Aerobic and resistance training effects compared to aerobic training alone in obese type 2 diabetic patients on diet treatment

Aims

The study was designed to compare a combined aerobic and resistance training (ART) with an aerobic training (AT) over hemodynamic, glucose metabolism and endothelial factors, adipokines and pro-inflammatory marker release in a population of obese type 2 diabetic patients.

Methods

Forty-seven patients were randomly assigned to aerobic (27 patients) or aerobic plus resistance (20 patients) exercise trainings, on the top of a diet regime. Anthropometric, metabolic, hormonal and inflammatory variables were measured at hospitalization and discharge.

Results

Both exercise programs equally improved body weight and fructosamine levels however ART only partially decreased HOMA index compared with AT (ART: −25% vs AT: −54%, p < 0.01). Mean blood pressure (AT: −3.6 mmHg vs ART: +0.6 mmHg, p < 0.05) and endothelin-1 (ET-1) incremental areas during walking test (AT: −11% vs ART: +30%, p < 0.001) decreased after AT while increased after ART. Adiponectin levels increased by 54% after AT while decreased by 13% after ART (p < 0.0001) and matrix metalloproteinase-2 (MMP-2), tumor necrosis factor-alpha (TNF-alpha) and monocyte chemoattractan protein-1 (MCP-1) levels significantly decreased in AT while increased in ART group.

Conclusions

Compared with AT, ART similarly enhanced body weight loss but exerted less positive effects on insulin sensitivity and endothelial factors, adipokines and pro-inflammatory marker release.     

Effect of pioglitazone on diabetic nephropathy and expression of HIF-1α and VEGF in the renal tissues of type 2 diabetic rats

Objective

To investigate the effect of pioglitazone on the progression of diabetic nephropathy and the expression of hypoxia inducible factor-1α (HIF-1a) and vascular endothelial growth factor (VEGF) in a rat model of type-2 diabetes.

Methods

Streptozotocin-induced type-2 diabetes mellitus (DM) model was set up in male Sprague Dawley rats. DM rats were treated with or without pioglitazone (4 mg/kg/day for 8 weeks) and/or cobalt chloride. Normal rats were used as controls. The blood chemistry, urine albumin, kidney histology, and expression of HIF-1α and VEGF of the different groups were compared.

Results

The kidney weights and kidney weight indexes of DM rats were significantly higher than in NC rats (P < 0.01) and the kidney weights and kidney weight indexes of rats in pioglitazone and/or cobalt chloride treatment group were significantly less than in DM group. Relative to rats in the NC group, rats in the DM group had significantly disrupted serum chemistry, urinary albumin, and kidney histology, and significantly enhanced expression of HIF-1a and VEGF. Rats in the pioglitazone and/or cobalt chloride treatment group experienced significant amelioration of these effects.

Conclusion

In a rat model, pioglitazone ameliorated many of the physiological, cellular, and molecular processes associated with diabetic nephropathy.     

罗格列酮对高胰岛素培养的内皮细胞一氧化氮的影响及其机制研究

目的观察罗格列酮（RGZ）对高胰岛素培养的人脐静脉内皮细胞（HUVEC）NO浓度和内皮型一氧化氮合酶（eNOS）、磷酯酰肌醇3激酶（P13K）和蛋白激酶B（PKB）表达的影响,探讨RGZ改善高胰岛素状态下内皮功能障碍的信号转导机制。方法高浓度胰岛素培养HUVEC72h,并用不同浓度的RGZ进行干预。检测NO浓度,PI3K mRNA的表达,PKB、eNOS总蛋白和PKB丝氨酸473（PKB-Ser473）、eNOS丝氨酸1177（eNOS-Ser1177）的磷酸化表达。结果高浓度胰岛素培养HUVEC能呈剂帚和时间依赖性地降低N0的浓度,抑制内皮细胞P13KmRNA表达和PKB-Ser473、eNOS-Ser1177的磷酸化。用RGZ干预能硅著升高高胰岛素培养的内皮细胞NO的浓度和PKB、eNOS的磷酸化,增强PI3KmRNA表达;eNOS和P13K阻断剂均能阻断RGZ对高胰岛素培养的内皮细胞中NO浓度的升高,PI3K阻断剂还能阻断RGZ对高胰岛素培养内皮细胞PKB、eNOS的磷酸化。结论高胰岛素能下调P13K／PKB／eNOs信号通路而抑制内皮细胞NO的产生,RGZ能通过上调PI3K／PKB通路而增强高胰岛素培养的内皮细胞eNOS的活性和NO的产生。     

