MD = − 0.42 kg; SE = 0.15; p = 0.006) and grip strength (MD = − 3.02 kg; SE = 1.25; p = 0.025) after adjustment for age, race/ethnicity, and BMI.ConclusionsMen with T2DM have lower muscle mass and strength, but similar BMD, compared to their non-diabetic counterparts. These differences in non-skeletal factors might explain, at least in part, the higher incidence of falls and fractures observed in T2DM patients.     

Myocardial Performance Index (MPI) is not influenced by increased Left Ventricular Mass in healthy obese men

BackgroundNotwithstanding its clinical use as a reliable measure of left ventricular performance, little is known about whether myocardial performing index (MPI) is influenced by increased left ventricular mass (LVM) in healthy obese individuals.AimThe present study was targeted at investigating the impact of increased LVM on the LV MPI in healthy obese men.Subjects and MethodSixty-six normal male subjects were involved in this study. The subjects were divided according to their body mass index (BMI), into group I (BMI = 20–24.9, n = 37, mean age 33.405 ± 10.277 years) which served as the control group, and group II (BMI = ≥ 30, n = 29, mean age 39.208 ± 10.214 years). The MPI was determined in all subjects using the following formula proposed by Tei: MPI = IVCT + IVRT/ET. LVM was calculated according to the following Devereux formula as: LVM = 0.8[1.04(IVSd + PWTd + LVIDd)??(LVIDd)?] + 0.6.ResultsThere were no significant differences in MPI between control subjects and obese subjects with increased LVM (p > 0.05). Additionally, there was no linear correlation between MPI and LVM (R² = 0.0003, p = 0.89).ConclusionMPI is a simple and accurate tool for the quantitative assessment of left ventricular function. Because of its ease of application, cost effectiveness, and reproducibility, this tool could be regarded as a principal measurement for comprehensive hemodynamic studies. MPI values (according to the Tei index) did not vary significantly between healthy obese and morbidly obese individuals, and therefore may have limited utility for predicting cardiac diseases in at-risk obese individuals.     

Presence or Absence of Skeletal Muscle Dysfunction in Chronic Obstructive Pulmonary Disease is Associated With Distinct Phenotypes

IntroductionReduced skeletal muscle function and cognitive performance are common extrapulmonary features in Chronic Obstructive Pulmonary Disease (COPD) but their connection remains unclear. Whether presence or absence of skeletal muscle dysfunction in COPD patients is linked to a specific phenotype consisting of reduced cognitive performance, comorbidities and nutritional and metabolic disturbances needs further investigation.MethodsThirty-seven patients with COPD (grade II–IV) were divided into two phenotypic cohorts based on the presence (COPD dysfunctional, n = 25) or absence (COPD functional, n = 12) of muscle dysfunction. These cohorts were compared to 28 healthy, age matched controls. Muscle strength (dynamometry), cognitive performance (Trail Making Test and STROOP Test), body composition (Dual-energy X-Ray Absorptiometry), habitual physical activity, comorbidities and mood status (questionnaires) were measured. Pulse administration of stable amino acid tracers was performed to measure whole body production rates.ResultsPresence of muscle dysfunction in COPD was independent of muscle mass or severity of airflow obstruction but associated with impaired STROOP Test performance (p = 0.04), reduced resting O₂ saturation (p = 0.003) and physical inactivity (p = 0.01), and specific amino acid metabolic disturbances (enhanced leucine (p = 0.02) and arginine (p = 0.06) production). In contrast, COPD patients with normal muscle function presented with anxiety, increased fat mass, plasma glucose concentration, and metabolic syndrome related comorbidities (hypertension and dyslipidemia).ConclusionCOPD patients with muscle dysfunction show characteristics of a cognitive – metabolic impairment phenotype, influenced by the presence of hypoxia, whereas those with normal muscle function present a phenotype of metabolic syndrome and mood disturbances.     

The impact of angiotensin converting enzyme insertion/deletion gene polymorphism on diabetic kidney disease: A debatable issue

