Propofol Protects Against Focal Cerebral Ischemia via Inhibition of Microglia-Mediated Proinflammatory Cytokines in a Rat Model of Experimental Stroke

Ischemic stroke induces microglial activation and release of proinflammatory cytokines, contributing to the expansion of brain injury and poor clinical outcome. Propofol has been shown to ameliorate neuronal injury in a number of experimental studies, but the precise mechanisms involved in its neuroprotective effects remain unclear. We tested the hypothesis that propofol confers neuroprotection against focal ischemia by inhibiting microglia-mediated inflammatory response in a rat model of ischemic stroke. Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 2 h followed by 24 h of reperfusion. Propofol (50 mg/kg/h) or vehicle was infused intravenously at the onset of reperfusion for 30 minutes. In vehicle-treated rats, MCAO resulted in significant cerebral infarction, higher neurological deficit scores and decreased time on the rotarod compared with sham-operated rats. Propofol treatment reduced infarct volume and improved the neurological functions. In addition, molecular studies demonstrated that mRNA expression of microglial marker Cd68 and Emr1 was significantly increased, and mRNA and protein expressions of proinflammatory cytokines tumor necrosis factor-α, interleukin-1β and interleukin-6 were augmented in the peri-infarct cortical regions of vehicle-treated rats 24 h after MCAO. Immunohistochemical study revealed that number of total microglia and proportion of activated microglia in the peri-infarct cortical regions were markedly elevated. All of these findings were ameliorated in propofol-treated rats. Furthermore, vehicle-treated rats had higher plasma levels of interleukin-6 and C-reactive protein 24 h after MCAO, which were decreased after treatment with propofol. These results suggest that propofol protects against focal cerebral ischemia via inhibition of microglia-mediated proinflammatory cytokines. Propofol may be a promising therapeutic agent for the treatment of ischemic stroke and other neurodegenerative diseases associated with microglial activation.     

Anesthetic ketamine counteracts repetitive mechanical stress-induced learning and memory impairment in developing mice

The aim of this study is to investigate whether ketamine, a noncompetitive N-methyl-d-aspartate receptor (NMDAR) antagonist, had an influence on learning and memory in developing mice. Fifty Kunming mice aged 21 days were randomly divided into 5 subgroups (n = 10 for each) to receive intraperitoneal injection of equal volume of saline (S group) or ketamine (25, 50 or 100 mg/kg of body weight/day) for 7 consecutive days, or to be left untreated (C group). A step-down passive avoidance test was performed to evaluate learning and memory in these mice on days 8 and 9. Additionally, the expression of brain-derived neurotrophic factor (BDNF) in the hippocampus was determined. Rats receiving saline or sub-anesthetic dose of ketamine (25 mg/kg) showed significantly decreased abilities of learning and memory and reduced expression of BDNF, compared to the normal controls (P < 0.05). In contrast, comparable abilities of learning and memory and expression of BDNF were found for anesthetic doses of ketamine (50 or 100 mg/kg)-treated rats and controls (P > 0.05). Repetitive mechanical stress impairs learning and memory performance in developing mice, which may be associated with decreased BDNF expression. The stress-induced learning and memory impairment can be prevented by anesthetic doses of ketamine.     

Circulating progesterone dynamics after intravaginal instillation of prostaglandin-F2α to lactating dairy cows

