Repurposing Loperamide as an Anti-Infection Drug for the Treatment of Intracellular Bacterial Pathogens

Infections caused by intracellular bacterial pathogens are difficult to treat since most antibiotics have low cell permeability and undergo rapid degradation within cells.The rapid development and dissemination of antimicrobial–resistant strains have exacerbated this dilemma.With the increasing knowledge of host–pathogen interactions,especially bacterial strategies for survival and proliferation within host cells,host-directed therapy(HDT)has attracted increased interest and has emerged as a promising antiinfection method for treating intracellular infection.Herein,we applied a cell-based screening approach to a US Food and Drug Administration(FDA)-approved drug library to identify compounds that can inhibit the intracellular replication of Salmonella Typhimurium(S.Typhimurium).This screening allowed us to identify the antidiarrheal agent loperamide(LPD)as a potent inhibitor of S.Typhimurium intracellular proliferation.LPD treatment of infected cells markedly promoted the host autophagic response and lysosomal activity.A mechanistic study revealed that the increase in host autophagy and elimination of intracellular bacteria were dependent on the high expression of glycoprotein nonmetastatic melanoma protein B(GPNMB)induced by LPD.In addition,LPD treatment effectively protected against S.Typhimurium infection in Galleria mellonella and mouse models.Thus,our study suggested that LPD may be useful for the treatment of diseases caused by intracellular bacterial pathogens.Moreover,LPD may serve as a promising lead compound for the development of anti-infection drugs based on the HDT strategy.

A Comparative Analysis of the Administration of Oral Hypoglycemic Drugs in Second Affiliated Hospital of Guiyang Medical College during 2012-2014

[Objective] This study aimed to analyze the application and administration of oral hypoglycemic drugs in Second Affiliated Hospital of Guiyang Medical College,aiming at providing guidance and reference for clinical medication for treatment of diabetes.[Method] The main types,dosages and prices of oral hypoglycemic drugs in Second Affiliated Hospital of Guiyang Medical College during 2012-2014 were compared and analyzed using the computer network system.[Result] During 2012-2014,sales quantity and sales amount of oral hypoglycemic drugs in Second Affiliated Hospital of Guiyang Medical College demonstrated an upward trend.[Conclusion] Integrative medicine can significantly improve symptoms of diabetes complications.Certain achievements have been made in diabetes treatment by Second Affiliated Hospital of Guiyang Medical College.

Advances in Polysaccharide-Based Microneedle Systems for the Treatment of Ocular Diseases

The eye,a complex organ isolated from the systemic circulation,presents significant drug delivery challenges owing to its protective mechanisms,such as the blood-retinal barrier and corneal impermeability.Conventional drug administration methods often fail to sustain therapeutic levels and may compromise patient safety and compliance.Polysaccharidebased microneedles(PSMNs)have emerged as a transformative solution for ophthalmic drug delivery.However,a comprehensive review of PSMNs in ophthalmology has not been published to date.In this review,we critically examine the synergy between polysaccharide chemistry and microneedle technology for enhancing ocular drug delivery.We provide a thorough analysis of PSMNs,summarizing the design principles,fabrication processes,and challenges addressed during fabrication,including improving patient comfort and compliance.We also describe recent advances and the performance of various PSMNs in both research and clinical scenarios.Finally,we review the current regulatory frameworks and market barriers that are relevant to the clinical and commercial advancement of PSMNs and provide a final perspective on this research area.

Ophthalmic complications of injectable facial fillers

The recently published mini-review article by Miotti et al is an effort to clarify various aspects regarding the choice between fat grafts and fillers in facial aesthetic surgery.One of the complications associated with the administration of fillers is the possibility of vascular injury and spread of the dermal filler into the orbit,causing unexpected effects at a site distant from that of the initial injection,including ophthalmoplegia,ptosis and even visual compromise.Acute vision loss following filler injection is a devastating complication,occurring in up to 0.0008%of cases.The greatest risk of this complication occurs with nasal augmentation,followed by glabellar wrinkle treatment.While injected autologous fat predominantly occludes the proximal portion of the ophthalmic artery,hyaluronic acid fillers obstruct the ophthalmic artery comparatively distally.Treatment interventions include thrombolysis,hyperbaric oxygen therapy,oral aspirin,cobamamide and acetazolamide and administration of corticosteroids.However,most studies show a poor prognosis in the form of partial or no recovery of vision.Hence,prevention is of paramount importance.A high index of suspicion is also warranted on the part of both those administering as well as receiving injections of facial fillers to prevent potentially vision-threatening complications of this seemingly innocuous procedure.

