The Influence of Oral Magnesium Sulfate on Skin Microvasculature Blood Flow in Diabetic Rats

Microvascular disease is a major feature of type1 diabetes and results from long-standing structural and functional changes especially in the skin microvasculature. Magnesium (Mg) deficiency has recently been proposed as a novel factor implicated in the pathogenesis of diabetes complications such as vascular disturbance, but its mechanism of action is not completely elucidated. The present study was designed to determine whether chronic magnesium sulfate administration could control streptozocin-induced diabetes and improve endothelium-dependent and endothelium-independent dilatation, and identify its probable mechanism in the skin microvasculature of diabetic rats. Fifty male Wistar rats (220?±?10 g) were divided into two diabetic and one control groups. One subgroup of diabetic received magnesium sulfate (10 g/l) in their drinking water, while two other groups had only tap water. Laser Doppler flow meter with iontophoresis was used to measure the relative changes in skin blood flow. We used acetylcholine (Ach), sodium nitroprusside (SNP), and N ^w-nitro-l-arginine (LNNA; NO synthase inhibitor) with magnesium sulfate (0.1 M) in control and experimental animal by microsyringe pump microinjection. SNP- and Ach-induced cutaneous perfusion increased significantly by Mg treatment in the diabetic groups, and local microinjection of magnesium sulfate (0.1 M) increased cutaneous blood flow in all groups (p?<?0.01). However, the administration of LNNA prior to magnesium sulfate attenuated (p?<?0.05) but not abolished the increase in cutaneous blood flow in diabetic and normal rats. From the results of this study, it may be concluded that Mg could improve skin microvasculature of diabetic rats with potentiation of nitric oxide pathway.     

Impaired deformability of erythrocytes in diabetic rat and human: investigation by the nickel-mesh-filtration technique

Comprehensive research to quantify the deformability of erythrocytes in diabetic animals and humans has been lacking. The objective of this study was to compare the impairment of erythrocyte deformability in diabetic rats and patients by use of the same rheologic method. Deformability was investigated in streptozotocin-induced diabetic rats and diabetic patients, by using the highly sensitive and quantitative nickel-mesh-filtration technique. Erythrocyte filterability (whole-cell deformability) was defined as flow rate of hematocrit-adjusted erythrocyte suspension relative to that of saline (%). Hematological and biochemical data for diabetic rats did not differ from those for age-matched control rats except for hyperglycemia and malnutrition. Erythrocyte filterability for diabetic rats was significantly lower than that for control rats (69.4 ± 10.1%, n = 8, compared with 83.1 ± 4.2%, n = 8; p < 0.001). Likewise, erythrocyte filterability for diabetic patients was significantly impaired compared with that for controls (87.6 ± 3.4%, n = 174, compared with 88.6 ± 2.1%, n = 51; p = 0.046). Stepwise multiple regression analysis revealed that this impairment was mostly attributable to associated obesity (BMI, p = 0.029) and glycemic stress (HbA1c(JDS), p = 0.046). We therefore conclude that erythrocyte filterability is commonly impaired in diabetic rats and in humans. Moreover, metabolic risk accumulation further impairs erythrocyte filterability, resulting in derangement of the microcirculation.     

Effect of zinc and melatonin supplementation on cellular immunity in rats with toxoplasmosis

The effects of zinc (Zn) and/or melatonin supplementation on cellular immunity were investigated in rats infested with Toxoplasma gondii. Fifty Sprague-Dawley male rats were used for this study. All animals were fed a normal diet, ad libitum, containing 97 mg Zn/kg. They were divided into five experimental groups, as follows. Group I (n=10) received intraperitoneal injections of zinc sulfate at a dose of 3 mg/kg/d for 3 wk. Group II (n=10) received intraperitoneal injections of melatonin at a dose of 3 mg/kg/d for 3 wk. Group III (n=10) received intraperitoneal injections of zinc sulfate (3 mg/kg/d) and melatonin (3 mg/kg/d) for 3 wk. Group IV (n=10) was infested controls. Group V (n=10) was healthy controls. There were no differences in the percentage of CD3+ lymphocytes among all groups. For groups I–III, the CD4+ and CD8+ ratios were higher than those of the groups IV and V controls (p<0.01). Similarly, the total lymphocyte ratios in groups I–III were higher than those of infested and healthy controls (p<0.01). The total lymphocyte ratios in group III were significantly higher than those of groups I and II (p<0.01). The plasma Zn levels in the supplemented groups were significantly higher than those of control groups IV and V (p<0.01). These results suggest that melatonin and/or Zn supplementation may activate cellular immunity by stimulating CD4+ and CD8+ production in infected rats with T. gondii.     

