Correlations between serum kidney injury molecule-1,cystatin C and immunosuppressants:A cross-sectional study of renal transplant patients in Bahrain

Renal transplant patients receive several immunosuppressive drug regimens that are potentially nephrotoxic for treatment.Serum creatinine is the standard for monitoring kidney function;however,cystatin C(Cys C)and kidney injury molecule-1(KIM-1)have been found to indicate kidney injury earlier than serum creatinine and provide a better reflection of kidney function.Here,we assessed Cys C and KIM-1 serum levels in renal transplant patients receiving mycophenolate mofetil,tacrolimus,sirolimus,everolimus,or cyclosporine to evaluate kidney function.We used both the Chronic Kidney Disease Epidemiology Collaboration(CKD-EPI)2021 equation,which is based on creatinine and combined creatinine with Cys C,and the CKD-EPI 2012 equation,which is based on Cys C alone,to estimate glomerular filtration rate(GFR).Then,we assessed the association between serum KIM-1 and GFR<90 mL per minute per 1.73 m2.We observed significantly higher serum Cys C levels in patients with the elevated serum creatinine,compared with those with normal serum creatinine.The estimated GFRs based on creatinine were significantly higher than those based on the other equations,while a significant positive correlation was observed among all equations.Serum KIM-1 levels were negatively correlated with the estimated GFRs by the CKD-EPI Cys C and the combined creatinine with Cys C equations.A serum KIM-1 level above 0.71 ng/mL is likely to indicate GFR<90 mL per minute per 1.73 m2.We observed a significant correlation between serum creatinine and Cys C in our renal transplant patients.Therefore,serum KIM-1 may be used to monitor renal function when using potentially nephrotoxic drugs in renal transplants.

Associations of PNPLA3 and LEP genetic polymorphisms with metabolic-associated fatty liver disease in Thai people living with human immunodeficiency virus

BACKGROUND The prevalence of metabolic-associated fatty liver disease(MAFLD)is a growing public health issue in people living with human immunodeficiency virus(PLWH).However,the pathophysiology of MAFLD is still unknown,and the role of genetic variables is only now becoming evident.AIM To evaluate the associations of gene-polymorphism-related MAFLD in PLWH.METHODS The study employed transient elastography with a controlled attenuation parameter≥248 dB/m to identify MAFLD in patients from a Super Tertiary Hospital in central Thailand.Candidate single-nucleotide polymorphisms(SNPs)were genotyped using TaqMan®MGB probe 5'nuclease assays for seven MAFLD-related genes.Statistical analyses included SNP frequency analysis,Fisher's Exact and Chi-square tests,odds ratio calculations,and multivariable logistic regression.RESULTS The G-allele carriers of PNPLA3(rs738409)exhibited a two-fold rise in MAFLD,increasing by 2.5 times in MAFLD with human immunodeficiency virus infection.The clinical features and genetic patterns imply that LEP rs7799039 A-allele carriers had a nine times(P=0.001)more significant chance of developing aberrant triglyceride among PLWH.CONCLUSION The current study shows an association between PNPLA3 rs738409 and LEP rs7799039 with MAFLD in PLWH.

Development status of novel spectral imaging techniques and application to traditional Chinese medicine

Traditional Chinese medicine(TCM)is a treasure of the Chinese nation,providing effective solutions to current medical requisites.Various spectral techniques are undergoing continuous development and provide new and reliable means for evaluating the efficacy and quality of TCM.Because spectral techniques are noninvasive,convenient,and sensitive,they have been widely applied to in vitro and in vivo TCM evaluation systems.In this paper,previous achievements and current progress in the research on spectral technologies(including fluorescence spectroscopy,photoacoustic imaging,infrared thermal imaging,laser-induced breakdown spectroscopy,hyperspectral imaging,and surface enhanced Raman spectroscopy)are discussed.The advantages and disadvantages of each technology are also presented.Moreover,the future applications of spectral imaging to identify the origins,components,and pesticide residues of TCM in vitro are elucidated.Subsequently,the evaluation of the efficacy of TCM in vivo is presented.Identifying future applications of spectral imaging is anticipated to promote medical research as well as scientific and technological explorations.

