Renal effects of long-term leptin infusion and preventive role of losartan treatment in rats

BACKGROUND: Leptin has direct and indirect effects on renal pathophysiological characteristics. In the present study, the effects of long-term leptin infusion on the renal hemodynamics, renal excretory functions, and the expression of transforming growth factor-beta (TGF-beta), plasma endothelin-1 (ET-1) levels, and preventive effects of the angiotensin II type 1 receptor antagonist, losartan, on these renal changes were evaluated. METHODS: The study was performed by using forty Wistar albino rats. On day 0, osmotic mini-pumps filled with leptin or placebo were intraperitoneally placed under sterile conditions. The rats in Group L (Leptin group, n=15) and Group LL (Leptin-losartan group, n=15) were given recombinant murine leptin at a rate of 250 ng per hour for 28 days. Control rats (Group C, n=10) were administered placebo at the same infusion rate. The rats in Group LL were also administered losartan (10 mg kg(-1) d(-1)) perorally for 28 days. On day 28, the rats were placed in metabolic cages, and the food and water intakes were determined, and the urine was collected for 24 h. At the end of the study, systolic blood pressure (SBP), diastolic blood pressure (DBP) were determined directly from the left femoral artery, and renal blood flow (RBF) was recorded indirectly using a laser Doppler flow module. RESULTS: Leptin infusion did not produce any changes in systemic arterial blood pressures and urinary flow rate. The rates of creatinine (Cr), sodium (Na), and protein excretions of the animals infused leptin were significantly increased. The urinary Cr and Na excretions were decreased, while the urinary protein excretion was normalized with the losartan treatment. The rats infused leptin had also higher circulating ET-1 levels. ET-1 levels were also reversed to the normal values with the losartan treatment. Renal TGF-beta1 expression was determined immunohistochemically, and it was more prominent in the renal tubules from the rats treated with leptin. The losartan treatment had no effect on renal TGF-beta1 expression. CONCLUSIONS: Our results indicate that pathophysiological increases in plasma leptin concentrations cause enhanced renal Na, Cr and protein excretions, and high circulating ET-1 levels. Na and Cr excretions were decreased, while proteinuria and plasma ET-1 levels were normalized by losartan treatment, suggesting that renin-angiotensin system activation may have a role in leptin induced renal changes. TGF-beta1 may have an important role in leptin induced nephropathy.     

Comparison of partial excision with simple section of the transverse carpal ligament in the treatment of carpal tunnel syndrome

In the surgical treatment of carpal tunnel syndrome, debate has commonly focused on whether decompression should be performed by open or blind techniques. Contrarily, the goal of the present study was to determine whether instead of simple section, partial excision of the transverse carpal ligament has contributed to better results. Because complete healing of the transverse carpal ligament observed during reoperations has been reported elsewhere, the charts of 75 carpal tunnel syndrome patients who had been treated with open technique at Dokuz Eylül University were reviewed. Statistical analysis was performed using the Fisher's exact test and Student's t test when appropriate. Thirty-five patients had been treated with simple section of the transverse carpal ligament, whereas 40 had been treated with partial excision. Internal neurolysis was also performed in 19 of the patients, 11 of whom were treated with partial excision. The average follow-up time was 3.8 years. The comparisons regarding the overall operative outcomes did not show any significant difference between the two different techniques of releasing the transverse carpal ligament. In patients treated without neurolysis, results of partial excision of the transverse carpal ligament improved when compared with those of simple section, but this superiority was not statistically significant. There seemed to be statistically higher reoperation rates and worse outcomes after neurolysis (p < 0.05). Reoperation was required in eight patients (11 percent). Five of the patients who underwent reoperation had initially been treated with partial excision and neurolysis, whereas two had been treated with simple section and neurolysis. Another patient who had undergone reoperation had initially undergone only simple section. The mean time to return to work or daily activities did not differ between the types of applied technique for releasing the transverse carpal ligament. However, neurolysis lengthened these periods significantly when performed (p < 0.05). In the present study, partial excision of the transverse carpal ligament without adding neurolysis offered relatively better results than simple section. Verification of this finding endoscopically, if applicable, may improve the success rate of surgical therapy in patients with carpal tunnel syndrome.     