Our objectives were to evaluate circulating progesterone (P4) concentration dynamics and test the feasibility of inducing luteal regression after intravaginal (IVG) instillation of the PGF2α analogue dinoprost (PGF) in lactating dairy cows. In two experiments, cows were synchronized using the Ovsynch protocol to induce the formation of a corpus luteum (CL). Cows with at least one functional (P4 ≥1 ng/mL) CL ≥15 mm 7.5 days after Ovsynch remained in the studies. In experiment 1, cows (n = 31) were stratified by parity group and received 5 mL of saline IVG (SAL-IVG, n = 6), 25 mg of PGF intramuscular (IM) (PGF25-IM, n = 7), 25 mg of PGF IVG (PGF25-IVG, n = 6), 50 mg of PGF IVG (PGF50-IVG, n = 6), and 125 mg of PGF IVG (PGF125-IVG, n = 6). Experiment 2 was conducted to test the hypothesis that IVG instillation of two 25 mg doses of PGF 12 hours apart would be more effective than a 25- or 50-mg dose in a single application. Cows (n = 32) were stratified by parity and received SAL-IVG (n = 7), PGF25-IM (n = 7), PGF25-IVG (n = 6), and PGF50-IVG (n = 6) as in experiment 1, whereas another group received two IVG instillations of 25 mg of PGF 12 hours apart (PGF25-2X-IVG, n = 6). Blood was collected at −1 hour, every 6 hours from 0 hour to 24 hours, and every 12 hours up to 96 hours after treatment (trt). In experiment 1, there was an effect of trt (P < 0.01), time (P < 0.001), and an interaction between trt and time on P4 concentrations (P < 0.001). All PGF-treated groups had lower (P < 0.05) concentrations of P4 than cows in the SAL-IVG group from 12 to 96 hours after trt. Although an initial decline in P4 concentrations was induced in all PGF-treated cows, some cows in the IVG-treated groups presented a rebound in plasma P4, indicating CL recovery. More cows in the PGF25-IVG and PGF125-IVG groups than in the PGF50-IVG and PGF25-IM groups presented CL recovery, suggesting that greater doses of PGF may not necessarily improve CL regression. In experiment 2, there was an effect of trt (P < 0.001), time (P < 0.001), and an interaction between trt and time on P4 concentrations (P < 0.001). All PGF-treated groups had lower (P < 0.05) P4 than the SAL-IVG group from 12 to 96 hours after trt. Cows in the PGF25-2X-IVG group had a P4 profile that was similar to that of cows in the PGF25-IM group and the lowest P4 concentrations after treatment among the IVG-treated groups, and all cows presented complete CL regression (defined as P4 <0.4 ng/mL). We conclude that CL regression can be induced through IVG instillation of PGF in lactating dairy cows and that instillation of two IVG doses of 25 mg of PGF 12 hours apart was the most effective strategy.     

Yangyin Tongnao granules enhance neurogenesis in the peri-infarct area and upregulate brain-derived neurotrophic factor and vascular endothelial growth factor after focal cerebral ischemic infarction in rats

Yangyin Tongnao granules (YYTNG) have been extensively applied in the treatment of brain injury, mainly due to its antioxidant effects, inhibition of apoptosis, and enhancement of blood circulation. To analyze the effect of YYTNG on the recovery of neurological function and neurogenesis in the peri-infarct area after cerebral ischemic infarction in rats and to elucidate its role in the neuroprotective mechanism of stroke, Sprague–Dawley (SD) rats were subjected to middle cerebral artery occlusion (MCAO) for 90 min followed by reperfusion. Rats were randomly divided into five groups: sham, MCAO, and YYTNG-treated rats given doses of 0.83, 1.65, or 3.3 g kg^?1 day^?1. The YYTNG-treated groups (1.65 and 3.3 g kg^?1 day^?1) showed higher neurological scores and a lower infarct volume than the MCAO group on day 3 after MCAO. Furthermore, the YYTNG-treated groups (0.83, 1.65, and 3.3 g kg^?1 day^?1) showed higher neurological scores on day 7 after MCAO. The number of BrdU⁺/nestin⁺, BrdU⁺/NeuN⁺, and BrdU⁺/GFAP⁺ cells in the peri-infarct area 7 days after MCAO was significantly increased in the YYTNG-treated groups in a dose-dependent manner. The protein expression levels of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) were significantly higher in all three YYTNG-treated groups than in the MCAO group. Based on these results, administration of YYTNG post ischemia could ameliorate neurological function deficits in rats with MCAO. The therapeutic effect of YYTNG may be due to the promotion of neurogenesis in the peri-infarct area and the upregulation of neuroprotective factors BDNF and VEGF in MCAO rats.

     

Insight into hypoxic preconditioning and ischemic injury through determination of nPKCε-interacting proteins in mouse brain

Cerebral hypoxic preconditioning (HPC) provides neuroprotection by intracellular signaling pathways. We previously demonstrated that novel protein kinase Cε (nPKCε) activation participated in cerebral HPC development. In this study, we explore the role of nPKCε in HPC-induced neuroprotection against middle cerebral artery occlusion (MCAO)-induced ischemic injury and identify its possible signaling molecules. A total of 131 adult male BALB/c mice were divided into eight groups: normoxic control (n = 9), HPC (n = 9), HPC + εV1–2 (n = 13), Sham (n = 19), HPC + sham (n = 6), Ischemia (I, 6 h MCAO, n = 31), HPC + I (n = 25) and HPC + εV1–2 + I (n = 19). nPKCε specific inhibitor εV1–2 was administered via intracerebroventricular injection. Western blot, 2,3,5-triphenyltetrazolium chloride staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling were applied to determine nPKCε membrane translocation, infarction volume and programmed cell death (PCD), respectively. Two-dimensional gel electrophoresis (2-De) and matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) were used to identify nPKCε-interacting proteins, followed by bioinformatics analysis of genee ontology (GO) to predict nPKCε-specific signaling pathways. Our results showed that HPC attenuates MCAO-induced brain injuries and stabilized nPKCεmembrane translocation in peri-infarct region, which was abolished by nPKCε-speecific inhibitor εV1–2. Proteomics analysis revealed 8 up- and 3 down-regulated nPKCε-interacting proteins both in cytosolic and particulate fractions of HPC mouse brain. GO analysis predicted 25 significant nPKCε-specific signaling pathways among the 16 identified nPKCε-interacting proteins in brain of HPC mice. This study is the first to report multiple nPKCε-interacting proteins and their signaling pathways in HPC mouse brain, suggesting that nPKCε signaling molecules is responsible for HPC-induced neuroprotection against cerebral ischemic injuries of mice.     

