Gut-microbiome-brain axis:the crosstalk between the vagus nerve,alpha-synuclein and the brain in Parkinson's disease

This critical review of the literature shows that there is a close link between the microbiome,the gut,and the brain in Parkinson's disease.The vagus nerve,the main component of the parasympathetic nervous system,is involved in the regulation of immune response,digestion,heart rate,and control of mood.It can detect microbiota metabolites through its afferents,transferring this gut information to the central nervous system.Preclinical and clinical studies have shown the important role played by the gut microbiome and gut-related factors in disease development and progression,as well as treatment responses.These findings suggest that the gut microbiome may be a valuable target for new therapeutic strategies for Parkinson's disease.More studies are needed to better understand the underlying biology and how this axis can be modulated for the patient's benefit.

Phosphate,calcium,and vitamin D signaling,transport,and metabolism in the endometria of cyclic ewes

Background Recent evidence suggests important roles for progesterone(P4)and interferon tau in the regulation of calcium,phosphate,and vitamin D signaling in the uteri of pregnant sheep.However,the effects of P4 and estradiol(E2),with respect to the expression of their receptors PGR and ESR1,respectively,in uterine epithelia on mineral signaling during the estrous cycle has not been investigated.Estrous cycles of mature Suffolk ewes were synchronized,prostaglandin F2αwas administered,and ewes were observed for estrus(designated as Day 0)in the presence of vasectomized rams.On Days 1,9,or 14 of the estrous cycle,hysterectomies were performed.Results 25-hydroxyvitamin D was more abundant in plasma from ewes on Day 14 than Day 1(P<0.05).Expression of fibroblast growth factor receptor 2(FGFR2),a disintegrin and metalloprotease 17(ADAM17),and parathyroid hormone-related protein(PTHrP)mRNAs was greater in endometria on Day 9 compared to Days 1 and 14(P<0.01).Similarly,expression of transient receptor potential cation channel subfamily V member 6(TRPV6)mRNA was greater in endometria on Day 9 than Day 1(P<0.05).ATPase plasma membrane Ca^(2+)transporting 4(ATP2B4)and S100 calcium binding protein G(S100G)mRNA expression was greater in endometria on Day 14 than on Days 1 and 9(P<0.01).In contrast,endometrial expression of vitamin D receptor(VDR)mRNA was lower on Days 9 and 14 than Day 1(P<0.01).Expression of klotho(KL)(P<0.05)and cytochrome P450 family 24 subfamily A member 1(CYP24)(P<0.01)mRNAs was lower on Day 14 than Days 1 and 9.ADAM17,FGF23,CYP2R1,CYP27B1,KL,and VDR proteins immunolocalized to the uterine myometrium,blood vessels,and uterine luminal(LE),superficial glandular(sGE),and glandular(GE)epithelia.S100A9 protein was weakly expressed in the uterine myometrium,LE,sGE,and GE.Immunoreactivity of CYP2R1 and KL proteins in uterine LE and sGE was less on Day 1 than on Days 9 and 14.In contrast,S100G protein was expressed exclusively by GE,and immunoreactive S100G protein was less on Day 9.S100A12 protein localized to stromal cells of the uterine stratum spongiosum and blood vessels,but not by uterine epithelial cells.Conclusion Collectively,these results implicate E2,P4,and PGR in the regulation of phosphate,calcium,and vitamin D signaling in cyclic ewes.

Anticancer potential of Ferula assa-foetida and its constituents,a powerful plant for cancer therapy

Cancer is one of the main challenges of the health system around the world.This disease is increasing in developing countries and imposes heavy costs on patients and governments.On the other hand,despite various drugs,the death rate among cancer patients is still high and the current treatments have many harmful effects.In the traditional medicine of different countries,there are many medicinal plants that can be effective in the treatment of cancer.Ferula plants are traditionally used as spices and food or for medicinal purposes.Ferula assa-foetida is one of the famous plants of this genus,which has been used for the treatment of various diseases since ancient times.Among the main compounds of this plant,we can mention monoterpenes,sulfide compounds and polyphenols,which can show different therapeutic effects.This article has been compiled with the aim of collecting evidence and articles related to the anti-cancer effects of extracts,derived compounds,essential oils and nanoparticles containing Ferula assa-foetida.This review article was prepared by searching the terms Ferula assa-foetida and cancer,and relevant information was collected through searching electronic databases such as ISI Web of Knowledge,PubMed,and Google Scholar.Fortunately,the results of this review showed that relatively comprehensive studies have been conducted in this field and shown that Ferula assa-foetida can be very promising in the treatment of cancer.