ObjectiveThe objective of this study was to evaluate the influence of ACE I/D gene polymorphisms on diabetic kidney disease (DKD) risk.MethodsAll eligible investigations were identified, the number of various genotype in the case and control group were reviewed. The pooled analysis was performed using Stata software.ResultsIn overall subjects, 24,321 participants with 12,961 cases and 11,360 controls were included. the pooled analysis showed a significant link between D allele, DD or II genotype and DKD risk (D versus I: OR = 1.316, 95% CI: 1.213–1.427, P = 0.000; DD versus ID + II: OR = 1.414, 95% CI: 1.253–1.595, P = 0.000; II versus DD + ID: OR = 0.750, 95% CI: 0.647–0.869, P = 0.000). The subgroup pooled analysis showed that ACE I/D gene polymorphism was correlated with DKD both in Asian and in Chinese population. In addition, ACE I/D gene polymorphism was correlated with type 2 DKD (D versus I: OR = 1.361, 95% CI: 1.243–1.490, P = 0.000; DD versus ID + II: OR = 1.503, 95% CI: 1.310–1.726, P = 0.000; II versus DD + ID: OR = 0.738, 95% CI: 0.626 –0.870, P = 0.000). However, there was no obvious correlation in Caucasian subjects and type 1 diabetic patients.ConclusionACE I/D polymorphisms were correlated with DKD in Asian and type 2 diabetic populations. ACE D allele/DD genotype might be a risk factor, while ACE II genotype might be a protective factor for DKD.     

Relationship between circulating endothelial progenitor cells and insulin resistance in non-diabetic patients with ischemic chronic heart failure

AimThe objective of this study was to assess a relationship between insulin resistance (IR) and counts of CD45⁻CD34⁺, CD14⁺CD309⁺, and CD14⁺CD309⁺Tie2⁺ phenotyped circulating endothelial progenitor cells (EPCs) in patients with ischemic chronic heart failure (CHF).MethodsThe study involved 300 CHF patients (186 males) aged 48–62 years with angiografically proven coronary artery disease and/or previously defined myocardial infarction. Insulin resistance was assessed by the homeostasis model assessment for insulin resistance (HOMA-IR). EPC populations were phenotyped by flow cytofluorimetry.ResultsCirculating EPCs counts were statistically significantly lower in CHF patients with IR than in patients without IR. We found that the most valuable multivariable predictors of the depletion of the CD45⁺CD34⁺ EPCs were NT-pro-brain natriuretic peptide (BNP) (1.32; 95% CI = 1.19–2.77; P = 0.001), left ventricular ejection fraction (OR = 1.30; 95% CI = 1.09–1.60; P = 0.002), NYHA class (OR = 1.12; 95% CI = 1.02–1.19; P = 0.001). NT-pro-BNP (OR = 1.45; 95% CI = 1.15–2.90; P = 0.003), left ventricular ejection fraction (OR = 1.32; 95% CI = 1.11–1.65; P = 0.001) were found as powerful predictors for depletion in CD45⁻CD34⁺ EPCs. We also identified six independent variables with high predictive value for depletion of CD14⁺CD309⁺ EPCs: NT-pro-BNP (OR = 1.41; 95% CI = 1.15–2.90; P = 0.003), left ventricular ejection fraction (OR = 1.18; 95% CI = 1.10–1.76; P = 0.036), NYHA class (OR = 1.15; 95% CI = 1.07–1.22; P = 0.001), hs-C reactive protein (OR = 1.02; 95% CI = 1.01–1.05; P = 0.012). As independent multivariable predictors for depletion in CD14⁺CD309⁺Tie2⁺ EPCs were selected five variables: NT-pro-BNP (OR = 1.65; 95% CI = 1.44–4.70; P = 0.006), left ventricular ejection fraction (OR = 1.07; 95% CI = 1.02–1.12; P = 0.018), NYHA class (OR = 1.13; 95% CI = 1.06–1.21; P = 0.001), hs-C-reactive protein (OR = 1.08; 95% CI = 1.03–1.16; P = 0.002).ConclusionIR may be an additional factor contributing decreased circulating level of proangiogenic EPCs in non-diabetic CHF patients.     

Cardiovascular risk assessment in patients with type 2 diabetes mellitus and metabolic syndrome: Role of biomarkers

ObjectivesMetabolic syndrome (MetS) and type 2 diabetes mellitus (DM) are associated with a high incidence of cardiovascular diseases. The aim of this study was to determine paraoxonase (PON), total sialic acid (TSA), and nitric oxide (NO) levels in addition to conventional risk markers in patients with DM, MetS and DM plus MetS.Material and methodsThe study has been carried out over 78 subjects which divided into four groups; control (n = 18), DM (n = 20), newly diagnosed MetS (n = 20) and DM plus MetS patient groups (n = 20).ResultsBoth insulin and triglyceride concentrations were significantly higher in DM + MetS group than in control and DM groups and serum HDL-C concentrations were significantly lower in DM + MetS group than other groups. Patients with MetS had higher LDL-C, total cholesterol and hsCRP concentrations than in the other groups. Interestingly, in addition to body mass index and waist circumference values, LDL-C, total cholesterol and hsCRP concentrations were decreased in patients who have both DM and MetS. Serum NO and TSA levels were higher in MetS and DM + MetS groups compared to control subjects. Unexpectedly, PON activity has been found lower in control group when compared to other groups.ConclusionsAlthough there is no doubt that association of DM and MetS elevates the risk of cardiovascular disease, occurrence of DM in patients with undiagnosed MetS might be encouraging patients to change their life styles and dietary habits.     