Zinc supplementation ameliorates glycoprotein components and oxidative stress changes in the lung of streptozotocin diabetic rats

Zinc (Zn) is a component of numerous enzymes that function in a wide range of biological process, including growth, development, immunity and intermediary metabolism. Zn may play a role in chronic states such as cardiovascular disease and diabetes mellitus. Zn acts as cofactor and for many enzymes and proteins and has antioxidant, antiinflammatory and antiapoptotic effects. Taking into consideration that lung is a possible target organ for diabetic complications, the aim of this study was to investigate the protective role of zinc on the glycoprotein content and antioxidant enzyme activities of streptozotocin (STZ) induced diabetic rat tissues. Female Swiss albino rats were divided into four groups. Group I, control; Group II, control + zinc sulfate; Group III, STZ-diabetic; Group IV, diabetic + zinc sulfate. Diabetes was induced by intraperitoneal injection of STZ (65 mg/kg body weight). Zinc sulfate was given daily by gavage at a dose of 100 mg/kg body weight every day for 60 days to groups II and IV. At the last day of the experiment, rats were sacrificed, lung tissues were taken. Also, glycoprotein components, tissue factor (TF) activity, protein carbonyl (PC), advanced oxidative protein products (AOPP), hydroxyproline, and enzyme activities in lung tissues were determined. Glycoprotein components, TF activity, lipid peroxidation, non enzymatic glycation, PC, AOPP, hydroxyl proline, lactate dehydrogenase, catalase, superoxide dismutase, myeloperoxidase, xanthine oxidase, adenosine deaminase and prolidase significantly increased in lung tissues of diabetic rats. Also, glutathione levels, paraoxonase, arylesterase, carbonic anhydrase, and Na⁺/K⁺- ATPase activities were decreased. Administration of zinc significantly reversed these effects. Thus, the study indicates that zinc possesses a significantly beneficial effect on the glycoprotein components and oxidant/antioxidant enzyme activities.     

Effect of troxerutin on insulin signaling molecules in the gastrocnemius muscle of high fat and sucrose-induced type-2 diabetic adult male rat

Troxerutin is a trihydroxyethylated derivative of the flavonoid, rutin. It has been reported to possess the hepatoprotective, nephroprotective, antioxidant, anti-inflammatory, and antihyperlipidemic activities. Troxerutin treatment reduced the blood glucose and glycosylated hemoglobin levels in high-cholesterol-induced insulin-resistant mice and in type-2 diabetic patients. However, the mechanism by which it exhibits antidiabetic property was unknown. Therefore, the present study was designed to evaluate the effect of troxerutin on insulin signaling molecules in gastrocnemius muscle of high fat and sucrose-induced type-2 diabetic rats. Wistar male albino rats were selected and divided into five groups. Group I: Control. Group II: High fat and sucrose-induced type-2 diabetic rats. Group III: Type-2 diabetic rats treated with troxerutin (150 mg/kg body weight/day orally). Group IV: Type-2 diabetic rats treated with metformin (50 mg/kg body weight/day orally). Group V: Normal rats treated with troxerutin (150 mg/kg body weight/day orally). After 30 days of treatment, fasting blood glucose, oral glucose tolerance, serum lipid profile, and the levels of insulin signaling molecules, glycogen, glucose uptake, and oxidation in gastrocnemius muscle were assessed. Diabetic rats showed impairment in insulin signaling molecules (IR, p-IRS-1^Tyr632, p-Akt^Ser473, β-arrestin-2, c-Src, p-AS160^Thr642, and GLUT4 proteins), glycogen concentration, glucose uptake, and oxidation. Oral administration of troxerutin showed near normal levels of blood glucose, serum insulin, lipid profile, and insulin signaling molecules as well as GLUT4 proteins in type-2 diabetic rats. It is concluded from the present study that troxerutin may play a significant role in the management of type-2 diabetes mellitus, by improving the insulin signaling molecules and glucose utilization in the skeletal muscle.     