Comparison of emergency surgical cricothyroidotomy and percutaneous cricothyroidotomy by experienced airway providers in an obese,in vivo porcine hemorrhage airway model

Background: Emergency front-of-neck airway(eFONA) is a life-saving procedure in “cannot intubate, cannot oxygenate”(CICO). The fastest and most reliable method of eFONA has not been determined. We compared two of the most advocated approaches: surgical cricothyroidotomy and percutaneous cricothyroidotomy, in an obese, in vivo porcine hemorrhage model, designed to introduce real-time physiological feedback, relevant and high provider stress. The primary aim was to determine the fastest method to secure airway. Secondary aims were arterial saturation and partial pressure of oxygen, proxy survival and influence of experience.Methods: Twelve pigs [(60.3±4.1) kg] were anesthetized and exposed to 25%–35% total blood volume hemorrhage before extubation and randomization to Seldinger technique “percutaneous cricothyroidotomy”(n=6) or scalpelbougie-tube technique “surgical cricothyroidotomy”(n=6). Specialists in anesthesia and intensive care in a tertiary referral hospital performed the eFONA, simulating an actual CICO-situation.Results: In surgical cricothyroidotomy vs. percutaneous cricothyroidotomy, the median(interquartile range, IQR) times to secure airway were 109(IQR 71–130) s and 298(IQR 128–360) s(P=0.0152), arterial blood saturation(SaO2) were 74.7(IQR 46.6–84.2)% and 7.9(IQR 4.1–15.6)%(P=0.0167), PaO_(2) were 7.0(IQR 4.7–7.7) kPa and 2.0(IQR 1.1–2.9) kPa(P=0.0667), and times of cardiac arrest(proxy survival) were 137–233 s, 190(IQR 143–229) s, from CICO. All six animals survived surgical cricothyroidotomy, and two of six(33%) animals survived percutaneous cricothyroidotomy. Years in anesthesia, 13.5(IQR 7.5–21.3), did not influence time to secure airway.Conclusions: eFONA by surgical cricothyroidotomy was faster and had increased oxygenation and survival, when performed under stress by board certified anesthesiologists, and may be an indication of preferred method in situations with hemorrhage and CICO, in obese patients.

Zataria multiflora and its constituent,carvacrol,counteract sepsis-induced aortic and cardiac toxicity in rat:Involvement of nitric oxide and oxidative stress

Background:Zataria multiflora and carvacrol showed various pharmacological prop-erties including anti-inflammatory and anti-oxidant effects.However,up to now no studies have explored its potential benefits in ameliorating sepsis-induced aortic and cardiac injury.Thus,this study aimed to investigate the effects of Z.multiflora and carvacrol on nitric oxide(NO)and oxidative stress indicators in lipopolysaccharide(LPS)-induced aortic and cardiac injury.Methods:Adult male Wistar rats were assigned to:Control,lipopolysaccharide(LPS)(1 mg/kg,intraperitoneal(i.p.)),and Z.multiflora hydro-ethanolic extract(ZME,50–200 mg/kg,oral)-and carvacrol(25–100 mg/kg,oral)-treated groups.LPS was in-jected daily for 14 days.Treatment with ZME and carvacrol started 3 days before LPS administration and treatment continued during LPS administration.At the end of the study,the levels of malondialdehyde(MDA),NO,thiols,and antioxidant enzymes were evaluated.Results:Our findings showed a significant reduction in the levels of superoxide dis-mutase(SOD),catalase(CAT),and thiols in the LPS group,which were restored by ZME and carvacrol.Furthermore,ZME and carvacrol decreased MDA and NO in car-diac and aortic tissues of LPS-injected rats.Conclusions:The results suggest protective effects of ZME and carvacrol on LPS-induced cardiovascular injury via improved redox hemostasis and attenuated NO pro-duction.However,additional studies are needed to elucidate the effects of ZME and its constituents on inflammatory responses mediated by LPS.