Bioactive Components of Chinese Herbal Medicines in the Treatment of Glucose and Lipid Metabolism Disorders:Evidence and Potential Mechanisms

Disturbed cholesterol and glucose homeostasis play crucial roles in the development of various diseases such as cardiovascular diseases,cerebrovascular diseases,central nervous system diseases,and cancer.An increasing number of studies have shown that excessive body fat accumulation is associated with type 2 diabetes or insulin resistance in a vicious cycle.This vicious cycle promotes the occurrence and development of the aforementioned diseases.Therefore,stabilizing the blood lipids and blood glucose of patients is the predominant strategy for improving the symptoms of patients with cardiovascular,cerebrovascular,and central nervous system diseases.Traditional Chinese medicine,mainly Chinese herbal medicine(CHM),has a history of more than 2000 years in China,which has established a unique theory and accumulated a great wealth of clinical experience.Moreover,CHM has been widely used in China and other countries for the treatment of cardiovascular and cerebrovascular diseases,with the advantages of preventing and curing hyperlipidemia,diabetes,hypertension,and other diseases.However,the use of CHM in Western countries remains rather limited,partly because of the incomplete understanding of multiple complex components and uncertain pharmacological mechanisms.Herein,we review and discuss the benefits,molecular mechanisms,and clinical research progress of bioactive components of CHM and their preparations as therapeutics for hyperlipidemia and hyperglycemia.

Synergistic Mixture of Cyperus esculentus, Phoenix dactylifera and Cocos nucifera Aqueous Extract: Its Liver and Kidney Benefits in Male Albino Rat Model

Background: The synergistic mixture of Cyperus esculentus, Phoenix dactylifera and Cocos nucifera (STCD) aqueous extract is a common drink in Port Harcourt, Nigeria. It is assumed to have various health benefits. However, the synergistic mixture of the content has not been studied scientifically, hence the need to evaluate its effect on the liver and kidney being part of the body’s metabolic organs. Aim: This study evaluated the synergistic mixture of Cyperus esculentus, Phoenix dactylifera and Cocos nucifera (STCD) aqueous extract in male albino rats. Methods: Acute toxicity LD50 of STCD was carried out, afterwards, fifteen male albino rats were grouped into three groups with 5 rats in each group;Control, 200 mg/kg, 400 mg/kg STCD. The rats were administered STCD orally 24 hourly, for 21 days, with feed and water ad libitum. At the end of the experiment, blood samples were collected for biochemical analysis of the liver and kidney biomarkers, while the liver and kidney tissues were harvested for histopathological examination using standard laboratory methods. Descriptive statistics were computed and expressed as Mean ± SD. One-way ANOVA and Turkeys test was performed. P value ≤0.05 was considered statistically significant. Results: Acute toxicity LD50 of STCD was observed to be ≥2404.2 mg/kg body weight. An increase in the percentage body weight difference of 8.39% and 2.86% was observed for 200 and 400 mg/kg STCD groups. Also, the liver weight was observed to increase in 400 mg/kg (3.92 ± 1.42) in comparison to the control group (3.48 ± 1.61), a decrease in the kidney weight was observed in all groups administered STCD in comparison to the control group. Administration of STCD at both 200 and 400 mg/kg revealed a decrease in the concentration of the hepatic biomarkers AST, ALT, ALP, TP, Albumin, Total and conjugated bilirubin. The kidney biomarker Urea was observed to decrease in concentration for 200 mg/kg STCD (4.60 ± 1.83) and 400 mg/kg STCD (4.76 ± 0.74) when compared to the control group (6.32 ± 2.74). A decrease in Creatinine was observed in 200 mg/kg (91.80 ± 34.69) and 400 mg/kg (98.60 ± 15.53) in comparison to the control group (117.60 ± 42.88). The histological examination of the liver of rats administered STCD revealed structural normal central vein, hepatocytes and portal tract. The kidney examination revealed normal glomeruli and normal tubule. Conclusion: The findings of this study opine that STCD improved the health of both the liver and kidney as evidenced via the biomarkers and histological examinations of the liver and kidney. This study therefore recommends the intake of STCD at moderate doses for improved liver and kidney function due to its bioactive compounds and nutritional content.

