The superiority of PMFs on reversing drug resistance of colon cancer and the effect on aerobic glycolysis-ROS-autophagy signaling axis

Background:Polymethoxylatedflavones(PMFs)are compounds present in citrus peels and other Rutaceae plants,which exhibit diverse biological activities,including robust antitumor and antioxidant effects.However,the mechanism of PMFs in reversing drug resistance to colon cancer remains unknown.In the present study,we aimed to investigate the potential connection between the aerobic glycolysis-ROS-autophagy signaling axis and the reversal of PTX resistance in colon cancer by PMFs.Methods:MTT Cell viability assay and colony formation assay were used to investigate the effect of PMFs combined with PTX in reversing HCT8/T cell resistance ex vivo;the mRNA and protein levels of the target were detected by SDS-PAGE(sodium dodecyl sulfate-polyacrylamide gel electrophoresis),quantitative real-timefluorescence polymerase chain reaction(qRT-PCR)and Western blot protein immunoblotting(WB);An HCT8/T cell xenograft model was established to investigate the MDR reversal activity of PMFs in vivo;The extracellular acidification rate(ECAR)and the oxygen consumption rate(OCR)were detected to assess the cellular oxygen consumption rate and glycolytic process.Results:HCT8/T cells demonstrated significant resistance to PTX,up-regulating the expression levels of ABCB1 mRNA,P-gp,LC3-I,and LC3-II protein,and increasing intracellular reactive oxygen species(ROS)content.PMFs mainly contain two active ingredients,nobiletin,and tangeretin,which were able to reverse drug resistance in HCT8/T cells in a concentration-dependent manner.PMFs exhibited high tolerance in the HCT8/T nude mouse model while increasing the sensitivity of PTX-resistant cells and suppressing tumor growth significantly.PMFs combined with PTX reduced extracellular acidification rate(ECAR)and oxygen consumption rate(OCR)in HCT8/T cells.Additionally,PMFs reduced intracellular ROS content,down-regulated the expression levels of autophagy-related proteins LC3-I,LC3-II,Beclin1,and ATG7,and significantly reduced the number of autophagosomes in HCT8/T cells.Conclusions:The present study demonstrated that PMFs could potentially reverse PTX resistance in colon cancer by regulating the aerobic glycolysis-ROS-autophagy signaling axis,which indicated that PMFs would be potential potentiators for future chemotherapeutic agents in colon cancer.

Vitamin D,selenium,and antidiabetic drugs in the treatment of type 2 diabetes mellitus with Hashimoto's thyroiditis

BACKGROUND Diabetes and thyroiditis are closely related.They occur in combination and cause significant damage to the body.There is no clear treatment for type-2 diabetes mellitus(T2DM)with Hashimoto's thyroiditis(HT).While single symptomatic drug treatment of the two diseases is less effective,combined drug treatment may improve efficacy.AIM To investigate the effect of a combination of vitamin D,selenium,and hypoglycemic agents in T2DM with HT.METHODS This retrospective study included 150 patients with T2DM and HT treated at The Central Hospital of Shaoyang from March 2020 to February 2023.Fifty patients were assigned to the control group,test group A,and test group B according to different treatment methods.The control group received low-iodine diet guidance and hypoglycemic drug treatment.Test group A received the control treatment plus vitamin D treatment.Test group B received the group A treatment plus selenium.Blood levels of markers of thyroid function[free T3(FT3),thyroid stimulating hormone(TSH),free T4(FT4)],autoantibodies[thyroid peroxidase antibody(TPOAB)and thyroid globulin antibody(TGAB)],blood lipid index[low-density lipoprotein cholesterol(LDL-C),total cholesterol(TC),triacylglycerol(TG)],blood glucose index[fasting blood glucose(FBG),and hemoglobin A1c(HbA1c)]were measured pre-treatment and 3 and 6 months after treatment.The relationships between serum 25-hydroxyvitamin D3[25(OH)D3]level and each of these indices were analyzed.RESULTS The levels of 25(OH)D3,FT3,FT4,and LDL-C increased in the order of the control group,test group A,and test group B(all P<0.05).The TPOAB,TGAB,TC,TG,FBG,HbA1c,and TSH levels increased in the order of test groups B,A,and the control group(all P<0.05).All the above indices were compared after 3 and 6 months of treatment.Pre-treatment,there was no divergence in serum 25(OH)D3 level,thyroid function-related indexes,autoantibodies level,blood glucose,and blood lipid index between the control group,test groups A and B(all P>0.05).The 25(OH)D3 levels in test groups A and B were negatively correlated with FT4 and TGAB(all P<0.05).CONCLUSION The combination drug treatment for T2DM with HT significantly improved thyroid function,autoantibody,and blood glucose and lipid levels.