Adenosine A_(2A)receptor blockade attenuates excitotoxicity in rat striatal medium spiny neurons during an ischemic-like insult

During brain ischemia,excitotoxicity and peri-infarct depolarization injuries occur and cause cerebral tissue damage.Indeed,anoxic depolarization,consisting of massive neuronal depolarization due to the loss of membrane ion gradients,occurs in vivo or in vitro during an energy failure.The neuromodulator adenosine is released in huge amounts during cerebral ischemia and exerts its effects by activating specific metabotropic receptors,namely:A_(1),A_(2A),A_(2B),and A_(3).The A_(2A)receptor subtype is highly expressed in striatal medium spiny neurons,which are particularly susceptible to ischemic damage.Evidence indicates that the A2Areceptors are upregulated in the rat striatum after stroke and the selective antagonist SCH58261 protects from exaggerated glutamate release within the first 4 hours from the insult and alleviates neurological impairment and histological injury in the following 24 hours.We recently added new knowledge to the mechanisms by which the adenosine A2Areceptor subtype participates in ischemia-induced neuronal death by performing patch-clamp recordings from medium spiny neurons in rat striatal brain slices exposed to oxygen and glucose deprivation.We demonstrated that the selective block of A2Areceptors by SCH58261 significantly reduced ionic imbalance and delayed the anoxic depolarization in medium spiny neurons during oxygen and glucose deprivation and that the mechanism involves voltage-gated K+channel modulation and a presynaptic inhibition of glutamate release by the A2Areceptor antagonist.The present review summarizes the latest findings in the literature about the possibility of developing selective ligands of A2Areceptors as advantageous therapeutic tools that may contribute to counteracting neurodegeneration after brain ischemia.

Unraveling the potential of acute intermittent hypoxia as a strategy for inducing robust repair in multiple sclerosis

Multiple sclerosis(MS)is a debilitating inflammatory disease of the central nervous system characterized by immune-mediated segmental demyelination and variable degrees of axonal and neuronal degeneration that contribute to disability.Inducing efficient and effective repair programs following demyelination is a major goal and challenge in MS.Conventional MS therapies focus largely on modulating the immune aspects of the disease contributing to lesions.While this alleviates some symptoms and mitigates damage,it does not tackle the fundamental challenge of effective remyelination,which few MS patients experience,especially in the progressive phase of the disease.

Physiology of bile secretion

The formation of bile depends on the structural and functional integrity of the bile-secretory apparatus and its impairment, in different situations, results in the syndrome of cholestasis. The structural bases that permit bile secretion as well as various aspects related with its composition and flow rate in physiological conditions will first be reviewed. Canalicular bile is produced by polarized hepatocytes that hold transporters in their basolateral (sinusoidal) and apical (canalicular) plasma membrane. This review summarizes recent data on the molecular determinants of this primary bile formation. The major function of the biliary tree is modification of canalicular bile by secretory and reabsorptive processes in bileduct epithelial cells (cholangiocytes) as bile passes through bile ducts. The mechanisms of fluid and solute transport in cholangiocytes will also be discussed. In contrast to hepatocytes where secretion is constant and poorly controlled, cholangiocyte secretion is regulated by hormones and nerves. A short section dedicated to these regulatory mechanisms of bile secretion has been included. The aim of this revision was to set the bases for other reviews in this series that will be devoted to specific issues related with biliary physiology and pathology.