Evaluation of Mass Drug Administration Impact on Transmission of Lymphatic Filariasis in 13 Sanitary Districts in Burkina Faso

Introduction: Lymphatic filariasis (LF) is one of the neglected tropical diseases targeted for elimination as a public health issue in the world by 2020. To achieve this goal, one of the strategies is interruption of transmission using chemotherapy (mass drug administration). Burkina Faso in west Africa, an endemic country, has endorsed this resolution. In 2000, all Sanitary Districts (SD) in the country were endemic, and then a national elimination program has made it possible to stop mass treatment in 45 out of 70 SD over 12 years. Sixteen years later, 13 other SD were reeligible for Transmission Assessment Surveys (TAS). This study aimed to determine the current level of the Mass drugs Administration (MDA) impact indicators in these 13 targeted SD in order to decide whether we need to continue MDA. Method: It was a descriptive study that took place from June to September 2017 in 13 SD regrouped into 7 Evaluation Units (EU). The population of the study was 6 to 7 years old children. The community-based cluster survey method was used. The diagnostic test used to detect Wuchereria bancrofti’s circulating antigen (W. bancrofti) is the Filariasis Test Strip (FTS). The critical threshold of positivity was set at 18 positive subjects per EU. Results: We sampled a total of 12,060 children, 48.9% were female and 51.1% male. In the 7 EU, 13 children were positive to W. bancrofti test. The average antigenic prevalence was 0.11% (13/12,060). In all EU, the number of positive subjects was below the critical threshold. Conclusion: At the end of this evaluation of the transmission of lymphatic filariasis in 13 SD of Burkina Faso, we can tell the MDA could be stopped in these areas without risk of resurgence of the disease, according to the current recommendations of WHO. This can be possible by setting up post-TMM surveillance, considering migratory flows, and including villages where positive cases were found to search possible residual transmission zones.

Work Hard to Ensure Food,Drugs Safety for the People——An interview with Shao Mingli,director-general of the State Food and Drug Administration(SFDA)

Following is an interview given by Shao Mingli, director-general of China＇s State Food and Drug Administration to our reporter on what is being done to ensure food and drug safety in China. As everybody knows, food and drug safety is vital to people＇s lives.

Detecting drug resistant genetic mutation among pneumoconiosis patients complicated with tuberculosis in Mycobacterium tuberculosis L-forms application of PCR-SSCP technique in Huainan mining district

Objective： To study the relationship between drug resistant genetic mutation and drug resistance in Mycobacterium tuberculosis L-form, discuss the internal relationship between drug resistances and drug-resistant related genes and explore the value of PCR- SSCP to clinical application. Methods： A total of 52 clinically isolated strains of tuberculosis L-form were collected among 97 pneumoconiosis patients complicated with tuberculosis. The gene mutations of katG, rpoB and rpsL were detected by PCR-SSCP, and the results were compared with those analyzed by traditional antimicrobial susceptibility test（AST）. Results： The gene muta- tion rates of katG, rpoB and rpsL by PCR-SSCP were respectively 57.70% （30/52）, 65.38% （32/52） and 40.38% （21/52）. The rate of reversion was 78.85%（41/52） and the result of drag-resistant genes was invariable. The results of AST showed that there were 40 （76.92%） multi-drug resistant strains in 52 clinically isolated strains. The number for three-drug resistant strain was 21 （40.38%） and that of two-drug resistant was 19（36.54%）, but only 12（23.08%） strains were one drug resistant. The rate of total drug-resistance was 100%, but there were 15 strains of allied mutation of three genes, 16 of two mutations and 6 of only one by PCR-SSCP. The coincidences were respectively 71.43%, 84.12% and 50.00%. Then there was no significant difference between the allied mutations of multi-drug resistant gene and the mutations of only one drug resistant gene （P 〉 0.05）. Conclusion： PCR-SSCP technique has a higher sensibility and specificity to detect the genes of katG, rpoB and rpsL in tuberculosis L-form among pneumoconiosis complicated with tuberculosis,and the detecting rate of two drug resistant strains and three drug resistant strains was higher. The combined application of PCR-SSCP and AST has advantages at earlier diagnosis and guidance of clinical medications.