The preventive effect of uncarboxylated osteocalcin against free fatty acid-induced endothelial apoptosis through the activation of phosphatidylinositol 3-kinase/Akt signaling pathway

Objective

Increasing evidence suggests that osteocalcin (OC), one of the osteoblast-specific proteins, has been associated with atherosclerosis, but results are conflicting. The aim of this study was to elucidate the independent effect of uncarboxylated osteocalcin (ucOC), an active form of osteocalcin which has been suggested to have an insulin sensitizing effect, on vascular endothelial cells.

Materials and Methods

We used human aortic endothelial cells and treated them with ucOC. Linoleic acid (LA) was used as a representative free fatty acid. Apoptosis was evaluated using various methods including a terminal deoxyribonucleotide transferase-mediated deoxyuridine triphosphate nick-end labeling analysis kit and Western blotting for cleaved caspase 3, cleaved poly (ADP-ribose) polymerase and Bcl-xL. The phosphorylations of Akt and endothelial nitric oxide synthase (eNOS) as well as the level of NO were measured to confirm the effect of ucOC on insulin signaling pathway.

Results

Pretreatment of ucOC (30 ng/ml) prevented LA-induced apoptosis in insulin-stimulated endothelial cells; effects were abolished by pretreatment with the phosphatidylinositol 3-kinase (PI3-kinase) inhibitor, wortmannin. Treatment of ucOC (ranged from 0.3 to 30 ng/ml) significantly increased the phosphorylation of Akt and eNOS and nitric oxide secretion from endothelial cells in a PI3-kinase dependent manner.

Conclusions

Our study is the first to demonstrate the independent effect of ucOC on vascular endothelial cells. Our results further suggest that ucOC could have beneficial effects on atherosclerosis.     

Transduction of the liver with activated Akt normalizes portal pressure in cirrhotic rats

Background & Aims:

Portal hypertension in cirrhosis is secondary to an increase in hepatic resistance that occurs mainly through collagen deposition. However, recent evidence points to a major contribution by other factors, such as an intrahepatic reduction in nitric oxide production. Akt is a major activator of the endothelial nitric oxide synthase (eNOS) enzyme, but its potential role in intrahepatic resistance in cirrhosis is unknown. For this reason the aims of the present study were to determine whether there is an impaired Akt activation in cirrhotic livers and how this phenomenon relates to the decrease in NO production associated with portal hypertension.

Methods:

Cirrhosis was induced in rats by carbon tetrachloride inhalation. Protein abundance and phosphorylation status of Akt and eNOS were examined by Western blotting. The role of Akt in the liver of cirrhotic rats was investigated through infection with adenoviruses encoding either β-galactosidase (β-gal) or constitutively active Akt (myr-Akt).

Results:

The liver of cirrhotic animals showed a significant reduction in Akt and eNOS phosphorylation. Adenoviral delivery of myr-Akt restored eNOS phosphorylation and increased the intrahepatic concentration of guanosine 3′,5′-cyclic monophosphate. These events were associated with normalization in portal pressure and a significant increase in mean arterial pressure after 3 days of adenoviral infection. In contrast, transduction of livers with β-gal did not produce any change in these hemodynamic parameters.

Conclusions:

myr-Akt gene therapy restored Akt activation and NO production in the cirrhotic liver, suggesting that this therapy may be useful for the treatment of portal hypertension.     

Molecular changes in diabetic foot ulcers

Aim

This study investigated the molecular changes of extracorporeal shockwave therapy (ESWT) and hyperbaric oxygen therapy (HBOT) in chronic diabetic foot ulcers.