The neuroprotective effects of the anti-diabetic drug linagliptin against Aβ-induced neurotoxicity

Impaired insulin signaling in Alzheimer’s disease（AD）brains：The insulin signaling pathway is a fundamental physiological mechanism that presents in nearly all vertebrate cells.However,sometimes cells stop responding properly to insulin stimulation.This condition is known as insulin resistance,which is a hallmark of two very common conditions,metabolic syndrome and type 2 diabetes（T2D）.

Excellent effects and possible mechanisms of action of a new antibody–drug conjugate against EGFR-positive triple-negative breast cancer

Background:Triple-negative breast cancer(TNBC)is the most aggressive subtype and occurs in approximately 15%–20%of diagnosed breast cancers.TNBC is characterized by its highly metastatic and recurrent features,as well as a lack of specific targets and targeted therapeutics.Epidermal growth factor receptor(EGFR)is highly expressed in a variety of tumors,especially in TNBC.LR004-VC-MMAE is a new EGFR-targeting antibody–drug conjugate produced by our laboratory.This study aimed to evaluate its antitumor activities against EGFR-positive TNBC and further studied its possible mechanism of antitumor action.Methods:LR004-VC-MMAE was prepared by coupling a cytotoxic payload(MMAE)to an anti-EGFR antibody(LR004)via a linker,and the drug-to-antibody ratio(DAR)was analyzed by HIC-HPLC.The gene expression of EGFR in a series of breast cancer cell lines was assessed using a publicly available microarray dataset(GSE41313)and Western blotting.MDA-MB-468 and MDA-MB-231 cells were treated with LR004-VC-MMAE(0,0.0066,0.066,0.66,6.6 nmol/L),and the inhibitory effects of LR004-VC-MMAE on cell proliferation were examined by CCK-8 and colony formation.The migration and invasion capacity of MDA-MB-468 and MDA-MB-231 cells were tested at different LR004-VCMMAE concentrations(2.5 and 5 nmol/L)with wound healing and Transwell invasion assays.Flow cytometric analysis and tumorsphere-forming assays were used to detect the killing effects of LR004-VC-MMAE on cancer stem cells(MDA-MB-468 and MDA-MB-231 cells).The mouse xenograft models were also used to evaluate the antitumor efficacy of LR004-VC-MMAE in vivo.Briefly,BALB/c nude mice were subcutaneously inoculated with MDA-MB-468 or MDAMB-231 cells.Then they were randomly divided into 4 groups(n=6 per group)and treated with PBS,naked LR004(10 mg/kg),LR004-VC-MMAE(10 mg/kg),or doxorubicin,respectively.Tumor sizes and the body weights of mice were measured every 4 d.The effects of LR004-VC-MMAE on apoptosis and cell cycle distribution were analyzed by flow cytometry.Western blotting was used to detect the effects of LR004-VC-MMAE on EGFR,ERK,MEK phosphorylation and tumor stemness marker gene expression.Results:LR004-VC-MMAE with a DAR of 4.02 were obtained.The expression of EGFR was found to be significantly higher in TNBC cells compared with non-TNBC cells(P<0.01).LR004-VC-MMAE inhibited the proliferation of EGFRpositive TNBC cells,and the ICvalues of MDA-MB-468 and MDA-MB-231 cells treated with LR004-VC-MMAE for 72 h were(0.13±0.02)nmol/L and(0.66±0.06)nmol/L,respectively,which were significantly lower than that of cells treated with MMAE[(3.20±0.60)nmol/L,P<0.01,and(6.60±0.50)nmol/L,P<0.001].LR004-VC-MMAE effectively inhibited migration and invasion of MDA-MB-468 and MDA-MB-231 cells.Moreover,LR004-VC-MMAE also killed tumor stem cells in EGFR-positive TNBC cells and impaired their tumorsphere-forming ability.In TNBC xenograft models,LR004-VC-MMAE at 10 mg/kg significantly suppressed tumor growth and achieved complete tumor regression on day 36.Surprisingly,tumor recurrence was not observed until the end of the experiment on day 52.In a mechanistic study,we found that LR004-VC-MMAE significantly induced cell apoptosis and cell cycle arrest at G/M phase in MDAMB-468[(34±5)%vs.(12±2)%,P<0.001]and MDA-MB-231[(27±4)%vs.(18±3)%,P<0.01]cells.LR004-VC-MMAE also inhibited the activation of EGFR signaling and the expression of cancer stemness marker genes such as Oct4,Sox2,KLF4 and EpCAM.Conclusions:LR004-VC-MMAE showed effective antitumor activity by inhibiting the activation of EGFR signaling and the expression of cancer stemness marker genes.It might be a promising therapeutic candidate and provides a potential therapeutic avenue for the treatment of EGFR-positive TNBC.