A Survey of Drug Supply Organizations in Rural Areas in four Provinces of China

Aim To realize the present situation of drug purchase, supply, and use in the health service organizations and drug distributors in rural areas, and to put forward some suggestions. Methods An interview survey was conducted in 20 township hospitals, 26 countryside drugstores, and 84 village dispensaries in Hainan, Anhui, Henan, and Sichuan Provinces. Results （1） The main drug supplying organizations in the countryside are township hospitals and village dispensaries. （2） The personnel in the drug supplying organizations are rather inadequately educated. （3） The drug resources in the grass-roots countryside are complex and disordered. （4） Most of the countryside retail drugstores are small, and the number of drugstores is small, but their development potential is great. Conclusion （1） A basic drug catalogue for rural areas should be made up. （2） Legitimate drug wholesale companies should be encouraged to supply drugs for vast countryside. （3） Development of drug distributionstations in townships should be promoted. （4） The administration of drugs in the countryside should be strengthened.

Effectiveness of ivermectin mass drug administration in the control of soil-transmitted helminth infections in endemic populations: a systematic review and meta-analysis

Background Current soil-transmitted helminth(STH)control guidelines endorse the use of albendazole or meben-dazole for school-based targeted preventive chemotherapy(PC),yet their reduced efficacy against Strongyloides sterc-oralis and Trichuris trichiura presents significant limitations.Emerging evidence indicates that community-wide PC[or mass drug administration(MDA)]using ivermectin,commonly used in other neglected tropical disease(NTD)control programs,may play an important role in controlling these parasites.We conducted a systematic review and meta-analysis to evaluate the effectiveness of ivermectin PC in reducing STH prevalence in endemic populations.Methods We searched Pubmed,EMBASE,and Web of Science on February 14,2023,for studies that investigated the effectiveness of ivermectin PC,either alone or in combination with other anthelmintic drugs,on STH infec-tions,and provided a measure of STH prevalence before and after PC.We calculated pooled prevalence reductions for each STH using random-effects meta-analyses.Our protocol is available on PROSPERO(registration number CRD42023401219).Results A total of 21 were eligible for the systematic review,of which 15 were eligible for meta-analysis.All studies delivered ivermectin through MDA.The pooled prevalence reduction of S.stercoralis following MDA with ivermec-tin alone was 84.49%(95%CI:54.96-94.66)across five studies and 81.37%(95% CI:61.62-90.96)across seven studies with or without albendazole.The prevalence reduction of T.trichiura was 49.93%(95%CI:18.23-69.34)across five studies with ivermectin alone,and 89.40%(95%CI:73.66-95.73)across three studies with the addition of albendazole.There was high heterogeneity for all syntheses(I^(2)>65%).Conclusions This study underscores the key role of ivermectin-based MDA in addressing limitations in current global STH guidelines in terms of limited efficacy against S.stercoralis and T.trichiura.Based on these findings,revising inter-national STH guidelines to include ivermectin is a promising option to progress the control and eventual elimination ofSTHsandotherNTDs.

Current Regulatory Status and Development Trend of Drug Inserts in China

Regulatory status of drug inserts in China is described in terms of its legalsystem, administrative ramifications and existing problems. Lack of government regulatoryenforcement, industry self-control mechanisms and academic research are blamed to be the root ofthese problems. The trend of regulatory policies on the issue is outlined and suggestions on severalimportant issues are made.