Methods

A cohort study consisted of 39 patients (44 ulcers) in the ESWT group and 38 patients (40 ulcers) in the HBOT group with similar demographic characteristics. The ESWT group received shockwave therapy twice per week for total six treatments. The HBOT group received hyperbaric oxygen therapy daily for total 20 treatments. Biopsy was performed from the periphery of the ulcer before and after treatment. The specimens were immuno-stained, and the positive immuno-activities of vWF, VEGF, eNOS, PCNA, EGF and TUNEL expressions were examined and quantified microscopically.

Results

Significant increases in vWF, VEGF, eNOS, PCNA and EGF expressions and a decrease in TUNEL expression were noted after ESWT (P < 0.05), whereas the changes after HBOT were statistically not significant (P > 0.05). The differences of vWF, VEGF, eNOS, PCNA, EGF and TUNEL expressions between the two groups were comparable before treatment (P > 0.05), however, the differences became statistically significant after treatment (P < 0.05) favoring the ESWT group.

Conclusion

ESWT showed significant increases in angiogenesis and tissue regeneration over HBOT in diabetic foot ulcers.     

Effect of metformin on oxidative stress, nitrosative stress and inflammatory biomarkers in type 2 diabetes patients

Aim

Advanced research has radically changed both diagnosis and treatment of diabetes during last three decades; a number of classes of oral antidiabetic agents are currently available for better glycemic control. Present study aims to evaluate the effect of metformin on different stress and inflammatory parameters in diabetic subjects.

Methods

208 type 2 diabetes patients were randomly assigned for metformin and placebo.

Results

Reactive oxygen species generation, advanced oxidation protein products (179.65 ± 13.6, 120.65 ± 10.5 μmol/l) and pentosidine (107 ± 10.4, 78 ± 7.6 pmol/ml) were found to be reduced by metformin treatment compared to placebo. On the other hand metformin administration enhanced total thiol and nitric oxide level (p < 0.05). But nutrient level (Mg⁺², Ca⁺²) in plasma was not altered by the treatment. Significant restoration of C reactive protein (p < 0.05) was noticed after metformin therapy. Metformin administration also improved Na⁺K⁺ATPase activity (0.28 ± 0.08, 0.41 ± 0.07 μmol Pi/mg/h) in erythrocyte membrane.

Conclusions

This study explores that metformin treatment restores the antioxidant status, enzymatic activity and inflammatory parameters in type 2 diabetic patients. Metformin therapy improves the status of oxidative and nitrosative stress altered in type 2 diabetes. This study unfolds the cardio protective role of metformin as an oral hypoglycemic agent.     

The PI3K/p-Akt signaling pathway participates in calcitriol ameliorating podocyte injury in DN rats

Objectives

The present study aimed to investigate the relationship between PI3K/p-Akt signaling pathway and podocyte impairment in DN rats as well as the protective effect of calcitriol.

Methods

SD rats were randomly divided into four groups: normal control (NC), normal treated with calcitriol (NC + VD), diabetic nephropathy (DN) and DN treated with calcitriol (DN + VD); all VD rats were treated with 0.1 μg/kg/d calcitriol by gavage. DN model rats were established by intraperitoneal injections of streptozotocin (STZ). Rats were sacrificed after 18 weeks of treatments.

Results

In the present study, increased albuminuria was observed as early as 3 weeks of diabetes and continued to increase more than six-fold throughout the length of the study (18 weeks). Expectedly, animals receiving the treatment with calcitriol was protected from this increase, lower about one third. Meanwhile, the expression of podocyte specific markers, including nephrin and podocin, together with PI3K/p-Akt was significantly decreased in DN rats, whereas calcitriol reversed these above changes accompanied by elevated the expression levels of VDR. Additionally, a positive correlation was observed between the expression levels of nephrin and VDR (r = 0.776, P < 0.05). Likewise, the expression of nephrin was positively correlated with both PI3K-p85 and p-Akt (r = 0.736, P < 0.05; r = 0.855, P < 0.05, respectively).