Why Don’t We Adequately Identify and Manage Adverse Drug Reactions despite Having the Needed Information?

Importance/Objective: Adverse Drug Reactions (ADRs) are unavoidable, but recognizing and addressing ADRs early can improve wellness and prevent permanent injury. We suggest that available medical information and digital/electronic methods could be used to manage this major healthcare problem for individual patients in real time. Methods: We searched the available digital applications and three literature databases using the medical subject heading terms, adverse drug reaction reporting systems or management, filtered by clinical trial or systemic reviews, to detect publications with data about ADR identification and management approaches. We reviewed the reports that had abstract or summary data or proposed or implemented methods or systems with potential to identify or manage ADRs in clinical settings. Results: The vast majority of the 481 reports used retrospectively collected data for groups of patients or were limited to surveying one population group or class of medication. The reports showed potential and definite associations of ADRs for specific drugs and problems, mostly, but not exclusively, for patients in hospitals and nursing homes. No reports described complete methods to collect comprehensive data on ADRs for individual patients in a healthcare system. The digital applications have ADR information, but all are too cumbersome or incomplete for use in active clinical settings. Several studies suggested that providing information about potential ADRs to clinicians can reduce these problems. Conclusion and Relevance: Although investigators and government agencies agree with the need, there is no comprehensive ADR management program in current use. Informing the patient’s healthcare practitioners of potential ADRs at the point of service has the potential for reduction of these complications, which should improve healthcare and reduce unneeded costs.

Effect of Ultrasound-Guided Transversus Abdominis Plane Block Combined with Lornoxicam on Pain and Recovery Quality After Abdominal Surgery in Patients with Drug Addiction

Objective:This paper aims to analyze the analgesic effect of ultrasound-guided transversus abdominis plane block(TAPB)combined with non-steroidal anti-inflammatory analgesic drug lornoxicam on abdominal surgery in patients with a history of drug addiction.Methods:32 patients aged 18-60 who underwent lower abdominal surgery in the First People's Hospital of Liangshan Yi Autonomous Prefecture and Butuo County People's Hospital of Liangshan Yi Autonomous Prefecture from January 2022 to March 2023 were selected,the patients must have drug abuse history for more than 1 year,with a history of drug withdrawal and relapse.The patients were divided into observation group and control group by the envelope method,with 16 cases in the observation group and 16 cases in the control group.Two groups of patients underwent ultrasound-guided bilateral transversus abdominis plane block after the operation.The observation group was treated with dexmedetomidine hydrochloride 1μg/kg+0.25%ropivacaine hydrochloride 40ml,and the control group was treated with 40ml 0.9%sodium chloride injection,the two groups of patients returned to the ward after operation and given intravenous infusion of lornoxicam for relieving the pain.The visual analogue scale(VAS)score of postoperative pain,the times of rescue analgesia,the time of postoperative anal exhaust,the time of ambulation,nausea and vomiting,withdrawal symptoms,related adverse reactions,and hospitalization days were compared between the two groups.Results:The VAS score of postoperative pain in the observation group was significantly lower than that in the control group,P<0.05.Patients in the observation group used less postoperative rescue analgesics than those in the control group,P<0.05.For postoperative anal exhaust time,the difference between the two groups of patients was relatively small,and the time in the observation group was shorter,P>0.05.The time to get out of bed and the length of hospital stay were not significantly different between the control group and the observation group,P>0.05.The withdrawal symptoms of the patients in the observation group were better,P<0.05,nausea and vomiting,and other adverse reactions were lower in the control group,P<0.05.Conclusion:Ultrasound-guided transversus abdominis plane block combined with lornoxicam can be used to relieve pain in abdominal surgery for patients with drug addiction,which can effectively improve the therapeutic effect of patients and reduce the number of postoperative rescue analgesia.Thus,it has high clinical application value.