Protective effects of the nuclear factor kappa B inhibitor pyrrolidine dithiocarbamate in bladder ischemia–reperfusion injury in rats

The aim of the present study was to evaluate the protective effects of the NF-кB inhibition with pyrrolidine-dithiocarbamate (PDTC) in ischemia–reperfusion (I/R) injury in the rat bladder. Twenty-four Sprague-Dawley male rats were divided into three groups. Group I; (n = 8) control, group II; (n = 8) I/R group; group III (n = 8) I/R and PDTC treatment. Superoxide dismutase (SOD), catalase (CAT), and gluatathione-S-transferase (GST) enzymes was studied in bladder tissue. Lipid peroxidation (as TBARS) levels in tissue homogenate were measured with thiobarbituric acid reaction. All the slides were stained with NF-кB, p53 and HSP60 immunohistochemistry for detection genome destruction and tissue stress, respectively. Our results show that the mean TBARS levels were significantly higher in group II (p < 0.05). The TBARS levels were significantly decreased in group III compared with the group II (p < 0.05). CAT, SOD and GST activities were decreased in group II, but these enzymes levels were significantly increased in group III according to the group II (p < 0.05). Under microscopic evaluation NF-кB expression increased significantly in group II compared to the group I (p < 0.05) and then decreased in group III (p < 0.05). HSP60 and p53 expression in group II was increased significantly compared with group I. Under microscopic evaluation we detected that HSP60 and p53 expression was increased significantly in group II compared with group I. In group III PDTC administration was decreased the HSP60 and p53 expression, this difference was statistically significant (p < 0.05). The results of the present study have demonstrated that NF-кB inhibition with PDTC protects and provides beneficial effects on ischemia/reperfusion stress related bladder tissue destruction.     

Contractile properties of the isolated rat soleus muscle and its single skinned soleus fibers at the early stage of gravitational unloading: Facts and hypotheses

The contractile properties of the postural soleus muscle were studied in rats at the early stage of gravitational unloading (three-day hindlimb suspension) with regard to different modes of muscle contraction (twitch and tetanic contraction of the isolated muscle and calcium-induced contraction of isolated skinned fibers). A significant (p < 0.01) enhancement of the peak twitch tension of the muscles of suspended rats without changes in time-dependent characteristics was observed, although the half-relaxation time tended to decrease. The fiber diameter did not change (42.37 ± 0.76 vs. 43.43 ± 1.15 μm in controls). The calcium-induced peak isometric tensions in control and unloaded soleus muscles were 37.6 ± 1.52 and 32.1 ± 1.05 mg, respectively (decrease significant at p < 0.05). No changes in threshold calcium concentration were recorded, but the pCa₅₀ value in unloaded muscles decreased from 6.05 ± 0.02 in controls to 5.97 ± 0.02 (p ≤ 0.05), indicating loss of myofibrillar calcium sensitivity. The cooperativity coefficient ηn in control animals was 3.46 ± 0.16, and in suspended ones it decreased to 3.08 ± 0.11 (p < 0.05). Analysis with the Fluo-4AM calcium probe demonstrated that the intracellular Ca²⁺ concentration increased significantly after hindlimb suspension, whereas the relative contents of titin or nebulin did not change.     