Spondias mombin L. attenuates ventricular remodelling after myocardial infarction associated with oxidative stress and inflammatory modulation

The objective of this study was to evaluate Spondias mombin L. (SM) pulp and its influence on cardiac remodelling after myocardial infarction (MI). Male Wistar rats were assigned to four groups: a sham group (animals underwent simulated surgery) that received standard chow (S; n = 20), an infarcted group that received standard chow (MI; n = 24), an infarcted group supplemented with 100 mg of SM/kg bodyweight/d, (MIS100; n = 23) and an infarcted group supplemented with 250 mg of SM/kg bodyweight/d (MIS250; n = 22). After 3 months of treatment, morphological, functional and biochemical analyses were performed. MI induced structural and functional changes in the left ventricle with worsening systolic and diastolic function, and SM supplementation at different doses did not influence these variables as analysed by echocardiography and an isolated heart study (P > .05). However, SM supplementation attenuated cardiac remodelling after MI, reducing fibrosis (P = .047) and hypertrophy (P = .006). Biomarkers of oxidative stress, inflammatory processes and energy metabolism were further investigated in the myocardial tissue. SM supplementation improved the efficiency of energy metabolism and decreased lipid hydroperoxide in the myocardium [group S (n = 8): 267.26 ± 20.7; group MI (n = 8): 330.14 ± 47.3; group MIS100 (n = 8): 313.8 ± 46.2; group MIS250: 294.3 ± 38.0 nmol/mg tissue; P = .032], as well as decreased the activation of the inflammatory pathway after MI. In conclusion, SM supplementation attenuated cardiac remodelling processes after MI. We also found that energy metabolism, oxidative stress and inflammation are associated with this effect. In addition, SM supplementation at the highest dose is more effective.     

Protective effect of tea polyphenols on renal ischemia/reperfusion injury via suppressing the activation of TLR4/NF-κB p65 signal pathway

Tea polyphenols (TP) was investigated in rats for its protective effect on renal ischemia/reperfusion injury (RIRI). Rats were randomized into groups as follows: (I) sham group (n = 10); (II) RIRI group (n = 10); (III) RIRI + TP (100 mg/kg) group (n = 5); (IV) RIRI + TP (200 mg/kg) group (n = 5); (V) RIRI + TP+ Astragalus mongholicus aqueous extract (AMAE) (300 mg/kg + 100 mg/kg) group (n = 5). For the IRI + TP groups, rats were orally given with tea polyphenols (100, 200 and 300 mg/kg body weight) once daily 10 days before induction of ischemia, followed by renal IRI. For the sham group and RIRI group, rats were orally given with equal volume of saline once daily 10 days before induction of ischemia, followed by renal IRI. Results showed that tea polyphenol pretreatment significantly suppressed ROS level and MDA release. On the other hand, in rats subjected to ischemia–reperfusion, the activities of endogenous antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR) and glutathione peroxidase (GSH-Px) showed recovery, whereas the levels of urea nitrogen and serum creatinine were reduced by administration of tea polyphenols orally for 10 days prior to ischemia–reperfusion. Moreover, tea polyphenol pretreatment significantly decreased TLR4 and NF-κB p65 protein expression levels in RIRI rats. At the same time, tea polyphenol pretreatment attenuated the increased level of serum IL-1β, IL-6, ICAM-1 and TNF-α, and enhanced IL-10 production in RIRI rats. Furthermore, tea polyphenol pretreatment significantly decreased renal epithelial tubular cell apoptosis induced by renal ischemia/reperfusion, alleviating renal ischemia/reperfusion injury. These results cumulatively indicate that tea polyphenol pretreatment could suppress the TLR4/NF-κB p65 signaling pathway, protecting renal tubular epithelial cells against ischemia/reperfusion-induced apoptosis, which implies that antioxidants may be a potential and effective agent for prevention of the ischemic/reperfusion injury through the suppression extrinsic apoptotic signal pathway induced by TLR4/NF-κB p65 signal pathway. Moreover, supplement of AMAE can increased renal protection effect of TP.     