Sitagliptin in patients with non-alcoholic steatohepatitis: A randomized, placebo-controlled trial

AIM To evaluate the effect of sitagliptin vs placebo on histologic and non-histologic parameters of nonalcoholic steatohepatitis(NASH).METHODS Twelve patients with biopsy-proven NASH were randomized to sitagliptin(100 mg daily)(n=6)or placebo(n=6)for 24 wk.The primary outcome was improvement in liver fibrosis after 24 wk.Secondary outcomes included evaluation of changes in NAFLD activity score(NAS),individual components of NAS(hepatocyte ballooning,lobular inflammation,and steatosis),glycemic control and insulin resistance[including measurements of glycated hemoglobin(Hb A1C)and adipocytokines],lipid profile including free fatty acids,adipose distribution measured using magnetic resonance imaging(MRI),and thrombosis markers(platelet aggregation and plasminogen activator inhibitor 1 levels).We also sought to determine the correlation between changes in hepatic fat fraction(%)[as measured using the Iterative Decomposition of water and fat with Echo Asymmetry and Least-squares estimation(IDEAL)MRI technique]and changes in hepatic steatosis on liver biopsy.RESULTS Sitagliptin was not significantly better than placebo at reducing liver fibrosis score as measured on liver biopsy(mean difference between sitagliptin and placebo arms,0.40,P=0.82).There were no significant improvements evident with the use of sitagliptin vs placebo for the secondary histologic outcomes of NAS total score as well as for the individual components of NAS.Compared to baseline,those patients who received sitagliptin demonstrated improved Hb A1C(6.7%±0.4%vs 7.9%±1.0%,P=0.02),and trended towards improved adiponectin levels(4.7±3.5μg/m L vs 3.9±2.7μg/m L,P=0.06)and triglyceride levels(1.26±0.43 mmol/L vs 2.80±1.64 mmol/L,P=0.08).However,when compared with placebo,sitagliptin did not cause a statistically significant improvement in Hb A1C(mean difference,-0.7%,P=0.19)nor triglyceride levels(mean difference-1.10mmol/L,P=0.19)but did trend towards improved adiponectin levels only(mean difference,0.60μg/m L,P=0.095).No significant changes in anthropometrics,liver enzymes,other adipocytokines,lipid profile,thrombosis parameters,or adipose distribution were demonstrated.The MRI IDEAL procedure correlated well with steatosis scores obtained on liver biopsy in both groups at baseline and post-treatment,and the Spearman correlation coefficients ranged from r=0.819(baseline)to r=0.878(post-treatment),P=0.002.CONCLUSION Sitagliptin does not improve fibrosis score or NAS after 24 wk of therapy.The MRI IDEAL technique may be useful for non-invasive measurement of hepatic steatosis.

Crosstalk of liver immune cells and cell death mechanisms in different murine models of liver injury and its clinical relevance

BACKGROUND: Liver inflammation or hepatitis is a result of pluripotent interactions of cell death molecules, cytokines, chemokines and the resident immune cells collectively called as microenvironment. The interplay of these inflammatory mediators and switching of immune responses during hepatotoxic, viral, drug-induced and immune cell-mediated hepatitis decide the fate of liver pathology. The present review aimed to describe the mechanisms of liver injury, its relevance to human liver pathology and insights for the future therapeutic interventions.DATA SOURCES: The data of mouse hepatic models and relevant human liver diseases presented in this review are systematically collected from Pub Med, Science Direct and the Web of Science databases published in English. RESULTS: The hepatotoxic liver injury in mice induced by the metabolites of CCl4, acetaminophen or alcohol represent necrotic cell death with activation of cytochrome pathway, formation of reactive oxygen species(ROS) and mitochondrial damage. The Fas or TNF-α induced apoptotic liver injury was dependent on activation of caspases, release of cytochrome c and apoptosome formation. The Con A-hepatitis demonstrated the involvement of TRAIL-dependent necrotic/necroptotic cell death with activation of RIPK1/3. The α-Gal Cer-induced liver injury was mediated by TNF-α. The LPS-induced hepatitis involved TNF-α, Fas/Fas L, and perforin/granzyme cell death pathways. The MHV3 or Poly(I:C) induced liver injury was mediated by natural killer cells and TNF-α signaling. The necrotic ischemia-reperfusion liver injury was mediated byhypoxia, ROS, and pro-inflammatory cytokines; however, necroptotic cell death was found in partial hepatectomy. The crucial role of immune cells and cell death mediators in viral hepatitis(HBV, HCV), drug-induced liver injury, non-alcoholic fatty liver disease and alcoholic liver disease in human were discussed.CONCLUSIONS: The mouse animal models of hepatitis provide a parallel approach for the study of human liver pathology. Blocking or stimulating the pathways associated with liver cell death could unveil the novel therapeutic strategies in the management of liver diseases.