Influence of vanadium supplementation on oxidative stress factors in the muscle of STZ-diabetic rats

In recent years, the role of free radical damage consequent to oxidative stress is widely discussed in diabetic complications. In this aspect, the protection of cell integrity by trace elements is a topic to be investigated. Vanadium is a trace element believed to be important for normal cell function and development. The aim of the present study was to investigate the effect of vanadyl sulfate supplementation on the antioxidant system in the muscle tissue of diabetic rats. Diabetes was induced by intraperitoneal injection of streptozotocin (STZ, 65 mg/kg body weight) to male Swiss albino rats. The rats were randomly divided into 4 groups: Group I, control; Group II, vanadyl sulfate control; Group III, STZ-diabetic untreated; Group IV, STZ-diabetic treated with vanadyl sulfate. Vanadyl sulfate (100 mg/kg) was given daily by gavage for 60 days. At the last day of the experiment, rats were killed, muscle tissues were taken, homogenized in cold saline to make a 10% (w/v) homogenate. Body weights and blood glucose levels were estimated at 0, 30 and 60th days. Antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx), glutathione-S-transferase (GST), as well as carbonic anhydrase (CA), myeloperoxidase (MPO) activities and protein carbonyl content (PCC) were determined in muscle tissue. Vanadyl sulfate administration improved the loss in body weight due to STZ-induced diabetes and decreased the rise in blood glucose levels. It was shown that vanadium supplementation to diabetic rats significantly decrease serum antioxidant enzyme levels, which were significantly raised by diabetes in muscle tissue showing that this trace element could be used as preventive for diabetic complications.     

The effect of muscle fatigue on the isometric contractile characteristics of skeletal muscle in the cat

The rise time of an isometric twitch, the tetanic tension, the twitch tetanus ratio, the frequency-tension relationship, and the height of the MUAP (motor unit action potential) were measured in fast twitch (medial gastrocnemius) and slow twitch (soleus) muscles of the cat immediately before, in the middle, and immediately after fatiguing isometric contractions at tensions of 30, 50 and 80% of each muscle's initial strength (tetanic tension recorded from the unfatigued muscle). Although the twitch-tetanus ratio was always less for the soleus than for the medial gastrocnemius muscles, the twitch-tetanus ratio for any one muscle was constant throughout the duration of fatiguing isometric contractions at any of the tensions examined. In contrast, the twitch tension and tetanic tension of the muscles were both less after the contractions, the largest reduction occurring for both muscles during contractions sustained at the lowest isometric tensions. The time to peak tension of an isometric twitch was prolonged for both muscles following the contractions. This was associated with a corresponding shift in the frequency tension relationship such that at the point of muscular fatigue, the muscles tetanized at lower frequencies of stimulation than did the unfatigued muscle. In contrast, the amplitude of the MUAP showed only a modest reduction throughout the duration of the fatiguing contractions.     

Ultrasound-Microbubble Transplantation of Bone Marrow Stromal Cells Improves Neurological Function after Forebrain Ischemia in Adult Mice

In this study, bone marrow stromal cells (MSCs) were transplanted into the brain of adult rats after forebrain ischemia induced by 4VO. SD rats (n = 60) were randomly divided into three groups: (I) rats (n = 20) were subjected to 4VO and transplanted with MSCs into the ischemic region using ultrasound-microbubble method, (2) rats (n = 20) were subjected to 4VO and transplanted with MSCs into the ischemic region (n = 20), and (3) 4VO alone (n = 20). Rats were sacrificed 28 days after treatment. Neurological functions of rats were evaluated by Morris Water Maze. The current findings suggest that the ultrasound microbubble transplanted MSCs survived in the ischemic brain and significantly improved functional recovery of adult rats compared to regular transplantation.     

Multichannel EMG-based estimation of fiber conduction velocity during isometric contraction of patients with different stages of diabetic neuropathy

This study compares muscle fiber conduction velocities estimated using surface electromyography during isometric maximal voluntary contraction in different stages of diabetic neuropathy. Eighty-five adults were studied: 16 non-diabetic individuals and 69 diabetic patients classified into four neuropathy stages, defined by a fuzzy expert system: absent (n = 26), mild (n = 21), moderate (n = 11) and severe (n = 11). Average muscle fiber conduction velocities of gastrocnemius medialis, tibialis anterior, vastus lateralis and biceps femoris were assessed using linear array electrodes, and were compared by ANOVA. Conduction velocities were significantly decreased in the moderate neuropathy group for the vastus lateralis compared to other groups (from 18% to 21% decrease), and were also decreased in all diabetic groups for the tibialis anterior (from 15% to 20% from control group). Not only the distal anatomical localization of the muscle affects the conduction velocity, but also the proportion of muscle fiber type, where the tibialis anterior with greater type I fiber proportion is affected earlier while the vastus lateralis with greater type II fiber proportion is affected in later stages of the disease. Generally, the muscles of the lower limb have different responsiveness to the effects of diabetes mellitus and show a reduction in the conduction velocity as neuropathy progresses.     

