Design,delivery and efficacy testing of therapeutic nucleic acids used to inhibit hepatitis C virus gene expression in vitro and in vivo

Despite major achievements in the treatment ofchronic hepatitis C with the combination ofinterferons and the nucleoside analog ribavirin themajority of patients with chronic hepatitis C virus(HCV) infection cannot be treated effectively.Toimprove this response rate we used antisensetechnologies to inhibit HCV translation as possibleadditional option for experimental treatment.Antisense oligodeoxynucleotides(ODN) are

Therapeutic and Medicinal Uses of <i>Aloe vera</i>: A Review

The plant Aloe vera is used in Ayurvedic, Homoeopathic and Allopathic streams of medicine, and not only tribal community but also most of the people for food and medicine. The plant leaves contains numerous vitamins, minerals, enzymes, amino acids, natural sugars and other bioactive compounds with emollient, purgative, anti-microbial, anti inflammatory, antioxidant, aphrodisiac, anti-helmenthic, antifungal, antiseptic and cosmetic values for health care. This plant has potential to cure sunburns, burns and minor cuts, and even skin cancer. The external use in cosmetic primarily acts as skin healer and prevents injury of epithelial tissues, cures acne and gives a youthful glow to skin, also acts as extremely powerful laxative.

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.

Clinical pharmacists’ involvement in carbapenem antibiotics management at Wenzhou Integrated Hospital

BACKGROUND Carbapenem antibiotics are a pivotal solution for severe infections,particularly in hospital settings.The emergence of carbapenem-resistant bacteria owing to the irrational and extensive use of carbapenems underscores the need for meticulous management and rational use.Clinical pharmacists,with their specialized training and extensive knowledge,play a substantial role in ensuring the judicious use of carbapenem.This study aimed to elucidate the patterns of carbapenem use and shed light on the integral role played by clinical pharmacists in managing and promoting the rational use of carbapenem antibiotics at Wenzhou Integrated Traditional Chinese and Western Medicine Hospital.AIM To analyze carbapenem use patterns in our hospital and role of clinical pharmacists in managing and promoting their rational use.METHODS We performed a retrospective analysis of carbapenem use at our hospital between January 2019 and December 2021.Several key indicators,including the drug utilization index,defined daily doses(DDDs),proportion of antimicrobial drug costs to total hospitalization expenses,antibiotic utilization density,and utilization rates in different clinical departments were comprehensively analyzed.RESULTS Between 2019 and 2021,there was a consistent decline in the consumption and sales of imipenem-cilastatin sodium,meropenem(0.3 g),and meropenem(0.5 g).Conversely,the DDDs of imipenem-cilastatin sodium for injection increased in 2020 and 2021 vs 2019,with a B/A value of 0.67,indicating a relatively higher drug cost.The DDDs of meropenem for injection(0.3 g)exhibited an overall upward trend,indicating an increasing clinical preference.However,the B/A values for 2020 and 2021 were both>1,suggesting a relatively lower drug cost.The DDDs of meropenem for injection(0.5 g)demonstrated a progressive increase annually and consistently ranked first,indicating a high clinical preference with a B/A value of 1,signifying good alignment between economic and social benefits.CONCLUSION Carbapenem use in our hospital was generally reasonable with a downward trend in consumption and sales over time.Clinical pharmacists play a pivotal role in promoting appropriate use of carbapenems.

Evaluation of antibiotic use among inpatients in surgical ward at Mbarara Regional Referral Hospital,South-Western Uganda

Objective The main aim of this study was to evaluate antibiotic use among inpatients in surgical ward at South-Mbarara Regional Referral Hospital,South-Western Uganda.Methodology:A retrospective cross-sectional study was carried out on patients'follow-up forms of Mbarara Regional Referral Hospital,surgical ward from 15th November to 15th December.Data abstraction tool was employed to extracted data,entered in excel version 2010 then imported into SPSS software version 2010 where different variables were analyzed.Results:A total of 136 patient forms were studied.At least one antibiotic was prescribed in 76(56%).Majority(81.58%)of the antibiotics were prescribed for therapeutic purpose while some lacked documented and approved indications.Specific indications were not documented in 15(19.73%)of the forms.Sepsis without culture and sensitivity was the most frequent indication 14(18.42%)for antibiotics followed by prophylactic use 12(15.79%).Ceftriaxone was the most commonly(82.9%)prescribed antibiotic;followed by metronidazole for 31(40.8%)and Ampicillin/Cloxacillin for 8(10.5%)of the patients.Out of the 76 patients who used antibiotics,the overall use was found to be appropriate in only 20(26.3%).Most prescriptions had right doses 57(75.0%)followed by right frequencies 53(69.7%);whereas the duration was the least appropriate with only 46(60.5%)of the 76 patients.Conclusion:More than half of the patients had at least one antibiotic prescribed to them.Ceftriaxone and metronidazole were the most prescribed,the majority of antibiotics were used for treatment and some of the patients were on antibiotics without specific indications.Sepsis was the most common indication for the antibiotics used.Most antibiotics were inappropriately used.Duration of treatment was the most inappropriate parameter and antibiotic use varied greatly with guidelines.