Mixed Herbs Drugs: Inhibitory Effect on Growth of the Endogenous Mycoflora and Aflatoxin Production

Twenty commercial mixed herbal drugs were examined for mycological profile. Aspergillus species were the predominant fungi found in the drugs. Other fungi harboured in the drugs with less frequency were Paecilomyces species, Eurotium species, Monascus species, Acremonium species, Penicillium species, Cladosporium species, Scopulariopsis species, Phialophora species and Fonseceae species. Fungal count was between 1.0 log₁₀ CFU and 2.4 log₁₀ CFU per gram of sample. When the drugs were incubated in 85% humidity at 25°C, fungal colonies grew on only two of the drugs. The mixed herbal drugs were extracted with water and the extracts were used to grow Aspergillus parasiticus. All extracts reduced aflatoxin B₁ and aflatoxin G₁ production by 62–97%. All but two of the extracts reduced aflatoxin B₂ and aflatoxin G₂ production by 39–95%. It can be concluded that the commercial powdered mixed herbal drugs contained low number of endogenous fungi, and these drugs are inhibitory to the growth of its endogenous fungi and aflatoxins production by aflatoxigenic fungi.     

Increased sister chromatid exchanges in workers exposed to occupational lead and Zinc

Sister chromatid exchange (SCE) in blood lymphocytes was determined in 32 male workers occupationally exposed to lead (Pb) and zinc (Zn) and in 20 controls matched for age and smoking habits. Exposed workers have higher SCE mean values than control workers (p < 0.01). In exposed persons, blood Pb concentrations were also significantly higher than controls (p < 0.0001), but the difference between Zn levels in the blood of these groups was not found to be significant (p > 0.05). Our results indicate that Pb may be genotoxic and harmful to human health.     

Role of Oxidative Stress and Ca2+ Signaling on Molecular Pathways of Neuropathic Pain in Diabetes: Focus on TRP Channels

Diabetes mellitus, a debilitating chronic disease, affects ~100?million people. Peripheral neuropathy is one of the most common early complications of diabetes in ~66?% of these patients. Altered Ca(2+) handling and Ca(2+) signaling were detected in a huge variety of preparations isolated from animals with experimentally induced type 1 and 2 diabetes as well as patients suffering from the disease. We reviewed the role of Ca(2+) signaling through cation channels and oxidative stress on diabetic neuropathic pain in sensory neurons. The pathogenesis of diabetic neuropathy involves the polyol pathway, advanced glycation end products, oxidative stress, protein kinase C activation, neurotrophism, and hypoxia. Experimental studies with respect to oxidative stress and Ca(2+) signaling, inhibitor roles of antioxidants in diabetic neuropathic pain are also summarized in the review. We hypothesize that deficits in insulin, triggers alterations of sensory neurone phenotype that are critical for the development of abnormal Ca(2+) homeostasis and oxidative stress and associated mitochondrial dysfunction. The transient receptor potential channels are a large family of proteins with six main subfamilies. The sheer number of different TRPs with distinct functions supports the statement that these channels are involved in a wide range of processes ranging in diabetic neuropathic pain and it seems that the TRPC, TRPM and TRPV groups are mostly responsible from diabetic neuropathic pain. In conclusion, the accumulating evidence implicating Ca(2+) dysregulation and over production of oxidative stress products in diabetic neuropathic pains, along with recent advances in understanding of genetic variations in cation channels such as TRP channels, makes modulation of neuronal Ca(2+) handling an increasingly viable approach for therapeutic interventions against the painful and degenerative aspects of many diabetic neuropathies.     

Association between IL-18 gene polymorphisms and Hashimoto thyroiditis

Molecular Biology Reports - Hashimoto’s thyroiditis (HT), which is also called lymphocytic thyroiditis, is the most frequent autoimmune thyroid disease (AITD), in which T helper-1 lymphocytes...     

Activation of pine cone using Fenton oxidation for Cd(II) and Pb(II) removal

This paper describes activation of pine cone with Fenton reagent and determines the removal of Cd(II) and Pb(II) ions from aqueous solution. Changes of the surface properties of adsorbent materials were determined by the FT-IR and SEM analysis after activation of pine cone. The effect of Fe(2+)/H(2)O(2) ratio, ORP, pH and contact time were determined. Different adsorption isotherms were also obtained using concentrations of heavy metal ions ranging from 0.1 to 150mgL(-1). The adsorption process follows pseudo-first-order reaction kinetics and follows the Langmuir adsorption isotherm. The study discusses thermodynamic parameters, including changes in Gibbs free energy, entropy, and enthalpy, for the adsorption of Cd(II) and Pb(II) on activated cone, and revealed that the adsorption process was spontaneous and exothermic under natural conditions. The maximum removal efficiencies were obtained as 91% and 89% at pH 7 with 90 and 105-min contact time for Cd(II) and Pb(II), respectively.     