Conclusion

PI3K/p-Akt signaling pathway participates in calcitriol ameliorating podocyte injury in DN rats. The manipulation of calcitriol might act as a promising therapeutic intervention for diabetic nephropathy.     

Platelet aggregability is modulated by eNOS locus in non-type 2 diabetic patients with acute coronary syndrome

Background and aim

Platelet nitric oxide (NO) synthesis is compromised in patients with acute coronary syndrome (ACS), and platelet NO availability may be critically relevant in determining the extent of thrombosis in ACS patients. It has been demonstrated that an impaired responsiveness to the antiaggregatory effects of NO may affect platelet dysfunction in diabetic patients with ACS. Since NO availability may be genetically determined, we have investigated the role of endothelial nitric oxide synthase (eNOS) gene in influencing platelet aggregability in relation to the presence (n = 247) or absence (n = 883) of type 2 diabetes in ACS patients.

Methods and results

We have genotyped 1130 consecutive high risk ACS patients on dual antiplatelet therapy, previously investigated in relation to platelet function. eNOS 4a allele frequency was significantly higher in diabetic vs. non-diabetic patients (p = 0.02). In non-diabetic patients the eNOS 4a allele significantly modulated platelet aggregability in response to arachidonic acid (AA), but not to collagen and adenosine diphosphate (ADP) stimulus, after Bonferroni correction for multiple testing. After adjustment for age, gender, smoking habit, hypertension and ejection fraction ≤40%, the eNOS 4a allele remained significantly and independently associated with platelet aggregability in response to AA stimulus [β (SE) = 0.17 (0.07), p = 0.01]. When platelet aggregation values were considered according to the presence or absence of high residual platelet reactivity (RPR) eNOS 4a, but not −786C and 894T, allele was significantly associated with RPR by AA stimulus. The haplotype reconstruction analysis for eNOS gene showed that the −786C/894G/4a and −786C/894G/4b haplotypes significantly influenced platelet aggregation after AA stimulus.

Conclusions

Our study indicates that eNOS 4a allele, may be a determinant of higher platelet aggregability and residual platelet reactivity in non-diabetic ACS patients.     

Polyenylphosphatidylcholine pretreatment protects rat liver from ischemia/reperfusion injury

Background

Hepatic injury induced by ischemia/reperfusion following surgery, transplantation, or circulatory shock combined with resuscitation is a major clinical problem. Polyenylphosphatidylcholine (PPC) has strong antioxidant, cytoprotective and anti-inflammatory effects.

Aim

In this study, the influence of PPC pretreatment on ischemia-reperfusion (I/R) injury of the liver was examined in rats.

Methods

The animals were divided into three groups: control (n = 10), I/R (n = 15) and I/R + PPC (n = 15). PPC was given 100 mg/day for 7 days before experiment. Several parameters of hepatic damage, oxidative stress, neutrophil infiltration and nuclear factor kappa beta (NF-κB) expression were measured as well as microscopic examination.

Results

We observed that a significant reduction in AST and ALT values in the PPC treated group when compared with the ischemic group. The increases in hepatic total NO₂ + NO₃ and MDA, and decreases in SOD and GSH levels after reperfusion were partially, but significantly, inhibited by PPC pretreatment. I/R induced increase in hepatic myeloperoxidase content and NF-κB expression were also lowered by PPC pretreatment. Animals pretreated with PPC presented minimal hemorrhage and reduced signs of liver injury.

Conclusion

PPC pretretament provided significant protection againts I/R injury to the liver. This treatment could be therapeutic in liver transplantation and other conditions associated with I/R injury.     

Elevated alanine aminotransferase is associated with metabolic syndrome but not consistently associated with impaired fasting glucose or type 2 diabetes mellitus

Background

Abnormally elevated alanine aminotransferase (ALT) of nonspecific causes is a common outpatient problem. Without considering ethnicity, several studies had suggested that it was associated with insulin resistance (IR).