Effect of dietary incorporation of peanut and linseed meals with or without enzyme mixture on physiological performance of broilers

The present study aimed to evaluate the impact of feeding peanut meal and linseed meal (LSM) with or without enzyme mixture on growth, plasma metabolites, muscle amino acid (AA) profile, nutrient digestibility, and expression of nutrient absorption-related genes in broilers. A total of 560 one-day-old Cobb-500 male broiler chicks were distributed into eight experimental treatments (7 replications of 10 chicks each) as follows: This study was designed by using 560 one-day-old Cobb-500 male broiler chicks were distributed into eight experimental groups (7 replications of 10 chicks each) to evaluate the differences in body weight, body weight gain, feed intake, feed conversion rate, carcass parts, blood biochemical and mRNA expression genes. Group 1 (C) control fed the basal diet without supplements, Group 2 (C + E) is control group fed on 350 g/ton enzyme mixture, Group 3 (C + PNM100) is control group fed 100 kg/ton peanut meal, Group 4 (C + E + PNM100) is a control group fed on 350 g/ton enzyme mixture and 100 kg/ton peanut meal, Group 5 (C + LSM100) is a control group fed on 100 kg/ton linseed meal, Group 6 (C + E + LSM100) is a control group fed on 350 g/ton enzyme mixture and 100 kg/ton linseed meal, Group 7 (C + PNM50 + LSM50) is control group fed on 50 kg/ton peanut meal and 50 kg/ton linseed meal. Group 8 (C + E + PNM50 + LSM50) is the control group fed on 50 kg/ton peanut meal and 50 kg/ton linseed meal. Each gram of the enzyme mixture contains 11,000 U Xylanase, 6000 U Cellulase, 700 U β-Mannanase, 1500 U Phytase, 5 mg α-Amylase, and 2 mg Protease. No differences in Bodyweight, Bodyweight gain, Feed intake, and carcass parts were noticed among experimental groups, while abdominal fat (%) and FCR were reduced (P < 0.05) in PNM50 + LSM50 + E and LSM100 groups. Plasma metabolites were not altered except total cholesterol, triglyceride, and LDL, reduced (P < 0.01) in treated birds. Dietary inclusion of 100 kg PNM or LSM reduced (P < 0.05) methionine concentration in muscle, while all remaining AA and ammonia concentrations were unaffected. Hepatic MDA contents were reduced (P < 0.001) in treated groups. Nutrient digestibility was not altered among groups except for protein digestibility, which was elevated (P < 0.05) in PNM50 + LSM50 + E, E, and PNM100 + E groups. The highest mRNA expressions of PepT1, APN, SGLT1, HMGCR, GHr, and IGF-1 genes were noticed in PNM50 + LSM50 + E. Conclusively, PNM and LSM can efficiently substitute corn and soybean meal in broiler diets, particularly when fortified with exogenous enzymes, without negative impacts on broiler performance.     

Moringa peregrina leaf extracts produce anti-obesity,hypoglycemic, anti-hyperlipidemic,and hepatoprotective effects on high-fat diet fed rats

This present research investigated the anti-obesity and hepatoprotective effects of ethanolic Moringa peregrina leaf (MPLE) and bark extracts (MPBE), in the rats fed with a high-fat diet (HFD). Healthy male rats (n = 48) were randomly distributed to six groups (n = 8): control AIN-93 diet; HFD; HFD + MPBE bark extracts ((300 mg/kg); HFD + MPBE (600 mg/kg); HFD + MPLE (300 mg/kg); HFD + MPLE (600 mg/kg). HFD-fed rats in the Moringa peregrina (MP) treatment groups received orally administered MP leaf or bark extract daily for eight weeks. The results revealed that both doses of MP leaf extract significantly reduced HFD-induced increases in their food intake and the gained body weight, fat pad weights (visceral, subcutaneous, and epididymal), glucose and insulin plasma levels, and leptin and resistin serum levels in HFD-fed rats. Concomitantly, MP leaf extract improved glucose levels after oral or intraperitoneal glucose tolerance tests, reduced serum cholesterol, triglycerides, and the low-density lipoprotein LDL concentration, reduced hepatic triglycerides and cholesterol levels, and increased serum high-density lipoproteins HDL levels and triglycerides and cholesterol levels in fecal. Moreover, the administration of MPLE to HFD-fed rats improved liver architecture, reduced fat accumulation, reduced hepatic malondialdehyde, tumor necrosis factor-α, and interleukin-6 levels. Hepatic glutathione peroxidase, superoxide dismutase, and catalase activities were significantly increased. All observed effects were more pronounced in HFD-fed rats treated with a 600 mg/kg MP dose. However, neither dose of MPBE altered the measured markers in the HFD-fed rats. In conclusion, MPLE showed potential anti-obesity and hepatoprotective activity in HFD-induced obese rats, mediated by reduced lipid absorption, anti-hyperlipidemic effects, and hepatic antioxidant effects.     