Impact of repeated intravenous bone marrow mesenchymal stem cells infusion on myocardial collagen network remodeling in a rat model of doxorubicin-induced dilated cardiomyopathy

Bone marrow mesenchymal stem cells (MSCs) transplantation improved cardiac function and reduced myocardial fibrosis in both ischemic and non-ischemic cardiomyopathies. We evaluated the effects of repeated peripheral vein injection of MSCs on collagen network remodeling and myocardial TGF-β1, AT1, CYP11B2 (aldosterone synthase) gene expressions in a rat model of doxorubicin (DOX)-induced dilated cardiomyopathy (DCM). Thirty-eight out of 53 SD rats survived at 10 weeks post-DOX injection (2.5 mg/kg/week for 6 weeks, i.p.) were divided into DCM blank (without treatment, n = 12), DCM placebo (intravenous tail injection of 0.5 mL serum-free culture medium every other day for ten times, n = 13), and DCM plus MSCs group (intravenous tail injection of 5 × 10⁶ MSCs dissolved in 0.5 mL serum-free culture medium every other day for 10 times, n = 13). Ten untreated rats served as normal controls. At 20 weeks after DOX injection, echocardiography, myocardial collagen content, myocardial expressions of types I and III collagen, TGF-β1, AT1, and CYP11B2 were compared among groups. At 20 weeks post-DOX injection, 8 rats (67 %) survived in DCM blank group, 9 rats (69 %) survived in DCM placebo group while 13 rats (100 %) survived in DCM plus MSCs group. Left ventricular end-diastolic diameter was significantly higher and ejection fraction was significantly lower in DCM blank and DCM placebo groups compared to normal control rats, which were significantly improved in DCM plus MSCs group (all p < 0.05 vs. DCM blank and DCM placebo groups). Moreover, myocardial collagen volume fraction, types I and III collagen, myocardial mRNA expressions of TGF-β1, AT1, CYP11B2, and collagen I/III ratio were all significantly lower in DCM plus MSCs group compared to DCM blank and DCM placebo groups (all p < 0.05). Repeated intravenous MSCs transplantation could improve cardiac function by attenuating myocardial collagen network remodeling possibly through downregulating renin–angiotensin–aldosterone system in DOX-induced DCM rats.     

Circulating proinflammatory cytokines and N-terminal pro-brain natriuretic peptide significantly decrease with recovery of left ventricular function in patients with dilated cardiomyopathy

Background Increased levels of TNF-α, IL-6, their soluble receptors, and NT-proBNP have been observed in patients with dilated cardiomyopathy (DCM). In the present study, we assessed the possible involvement of proinflammatory cytokines and their soluble receptors with and without recovery of LV function in DCM patients. Methods and results Forty patients with DCM were enrolled and divided into two groups: Group I consisted of DCM patients (n = 30) whose left ventricular ejection fraction (LVEF) had not recovered on follow up and Group II comprised DCM patients (n = 10) whose LVEF had recovered. Ten healthy subjects were included as controls (Group III). TNF-α, IL-6,TNFR1, TNFRII, gp130, and NT-proBNP levels were significantly increased in Group I and were significantly lower in patients with LVEF recovery as compared to those without recovery of LVEF (P < 0.05). Conclusion Circulating TNF-α, IL-6, and NT-proBNP appear to correlate with the LV function recovery of patients with DCM and could be used as prognostic biomarkers.     