Objective

To investigate whether nonspecific elevated ALT in Taiwanese population could reflect a likely underlying IR and was associated with impaired fasting glucose or type 2 diabetes mellitus (IFG/T2DM).

Methods

The health examination profiles of 1313 Taiwanese were investigated cross-sectionally. The prevalence and odds ratios (ORs) for IFG/T2DM and metabolic abnormalities in relation to elevated ALT were analyzed.

Results

Subjects with metabolic syndrome (MS) all had IFG/T2DM. The elevated ALT significantly correlated with MS and IFG/T2DM (i.e., 19.9-29.2% vs. 7.8% for MS, and 27.0-31.5% vs. 16.1% for IFG/T2DM). However, after excluding MS and adjustment for age and sex, the elevated ALT alone was not consistently associated with IFG/T2DM (36 < ALT ≤ 80 IU/L with OR 0.97, 95% CI 0.58-1.61; 80 < ALT ≤ 120 IU/L with OR 0.55, 95% CI 0.13-2.37; none with ALT > 120 had IFG).

Conclusions

In a cross-sectional analysis of Taiwanese industrial employees, elevated ALT associated with MS, but in subjects who did not meet MS criteria, elevated ALT by itself did not associate with IFG/T2DM.     

Changes in serum adiponectin concentrations and endothelial function after intensive insulin treatment in people with newly diagnosed type 2 diabetes: a pilot study

Aims

We aimed to assess changes in serum adiponectin and endothelial function after intensive insulin treatment in patients with newly diagnosed type 2 diabetes mellitus (T2DM).

Methods

Patients with newly diagnosed T2DM were randomly assigned to Group A (intensive insulin treatment) or Group B (conventional insulin treatment). Before treatment and 2 weeks after plasma glucose concentrations had been maintained at the specified concentrations, blood samples were obtained to measure serum adiponectin and nitric oxide (NO) concentrations. A total of 21 patients were randomized to each Group.

Results

Adiponectin, NO, endothelium-dependent vasodilation (EDD), and endothelium-independent vasodilation (EID) measures were significantly higher post-treatment than pre-treatment in Group A (all P < 0.05). Only EID was significantly higher in Group B (P < 0.05). Post-treatment adiponectin and NO concentrations, and EDD were significantly higher in Group A compared with Group B (all P < 0.05). Both treatment regimens were well tolerated (all patients completed the study). The most common adverse event was hypoglycemia. Thus, early intensive insulin therapy can increase serum adiponectin and NO concentrations and improve endothelial function in patients with newly diagnosed T2DM.

Conclusions

These effects may underlie the reduced incidence of microvascular and macrovascular in patients who receive early intensive hypoglycemic therapy.     

Atorvastatin prevents mesenchymal stem cells from hypoxia and serum-free injury through activating amp-activated protein kinase

Background

Mesenchymal stem cells (MSCs) are the optimal candidate of treating myocardial infarction; however, the lower survival ratio of implanted cell discourages the advantages of this treatment. Recent studies have displayed statins, which exert pleiotropic effects on the cardiovascular system partially through the increase in endothelial nitric oxide synthase (eNOS) activity, could increase the livability of cells under hypoxia and serum-free (H/SF) conditions. AMP-activated protein kinase (AMPK) is the essential part in keeping the balance of energy production and metabolism in various tissues, which is the dominant factor modulating the programmed cell death. Therefore, we hypothesized that atorvastatin could protect MSCs from H/SF injury through AMPK-eNOS pathway.

Methods and results

Stained with Annexin V/propidine iodine (PI), we found atorvastatin (0.001 μM-10 μM) reduced apoptosis of porcine bone marrow-derived MSCs cultured in H/SF condition; however, this effect was obstructed by compound C, an inhibitor of AMPK. This trend was similar as what bax protein, a pro-apoptosis protein, showed analyzed by Western blotting; whereas the bcl-2 protein, an anti-apoptosis protein, increased in atorvastatin treated cells. Meanwhile, MSCs treated with atorvastatin increased phosphorylation of AMPK and eNOS. The uptrend was partially inhibited by compound C.