Human amniotic fluid stem cells can improve cerebral vascular remodelling and neurological function after focal cerebral ischaemia in diabetic rats

Diabetes causes vascular injury and carries a high risk of ischaemic stroke. Human amniotic fluid stem cells ( hAFSCs) can enhance cerebral vascular remodelling and have the potential to improve neurological function after stroke in diabetic rats. Five groups of female rats were examined: (1) normal control, (2) type 1 diabetic (T1DM) rats induced by streptozotocin injection (DM), (3) non-DM rats receiving 60-minute middle cerebral artery occlusion (MCAO), (4) T1DM rats receiving 60-minute MCAO (DM + MCAO) and (5) T1DM rats receiving 60-minute MCAO and injection with 5 × 10⁶ hAFSCs at 3 h after MCAO (DM + MCAO + hAFSCs). Neurological function was examined before, and at 1, 7, 14, 21 and 28 days, and cerebral infarction volume and haemorrhage, cerebral vascular density, angiogenesis and inflammatory were examined at 7 and 28 days after MCAO. hAFSCs treatment caused a significant improvement of neurological dysfunction, infarction volume, blood-brain barrier leakage, cerebral arterial density, vascular density and angiogenesis and a reduction of brain haemorrhage and inflammation compared with non-treatment. Our results showed that the effect of hAFSCs treatment against focal cerebral ischaemia may act through the recovery of vascular remodelling and angiogenesis and the reduction of inflammation in ischaemic brain.     

Morin attenuates STZ-induced diabetic retinopathy in experimental animals

Diabetic retinopathy (DR) occurs in untreated diabetic patients due to the strong influence of oxidative stress. Bioflavonoids are well known for their antioxidant property. Morin, a bioflavonoid, has been demonstrated for its antioxidant as well as antidiabetic activity. Thus, this research work intended to determine the ameliorative impact of morin in DR rats using STZ-induced type 1 diabetic model. To induce type 1 diabetic in rats STZ (60 mg/kg) was administered intraperitoneally. Grouping of animals was done as described below (n = 6), where, group I – normal control, group II – diabetic control, group III – morin (25 mg/kg), group IV – morin (50 mg/kg), and group V – metformin (350 mg/kg) were used. All the animals underwent treatment for 60 days as given above. It was observed that supplementation of morin (25 and 50 mg/kg) showed a noteworthy decline in elevated serum glucose level. Moreover, decrease in the level of LPO and improved activity of endogenous antioxidants (GPx, CAT, and SOD) was observed in morin treated groups. It also notably drops the concentration of TNF-α, IL-1β, and VEGF in the tissue homogenate of the retina. Furthermore, it increased the retinal thickness and cell count in the ganglion cell layer of the retina in diabetic animals. Hence, we can conclude that morin encumbers the progression of DR in diabetic animals, which may be via antioxidant property and suppression of TNF-α, IL-1β, and VEGF.     

Biogenic zinc-oxide nanoparticles of Moringa oleifera leaves abrogates rotenone induced neuroendocrine toxicity by regulation of oxidative stress and acetylcholinesterase activity

Zinc oxide nanoparticles (ZnONPs) from plant origin were postulated to regulate complex hormonal control through the hypothalamus– pituitary–testicular axis and somatic cells due to their unique small size and effective drug delivery to target tissues. This study therefore investigates the biogenic synthesis of zinc oxide nanoparticles (ZnO NPs) from Moringa oleifera leaves on key endocrine hormones (LH, FSH and testosterone), MDA level, antioxidant enzymes (SOD and CAT), acetylcholineesterase (AChE) activity and reactive nitrogen species (NO^?) level in rotenone induced male rat. The animals were divided into six groups (n = 8). Group I was orally given olive oil as vehicle; Group II received 60 mg/kg of rotenone (RTNE) only; Group III (RTNE + ZnONPs) received 60 mg/kg RTNE + 10 mg/kg ZnONPs; Group IV (RTNE + ZnCAP) received 60 mg/kg RTNE + 50 mg/kg zinc capsule; Group V (ZnONPs only) received 10 mg/kg ZnONPs only. Group VI received 50 mg/kg ZnCAP only. The experiment lasted 10 days. TEM and XRD images revealed ZnO NPs. Moreover, the presence of organic molecules in bio-reduction reactions from the FTIR spectrum showed the stabilization of the nanoparticles. Also, animals induced with rotenone exhibited impairment in the leydig cells by depleting LH, FSH, and testosterone levels with reduced AChE activity and significant (p < 0.05) alteration in cerebral enzymatic antioxidants. There was also brain increase in NO^? production: marker of pro-inflammation. Nanotherapeutically, ZnONPs regulated hypothalamus–pituitary–testicular axis via modulation of cerebral NO^?, FSH, LH, testosterone and AChE activity with induction of anti-oxidative enzymes.     