EFFECTS OF COMBINATION OF ACUPUNCTURE AND MOXIBUSTION WITH CHINESE DRUGS ON LIPIDS PEROXIDE AND ANTIOXIDASE IN PATIENTS OF VASCULAR DEMENTIA

In the present paper, blood lipids peroxide(LPO) level and activities of glutathione peroxidase(GSH-Px) and superoxide dismutase(SOD) were investigated before and after combined treatment of acupuncture and moxibustion and Chinese drugs in patients of vascular dementia(VD), and their results were compared with those in healthy persons with the similar ages to the patients. The results showed that the blood LPO level increased significantly, and the activities of SOD and GSH-Px reduced significantly in patients of VD as compared with those in the control group. Degrees of patient’s condition were related with amplitudes of the increase of LPO and the reduction of activities of GSHPx and SOD. Combined treatment of acupuncture and moxibustion and Chinese drugs could raise markedly activitles of blood GSH-Px and SOD, and lowered LPO level in the patients of VD, which are related to clinical therapeutic effects. It is considered that combination of acupuncture and moxibustion with Chinese drugs can increase the action of the antiperoxidative system in the patients of VD, exerting anti-peroxidative ability and clearing LPO and reducing the oxidative injury of the organism by oxygen free radical, which is one of mechanisms of combined treatment of acupuncture and moxibustion with Chinese drugs.

Drug-Drug Interactions in Patients with Breast Cancer

The research paper investigates the intricate landscape of drug-drug interactions (DDIs) within the context of breast cancer treatment, with a particular focus on the elderly population and the use of complementary and alternative medicine (CAM). The study underscores the heightened susceptibility of elderly patients to DDIs due to the prevalence of polypharmacy and the widespread utilization of CAM among breast cancer patients. The potential ramifications of DDIs, encompassing adverse drug events and diminished treatment efficacy, are elucidated. The paper accentuates the imperative for healthcare providers to comprehensively understand both conventional and CAM therapies, enabling them to provide patients with informed guidance regarding safe and efficacious treatment options, culminating in enhanced patient outcomes.

Three-dimensional aspects of formulation excipients in drug discovery:a critical assessment on orphan excipients,matrix effects and drug interactions

Formulation/pharmaceutical excipients play a major role in formulating drug candidates,with the objectives of ease of administration,targeted delivery and complete availability.Many excipients used in pharmaceutical formulations are orphanized in preclinical drug discovery.These orphan excipients could enhance formulatability of highly lipophilic compounds.Additionally,they are safe in preclinical species when used below the LD50 values.However,when the excipients are used in formulating compounds with diverse physico-chemical properties,they pose challenges by modulating study results through their bioanalytical matrix effects.Excipients invariably present in study samples and not in the calibration curve standards cause over-/under-estimation of exposures.Thus,the mechanism by which excipients cause matrix effects and strategies to nullify these effects needs to be revisited.Furthermore,formulation excipients cause drug interactions by moderating the pathways of drug metabolizing enzymes and drug transport proteins.Although it is not possible to get rid of excipient driven interactions,it is always advised to be aware of these interactions and apply the knowledge to draw meaningful conclusions from study results.In this review,we will comprehensively discuss a)orphan excipients that have wider applications in preclinical formulations,b)bioanalytical matrix effects and possible approaches to mitigating these effects,and c)excipient driven drug interactions and strategies to alleviate the impacts of drug interactions.