Neuroprotective effects of G9a inhibition through modulation of peroxisome-proliferator activator receptor gamma-dependent pathways by miR-128

Dysregulation of G9a,a histone-lysine N-methyltransferase,has been observed in Alzheimer’s disease and has been correlated with increased levels of chronic inflammation and oxidative stress.Likewise,microRNAs are involved in many biological processes and diseases playing a key role in pathogenesis,especially in multifactorial diseases such as Alzheimer’s disease.Therefore,our aim has been to provide partial insights into the interconnection between G9a,microRNAs,oxidative stress,and neuroinflammation.To better understand the biology of G9a,we compared the global microRNA expression between senescence-accelerated mouse-prone 8(SAMP8)control mice and SAMP8 treated with G9a inhibitor UNC0642.We found a downregulation of miR-128 after a G9a inhibition treatment,which interestingly binds to the 3′untranslated region(3′-UTR)of peroxisome-proliferator activator receptor γ(PPARG)mRNA.Accordingly,Pparg gene expression levels were higher in the SAMP8 group treated with G9a inhibitor than in the SAMP8 control group.We also observed modulation of oxidative stress responses might be mainly driven Pparg after G9a inhibitor.To confirm these antioxidant effects,we treated primary neuron cell cultures with hydrogen peroxide as an oxidative insult.In this setting,treatment with G9a inhibitor increases both cell survival and antioxidant enzymes.Moreover,up-regulation of PPARγby G9a inhibitor could also increase the expression of genes involved in DNA damage responses and apoptosis.In addition,we also described that the PPARγ/AMPK axis partially explains the regulation of autophagy markers expression.Finally,PPARγ/GADD45αpotentially contributes to enhancing synaptic plasticity and neurogenesis after G9a inhibition.Altogether,we propose that pharmacological inhibition of G9a leads to a neuroprotective effect that could be due,at least in part,by the modulation of PPARγ-dependent pathways by miR-128.

Emergence of taurine as a therapeutic agent for neurological disorders

Taurine is a sulfur-containing,semi-essential amino acid that occurs naturally in the body.It alternates between inflammation and oxidative stress-mediated injury in various disease models.As part of its limiting functions,taurine also modulates endoplasmic reticulum stress,Ca^(2+)homeostasis,and neuronal activity at the molecular level.Taurine effectively protects against a number of neurological disorders,including stro ke,epilepsy,cerebral ischemia,memory dysfunction,and spinal cord injury.Although various therapies are available,effective management of these disorders remains a global challenge.Approximately 30 million people are affected worldwide.The design of taurine fo rmation co uld lead to potential drugs/supplements for the health maintenance and treatment of central nervous system disorders.The general neuroprotective effects of taurine and the various possible underlying mechanisms are discussed in this review.This article is a good resource for understanding the general effects of taurine on various diseases.Given the strong evidence for the neuropharmacological efficacy of taurine in various experimental paradigms,it is concluded that this molecule should be considered and further investigated as a potential candidate for neurotherapeutics,with emphasis on mechanism and clinical studies to determine efficacy.

Sexual dimorphism of G protein-coupled receptor signaling in the brain

G protein-coupled receptors(GPCRs)represent the most substantial family of membrane receptors that are targeted by U.S.Food and Drug Administration-approved drugs.Much of the preclinical research to understand the pharmacology of many membrane receptors including GPCRs is derived from studies in male animal models(Karp and Reavey,2019).