Microscopic colitis patients have increased proportions of Ki67+ proliferating and CD45RO+ active/memory CD8+ and CD4+8+ mucosal T cells

BackgroundCollagenous colitis (CC) and lymphocytic colitis (LC) are chronic inflammatory bowel disorders of unknown etiology. This study investigated phenotypic characteristics of the mucosal lymphocytes in CC and LC.MethodsLamina propria and intraepithelial lymphocytes (LPLs, IELs) isolated from mucosal biopsies from CC (n = 7), LC (n = 6), as well as LC or CC patients in histopathological remission, (LC-HR) (n = 6) and CC-HR (n = 4) and non-inflamed controls (n = 10) were phenotypically characterized by four-color flow cytometry.ResultsThe proportions of CD8⁺ IELs were increased in CC and LC (p < 0.01) compared to controls. Increased proportions of CD45RO⁺CD8⁺ IELs and LPLs were observed in LC and even more in CC patients (p < 0.01). Both CC (p < 0.05) and LC patients had elevated proportions of CD4⁺8⁺ IELs and LPLs compared to controls. The proportions of CD45RO⁺ cells were increased in CD4⁺8⁺ IELs and LPLs (p < 0.05) in CC and LC patients compared to controls. Both CC (p < 0.05) and LC patients had higher proportions of Ki67⁺CD8⁺ IELs and LPLs compared to controls.In contrast, decreased proportions of CD4⁺ LPLs were observed in CC and LC as well as CD4⁺ IELs in LC compared to controls. Increased proportions of Ki67⁺CD4⁺ IELs and LPLs (p < 0.05) were observed in CC and LC patients.CC-HR but not LC-HR patients demonstrated normalized proportions of both IELs and LPLs compared to CC and LC patients respectively.ConclusionLC and CC patients have differences in mucosal lymphocyte subsets, with increased proportions of Ki67⁺ and CD45RO⁺ CD8⁺ and CD4⁺8⁺ mucosal T cells.     

An association of serum vistafin level and number of circulating endothelial progenitor cells in type 2 diabetes mellitus patients

BackgroundThe decreased number and impaired functions of endothelial progenitor cells (EPCs) may associate with cardiovascular disease (CV) including atherosclerosis. However, the role of vistafin in regulation of angiogenic EPC subset maturation in T2DM patients without known atherosclerosis is still not fully understood.The aim of the studyTo investigate an association of serum vistafin level and number of circulating EPCs in T2DM patients beyond known CV disease.MethodsThis case–control observational investigation was evolved 54 subjects with T2DM and 35 healthy volunteers. The flow cytometry was used for predictably distinguishing cell subsets, which depend on expression of CD45, CD34, CD14, Tie-2, and VEGFR2. Biomarkers were measured at baseline of the study.ResultsAll T2DM patients were divided depending median of vistafin level (5.88 ng/mL) in to two cohorts with low vistafin level (<5.88 ng/mL; n = 29) and high vistafin level (≥5.88 ng/mL; n = 25) respectively. Logistic regression analysis has shown that visfatin, hs-CRP, age and BMI were the best variables in the prediction of EPC number labeled as CD14⁺CD309⁺ and CD14⁺CD309⁺Tie²⁺ cells. After adjustment of the model to age and BMI elevated visfatin level remained the best predictor for both CD14⁺CD309⁺ and CD14⁺CD309⁺Tie²⁺ EPCs (OR 0.92, 95% CI: 0.88–0.95; P = 0.001 and OR 0.90, 95% CI: 0.87–0.96; P = 0.001 respectively).ConclusionWe found that elevated level of vistafin was an independent predictor for declined numerous of non-classical EPCs labeled as CD14⁺CD309⁺ and CD14⁺CD309⁺Tie²⁺, whereas CD34⁺ subsets of EPCs did not associate with vistafin level in T2DM individuals.     