Upregulation of microRNA-146a was not accompanied by downregulation of pro-inflammatory markers in diabetic kidney

The present study was designed to evaluate whether microRNA-146a and its adapter proteins (TRAF6 and IRAK1) are involved in the pathogenesis of diabetes-induced kidney damage. Male Sprague–Dawley rats were divided into control and diabetic groups (n = 6 in each). Diabetes was induced by injection of streptozotocin (55 mg/kg; i.p.) in 12 h fasted rats. Diabetic kidney damage was diagnosed by renal hypertrophy, thickened glomerular basement membrane, widened filtration slits, mesangial expansion, as well as by elevated levels of blood urea and creatinine in diabetic rats 2 months after induction of diabetes. While the expression of NF-κB mRNA and miR-146a were increased in diabetic kidney compared to the sham controls (p < 0.01 for both comparisons), the mRNA levels of IRAK1 and TRAF6 did not statistically reduce. The NF-κB activity and the concentrations of TNF-α, IL-6 and IL-1β in the kidney of diabetic rats were higher than the kidney of controls (p < 0.05 for TNF-α and NF-κB; p < 0.01 for IL-6 and IL-1β). Our results indicate that the upregulation of miR-146a was not accompanied by downregulation of inflammatory mediators in diabetic kidney. It is possible that a defect in the miR-146a-mediated negative loop provides a situation for sustained activation of NF-κB and its targets to promote cells toward abnormalities.     

Classifying the Stage IV Colorectal Cancer: Prognostic Impact of Radical Resection for Colorectal liver Metastases and Proposal for a New Staging System

Currently, there is no universally accepted system to classify the stage IV colorectal cancer. Here, we analyze the prognostic impact of radical resection for colorectal liver metastases and propose a new staging system for stage IV colorectal cancer. A retrospective review was undertaken of 126 consecutive patients who underwent surgical treatment for colorectal liver metastases from January 1997 to January 2004. Based on the overall survival rates (Kaplan–Meier method) and surgical outcomes, we propose a new staging system for stage IV colorectal cancer. Patients were divided into two groups: patients who underwent initial hepatic resections (R0 resection) for liver metastases (group 1, n = 22), and patients who underwent palliative resection for unresectable liver metastases (group 2, n = 104). The overall survival rates in group 1 at 1, 3, and 5 years were 68.2 % (15/22), 40.9 % (9/22), and 18.2 % (4/22), respectively. The overall survival rates in group 2 at 1, 3, and 5 years were 54.8 % (57/104), 16.3 % (17/104), and 0 % (0/104), respectively. There was a significant difference in overall survival rates between both groups (p < 0.05). Based on the study results, we propose a new staging system where all distant metastases are grouped within stage IV and subclassified into resectable (R0 resection) and unresectable stages. Curative surgical treatment is a critical prognostic factor in colorectal liver metastases. The proposed new staging system for stage IV colorectal cancer is simple and is clinically useful to estimate the prognosis.     

Downregulation of Apoptosis and Modulation of TGF-β1 by Sodium Selenate Prevents Streptozotocin-Induced Diabetic Rat Renal Impairment