Continuous Wear of Hydrogel Contact Lenses for Therapeutic Use

Purpose: To investigate the efficacy and complications of continuous wear of etafilcon A for therapeutic use. Materials and Methods: The subjects were 228 eyes of 219 outpatients prescribed contact lens (CL) for one week of continuous therapeutic wear during 10 years. The reason for prescription of CLs, the primary disease, the duration of CL wear and the complications were assessed retrospectively. Results: The predominant reason for prescription of CLs was relief of pain or a foreign-body sensation (62.3%) and protection of the corneal epithelium (20.6%). The primary disease was post-penetrating keratoplasty (36.8%), followed by corneal epithelial erosion (14.5%), post-lamellar keratoplasty (14.0%) and bullous keratopathy (12.2%). The average duration of wearing single lens was 6.5 ± 3.2 days. The average duration of wearing CLs in total was 9.2 ± 10.7 months. The most frequent problem associated with continuous wear of CLs was their dropping out of CLs (12.3%). The complications associated with CLs included conjunctivitis with papillary hyperplasia, corneal erosion and superficial punctate keratitis, but corneal ulcer and corneal infiltrates were not found. Conclusion: Serious complications were not shown changing the lenses every week to keep to the prescribed time limit for continuous therapeutic wear, even if corneal epithelial barrier function is impaired.

Comparison of long-lasting therapeutic effects between succimer and penicillamine on hepatolenticular degeneration

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Functional dyspepsia of ulcer-dysmotility type:clinical incidence and therapeutic strategy

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Therapeutic role of template-based lymphadenectomy in urothelial carcinoma of the upper urinary tract

Lymphadenectomy for urothelial carcinoma of the upper urinary tract has attracted the attention of physicians. The mapping study of lymphatic spread has shown that a relatively wide area should comprise the regional nodes for tumors of the right renal pelvis or the right upper two-thirds of the ureter. A prospective study showed that an anatomical templatebased lymphadenectomy significantly improved patient survival in tumors of the renal pelvis. This benefit was more evident for patients with p T2 stage tumors or higher. The risk of regional node recurrence is significant reduced by template-based lymphadenectomy,which is likely to be associated with improved patient survival. The removal of lymph node micrometastases is assumed to be the reason for therapeutic benefit following lymphadenectomy. The number of resected lymph nodes can be used to assess the quality of lymphadenectomy,but not to determine the extent of lymphadenectomy. The guidelines currently recommend lymphadenectomy for patients with muscle-invasive disease,even though the current recommendation grades are still low. The present limitation of lymphadenectomy is the lack of standardization of the extent of lymphadenectomy and the randomized trials. Further studies are warranted to collect the evidence to support lymphadenectomy.

Antibiotic Use in a Cohort of Extremely Low Birth Weight Neonates: Focus on Off-Label Uses and Prescription Behaviour

Aim: To analyse antibiotic prescriptions in a cohort of extremely low birth weight neonates admitted to Italian level III Neonatal intensive Care Units. Methods: An online questionnaire was used to collect detailed information for each newborn. Antibiotic prescriptions were classified about their license status and compared with British National Formulary for Children (BNFC) and with a practical guide prepared by the Italian Society of Neonatology (ISN). Results: During the study period (May-July 2014) among 93 neonates admitted to 30 Italian Neonatal intensive Care Units, 56 (60%) received at least an antibiotic (92 prescriptions in total). Ampicillin, gentamicin and vancomycin were the antibiotics most commonly used for the prevention/treatment of bacterial infections. 56/92 antibiotic prescriptions (61%) resulted off-label mainly as regards dosing frequency, while 13 prescriptions (14%) regarded antibiotics used in absence of specific indication for newborns (meropenem, imipenem, piperacillin/tazobactam, clindamycin, clarithromycin). 50/56 neonates (89.3%) received at least one off-label antibiotic prescription. Differences have been observed in dosing regimens between current study and recommendations contained in BNFC, while prescriptions adhered more frequently to ISN indications. Conclusions: Our results confirm the high prevalence of off-label antibiotic use in ELBW neonates and underline a better adherence to indications based on clinical practice.