Methodological challenges to control for immortal time bias in addressing drug effects in type 2 diabetes

There are multiple biases in using observational studies to examine treatment effects such as those from prevalent drug users, immortal time and drug indications. We used renin angiotensin system(RAS) inhibitors and statins as reference drugs with proven efficacies in randomized clinical trials(RCTs) and examined their effectiveness in the prospective Hong Kong Diabetes Registry using adjustment methods proposed in the literature. Using time-dependent exposures to drug treatments yielded greatly inflated hazard ratios(HR) regarding the treatment effects of these drugs for cardiovascular disease(CVD) in type 2 diabetes. These errors were probably due to changing indications to use these drugs during follow up periods, especially at the time of drug commencement making time-dependent analysis extremely problematic. Using time-fixed analysis with exclusion of immortal time and adjustment for confounders at baseline and/or during follow-up periods, the HR of RAS inhibitors for CVD was comparable to that in RCT. The result supported the use of the Registry for performing pharmacoepidemiological analysis which revealed an attenuated low low-density lipoprotein cholesterol related cancer risk with RAS inhibitors. On the other hand, time-fixed analysis with including immortal time and adjustment for confounders at baseline and/or during follow-up periods, the HR of statins for CVD was similar to that in the RCT. Our results highlight the complexity and difficulty in removing these biases. We call for validations of the methods to cope with immortal time and drug use indications before applying them to particular research questions, so to avoid making erroneous conclusions.

Preventive Effects of Five Drugs on Mycoplasma Pneumonia of Swine (MPS)

The paper was to explore the preventive effects of five drugs on mycoplasma pneumonia of swine （MPS） and to provide reference for clinical medication of pig farms in Hainan Province. A total of 444 health piglets were randomly divided into 6 groups, including five medication groups （72 piglets in group A, 74 pig- lets in group B, 72 piglets in group C, 76 piglets in group D, 76 piglets in group E） and one control group （74 piglets）. The piglets in experimental groups were treated drugs once a day for successive 5 days at 30, 60, 90, 120 and 150 of age. The piglets in control group were free of medication. At 70 and 140 days of age, 15 piglets of each group were randomly selected to collect their blood sermn. The Mycoplasma hyopneumoniae （M-Hyo） antibodies in serum were measured by en- zyme-linked immunosorbent assay （ELISA）. During the experiment, the incidence rates of respiratory disease, lung lesion, feed conversion rate, average daily gain （ADG）, and mortality rate of pigs were also observed and recorded. The results showed that the five drugs had significant difference in preventative effects. Group C （Zhiyuanjing group） received the best preventive effect and the highest economic benefits. Compared with control group, the ADG and feed conversion rate in group C were increased by 7.53% and 9.09%, respectively; the incidence rate of respiratory disease was reduced by 13.44% and lung lesion was alleviated by 81.43% ; and the earnings of each pig could rise by 132.70 yuan. The preventative effect and economic benefit of the drugs was sequenced by Chansu Kechuanling and Bingchan Kechuanwang. Wante Feilin and amoxicillin had weaker preventive effects against MPS but greatly influenced growth performance of pigs, so they should be used alternatively with other drugs.

The Effects of Antiretroviral Drugs on the Absorbance Characteristics of HIV-Infected Blood

In the twenty first century research works, there may be a need to achieve a more reliable research result through a synergy between engineers and biological researchers. The peak absorbance data for various interacting systems were measured. These were used to show that the antiretroviral drug has the effect of increasing the peak absorbance values of both the uninfected and infected blood components, i.e., the drugs are made able to increase the light absorption capacity of the blood cells. For drug 2 that contains three components including Efavirenz, the drug effect on lymphocytes was increased by about 38% for patients that had been on antiretroviral drug treatment. Mathematical models were proposed and used in determining the coating effectiveness of antiretroviral drugs in the presence and absence of HIV. The use of the findings of this work by pharmaceutical industries may help in the search for more effective antiretroviral drugs for the treatment of HIV patients.