Preconception Vitamin D Level and In Vitro Fertilization: Pregnancy Outcome

ObjectiveVitamin D deficiency impairs female fertility and the success of in vitro fertilization (IVF). The recommended serum 25-hydroxyvitamin D (25(OH)D) level in IVF-conceived pregnancies is still debated. We aimed to explore the relationship of the preconception serum 25(OH)D level with pregnancy outcome following IVF treatment. We also explored the utility of the currently recommended serum 25(OH)D cutoff of ≥50 nmol/L for women undergoing IVF therapy.MethodsRetrospective cohort of women who had undergone IVF therapy. Of the women who started IVF therapy (n = 354), 218 completed the study. They were divided into 2 groups: (1) women who achieved a successful pregnancy (pregnant group, n = 160) and (2) those who did not achieve a successful pregnancy (nonpregnant group, n = 58). Preconception serum samples were analyzed for reproductive hormones, fasting glucose, insulin, and 25(OH)D levels.ResultsOverall, the median (interquartile range) age, body mass index, and hemoglobin A1c level were 32 (6) years, 25.7 (7.4) kg/m², and 5.2% (0.6%), respectively. The 25(OH)D level was significantly higher at preconception in the pregnant group (56.4 [21.4] vs 47.9 [29.16] for nonpregnant, P = .001). The preconception 25(OH)D level was a significant predictor of IVF outcome (B = 0.04; 95% CI, 1.01-1.06; P = .001), with greater IVF success associated with a serum 25(OH)D level of ≥50 nmol/L (odds ratio, 0.46; P = .01).ConclusionPreconception 25(OH)D sufficiency (≥50 nmol/L) is associated with successful pregnancy outcome following IVF therapy.     

Cathinone: An alkaloid of Catha edulis (Khat) exacerbated hyperglycemia in diabetes-induced rats

Cathinone, the main bioactive alkaloid of Catha edulis (khat), slightly increased the blood sugar levels of healthy animals, while its effect on blood sugar levels of diabetic animals has not yet been reported. This study investigated the in vitro inhibition of cathinone on α-amylase and α-glucosidase as well as its in vivo glycemic effects in diabetes-induced rats. Rats were fed on a high fat diet for five weeks, which then intraperitoneally injected with streptozotocin (30 mg/kg). Diabetic rats were distributed randomly into diabetic control (DC, n = 5), 10 mg/kg glibenclamide-treated group (DG, n = 5), and 1.6 mg/kg cathinone-treated group (CAD, n = 5). Additional healthy untreated rats (n = 5) served as a nondiabetic negative control group. Throughout the experiment, fasting blood sugar (FBS), caloric intake and body weight were recorded weekly. By the 28th day of treatment, rats were euthanized to obtain blood samples and pancreases. The results demonstrated that cathinone exerted a significantly less potent in vitro inhibition than α-acarbose against α-amylase and α-glucosidase. As compared to diabetic control group, cathinone significantly increased FBS of diabetic rats, while insulin levels of diabetic rats significantly decreased. In conclusion, cathinone was unable to induce a substantial in vitro inhibition on α-amylase and α-glucosidase, while it exacerbated the hyperglycemia of diabetes-induced rats.     

Effect of age,size and digestive tract development on weaning effectiveness in crucian carp,Carassius carassius (Linnaeus, 1758)