Global analysis of satellite tracking data shows that adult green turtles are significantly aggregated in Marine Protected Areas

Aim Tracking technologies are often proposed as a method to elucidate the complex migratory life histories of migratory marine vertebrates, allowing spatially explicit threats to be identified and mitigated. We conducted a global analysis of foraging areas of adult green turtles (Chelonia mydas) subject to satellite tracking (n= 145) and the conservation designation of these areas according to International Union for Conservation of Nature criteria. Location The green turtle has a largely circumtropical distribution, with adults migrating up to thousands of kilometres between nesting beaches and foraging areas, typically in neritic seagrass or algal beds. Methods We undertook an assessment of satellite tracking projects that followed the movements of green turtles in tropical and subtropical habitats. This approach was facilitated by the use of the Satellite Tracking and Analysis Tool ( http://www.seaturtle.org ) and the integration of publicly available data on Marine Protected Areas (MPAs). Results We show that turtles aggregate in designated MPAs far more than would be expected by chance when considered globally (35% of all turtles were located within MPAs) or separately by ocean basin (Atlantic 67%, Indian 34%, Mediterranean 19%, Pacific 16%). Furthermore, we show that the size, level of protection and time of establishment of MPAs affects the likelihood of MPAs containing foraging turtles, highlighting the importance of large, well‐established reserves. Main conclusions Our findings constitute compelling evidence of the world‐wide effectiveness of extant MPAs in circumscribing important foraging habitats for a marine megavertebrate.     

Protective Effects of Onion Extract on Cadmium-Induced Oxidative Stress,Histological Damage,and Apoptosis in Rat Heart

To date, there is no available information on the protective effect of onion (Allium cepa) extract (AcE) on cadmium (Cd)-induced cardiotoxicity. The present study was performed to assess the possible antioxidant and anti-apoptotic roles of AcE in Cd-induced cardiotoxicity in rats. A Cd group was injected subcutaneously with CdCl₂ dissolved in saline at a dose of 2 ml/kg/day for 30 days, resulting in a dosage of 1 mg/kg Cd. The rats in the AcE-treated group were given 1 ml of AcE via intragastric intubation for 30 days. The rats intoxicated with Cd for 30 days showed increased tissue malondialdehyde (MDA) levels and decreased levels of the enzymatic antioxidants superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) in cardiac tissue. AcE attenuated these adverse effects of Cd. After Cd exposure, histological abnormalities were observed, including myofibrillar loss, vacuolization of cytoplasm and irregularity of myofibrils. These histological alterations were effectively attenuated by the treatment with AcE. Furthermore, our data indicate a significant reduction of apoptosis in the cardiomyocytes of the Cd group treated with AcE therapy. Animal studies show antioxidant effects of AcE. But to date, no study reported the effect of AcE on biochemical and histopathological changes due to Cd induced on rat heart. Our study showed that AcE therapy reduced Cd-induced oxidative stress and apoptosis, possibly through its antioxidant and anti-apoptotic activity.     

Role of the Phosphatase PTEN in Early Vascular Remodeling

Background

The phosphatase PTEN represents an important physiological inhibitor of phosphatidylinositol-3 kinase (PI3-K)/protein kinase B (Akt) signalling, however, the functional role of PTEN in the initial phase of angioplasty-induced vascular injury remains elusive. In the present study we sought to determine PTEN''s effect on vascular smooth muscle cell (VSMC) apoptosis following acute injury in vivo and in vitro.

Methods and Results

Immunohistochemistry indicated a faint basal expression and equal distribution of PTEN in uninjured rat carotid arteries. 12 h following balloon-injury, PTEN expression was strongly increased in apoptotic (TUNEL+) VSMC. In vitro, stimulation with serum or different growth factors or subjecting VSMC to cyclic stretch had no effect on PTEN expression, whereas stimulation with H₂O₂ robustly increased PTEN expression in a time- and dose-dependent manner. To evaluate the functional role of PTEN expression, human VSMC were transduced with WT-PTEN. Overexpression of PTEN increased the number of apoptotic VSMC (19.8%±4.4 vs. 5.6%±2.3; P<0.001) as determined by TUNEL assay. In contrast, siRNA-mediated knock-down of PTEN attenuated the basal as well as H₂O₂-induced apoptosis of VSMC. Mechanistically, overexpression of PTEN prevented serum-induced Akt-phosphorylation, whereas siRNA-mediated knock down of PTEN augmented Akt-activation. Moreover, co-transfection of PTEN and a constitutive active Akt mutant prevented PTEN-dependent augmentation of VSMC apoptosis, indicating, that PTEN regulates VSMC apoptosis by inhibition of Akt phosphorylation/activation.

Conclusion

By interfering with the PI3-K/Akt-dependent survival signalling, the oxidative stress-induced up regulation of PTEN in VSMC of injured arteries augments the sensitivity of VSMC to apoptotic stimuli in the early phase following vascular injury, augmenting the initial injury and cell loss of the injured vessel wall. Thus, these data add to our understanding of PTEN''s role during vascular remodelling.