Increased alcohol consumption during the COVID-19 pandemic:A cross-sectional study

BACKGROUND The coronavirus disease 2019(COVID-19)pandemic has significantly impacted health,mental well-being,and societal functioning,particularly for individuals with psychiatric conditions and substance use disorders.Recent evidence highlights a concerning increase in alcohol consumption during the pandemic,with a study spanning 2015-2020 indicating heightened usage,especially among young and middle-aged adults,for relaxation and tension relief.Additionally,addressing challenges exacerbated by the pandemic,another study underscored persistent barriers to healthcare access,resulting in increased alcohol and tobacco use rates and limited healthcare options.These findings shed light on the unique vulnerabilities exposed by the pandemic,emphasizing the need to investigate further its impact on alcohol consumption in diverse non-urban American communities.AIM To investigate the impact of the COVID-19 pandemic on alcohol abuse using socioeconomic and medical parameters in diverse non-urban community in America.METHODS Based on a cross-sectional analysis of 416 participants the United States in 2021,the study utilized The Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition criteria to categorize alcohol consumption levels.Participants aged 21 years and above were surveyed through an online platform due to COVID-19 challenges.The survey was conducted from January 14 to January 31,2022,recruiting participants via social media and ensuring anonymity.Informed consent was secured,emphasizing the voluntary nature of participation,and participants could only take the survey once.RESULTS Out of 416 survey respondents,396 met eligibility criteria,with 62.9%reporting increased alcohol consumption during COVID-19.Males(68.8%)and ages 21-29 years(34.6%)predominated.Low alcohol consumption decreased by 2.8%(P=0.237),moderate by 21.4%(P<0.001),and heavy increased by 14.9%(P<0.001).Alcohol abuse rose by 6.5%(P=0.0439),with a 7%increase in self-identified alcohol abusers/alcoholics.Seeking treatment during COVID-19 rose by 6.9%.Easier alcohol access(76.0%)was reported,while 80.7%found it harder to access medical care for alcohol-related issues.These findings highlight the pandemic's impact on alcohol consumption and healthcare access,emphasizing the need for targeted interventions during public health crises.CONCLUSION The COVID-19 pandemic exacerbated alcoholism and abuse,with increased heavy consumption(P<0.001)and abuse(P=0.0439).Access to medical programs for addressing alcohol abuse declined,highlighting the need for targeted intervention.

Androgenic regulation of novel genes in the epididymis

The epididymis is critically dependent on the presence of the testis. Although several hormones, such as retinoids and progestins, and factors secreted directly into the epididymal lumen, such as androgen binding protein and fibroblast growth factor, might play regulatory roles in epididymal function, testosterone （T） and its metabolites, dihydrotestosterone （DHT） and estradiol （E2）, are accepted as the primary regulators of epididymal structure and functions, with the former playing the greater role. To ascertain the molecular action of androgens on the epididymis, three complementary approaches were pursued to monitor changes in gene expression in response to different hormonal milieux. The first was to establish changes in gene expression along the epididymis as androgenic support is withdrawn. The second was to determine the sequence of responses that occur in an androgen deprived tissue upon re-administration of the two metabolites of T, DHT and E2. The third was to study the effects of androgen withdrawal and re-administration on gene expression in immortalized murine caput epididymidal principal cells. Specific responses were observed under each of these conditions, with an expected major difference in the panoply of genes expressed upon hormone withdrawal and re-administration; however, some key common features were the common roles of genes in insulin like growth factor/epidermal growth factor and the relatively minor and specific effects of E2 as compared to DHT. Together, these results provide novel insights into the mechanisms of androgen regulation in epididymal principal cells. （Asian J Androl 2007 July; 9： 545-553）

Analgesic and anti-inflammatory activities of the ethanol extract of the leaves of Helianthus Annus in Wistar rats