The study aim was to determine the optimum age, wet body weight (WBW) and total length (TL) of the crucian carp, Carassius carassius (L.), to ensure the effectiveness of weaning directly without a gradual transfer from live food to a compound feed. Moreover, the state of development of the digestive tract was analyzed histologically based on the height of enterocytes. Experimental rearing was conducted between days 5 and 45 post hatch (DPH). Initial WBW of fish was 2.2 ± 0.6 (n = 30) mg and TL 6.1 ± 0.1 (n = 30) mm. Rearing was carried out at 27 ± 0.5°C, with fish divided into six groups: one control (C) fed with Artemia sp. nauplii, and five groups initially fed with Artemia sp. but later replaced by a compound feed. Weaning with the compound diet started at 15, 20, 25, 30 and 35 DPH in groups labeled F15, F20, F25, F30, F35, respectively. Larvae were fed three times per day (08.00 h, 13.00 h, 18.00 h) in equal portions (4% of larvae biomass per day, converted to the dry matter of the feed). Daily biomass growth was adopted as 15%. Each group was triplicated (n = 50 individuals per replicate). Highest values of TL 42.1 ± 0.7 (n = 30) mm and WBW 905.3 ± 50.3 (n = 30) mg were recorded in the control group at 45 DPH; lowest survival rate of 45 DPH was in group F15 (90.7 ± 1.2%, n = 30). The highest value of the enterocyte epithelial length was observed in individuals within groups F30, 34.8 ± 1.2 μm (n = 30) and F35, 35.4 ± 3.6 μm (n = 30), respectively, 30 and 35 DPH; highest percentage of deformations on the final day of the experiment was in group F15 (100 ± 0.0%, n = 30). The results indicate that an effective direct transfer from live food to prepared diets (with no gradual transfer) cannot be performed with crucian carp larvae before 30 DPH at 27°C, when the fish have reached TL = 31.1 ± 0.4 mm (n = 30) and WBW = 436.9 ± 13.7 mg (n = 30).     

Comparison of fertility,regular returns-to-estrus,and calving interval between Ovsynch and CO-synch + CIDR protocols in dairy cows

The main aims of the present study were to compare the pregnancy rate (PR), regular returns-to-estrus, and calving interval of a CO-Synch + controlled internal drug release (CIDR) device, commonly used to synchronize ovulations in beef cows, with the classical Ovsynch protocol in high-producing dairy cows. Holstein-Friesian cows (n = 128) from six commercial dairy herds, ≥40 days postpartum and not previously inseminated, were randomly assigned to one of two treatments. Cows submitted to Ovsynch protocol (group OS as control group; n = 66) received 10 μg of a GnRH analogue 7 days before and 48 hours after 25 mg PGF_2α, followed by artificial insemination (AI) 16 hours after the second GnRH administration. Cows submitted to CO-Synch + CIDR (1.38 g of progesterone) inserted for 7 days beginning at the first GnRH administration (group CoS + CD; n = 62) had the second administration of GnRH concurrent with AI, 64 hours after CIDR removal/PGF_2α administration. Nonpregnant cows with return-to-estrus between 18 and 24 days after first AI were reinseminated (second AI). Logistic regressions were used to analyze PR and returns-to-estrus. No effect of group or herd was observed in PR at first timed AI. However, the sum of cows pregnant at first AI and nonpregnant cows with regular returns-to-estrus and the total PR (first + second AI) were influenced by group treatment. Overall, cows of group CoS + CD (total PR = 56.5%) were 2.1 times more likely to became pregnant after AI and until first regular returns-to-estrus than cows of group OS. The calving interval was lower in group CoS + CD (425.9 ± 78.8 days; ±SD) than in group OS (475.3 ± 83.7 days). The CO-Synch + CIDR protocol was reliable to use in dairy herds and provided reproductive advantages when compared with Ovsynch protocol.     

Sevoflurane-induced delayed neuroprotection involves mitoK<Subscript>ATP</Subscript> channel opening and PKC ε activation

There is an increasing body of evidence that a brief exposure to anesthesia induces ischemic tolerance in rat brain (anesthetic preconditioning). However, it is unknown whether preconditioning with sevoflurane, a commonly used volatile anesthetic in current clinical practice, produces a delayed window of neuroprotection against ischemia and what the mechanisms are for this protection. To address these issues, adult male Sprague–Dawley rats were subjected to middle cerebral arterial occlusion (MCAO) for 2 h. Sevoflurane preconditioning was induced 24 h before brain ischemia by exposing the animals to sevoflurane at 1.0 minimum alveolar concentration (2.4%) in oxygen for 60 min. Animals preconditioned with sevoflurane had lower neurological deficit scores and smaller brain infarct volumes than animals with brain ischemia at 6 and 24 h after MCAO, respectively. Application of a selective antagonist for mitochondrial ATP-sensitive potassium (mitoK_ATP) channel, 5-hydroxydecanoate (5-HD, 40 mg/kg i.p.) 30 min before sevoflurane exposure attenuated this beneficial effect. Moreover, protein kinase C ε (PKC ε) was translocated to the membrane fraction at 6 h, but not 24 h, after brain reperfusion in animals preconditioned with sevoflurane and this effect was also abolished by 5-HD. We concluded that sevoflurane preconditioning induces a delayed neuroprotection and that mitochondrial K_ATP channels and PKC ε may be involved in this neuroprotection.     