Drug utilization of clarithromycin for gastrointestinal disease treatment

AIM： To evaluate the patterns of use of clarithromycin for gastrointestinal disease treatment and promote its rational use.METHODS： Using a structured pro forma, we conducted a two-month survey of the electronic prescriptions containing immediate-release （IR） or sustained-release （SR） product of clarithromycin for outpatients with gastrointestinal diseases in a 2200-bed general hospital. Suitability of the prescription was audited retrospectively. RESULTS： One hundred and sixty-four prescriptions of SR product and 110 prescriptions of IR product were prescribed for gastrointestinal disease treatment. Among prescriptions for anti-Helicobacter pylori （H pylori） therapy, triple therapy take the dominant position （91.8%）, followed by quadruple therapy （4.3%） and dual therapy （3.9%）. Amoxicillin was the most frequently co-prescribed antibiotic.Furazolidone and levofloxacin are used more widely than metronidazole or tinidazole. Clarithromycin SR was administered at inappropriate time points in all prescriptions. Fifty percent of all prescriptions of clarithromycin SR, and 6.4% of prescriptions of clarithromycin IR, were prescribed at inappropriate dosing intervals. Surprisingly, disconcordance between diagnoses and indications was observed in all prescriptions of clarithromycin SR which has not been approved for treating Hpy/ori infection although off-label use for this purpose was reported in literature. On the contrary, only one prescription （0.9%） of clarithromycin IR was prescribed for unapproved indication （i.e. gastro-oesophageal reflux disease）. 1.4% of prescriptions for chronic gastritis or peptic ulcer treatment were irrational in that clarithromycin was not co-prescribed with gastric acid inhibitors. Clinical significant CYP3A based drug interactions with clarithromycin were identified. CONCLUSION： There is a great scope to improve the quality of clarithromycin prescribing in patients with gastrointestinal disease, especially with regard to administration schedule, concordance between indications and diagnoses and management of drug interactions.

Efficacy and safety of rabeprazole in non-steroidal anti-inflammatory drug-induced ulcer in Japan

AIM: To investigate the effi cacy and safety of rabepra-zole under continuous non-steroidal anti-inflammatory drug (NSAID) administration for NSAID-induced ulcer in Japan. METHODS: Subjects comprised patients undergoing NSAID treatment in whom upper gastrointestinal en-doscopy revealed an ulcerous lesion (open ulcer) with diameter ≥ 3 mm, who required continuous NSAID treatment. Endoscopies were performed at the start of treatment, during the treatment period, and at the conclusion (or discontinuation) of treatment. Findings were evaluated as size (maximum diameter) and stage based on the Sakita-Miwa classifi cation. An ulcer was regarded as cured when the "white coating" was seen to have disappeared under endoscopy. As criteria for evaluating safety, all medically untoward symptoms and signs (adverse events, laboratory abnormalities, accidental symptoms, etc.) occurring after the start of rabeprazole treatment were handled as adverse events.RESULTS: Endoscopic cure rate in 38 patients in the efficacy analysis (endoscopic evaluation) was 71.1% (27/38). Among those 38 patients, 35 had gastric ulcer with a cure rate of 71.4% (25/35), and 3 had duodenal ulcer with a cure rate of 66.7% (2/3). Three adverse drug reactions were reported from 64 patients in the safety analysis (interstitial pneumonia, low white blood cell count and pruritus); thus, the incidence rate for adverse drug reactions was 4.7% (3/64).CONCLUSION: The treatment efficacy of rabeprazole for NSAID-induced ulcer under continuous NSAID ad-ministration was confi rmed.

Analysis of the application and practice of PDCA cycle in management of the naked medicine dispensing——the quality and safety of the drug

Objective:To explore the application of plan–do–check–action(PDCA)cycle in the management of the naked medicine dispensing about the automatic package and to analyze the practice improved in the quality of naked medicine dispensing medicine management.Methods:The PDCA theory was used to analyze the data,to find out the causes of the problem,and to formulate the corresponding countermeasures to intervene.The data of the naked medicine/adverse drug events satisfaction degree of the inpatients in 18 inpatient departments given for the adoption of PDCA cycle in January 2017 were set as the observation group.The number of the naked medicine/adverse drug events satisfaction degree of patients in 18 inpatient departments before adoption of PDCA cycle in December 2016 was set as the control group.The number of the naked medicine/adverse drug events satisfaction degree of patients in 18 inpatient departments before and after adoption of PDCA cycle was observed and analyzed.Results:The number of the naked medicine/adverse drug events after implementing the method of PDCA cycle management rate was significantly lower than before the implementation method of PDCA cycle management,and the difference had statistical significance(P<0.05).The satisfaction degree of the inpatients after implementing the method of PDCA cycle management rate was significantly higher than that before the implementation method of PDCA cycle management,and the difference had statistical significance(P<0.05).Conclusion:Application of PDCA cycle in the management of the naked medicine dispensing about the automatic package can help to reduce the adverse drug events,to improve the safety of drug treatment,and to increase the patients’satisfaction degree.