Objective:To investigate the anti-inflammatory and analgesic effects of the ethanol extract of leaves of Helianthus annus L.(H.annus) in acclimatized Wistar rats.Methods:It was undertaken using the albumin induced paw edema model of inflammation as well as both the hotplate and tail immersion analgesic test methods.Doses of the extract tested in experimental rats were 0.5 g/kg,2 g/kg and 4 g/kg while negative and positive control rats received distilled water and indomethacin respectively.Results:It was shown that treatment with the tested doses of the extract effectively inhibited paw edema induced by egg albumin.This effect was comparable if not better than the observations made in rats treated with 10 mg/kg of indomethacin orally.Treatment with the extract was also observed to have significantly increased the mean tolerance time of rats to thermal noxious stimuli compared to control animals that had distilled water and appeared to be more effective than 10 mg/kg of indomethacin treatment.Conclusions: These observations confirmed the presence of a strong anti-inflammatory and anti-noiciceptive activity in the ethanol extract of the leaves of H.annus and therefore validated the folkloric use of the leaves of this plant in treatment of pro-inflammatory,post traumatic situations.

Antibiotics/antibacterial drug use, their marketing and promotion during the post-antibiotic golden age and their role in emergence of bacterial resistance

During the post-antibiotic golden age, it has seen a massive antibiotic/antibacterial production and an increase in irrational use of these few existing drugs in the medical and veterinary practice, food industries, tissue cultures, agriculture and commercial ethanol production globally. The irrational drug use has been further exacerbated by the increased marketing and promotion of these drugs by the pharmaceutical companies thus increasing their accessibility in the public and hence their improper use. The lack of production and introduction of the newer and effective antibiotic/antibacterial drugs in clinical practice in the post-antibiotic golden age has seen an increase in the emergence of the resistant pathogenic bacterial infections creating a significant problem in the global health of humankind. The massive productions of the antibiotic/antibacterial drugs have contributed to the poor disposal of these drugs and hence many of them are discharged in various water bodies contributing to the environmental antibiotic/antibacterial drug pollution. In the environment, these drugs exert pressure on the environmental bacteria by destroying useful bacteria that are responsible for the recycling of the organic matter and as well as promoting the selection of the resistant pathogenic bacteria that can spread in human and animal population thus causing an increase in the observed bacterial disease burden and hence a significant global public health problem. The resistant bacterial diseases lead to the high cost, increased occurrence of adverse drug reactions, prolonged hospitalization, the exposure to the second- and third-line drugs like in MDR-TB and XDR-TB that leads to toxicity and deaths as well as the increased poor production in agriculture and animal industry and commercial ethanol production.

Safety assessment of Chlorophytum alismifolium tuber extract (Liliaceae):Acute and sub-acute toxicity studies in Wistar rats

To explore the toxicological profile of methanol extract of Chlorophytum alismifolium (MECA) tubers in Wistar rats. Methods: MECA was subjected to acute and sub-acute studies which were conducted according to Organization for Economic Co-operation and Development (OECD 425 and 407 guidelines respectively). In the acute toxicity experiment, a limit test (5000 mg/kg) was administered to five rats and monitored for 2 weeks. The sub-acute studies were conducted on 4 groups of rats. The first group served as control, while the 2nd, 3rd and 4th groups received MECA (150, 300 and 600 mg/kg respectively). The treatments were given orally and daily for 4 weeks. At the end of the experiment (29th day), the animals were euthanized to obtain blood samples and organs for haematological, biochemical and histological evaluations. Results: Acute toxicity study showed that the oral median lethal dose was >5000 mg/kg. In the sub-acute studies, the results showed no significant (P>0.05) changes in the haematological, hepatic and renal indices compared to control animals. In the fourth week, a significant (P<0.01) increase in body weight of the rats was observed at 150 mg/kg and 600 mg/kg compared to week one. However, there were no major changes in the organ/body weights of the rats. Histological examination of the kidney showed slight glomerular adhesion and tubular distortion. Moderate hepatic necrosis was observed at 150 mg/kg and 300 mg/kg. Conclusions: The results of this research revealed that the MECA tubers is virtually non-toxic after acute administration and it has low sub-acute toxicity potential in rats.