Astaxanthin Ameliorates high-fat diet-induced cardiac damage and fibrosis by upregulating and activating SIRT1

This study evaluated the protective effect of astaxanthin (ASX) against high-fat diet (HFD)-induced cardiac damage and fibrosis in rats and examined if the mechanism of protection involves modulating SIRT1. Rat were divided into 5 groups (n = 10/group) as: 1) control: fed normal diet (3.82 kcal/g), 2) control + ASX (200 mg/kg/orally), 3) HFD: fed HFD (4.7 kcal/g), 4) HFD + ASX (200 mg/kg/orally), and HFD + ASX + EX-527 (1 mg/kg/i.p) (a selective SIRT1 inhibitor). All treatments were conducted for 14 weeks. Administration of ASX reduced cardiomyocyte damage, inhibited inflammatory cell infiltration, preserved cardiac fibers structure, prevented collagen deposition and protein levels of TGF-β 1 in the left ventricles (LVs) of HFD-fed rats. In the LVs of both the control and HFD-fed rat, ASX significantly reduced levels of reactive oxygen species (ROS), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and p-smad2/3 (Lys19) but increased the levels of glutathione (GSH), catalase, and manganese superoxide dismutase (MnSOD). Concomitantly, it increased the nuclear activity of Nrf2 and reduced that of NF-κB p65. Furthermore, administration of ASX to both the control and HFD-fed rats increased total and nuclear levels of SIRT1, stimulated the nuclear activity of SIRT1, and reduced the acetylation of Nrf2, NF-κB p65, and Smad3. All these cardiac beneficial effects of ASX in the HFD-fed rats were abolished by co-administration of EX-527. In conclusion, ASX stimulates antioxidants and inhibits markers of inflammation under basal and HFD conditions. The mechanism of protection involves, at least, activation SIRT1 signaling.     

Propofol post-conditioning induced long-term neuroprotection and reduced internalization of AMPAR GluR2 subunit in a rat model of focal cerebral ischemia/reperfusion

We previously reported that propofol (20 mg/kg/h) post-conditioning provided acute (up to 24 h) neuroprotection in rats with transient middle cerebral artery occlusion. In this study, we extend these data by examining long-term protection and exploring underlying mechanisms involving AMPA receptor GluR2 subunit internalization. Rats were treated with propofol 20 mg/kg/h after 60 min of occlusion (beginning of reperfusion for 4 h). Propofol post-conditioning reduced infarct volume and improved spatial memory deficiencies (up to 28 days) induced by ischemia/reperfusion injury. Additionally, Propofol post-conditioning promoted neurogenesis in the dentate gyrus of hippocampus, as measured by bromodeoxyuridine and neuron-specific nuclear protein immunofluorescence-double staining at day 28 after reperfusion. Finally, propofol post-conditioning increased the surface expression of AMPA receptor GluR2 subunit, thus inhibited the internalization of this part until 28 days after stroke. In conclusion, our data suggest that propofol post-conditioning provides long-term protection against focal cerebral ischemia/reperfusion injury in rats. Furthermore, we found that the inhibition of AMPA receptor GluR2 subunit internalization may contributed to this long-term neuroprotection.     

Naringenin ameliorates Cyclophosphamide-induced nephrotoxicity in experimental model

Cyclophosphamide (CP) is widely described in the management of several nonneoplastic and neoplastic disorders. Renal damage is the most reported toxic effect of CP in clinical practice.Our study aimed to evaluate the effect of Naringenin (NG) in attenuating renal damage induced by CP in an experimental model.A total of 32 rats were divided into four groups (n = 8): negative control: rats fed on a basal diet, positive control: rats injected intraperitoneally with CP 50 mg/kg of body weight/day, NG 100: rats treated with NG 100 mg/kg/day body orally with concomitant administration of CP as described before, and NG 200: rats treated with NG 200 mg/kg/day body orally daily + CP. At the end of the experimental protocol (21 days), blood creatinine and urea levels were measured. The antioxidant activities and lipid peroxidation products were measured in the renal tissues as indicators of oxidative damage. Histopathological examination and immunohistochemistry staining were also performed on renal tissues.Coadministration of NG along with CP significantly (p < 0.001) improved the renal function and antioxidant capacities compared with positive control animals. Furthermore, histopathological, and immunological examination of renal tissue confirmed the protective effect of NG against CP-induced nephrotoxicity.The current study showed that NG has the potential to protect CP-induced renal damage, which may be beneficial for further studies and the design of NG analogs to be useful in clinical practice against CP-induced nephrotoxicity.