Intercalation of Ciprofloxacin in Naturally Occurring Smectite from Bana: Potentiality as Drug Delivery System and Antimicrobial Effects on <i>Escherichia coli</i>and <i>Staphylococcus aureus</i>

Ciprofloxacin (CFX) was loaded on Bana clay (Cameroon) and CFX loaded-clays have been evaluated as drug delivery system. Raw clays and CFX loaded compounds have been characterized by some physico-chemicals methods. In vitro release studies have been done in gastric and phosphate buffer experimental mediums;bacteriological studies have been made up on Escherichia coli and Staphylococcus aureus. X-ray diffractometry patterns of loaded compounds show a basal spacing increasing due to CFX intercalation. On Fourier-Transformed Infrared spectrometry spectra, appearance of CFX characteristic bands and shifting of certain bands already presents on clay confirmed CFX intercalation. After 96 h of CFX released from release mediums, prolonged and continue profiles have been observed. Diffusion tests displayed an inhibition radius of ~2 cm on gelose seeded with Escherichia coli and Staphylococcus aureus due to CFX. The overall results show a modified release of ciprofloxacin with an effective antibacterial activity, giving the way for a new ciprofloxacin drug delivery system using Bana clay as carrier.

Late Protective Effects of the Anticalmodulin Drug Fluphenazine on Carbon Tetrachloride-induced Liver Necrosis

Fluphenazine (FP) treatment (50mg/kg bw, ip in saline) 30 min before or 6 or 10 h after CCl4 administration (1 ml/kg ip in olive oil) significantly prevented the liver necrosis produced by the hepatotoxin at 24 h. FP had enhancing effects on the covalent binding of CCl4 reactive metabolites to cellular constituents and on CCl4 induced lipid peroaldation.FP lowered bOdy temperature of the CCl4-poisoned animals during the 24 h observation period. The obtained results are compatible but do not prove the hypothesis that calmodulin (CaM) had participation in late occurring events preceding necrosis. FP lowering action on body temperature, however, might also play a role in the effects of this drug on the onset of CCl4 induced liver necrosis. FP levels in liver tissue as determined by gas chromatography-mass spectrometry evidenced the presence of the drug in amounts suffi cient to inhibit CaM and that suggests that not all preventive effects of FP are due to its indirect actions on the central nervous system via decreased body temperature

Energy pharmacological effects of chemical drugs

Background:To study the energy pharmacological effects of chemical drugs.Methods:The energy pharmacological effects of chemical drugs were studied using a literature induction method.Results:Chemical drugs have energy properties,which can be expressed in terms of cold,hot,warm,and cool.The energy properties of chemical drugs have energy pharmacological effects,which are related to the bond energy release and absorption of intermolecular chemical bonds,where the release of energy from chemical bonds indicates a warm-hot energy pharmacological effect and the absorption of energy indicates a cold energy pharmacological effect.The mechanisms of chemical drug energy may be related to the presence of temperature-sensitive ion channels in the body.Conclusion:Chemical drugs exhibit energy pharmacological effects.

Pharmacological Effects of Botanical Drugs on Myocardial Metabolism in Chronic Heart Failure

Although there have been significant advances in the treatment of heart failure in recent years,chronic heart failure remains a leading cause of cardiovascular disease-related death.Many studies have found that targeted cardiac metabolic remodeling has good potential for the treatment of heart failure.However,most of the drugs that increase cardiac energy are still in the theoretical or testing stage.Some research has found that botanical drugs not only increase myocardial energy metabolism through multiple targets but also have the potential to restore the balance of myocardial substrate metabolism.In this review,we summarized the mechanisms by which botanical drugs(the active ingredients/formulas/Chinese patent medicines)improve substrate utilization and promote myocardial energy metabolism by activating AMP-activated protein kinase(AMPK),peroxisome proliferator-activated receptors(PPARs)and other related targets.At the same time,some potential protective effects of botanical drugs on myocardium,such as alleviating oxidative stress and dysbiosis signaling,caused by metabolic disorders,were briefly discussed.