Phloretin-induced suppression of oxidative and nitrosative stress attenuates doxorubicin-induced cardiotoxicity in rats

Objective:To compare the cardioprotective efficacy of equimolar doses(50 mM/kg,p.o.)of phloretin and genistein against doxorubicin-induced cardiotoxicity in rats.Methods:Cardiotoxicity was induced in rats by intraperitoneal injection of 6 mg/kg doxorubicin on alternative days till the cumulative dose reached 30 mg/kg.This study included four treatment groups of rats(n=6):the control group(0.5%carboxymethyl cellulose solution-treated),the doxorubicin-treated group(0.5%carboxymethyl cellulose solution along with doxorubicin),the genistein-treated group(50 mM/kg/day;p.o.along with doxorubicin)and phloretin-treated group(50 mM/kg/day;p.o.along with doxorubicin).On the 10th day of dosing,rats were anesthetized for recording ECG,mean arterial pressure,and left ventricular function.Oxidative stress,nitric oxide levels,and inflammatory cytokines were estimated in the cardiac tissue.Cardiac function parameters(creatine kinase MB,lactate dehydrogenase,aspartate aminotransferase,and alanine transaminase)were estimated in the serum samples.Results:Phloretin treatment inhibited doxorubicin-induced oxidative stress and also reduced nitric oxide levels in cardiac tissues of rats.Phloretin administration attenuated doxorubicin-induced alterations in hemodynamic parameters(heart rate,mean arterial blood pressure,and left ventricular function)and suppressed the expression of pro-inflammatory cytokines.The cardiac injury markers like creatine kinase MB,lactate dehydrogenase,aspartate aminotransferase,and alanine transaminase were reduced by both genistein and phloretin.All these effects of phloretin were more prominent than genistein.Conclusions:Phloretin offers cardioprotection that is comparable to genistein,a clinically validated cardioprotectant against doxorubicin-induced cardiotoxicity.Further studies are needed to confirm and establish the therapeutic utility of phloretin as a chemopreventive adjuvant to doxorubicin chemotherapy.

An enhanced chemopreventive effect of methyl donor S-adenosylmethionine in combination with 25-hydroxyvitamin D in blocking mammary tumor growth and metastasis

Therapeutic targeting of metastatic breast cancer still remains a challenge as the tumor cells are highly heterogenous and exploit multiple pathways for their growth and metastatic spread that cannot always be targeted by a single-agent monotherapy regimen.Therefore,a rational approach through simultaneous targeting of several pathways may provide a better anti-cancer therapeutic effect We tested this hypothesis using a combination of two nutraceutical agents S-adenosylmethionine(SAM)and Vitamin D(Vit.D)prohormone[25-hydroxyvitamin D;/25(OH)D,]that are individually known to exert distinct changes in the expression of genes involved in tumor growth and metastasis.Our results show that both SAM and 25(OH)D monotherapy significantly reduced proliferation and clonogenic survival of a panel of breast cancer cell lines in vitro and inhibited tumor growth,lung metastasis,and breast tumor cell colonization to the skeleton in vivo.However,these effects were significantly more pronounced in the combination setting.RNA-Sequencing revealed that the transcriptomic footprint on key cancer-related signaling pathways is broader in the combination setting than any of the monotherapies.Furthermore,comparison of the differentially expressed genes from our transcriptome analyses with publicly available cancer-related dataset demonstrated that the combination treatment upregulates genes from immune-related pathways that are otherwise downregulated in bone metastasis in vivo.Since SAM and Vit.D are both approved nutraceuticals with known safety profiles,this combination treatment may serve as a novel strategy to reduce breast cancer-associated morbidity and mortality。

Inhibitory effects of methanolic Olea europaea and acetonic Acacia laeta on growth of Babesia and Theileria