Evaluation of blank film forming polymeric dispersions based on Eudragit RL 30D and RS30D for transdermal drug delivery

The first approved transdermal drug delivery system in the United States in 1979 is a scopolamine patch for treatment of motion sickness. Transdermal drug delivery system has many advantages over oral route such as it is useful for vomiting and unconscious patients. It can avoid first pass metabolism by the liver. It is non-invasive way and self-administered system compared to injections. The film forming polymeric solutions are a novel transdermal drug delivery system. This system consists of an active drug, film forming polymer, plasticizer.

Recent advances in particulate drug delivery systems: Oral, pulmonary, and ophthalmic administrations

Colloidal drug carriers such as liposomes,lipid emulsions,and polymeric nanoparticles have great potential to deliver drugs effectively.Preparation of nano-crystals of API has also received much attention to design dosage forms to complete effective drug delivery.A variety of investigations have been carried out toward the design of an optimal particulate system.

Fifty-six Cases of Stubborn Eczema Treated by Oral Administration and Topical Application of Herbal Medicine

Eczema is a kind of very common dermatopathy. The cases with a long course of illness and hard to be cured are termed as stubborn eczema. We have obtained good results in its treatment since 1995 with the Chu Shi Tang (除湿汤Dampness-Clearing Decoction) for oral intake and the Fu Fang Ku Shen Xi Ye (复方苦参洗液) for topical application. The following is a clinical report for treating 56 patients with stubborn eczema.

Clinical Observation on Treatment of Acquired Paralytic Strabismus by Acupuncture Plus Oral Administration of Chinese Herbs

From June 1996 to June 2002, the author treated 38 cases of acquired paralytic strabismus by acupuncture plus oral administration of Zheng Rong Tang (正容汤), with another 38 cases of acquired paralytic strabismus treated only with oral administration of Chinese herbs as the controls. The results are reported as follows.

The Application of Standardization System in Corporate Management and Administration

This paper briefly discusses three important components of corporatestandardization system and their functions and how such a system can be used in corporate managementand administration. It also offers certain solutions and suggestions to some of the existingproblems in the process of implementing corporate standardization system. form of corporatestandardization system; product standard; technical standard; administrative standard; dutystandard.

TREATMENT OF 50 CASES OF SENILE DEMENTIA BY ACUPUNCTURE COMBINED WITH INHALATION OF HERBAL DRUGS AND OXYGEN

Clinical DataCase selection: 100 cases who met thediagnostic criteria of senile dementiaformulated by American Association ofPsychiatry in Handbook of Diagnosis andStatistics (DSM-Ⅲ-R, 3rd revised edition)

Multi-Drug Resistance Pattern of Lactose Non-Fermenting <i>Escherichia coli</i>as Causative Agent of Urine Tract Infections in Luanda, Angola

This prospective study was carried out to assess the sensitivity and resistance pattern of lactose non-fermenting Escherichia coli from July 2018 to December 2018 in the Laboratory of Microbiology at Luanda Medical Center, Angola. Out of 1170 patient, a total of 120 urine specimens infected with Escherichia coli (>105 CFU/ml) were collected according to the routine protocol of urinalysis. Among these 120 isolates, 25 (21%) isolates were determined as “atypical”, lactose non-fermenting E. colis trains. The twenty-five lactose non-fermenting Escherichia coli strains isolated from urine samples in Luanda Medical Center were declared as Multiple Drugs-Resistant strains with high resistance to Cefalexine (100%), Cefuroxime (100%), Ceftriaxone (92%), Gentamycin (92%), Ciprofloxacin (72%) and Amoxiciclin/Clavulanic (80%). The alarming resistance level to the first-choice drugs for the treatment of urinary tract infections caused by non-fermentative lactose E. coli was observed.