Food intake regulation by leptin:Mechanisms mediating gluconeogenesis and energy expenditure

Regulation of blood glucose levels and body fat is critical for survival.Leptin circulates freely in blood and controls body weight and food intake mainly through hypothalamic receptors and regulates glucose metabolism in the liver both directly through leptin receptors and indirectly via the hypothalamic receptors of central nervous system.Leptin affects food intake regulation and eventually glucose metabolism, lipometabolism,endocrine and immune functions, reproductive function, adipose tissue metabolism and energy expenditure.Leptin also exerts peripheral effects directly on glucose metabolism and gluconeogenesis.Most of obese human subjects have elevated plasma levels of leptin associated to the size of their total adipose tissue mass.Hence gluconeogenic function may be an essential factor in the regulation of nutritional intake and weight gain.The aim of this review is therefore to identify and module the possible effects of leptin with special application in gluconeogenesis.In addition, this review includes the study of fat consumption and energy expenditure in the body.Specific modulation of leptin receptors and adipose tissues functioning could have important inference on therapeutic strategies.

Optimization of Ultrasonic-Assisted Extraction Process of Polysaccharides from American Ginseng and Evaluation of Its Immunostimulating Activity

Ultrasonic-assisted extraction(UAE) of American ginseng polysaccharides(AGP) was investigated using response surface methodology. Three-factor-three-level Box-Behnken design was employed to optimize the ultrasonic power, extraction time and ratio of water to raw material to obtain a high AGP yield. The analysis of variance and response surface plots indicated that ultrasonic power was the most important factor affecting the extraction yield. The optimal conditions were ultrasonic power 400 W, extraction time 71 min, and ratio of water to raw material 33 m L g-1. Under these conditions, the yield of AGP was 8.09%, which was agreed closely to the predicted value. Gas chromatography(GC) analysis showed that AGP was composed of arabinose, rhamnose, galactose, glucose, and galacturonic acid. Fourier transform infrared spectra revealed the general characteristic absorption peaks of AGP. In addition, AGP exhibited good immunostimulating activities by up-regulating the production of nitric oxide and cytokines. Compared with hot water extraction, UAE required shorter extraction time and gave a higher extraction yield, without changing the structure and immunostimulating activity of AGP. The results indicated that UAE could be an effective and advisable technique for the large scale production of plant polysaccharides.

Screening of ethyl acetate extract of Bridelia micrantha for hepatoprotective and anti-oxidant activities on Wistar rats

Objective:To explore the hepatoprotective and anti-oxidant activities of the methanolic leaf extract of Bridelia micrantha(B.micrantha) on paracetamol induced liver damage in Wistar rats. Methods:Parameters were measured including alanine aminotransaminase(ALT),aspartate aminotransferase(AST),alkaline phosphatase(ALP),bilirubin and total protein.The anti-oxidant effects were studied using the 1,l-Diphenynl-2-Picrylhydrazyl(DPPH) and Ferric Reducing Antioxidant Power(FRAP) assay methods.Results:B.micrantha extract decreased the level of AST in the rats given PCM from(129.47±0.921) IU/L to(57.78±1.71) IU/L(P【0.05).This was lower than the value for Silymarin which was(59.92±1.41) IU/L.ALT concentration was reduced from (150.18±2.23) IU/L to(79.10±2.01) IU/L(P【0.05).ALP was reduced from(49.86±0.85) IU/L to(29.64±1.53) IU/L(P【0.05).Total bilirubin was reduced from(2.14±0.10 mg/dL) to(0.18±0.07) mg/dL (P【0.05) while total protein was increased from(4.26±0.30) mg/dL to(6.20±0.19) mg/dL(P【0.05). Concentrations ranging from 10 - 400μg/mL of B.micrantha were assayed for antioxidant activities.The DPPH assay showed 98%antioxidant activity at concentration of 400μg/mL. The FRAP values were 0.016,0.39,0.455,0.601 and 1.382μM at 10.50,100,200 and 400μg/ mL respectively.Conclusions:Results suggest that B.micrantha has hepatoprotective and anti oxidant potentials.However,further work involving fractionation needs to done to isolate the active compound responsible for the hepatoprotective activity.