Objective:To evaluate the antipiroplasmic activities of methanolic extract of Olea europaea(MOE)and acetonic extract of Acacia laeta(AAL)against Babesia and Theileria parasites in vitro and evaluate the chemotherapeutic effects of these extracts against Babesia(B.)microti in vivo.Methods:Fluorescence assay using SYBR Green 1 nucleic acid stain was used to detect inhibitory effects of the two extracts as well as the combination effects of the two extracts with diminazene aceturate and atovaquone on four Babesia species and Theileria equi in vitro while for in vivo experiments,8-weekold female BALB/c mice were injected intraperitoneally with 1× 107 B.microti-iRBCs and treated orally at a dose of 150 mg/kg of both extracts.Results:The half maximal inhibitory concentration(IC50)values of AAL against B.bovis,B.bigemina,B.divergens,B.caballi,and Theileria equi were lower than those of MOE extracts.Toxicity assay on Madin-Darby bovine kidney,mouse embryonic fibroblast(NIH/3T3),and human foreskin fibroblast cell lines showed that MOE and AAL affected only the viability of Madin-Darby bovine kidney cell line with half maximal effective concentrations(EC50)of(794.7±41.9)and(873.9±17.5)μg/mL,respectively.The oral treatments of MOE and AAL at 150 mg/kg inhibited the growth of B.microti in mice by 80.4% and 64.4%,respectively.The MOE and diminazene aceturate combination showed a higher chemotherapeutic effect than that of monotherapy.Conclusions:MOE and AAL have the potential to be an alternative remedy for treating piroplasmosis.Furthermore,the combination therapy of MOE + DA was more potent against B.microti infection in mice than their monotherapies.

Phytochemical screening and anticonvulsant studies of ethyl acetate fraction of Globimetula braunii on laboratory animals

Objective:To investigate the phytochemical properties and the anticonvulsant potential of the ethyl acetate soluble fraction of ethanol leaf extract of Globimetida braunii,a plant used in ethnomedicine for the treatment of epilepsy.Methods:The phytochemical screening was carried out using standard protocol while the anticonvulsant activity was studied using maximal electroshock test in chicks,pentylenetetrazole and 4-aminopyridine—induced seizures in mice.Results:The preliminary phytochemical screening carried out on the crude ethanol extract revealed the presence of saponins,carbohydrates,flavonoids,tannins,anthraquinones and steroids.Similarly,tannins,flavonoids and steroids/terpenes were found to be present in the ethyl acetate fraction,In the pharmacological screening,150 mg/kg of the fraction protected 83.33%of animals against pentylenetetrazole-induced seizure in mice whereas sodium valproate a standard anti-epileptic drug offered 100%protection.In the 4-aminopyridine-induced seizure model,the fraction produced a significant(P<0.05)increase in the mean onset of seizure in unprotected animals.The fraction did not exhibit a significant activity against maximal electroshock convulsion.The median lethal dose of the fraction was found to be 1261.91 mg/kg.Conclusions:These results suggest that the ethyl acetate fraction of Globimetula braunii leaves extract possesses psychoactive compound that may be useful in the management of petit mal epilepsy and lend credence to the ethnomedical use of the plant in the management of epilepsy.

Effects of Salacia lehmbachii ethanol root bark extract on estrous cycle and sex hormones of female albino rats

Objective:To evaluate the effect of Salacia lehmbachii (S. lehmbachii) ethanol root bark extract on estrous cycle and sex hormones in female rats. Methods: Forty-eight virgin rats with regular 4-day cycle were grouped into four and each group was further subdivided into 'a' and 'b' (n=6). Each group was orally treated for 28 days with 2 mL of distilled water (control), ethanol root bark extract ofS. lehmbachii in doses of 250, 500 and 750 mg/kg/body weight (groups 2, 3, 4, respectively). Estrous cycle was determined daily using the vaginal smear method. Rats in'a' subgroups were weighed and sacrificed on the 29th day, and blood was collected for serum generation which was used for hormonal assay and sex organs were removed and weighed. Rats in 'b' subgroups were discontinued from treatment for 2 weeks and the parameters above were reassessed.Results:The mean length of estrous cycle and duration of diestrous of treated rats were prolonged dose dependently compared to control. The increase was significant (P<0.05) at 500 and 750 mg/kg. The other estrous phases were shortened in the same pattern. Relative weights of sex organs were reduced significantly (P<0.05) at the highest dose. Sex hormones levels were significantly (P<0.05) reduced compared to control. The above changes reverted towards the control values two weeks post treatments.Conclusions: Ethanol root bark extract ofS. lehmbachii (high doses) has antifertility effect in female rats as it prolongs the estrous and diestrous cycle, and reduces serum sex hormones levels. The observed alterations were reversible.