Conclusions

Atorvastatin can activate AMPK and the phosphorylation of AMPK results in eNOS activated, which provides a novel explanation for the multi-effect of statins on cardiovascular system.     

Impairment of insulin action in non-obese, normal-glucose tolerant, first-degree relatives of Chinese type 2 diabetic patients

Aims

To investigate first-phase insulin release and peripheral insulin sensitivity of non-obese, normal-glucose tolerant, first-degree relatives of Chinese type 2 diabetic patients.

Methods

12 euglycemic first-degree relatives of type 2 diabetic patients (ERDM), 12 newly diagnosed type 2 diabetic patients (DM-2) and 12 healthy individuals (control) participated in the study. All subjects were non-obese (BMI < 25 kg/m²). Intravenous glucose tolerance test and euglycemic hyperinsulinemic clamp test were performed to evaluate first-phase insulin release and quantify insulin sensitivity, respectively.

Results

The first-phase insulin release did not differ between the ERDM and control subjects (p = 0.532), while the acute insulin response was absent in the DM-2 patients (p = 0.001). Peripheral glucose deposit rate (GDR) was significantly lower in the ERDM (10.6 ± 2.1 mg/kg·min, p = 0.000) and DM-2 (9.6 ± 1.1 mg/kg·min, p = 0.000) groups than that in the control group (13.2 ± 1.2 mg/kg·min). There was no statistical difference in GDR between the ERDM and DM-2 groups (p = 0.110). Fasting FFA levels of the ERDM (p = 0.007) and DM-2 (p = 0.000) subjects were significantly higher than those of the controls.

Conclusions

Non-obese, first-degree relatives of type 2 diabetic patients with normal glucose tolerance (NGT) exhibit remarkable impairment of insulin sensitivity and increased FFA levels. Insulin resistance is independent of obesity and blood glucose level. Progression from NGT to type 2 diabetes may mainly be attributed to deterioration of early insulin secretion.     

Anti-endothelial and anti-neuronal effects from auto-antibodies in subsets of adult diabetes having a cluster of microvascular complications

Aims

To test autoantibodies from subsets of diabetes with painful neuropathy, maculopathy and nephropathy for effects in neurons.

Methods

Protein-A eluates from plasma of 27 diabetic and 19 age-matched controls were tested for effects on endothelial cell survival, and neurite outgrowth in rat pheochromocytoma PC12 cells. Painful diabetic neuropathy or control autoantibodies were compared for binding to PC12-derived heparan sulfate proteoglycans. The mechanism of the effects from pathologic autoantibodies was investigated by changes in intracellular calcium in endothelial cells, whole cell current in neurons, or using the Rho kinase inhibitor Y27632.

Results

Autoantibodies from diabetic patients with maculopathy, nephropathy, and painful neuropathy (n = 5) caused significantly greater mean inhibition of neurite outgrowth (p < 0.005) than diabetic or control patients with fewer or no complications (n = 30). Painful diabetic autoantibodies (3 μg/mL) bound neuronal heparan sulfate proteoglycan (HSPG) more than autoantibodies from diabetic or control subjects without painful neuropathy (p < .0001). Inhibition of PC12 neurite outgrowth by the painful neuropathy antibodies was completely prevented by 1 μM concentrations of Y27632.

Conclusion

These results suggest anti-endothelial and anti-neuronal effects from auto-antibodies in a subset of diabetic patients with a cluster of microvascular complications.     

Nitric oxide and AQP2 in hypothyroid rats: A link between aging and water homeostasis

Objective

Hypothyroid state and aging are associated with impairment in water reabsorption and changes in aquaporin water channel type 2 (AQP2). Nitric oxide (NO) is involved in AQP2 trafficking to the apical plasma membrane in medullary collecting duct cells. The purpose of this study was to investigate whether aging and hypothyroidism alter renal function, and whether medullary NO and AQP2 are implicated in maintaining water homeostasis.