To investigate whether sodium selenate treatment would impact on the onset of diabetic nephropathy, we examined blood glucose, serum biochemical components, and interrelationship between oxidative stress, TGF-β1, and apoptosis in streptozotocin (STZ) induced diabetic rats. Sixty male Wistar rats were divided into six groups. Group I (n = 10), normal control; Group II (n = 10), diabetic control; Group III (n = 10), sodium selenate (16 μmoles/kg) + diabetic; Group IV (n = 10), sodium selenate (32 μmoles/kg) + diabetic; Group V (n = 10), sodium selenate (16 μmoles/kg) control; and Group VI (n = 10), sodium selenate (32 μmoles/kg) control. Sodium selenate was administered via orogastric route for 10 weeks. In the diabetic group, diabetes was induced by single intraperitoneal injection of STZ (50 mg/kg). The levels of blood glucose were estimated and total cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, creatinine, urea, and albumin were detected in serum. Antioxidant status was examined by measuring the superoxide dismutase (SOD), catalase, glutathione, and lipid peroxidation in kidney tissues. Histopathological studies were performed in the kidney tissue sections. The expression of TGF-β1 was estimated by the immunohistochemical analysis in kidneys. Apoptotic study in kidney was performed using the TdT-mediated dUTP nick end labeling technique. It was observed that blood glucose, serum, total cholesterol, HDL cholesterol, triglycerides, creatinine, urea, and albumin were significantly higher in diabetic control groups. Diabetic + sodium selenate (16 and 32 μmoles/kg) significantly reduced blood glucose, serum, total cholesterol, HDL cholesterol, triglycerides, creatinine, urea, and albumin levels. Selenium-treated groups significantly increased antioxidant enzyme activities (SOD, catalase, and glutathione) in kidneys of diabetic rats. All enzyme activities of selenium control groups did not differ compared with the normal control. Sodium selenate reduces significantly lipid peroxidation in diabetic rats. Cellular architecture of the diabetic rats was altered whereas sodium selenate administration rectifies the degenerative changes of the kidney. Profound immunopositivity of TGF-β1 was observed in the glomerular and tubulointerstitial cells of diabetic rat kidney. Immunopositivity of TGF-β1 was significantly reduced in both low and high dose of sodium-selenate-treated rats (P < 0.05, P < 0.01). High numbers of apoptotic cells were observed in diabetic rats whereas sodium selenate in both doses significantly reduces the incidence of apoptosis (P < 0.05, P < 0.01). We conclude herein that sodium selenate has the potential to play a significant role in limiting the renal impairment by altering the apoptosis and TGF-β1 in experimental diabetic rats.     

Effect of the duration of infusion of urogastrone* on intestinal regeneration in rabbits

Abstract Urogastrone (UG) increases the rate of mucosal regeneration on patched intestinal defects. Our aim was to determine the effect of the duration of UG administration on regeneration of serosa patched ileal defects in rabbits. Group I (n= 18) were controls. Group II (n= 15), Group III (n= 10) and Group IV (n= 5) received UG 1.5 μ/kg/h subcutaneously for 7 days, 14 days or 21 days respectively. Animals were sacrificed at 7 day intervals up to 21 days after patching. Neomucosal growth was significantly greater in the animals receiving UG and was greatest in Group IV. Group II and III animals had less contraction of the patched defect and greater neomucosal surface area than Group I animals at each interval but had a lesser effect than animals receiving UG continuously. Crypt cell production rate was significantly greater in UG treated animals at 7 and 14 days but fell to control levels at 21 days. Prolonging the duration of UG infusion increased the quantity of neomucosa produced by intestinal regeneration. However, UG stimulation of mucosal cell migration and proliferation occurred transiently within 14 days after patching.     

Myometrial LH/hCG receptors during the estrous cycle and pregnancy in pigs

Receptors for luteinizing hormone/human chorionic gonadotropin (LH/hCG) have been identified in porcine, rabbit, rat, and human myometrium. To determine the estrous cycle and pregnancy related changes in the receptor capacity and affinity, radioreceptor assays were performed with membrane homogenates of porcine uterine tissues. Cycling gilts were divided into four experimental groups: I (n=6), day 1–2; II (n=5), day 6–7; III (n=5), day 11–12; and IV (n=6), day 18–20 of the estrous cycle. Pregnant pigs were divided into three experimental groups: I (n=5), day 35–40; II (n=5), day 65–70; and III (n=4), day 95–105 of pregnancy. The concentrations [femtomoles/mg protein (fmol/mg protein)] and affinities of unoccupied LH/hCG binding sites were characterized in all samples of myometrium. Receptor concentrations were highest (P<0.01) in groups II and III (19.3±2.5 and 35.8±2.1 fmol/mg protein, respectively), and was lowest in groups I and IV (5.3±1.4 and 7.5±0.7 fmol/mg protein, respectively). Receptor affinity constants (K_a) were consistent (P>0.05) throughout the estrous cycle [I, (5.1±1.5)×10⁹; II, (3.0±0.8)×10⁹; III, (3.2±0.9)×10⁹; IV, 5.5±0.7×10⁹ lm⁻¹]. Plasma hormone concentrations of progesterone, estrogen and LH were typical of values noted at these times. During pregnancy, receptor concentrations were greatest (P<0.05) in group II (85.4±18.5 fmol/mg protein). In groups I and III receptor numbers were 10.8±2.3 and 26.7±6.6 fmol/mg protein, respectively. The K_a in group I was 10 times greater (P<0.05) than K_a in groups II and III, (I, 3.1±0.9×10¹⁰ lm⁻¹; II, 3.4±0.3×10⁹ lm⁻¹; III, 3.3±1.1×10⁹ lm⁻¹). Plasma hormone concentrations typically found during pregnancy were noted. The function of these LH/hCG binding sites remains unknown; however, changes in receptor capacity during the estrous cycle and pregnancy support a role for modulation of the receptor by hormonal factors.     