The Assessment of the Clinical Effect of the Drug Compatibility and Course of Treatment to the Brucellar Spondylitis

Objective: To evaluate five drug treatment regimens in the treatment of Brucella spondylitis. Methods: Patients with clinical symptoms compatible and diagnostic test consistent with Brucella spondylitis were randomly assigned to five drug treatment regimens. Results: Combination therapy with doxycycline, rifampin and sulfamethoxazole for 56 consecutive days showed the highest cure rate of 20% after a single course and of 85% after a double course with affectivity rates of 55% and 95%. Cure rate and affectivity rate was significant better (P 0.05) than for patients receiving doxycycline, rifampin and streptomycin for the same period and regimens containing doxycycline were significant better than regimens without this drug. Conclusion: Combination therapy of doxycycline, rifampin and sulfamethoxazole for 8 weeks using one or two full courses should be recommended for Brucella spondylitis.

Effects of octreotide on gallbladder pressure and myoelectric activity of Oddi sphincter in rabbits

AIM To observe the effect of octreotide (OT) and somatostatin (SS) on gallbladder pressure and myoelectric activity of SO in rabbits. METHODS Male rabbits fasted for 15h - 18h and anesthetized with urethane. The mean gallbladder pressure (GP) and myoelectric activity of SO were simultaneously measured with a frog bladder connected to a transducer and a pair of copper electrodes. RESULTS After injection of OT (10μg/kg, iv), the GP decreased in 2min and reached the lowest value in about 60min ( P <0 01, n =19), and completely or partially returned to the normal level in 120min. The frequency of myoelectric activity of SO was reduced, even disappeared in 2min ( P <0 01, n =19) and returned to normal in about 20min . Injection of SS (10μg/kg, iv) also decreased GP and myoelectric activity of SO ( P <0 01, n =7); Before and after injection of OT or SS, injection of CCK 8 ( 100ng or 200ng ) caused similar increase in myoelectric activity of SO and GP ( P >0 05). Before and after injection of OT, there were no significant differences in increases of myoelectric activity of SO and GP caused by electric stimulation of dorsal motor nucleus of vagus ( P >0 05). CONCLUSION OT and SS decreased GP and myoelectric activity of SO, demonstrating that effects of OT were similar to those of SS. Intravenous injection of OT did not affect the increase of myoelectric activity of SO and GP caused by CCK 8 or electric stimulation of dorsal motor nucleus of vagus.

Efficacy and side effects of praziquantel in the treatment of Schistosomiasis mansoni in schoolchildren in Shesha Kekele Elementary School,Wondo Genet,Southern Ethiopia

Objective:To evaluate the efficacy and side effects of praziquantel(PZQ) in the treatment of schistosomiasis in Ethiopia.Methods:In a cross-sectional study,stool specimens were collected from randomly selected 299 school children in Shesha Kekele Elementary School,Wondo Genet, Southern Ethiopia,in April 2010.Stool specimens were examined using a single Kato-Katz thick smear for Schistosoma mansoni(5.mansoni) ova.Children who were found positive for S.mansoni were treated with a single oral dose of PZQ at 40 mg/kg bw and interviewed for treatment-related symptoms 24 hours after drug administration.Four weeks post-treatment,stool specimens were collected from the same children and examined following the same procedure as in the pretreatment.Drug efficacy was determined based on cure and egg reduction rates.Results:Pretreatment prevalence of S.mansoni infection was 74.9%with geometric mean egg count of 268. The evaluated generic PZQ produced an overall cure rate of 73.6%(P<0.000 1,OR:8.33,CI:5.3-13.1) and egg reduction rate of 68.2%(P=0.03,F=0.64).The cure rate showed significant association with age(x^2=H,P=0.004),the highest rate being observed in the 15-22 age group.83%of S. mansoni infected children showed various treatment-related symptoms,the most frerjiient being headache,nausea,and abdominal pain.These symptoms were associated with age(P<0.001) and pre-treatment intensity of infection(P<0.05).Conclusions:The present observations revealed relatively lower cure and egg reduction rates of the PZQ evaluated as compared to previous reports for other PZQ brands in Ethiopia.Hence,in depth studies are recommended to clarify whether the present relatively lower cure rate is the actual cure rate of the praziquantel evaluated,treatment failure,or reduced susceptibility of the parasite.Treatment-related side effects observed were transient and tolerable.