Endoscopic balloon dilation of crohn's disease stricturessafety,efficacy and clinical impact

AIM To evaluate the incidence of anastomotic strictures after intestinal resection in Crohn's disease(CD), demonstrate long-term efficacy and safety of endoscopic balloon dilation(EBD) in CD strictures and its impact on the diagnosis of subclinical postoperative endoscopic recurrence. METHODS Retrospective single tertiary center study based on prospectively collected data between 2010 and 2015including anastomotic and non-anastomotic strictures. RESULTS29% of 162 CD patients included developed an anastomotic stricture. 43 patients with anastomotic strictures and 37 with non-anastomotic strictures underwent EBD; technical success was 97.7% and 100%, respectively, however, 63% and 41% needed repeat dilation during the 4.4-year follow-up. Longer periods between surgery and index colonoscopy and higher lactoferrin levels were associated with the presence of stricture after surgery. Calprotectin levels > 83.35 μg/g and current or past history of smoking were associated with a shorter time until need for dilation(HR = 3.877, 95%CI: 1.480-10.152 and HR = 3.041, 95%CI: 1.213-7.627). Anastomotic strictures had a greater need for repeat dilation(63% vs 41%, P = 0.047). No differences were found between asymptomatic and symptomatic cohorts. Disease recurrence diagnosis was only possible after EBD in a third of patients. CONCLUSION EBD is an effective and safe alternative to surgery, with a good short and long-term outcome, postponing or even avoiding further surgery. EBD may allow to diagnose disease recurrence in patients with no clinical signs/biomarkers of disease activity.

Role of chemokines and cytokines in the neuropathogenesis of African trypanosomiasis

Trypanosoma brucei spp. cause human African trypanosomiasis(HAT) or sleeping sickness in humans and nagana in animals. The early stages of the disease have no specific symptoms; however, the late stage of the disease involves neurological signs of the disease, including disturbance of sleep patterns from which the disease derives the name sleeping sickness. During the late stage of African trypanosomiasis parasites, increased numbers of white blood cells and levels of cytokines and/or chemokines are found in the brain parenchyma and/or cerebrospinal fluid of animal models and HAT patients. In this mini review, contemporary findings on how chemokines and cytokines are thought to play an important role in the central nervous system invasion by the parasites, inflammation and the neuropathology of the disease are discussed. The levels of various cytokines and chemokines, such as interferongamma(IFN-γ), interleukin-1 beta(IL-1β), IL-6, IL-10, tumor necrosis factor-alpha(TNF-α), C-C motif chemokine 2(CCL2), CCL3, C-X-C motif chemokine 8(CXCL8, IL-8) and CXCL10, in the cerebrospinal fluid(CSF) of HAT patients correlate with the severity or stage of the disease. Thus, these molecules are possible candidates for differentiating between early and late stage HAT. The role of cytokines and chemokines in parasite invasion of the central nervous system is also being eluci-dated. IFN-γ, TNF-α and CXCL-10 are some of the cytokines and chemokines now known to facilitate parasite penetration of the brain parenchyma. Interestingly, they also constitute some of the candidate molecules with potential to differentiate between stage 1 and 2 of HAT. The increased levels of cytokines, such as IL-1β, IL-6, IFN-γ and TNF-α, as well as prostaglandins, during African trypanosomiasis might contribute to the neurological dysfunctions that occur during HAT.