Immunohistochemical expression of SP-NK-1R-EGFR pathway and VDR in colonic inflammation and neoplasia

AIM:To determine the expression of neurokinin-1receptor(NK-1R),phosphorylated epidermal growth factor receptor(p EGFR),cyclooxygenase-2(Cox-2),and vitamin D receptor(VDR)in normal,inflammatory bowel disease(IBD),and colorectal neoplasia tissues from Puerto Ricans.METHODS:Tissues from patients with IBD,colitisassociated colorectal cancer(CAC),sporadic dysplasia,and sporadic colorectal cancer(CRC),as well as normal controls,were identified at several centers in Puerto Rico.Archival formalin-fixed,paraffin-embedded tissues were de-identified and processed by immunohistochemistry for NK-1R,p EGFR,Cox-2,and VDR.Pictures of representative areas of each tissues diagnosis were taken and scored by three observers using a4-point scale that assessed intensity of staining.Tissues with CAC were further analyzed by photographing representative areas of IBD and the different grades of dysplasia,in addition to the areas of cancer,within each tissue.Differences in the average age between the five patient groups were assessed with one-way analysis of variance and Tukey-Kramer multiple comparisons test.The mean scores for normal tissues and tissues with IBD,dysplasia,CRC,and CAC were calculatedand statistically compared using one-way analysis of variance and Dunnett’s multiple comparisons test.Correlations between protein expression patterns were analyzed with the Pearson’s product-moment correlation coefficient.Data are presented as mean±SE.RESULTS:On average,patients with IBD were younger(34.60±5.81)than normal(63.20±6.13,P<0.01),sporadic dysplasia(68.80±4.42,P<0.01),sporadic cancer(74.80±4.91,P<0.001),and CAC(57.50±5.11,P<0.05)patients.NK-1R in cancer tissue(sporadic CRC,1.73±0.34;CAC,1.57±0.53)and sporadic dysplasia(2.00±0.45)were higher than in normal tissues(0.73±0.19).p EGFR was significantly increased in sporadic CRC(1.53±0.43)and CAC(2.25±0.47)when compared to normal tissue(0.07±0.25,P<0.05,P<0.001,respectively).Cox-2 was significantly increased in sporadic colorectal cancer(2.20±0.23 vs 0.80±0.37 for normal tissues,P<0.05).In comparison to normal(2.80±0.13)and CAC(2.50±0.33)tissues,VDR was significantly decreased in sporadic dysplasia(0.00±0.00,P<0.001 vs normal,P<0.001 vs CAC)and sporadic CRC(0.47±0.23,P<0.001 vs normal,P<0.001 vs CAC).VDR levels negatively correlated with NK-1R(r=-0.48)and p EGFR(r=-0.56)in normal,IBD,sporadic dysplasia and sporadic CRC tissue,but not in CAC.CONCLUSION:Immunohistochemical NK-1R and p EGFR positivity with VDR negativity can be used to identify areas of sporadic colorectal neoplasia.VDR immunoreactivity can distinguish CAC from sporadic cancer.