Materials/Methods

Sprague–Dawley rats aged 2 and 18 months old were treated with 0.02% methimazole (w/v) during 28 days. Renal function was examined and NO synthase (NOS) activity ([¹⁴C (U)]-L-arginine to [¹⁴C (U)]-L-citrulline assays), NOS, caveolin-1 and -3 and AQP2 protein levels were determined in medullary tissue (Western blot). Plasma membrane fraction and intracellular vesicle fraction of AQP2 were evaluated by Western blot and immunohistochemistry.

Results

A divergent response was observed in hypothyroid rats: while young rats exhibited polyuria with decreased medullary NOS activity, adult rats exhibited a decrease in urine output with increased NOS activity. AQP2 was increased with hypothyroidism, but while young rats exhibited increased AQP2 in plasma membrane, adult rats did so in the cytosolic site.

Conclusions

Hypothyroidism contributes in a differential way to aging-induced changes in renal function, and medullary NO and AQP2 would be implicated in maintaining water homeostasis.     

The level of endothelin-1 and nitric oxide in patients with chronic viral hepatitis B and C and correlation with histopathological grading and staging

Background and aim

The aim of this study was to estimate the serum levels of endothelin-1 (ET-1) and nitric oxide (NO) and to analyze the correlation of their levels with histopathological grading and staging of the liver in patients with chronic hepatitis B (CHB) and C (CHC).

Methods

Eighty-nine patients who were either HBsAg positive (45 CHB patients, 34 inactive carriers (IC)) or had CHC (10 patients) and 36 healthy volunteers as a control group were included in this study. Fifty patients from the CHB (n = 43) or CHC (n = 7) groups with elevated serum alanine transaminase (ALT) levels underwent a liver biopsy. Histological activity was scored according to Ishak's activity and the fibrotic index. The ET-1 serum concentration was determined with a commercially available ELISA assay kit. Total nitrite was measured by the Griess reaction as an index for NO production.

Results

Serum levels of ET-1 and NO were significantly increased in CHB patients (7.67 ± 4.00 pg/ml and 172.44 ± 50.30 μmol/l, respectively) compared with the IC group (3.99 ± 5.42 pg/ml and 114.68 ± 32.22 μmol/l, respectively) and the control group (3.05 ± 0.65 pg/ml and 58.61 ± 24.18 μmol/l, respectively) (p < 0.0001). The CHC patients also had significantly higher serum levels of ET-1 (5.92 ± 4.24 pg/ml) and NO (147.50 ± 55.84 μmol/l) compared to the control group (p < 0.0001 and <0.001, respectively). Linear regression analysis identified that the level of ET-1 was an independent variable that correlated significantly with the stage score (r² = 0.348, p < 0.0001) in CHB patients but there was no correlation in the CHC group.

Conclusion

ET-1 and NO levels were increased in chronic hepatitis and there was a significant correlation between the ET-1 level and the stage in CHB patients.     

Diabetes and impaired glucose tolerance among Turkish immigrants in Sweden

Aim

To investigate whether the prevalence of diabetes and impaired glucose tolerance (IGT) was higher among Turkish immigrants in Sweden, than in their area of origin in Turkey.

Methods

238 Turkish immigrants aged 20 years and older living in Flemingsberg, Sweden, were compared with 1549 participants of the same age living in the Konya area of Turkey. Data collection included anthropometric measurements, blood pressure (BP) measurements, and an oral glucose tolerance test (OGTT).

Results

Prevalence of laboratory-verified diabetes was 11.8% among participants in Sweden compared to 7.1% among participants in Turkey (p 0.018). Turkish women in Sweden had a higher prevalence of diabetes than Turkish women in Turkey, 12.8% vs. 7.6% (p = 0.037). Similarly, IGT was 17.8% among Turkish men in Sweden compared to 4.9% among men in Turkey (p < 0.001) and 2-h blood glucose was higher among the immigrants (p < 0.001). Systolic BP was also higher among the immigrants, especially in men (p < 0.001) who also had a higher BMI (p = 0.003).