Bioavailability and metabolism of fucoxanthin in rats: structural characterization of metabolites by LC-MS (APCI)

This study reports bioavailability and metabolism of fucoxanthin (FUCO) from brown algae Padina tetrastromatica in rats. Rats were divided into two groups (n = 25/group). Group one was fed basal diet (control) while the group two received retinol deficient diet (RD group) for 8 weeks. After confirmed RD in blood (0.53 μmol/l), rats were further sub-grouped (n = 5/sub group), intubated a dose of FUCO (0.83 μmol) and killed after 0, 2, 4, 6 and 8 h. The plasma levels (area under curve/8 h) of FUCO (fucoxanthinol (FUOH) + amarouciaxanthin (AAx)) was 2.93 (RD group) and 2.74 pmol/dl (control), respectively. No newly formed retinol was detected in RD rats intubated with FUCO. Besides FUOH (m/z 617 (M+H)⁺) and AAx (m/z 617 (M+H^?)⁺), other deacetylated, hydrolyzed and demethylated metabolites of bearing molecular mass at m/z 600.6 (FUOH–H₂O), m/z 597 (AAx–H₂O), m/z 579 (AAx–2H₂O+1), m/z 551 (AAx–2H₂O–2CH₃+2) and m/z 523 (AAx–2H₂O–4CH₃+4) were also detected in plasma and liver by LC-MS (APCI). Although biological functions of FUCO metabolites need thorough investigation, this is the first detailed report on FUCO metabolites in rats.     

The PPARβ/δ agonist GW0742 modulates signaling pathways associated with cardiac myocyte growth via a non-genomic redox mechanism

The aim was to explore the effects of rapamycin on autophagy and injury of podocytes in streptozocin (STZ)-induced type 1 diabetic mice, and its role in delaying progression of diabetic nephropathy. In this study, male Balb/c mice were divided into three groups: control (n = 12), STZ-induced diabetic (n = 12), and rapamycin-treated diabetic (DM + Rapa) (n = 12), which received intraperitoneal injection of rapamycin (2 mg/kg/48 h) after induction of DM. Levels of urinary albumin (UA), blood urea nitrogen, serum creatinine, and kidney weight/body weight were measured at week 12. Renal pathologic changes, number of podocytes autophagy, and organelles injury were investigated by PAS staining, transmission electron microscopy, and immunofluorescence staining, respectively. Western blot was performed to determine the expression of LC3 (a podocyte autophagy marker), phosphorylated mammalian target of rapamycin, p-p70S6K, bax, and caspase-3 protein. Podocytes count was evaluated by immunofluorescence staining and Wilms tumor 1 immunohistochemistry, and Western blot of nephrin and podocin. The results indicated that rapamycin could reduce the kidney weight/body weight and UA secretion. It could alleviate podocyte foot process fusion, glomerular basement membrane thickening, and matrix accumulation, and increase the number of autophagosomes, and LC3-expressing podocytes. Down-regulation of bax and caspase-3 protein, and up-regulation of nephrin and podocin protein were observed in the glomeruli of diabetic mice after administration of rapamycin. In conclusion, rapamycin can ameliorate renal injury in diabetic mice by increasing the autophagy activity and inhibition of apoptosis of podocytes.