Effects of genistein and equol on human and rat testicular 3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase 3 activities

现在的学习的目的是在 3 尾 - hydroxysteroid 脱氢酶(3 尾 - HSD ) 和 17 尾 - hydroxysteroid 脱氢酶上调查 genistein 和 equol 的效果 3 (17 尾 - HSD3 ) 在里面人和老鼠睾丸微体。与二其它(细胞色素 P450 方面链劈开酶和细胞色素 P450 17 伪 - hydroxylase/17-20 lyase ) 一起，这些酶(3 尾 - HSD 和 17 尾 - HSD3 ) 催化把类固醇胆固醇变换成性荷尔蒙睾丸激素的反应。Genistein 禁止了 3 尾 - HSD 活动(0.2 渭 m ol L ? 1 pregnenolone ) 与一半最大的抑制或 87 卤的一半最大的禁止的集中(IC50 ) 15 (人) 并且 636 卤 155 nmol L ? 1 (老鼠) 。Genistein 在 3 尾 - HSD 活动的行动的模式为余因子 NAD+ 为底层 pregnenolonrge 和 noncompetitive 是竞争的。在 genistein 在未经触动的老鼠 Leydig 房间和睾丸微体之间的 3 尾 - HSD 抑制的力量没有差别。与它 3 尾 - HSD 的有势力抑制相对照， genistein 在人和老鼠上有更小的效果 17 尾 - HSD3 (0.1 渭 m ol L ? 1 androstenedione ) ，与 IC50 鈮 ? 100 渭 m ol L ? 1。在另一方面， equol 仅仅在 42% 禁止了人 3 尾 - HSD，并且没在老鼠纸巾在 3 尾 - HSD 和 17 尾 - HSD3 上有效果。这些观察暗示酱油 isoflavones 到的能力在 Leydig 房间调整雄激素生合成对在 Leydig 房间 3 尾 - HSD 活动的行动部分地到期。在血雄激素层次上给基于酱油的食物产品和他们的潜在的效果的增加的吸入，这些调查结果是极大地与公共健康相关。

Pacing and predictors of performance during cross-country skiing races:A systematic review

Background: Cross-country skiing(XCS) racing, a popular international winter sport, is complex and challenging from physical, technical, and tactical perspectives. Despite the vast amount of research focusing on this sport, no review has yet addressed the pacing strategies of elite XCS racers or the factors that influence their performance. The aim was to review the scientific literature in an attempt to determine the effects of pacing strategy on the performance of elite XCS racers.Methods: Four electronic databases were searched using relevant subject headings and keywords. Only original research articles published in peerreviewed journals and the English language and addressing performance, biomechanics, physiology, and anthropometry of XCS racers were reviewed.Results: All 27 included articles applied correlative designs to study the effectiveness of different pacing strategies. None of the articles involved the use of an experimental design. Furthermore, potential changes in external conditions(e.g., weather, ski properties) were not taken into consideration. A comparable number of studies focused on the skating or classical technique. In most cases, positive pacing was observed, with certain indications that higher-level athletes and those with more endurance and strength utilized a more even pacing strategy. The ability to achieve and maintain a long cycle length on all types of terrain was an important determinant of performance in all of the included studies, which was not the case for cycle rate. In general, uphill performance was closely related to overall race performance, with uphill performance being most closely correlated to the success of female skiers and performance on flat terrain being more important for male skiers. Moreover, pacing was coupled to the selection and distribution of technique during a race, with faster skiers employing more double poling and kick double poling,less diagonal stride, and more V2(double dance) than V1(single dance) skating across a race.Conclusion: We propose that skiers at all levels can improve their performance with more specific training in techniques(i.e., maintaining long cycles without compromising cycle rate and selecting appropriate techniques) in combination with training for endurance and more strength. Furthermore, we would advise less experienced skiers and/or those with lower levels of performance to apply a more even pacing strategy rather than a positive one(i.e., starting the race too fast).