Conclusions

The higher prevalence of diabetes and IGT among Turkish immigrants in Flemingsberg, Sweden, suggests that migration is associated with diabetes and that there are important implications for public health in Sweden.     

Pazopanib, a multitargeted tyrosine kinase inhibitor, reduces diabetic retinal vascular leukostasis and leakage

Objective

To determine the efficacy of pazopanib eye drops in the streptozotocin induced diabetic retinopathy rat model.

Methods

A 0.5% w/v pazopanib suspension was prepared in phosphate buffered saline (PBS, pH 7.4) in the presence of 0.5% w/v sodium carboxymethyl cellulose. Brown Norway rats were divided into three groups (n = 4) — (1) healthy, (2) diabetic, and (3) diabetic with treatment. The drug suspension was administered twice daily as eye drops to group 3 for 30 days. Efficacy parameters including the number of adherent leukocytes in the retinal vasculature (leukostasis), blood-retinal FITC-dextran leakage, and vitreous-to-plasma protein ratio were measured.

Results

Pazopanib suspension in the form of eye drops significantly reduced leukostasis (32%), FITC-dextran leakage (39%), and the vitreous-to-plasma protein ratio (64%) in diabetic animals compared to untreated diabetic group.

Conclusion

Pazopanib eye drops can alleviate retinal complications of diabetic retinopathy.     

The effects of serum estrogen levels on hypoxemia and blood nitric oxide levels in experimental hepatopulmonary syndrome

Background:

Hepatopulmonary syndrome (HPS) is a well-defined cause of hypoxemia in patients who have liver disease due to abnormal intrapulmonary vascular dilatation. The pulmonary symptoms of HPS are the result of oxygenation defects that occur as a result of acquired dilatations of the pulmonary blood vessels. In this study, we investigated the effects of estrogen and nitric oxide (NO) in experimental HPS, especially in intrapulmonary vascular dilatation.

Methods:

Fifty female Sprague-Dawley rats were used in this study. The animals were divided into five groups of 10. Group l (the control group): the common bile duct (CBD) was dissected but not ligated. Group 2 (the cirrhosis group): the CBD was ligated. Group 3 (the cirrhosis + oophorectomized group): the CBD was ligated and a bilateral oophorectomy performed. Group 4 (the cirrhosis + estrogen group): the CBD was ligated and exogenous estrogen (5000 U/kg) given. Group 5 (the control + estrogen group): the CBD was dissected, but not ligated and exogenous estrogen (5000 U/kg) given. A 5-week waiting period was observed for the development of cirrhosis and the rats’ lungs and liver were taken for histopathological examination. Pulmonary vessel diameters were measured. The total bilirubin, direct bilirubin, alkaline phosphatase (ALP), estrogen and serum nitric oxide (NO) levels were measured.

Results:

The mean perialveolar vessel diameters were significantly higher in the cirrhotic rats (Groups 2, 3, and 4) than the control and control + estrogen administered groups. Again, when we compared the cirrhosis + oophorectomized group and the cirrhosis + estrogen group, the mean perialveolar vessel diameter was significantly lower in the cirrhosis + oophorectomized group than the cirrhosis + estrogen administered group (p = 0.001). The mean perialveolar vessel diameter in the cirrhosis + oophorectomized group was significantly lower than the cirrhosis group (p = 0.01). When we compared the cirrhotic rats (Groups 2, 3, and 4) and the control group, the plasma NO levels were significantly higher in the cirrhotic rats than the control group (p < 0.001). Among the cirrhotic rats, the plasma NO levels were 47.2 ± 0.7 and 70.9 ± 1.5 μmol/l in the cirrhosis + oophorectomized group and the cirrhosis + estrogen administered group, respectively (p = 0.004).

Conclusions:

We consider that raised levels of estrogen have a potential role in intrapulmonary vascular dilatation and hypoxemia in HPS. Also, we consider that this effect of estrogen is due to increased levels of NO. Antiestrogenic surgical therapy may decrease the serum estrogen and NO levels, and may decrease the diameter of perialveolar vessels in order to relieve hypoxia in cirrhotic cases.