Prolonged K+ deficiency increases intracellular ATP,cell cycle arrest and cell death in renal tubular cells

BackgroundChronic potassium (K⁺) deficiency can cause renal damage namely hypokalemic nephropathy with unclear pathogenic mechanisms. In the present study, we investigated expression and functional alterations in renal tubular cells induced by prolonged K⁺ deficiency.MethodsMDCK cells were maintained in normal-K⁺ (CNK) (K⁺ = 5.3 mmol/L), low-K⁺ (CLK) (K⁺ = 2.5 mmol/L), or K⁺-depleted (CKD) (K⁺ = 0 mmol/L) medium for 10 days (n = 5 independent cultures/condition). Differentially expressed proteins were identified by a proteomics approach followed by various functional assays.ResultsProteomic analysis revealed 46 proteins whose levels significantly differed among groups. The proteomic data were confirmed by Western blotting. Gene Ontology (GO) classification and protein network analysis revealed that majority of the altered proteins participated in metabolic process, whereas the rest involved in cellular component organization/biogenesis, cellular process (e.g., cell cycle, regulation of cell death), response to stress, and signal transduction. Interestingly, ATP measurement revealed that intracellular ATP production was increased in CLK and maximum in CKD. Flow cytometry showed cell cycle arrest at S-phase and G2/M-phase in CLK and CKD, respectively, consistent with cell proliferation and growth assays, which showed modest and marked degrees of delayed growth and prolonged doubling time in CLK and CKD, respectively. Cell death quantification also revealed modest and marked degrees of increased cell death in CLK and CKD, respectively.ConclusionsIn conclusion, prolonged K⁺ deficiency increased intracellular ATP, cell cycle arrest and cell death in renal tubular cells, which might be responsible for mechanisms underlying the development of hypokalemic nephropathy.     

Urinary podocalyxin positive-element occurs in the early stage of diabetic nephropathy and is correlated with a clinical diagnosis of diabetic nephropathy

AimsWe tested whether urinary podocalyxin-positive element (PCX + EL) can be a marker of early stage of diabetic nephropathy (DN).MethodsDN patients (n = 68) and health controls (n = 28) were enrolled in this study. Patients were classified into three groups: normoalbuminuria, microalbuminuria and macroalbuminuria. Urinary PCX + EL, serum cystatin C (Scys C) and serum creatinine (SCr) were quantified, and correlations between urinary PCX + EL and urinary albumin, Scys C and SCr were examined. The comparison of diagnosis efficiency among urinary PCX + EL, Scys C and SCr was made by receiver operating characteristic (ROC) analysis.ResultsUrinary PCX + EL, Scys C and SCr significantly increased in DN patients compared with controls. Urinary PCX + EL increased significantly in all three patients groups compared with controls. However, the concentration of Scys C and SCr did not increase in normoalbuminuria group. Urinary albumin, Scys C and SCr correlated with urinary PCX + EL. ROC curve analysis indicated that area under the curve (AUC) of urinary PCX + EL (0.966) is higher than that of Scys C (0.857) and SCr (0.726) for discriminating nephropathy between DN patients and controls.ConclusionUrinary PCX + EL may be a noninvasive marker for the early stage of DN.     

A Multicenter Study of Noninvasive Cardiac Output by Bioreactance During Symptom-limited Exercise

BackgroundHemodynamic responses to exercise were assessed in patients with varying degrees of chronic heart failure (CHF) to determine the feasibility of using bioreactance during exercise testing in multicenter studies of CHF.Methods and ResultsA total of 210 symptomatic CHF patients and 22 subjects without heart failure were subjected to symptom-limited exercise testing on a bicycle (105) or treadmill (127) while measuring gas exchange for VO₂, cardiac output (CO) noninvasively by a bioreactance technique, heart rate, and blood pressure. Peak CO (pCO) and VO₂ (pVO₂) during exercise were lower in patients with higher New York Heart Association (NYHA) class, in females and in older patients. Multiple linear regression analysis showed that pCO (L/min) = 19.6 + 4·M – 2.1·NYHA + 1.9·G – 0.09·Age, where M = 1 for treadmill and 0 for bicycle and G = 1 for males and 0 for females. Similarly, pVO₂ (mL/kg/min) = 24 + 2.1·M – 2.9·NYHA + 1.26·G – 0.08·Age. VO₂ and CO were also highly correlated to each other: pCO (mL/kg/min) = 0.059 + 0.007·pVO₂ + 0.036·M – 0.025·G. Similar correlations were determined for other parameters of exercise, including left ventricular power, and the ratio of peak/resting VO₂ (cardiovascular reserve), the ratio of peak/resting CO (cardiac reserve), and total peripheral vascular resistance.ConclusionBioreactance-based noninvasive measurements of CO at rest and during exertion identified abnormalities of cardiovascular function consistent with those identified by pVO₂ and in prior studies using invasive CO measurements. This technique might therefore be useful for indexing disease severity, prognostication, and for tracking responses to treatment in clinical practice and in clinical trials.