Antihyperglycemic effects of the methanol leaf extract of Diaphananthe bidens in normoglycemic and streptozotocin—induced hyperglycemic rats

Objective:To evaluate the methanol leaf extract of Diaphonathe bidem(D.bidenx)(AFZEL EX SW) SCHLTR for antihyperglycemic activity in order to confirm it antidiabetic potential.Methods: D.bidenx was extracted by cold maceration for 48 h and concentrated in vacuo to yield D.bidenx extract(DBE).Hyperglycemia was induced by intraperitoneal administration of slreplozotocin (75 mg/kg).Oral glucose tolerance test was done with 2 g/kg glucose load in normal rats.DBE (150.300 and 600 mg/kg) was administered orally,while tolbutamide(100 mg/kg.p.o.) was used as the standard reference drug.Blood glucose levels determined using ACCUCHEK glucose autoanalyzer. The acute toxicity and phytochemical studies were also carried out.Results:DBF. (600 mg/kg) and tolbutamide(100 mg/kg) significantly(P【0.05,0.005) reduced blood glucose levels of rats between 120 and 480 nun post administration in normal rats.In the streptozotoeininduced hyperglycemic rats,DBE(150.300.600 mg/kg) caused significant(P【0.001)dose- and time- dependent reduction in the blood glucose levels by 1.7%.22.8%and 43.4%,respectively at 480 min compared to the negative control group.DBE(600 mg/kg) reduced the blood glucose level of rats by 1.2%in the oral glucose tolerance test when compared with the normal saline treated group.The acute toxicity test showed that DBE was safe at the doses used and the phytochemical screening revealed the presence of saponins,steroids,tannins and terpernoids.Conclusions:D. bidens extract possess antihyperglycemic activity which may be mediated through pancreatic and extra-pancreatic pathways,thereby justifying it folkloric use.

Relationship between entero-hepatic bile acid circulation and interdigestive migrating myoelectrical activity in rats

AIM: To investigate the effects of entero-hepatic bile acid circulation on the inter-digestive migrating myoelectrical complex (MMC) in rats.METHODS: Thirty-two rats were divided into four groups.Three pairs of bipolar silver electrodes were chronically implanted in the antrum, duodenum and jejunum. Three groups of them were ligated around the upper part of common bile duct (CBD). The experiments were performed in conscious and fasting state. The gastrointestinal myoelectrical activity was recorded. Ursodeoxycholic acid (UDCA) and saline were then perfused into stomachs of two groups with CBD obstruction and the effects of them on the MMC were observed.RESULTS: A typical pattern of MMC was observed in normal fasting rats. MMC of antral and duodenal origin disappeared temporarily in earlier stage of CBD obstruction. While MMC of jejunum origin appeared.increased MMC cycle duration was seen after 4 d in rats with CBD obstruction. The MMC after CBD obstruction was characterized by an increased duration of phase Ⅱ-like activity and decreased duration of phase Ⅰ & Ⅲ activity.Perfusion into stomachs with UDCA resulted in a shorter MMC cycle duration and a longer duration of phase Ⅲ of duodenal origin compared to the normal group.CONCLUSION: Entero-hepatic bile acid circulation initiates inter-digestive MMC of duodenal origin.

Synergy in antibacterial activities of Ampicillin trihydrate, stabilized with a synthetic aluminum-magnesium silicate and immune-stimulants, on resistant <i>Escherichia coli</i>infection

To treat resistant Escherichia coli infection in chicks, Ampicillin was stabilized with a synthetic aluminum-magnesium silicate (AMS) to prolong its bioavailability. Its dose was also reduced to minimize adverse side effects. Vitamins A, C, E and Selenium levels in the chicks’ feeds were increased to enhance immune response of the chicks. E. coli coloning forming units, per ml of bile of the chicks, treated with Ampicillin and with Ampicillin in AMS, were: 228800.00 ± 90103.50 and 134500.00 ± 44937.97 at 10 mg/kg, 104400.00 ± 36024.44 and 34800.00 ± 8014.97 at 7.5 mg/kg, 198400.00 ± 129301.80 and 156800.00 ± 109392.70 at 5 mg/kg. Mean bacterial loads of the untreated groups, fed normal feed and those fed the fortified feed were 824400.00 ± 322424.80 and 534800.00 ± 277832.80. At 7.5 mg/kg. Ampicillin in the AMS, effectively (P E. coli infection in chicks, fed immune-stimulants, with the infection rate reduced by 95.8%.