Antibiotics for complicated urinary tract infection and acute pyelonephritis: A systematic review

BACKGROUND The increasing rates of antibiotic-resistance in the recent years has caused the emergence of multiple drug-resistant bacteria.Therefore,antibiotics that are recommended by the current clinical guidelines may not be effective for the treatment of complicated urinary tract infection(UTI)and acute pyelonephritis.AIM To determine the clinical efficacy and safety of antibiotics for the treatment of complicated urinary tract infection and acute pyelonephritis.METHODS A search of three medical databases(PubMed,EMBASE and Google Scholar)were conducted for eligible articles describing the use of antibiotics in managing complicated UTI and acute pyelonephritis.The following keywords were used to perform the literature search:“urinary tract infection”,“complicated UTI”,“pyelonephritis”,“treatment”and“antibiotics”.Additional articles of interest were retrieved from the reference list of selected papers.Eligibility criteria for this systematic review were diagnosis of either complicated urinary tract infection or acute pyelonephritis and the use of antibiotics in management.Clinical trials and observational studies were included in this review while case reports and reviews were excluded.The methodological quality of clinical trials and observational studies was assessed.A descriptive approach was adopted to analyze the data due to the variation of methodology and interventions.RESULTS A total of 183 studies were screened;eight studies that matched all the eligibility criteria were included in this review.The antibiotics included in this systematic review were ceftazidime-avibactam,doripenem,levofloxacin,meropenemvaborbactam,piperacillin-tazobactam,plazomicin,tazobactam-ceftolozane and gentamicin.Two clinical trials reported that shorter duration of levofloxacin or non-fluoroquinolone antibiotics treatment was as effective as the duration of antibiotic therapy recommended by the current guidelines in treating complicated UTI and pyelonephritis.Besides that,ceftazidime-avibactam,piperacillintazobactam and tazobactam-ceftolozane can be used as an alternative to carbapenem in treating extended-spectrumβ-lactamase-producing Escherichia coli.In the included studies,the cure rates of the complicated UTI and pyelonephritis by meropenem-vaborbactam,piperacillin-tazobactam and tazobactam-ceftolozane was comparable at between 95.6%and 98.4%.Furthermore,the clinical trials showed that levofloxacin had a relatively high rate of adverse events(33.1%and 47.7%in two clinical trials)while tazobactamceftolozane had a relatively low rate of adverse events(17.5%).All studies have limitations and a potential for bias.CONCLUSION The use of novel antibiotics and combination antibiotic therapy can be considered in treating complicated UTI and acute pyelonephritis when resistance to recommended antibiotics occurs.

Knowledge, Attitudes and Practices of Antibiotic Use and Antimicrobial Resistance among Medical Students in a Private University in Dominica, West Indies

Antibiotics are indispensable to maintaining human health, however, their overuse has resulted in resistant organisms which present a significantly higher burden to the low to middle income countries, due to the high incidence of communicable diseases. Insufficient antimicrobial-related training for physicians during their undergraduate education could have a negative impact on their prescribing. This study assessed the knowledge, attitudes and practices of antibiotic use and antimicrobial resistance among medical students in a private university in Dominica, a resource-limited country, in order to facilitate more effective education of these future prescribers. A cross-sectional study was undertaken with the medical students from February 2021 to April 2021 using a 36-item questionnaire. Data analysis was achieved using descriptive statistics. A total of 85 students participated in the study, majority (70%) were female, African, aged 23.8 ± 4.6 years and single. Between 64 and 99% of the respondents reported no risk factors for communicable diseases and demonstrated a low to moderate (10% - 40%) negative response to knowledge-related questions. The majority (70%) of the respondents who had used antibiotics in the past 12 months reported efficacy and limited side-effects, but confirmed lack of knowledge about the classes of antibiotics prescribed to them. Almost half of the medical students (48%) reported having abused antibiotics, while about a third (35%) of the respondents reported sharing antibiotics with friends or loved ones in the past. There was no significant association between age, gender, and the medical students’ knowledge of antibiotic resistance (p > 0.05). However, they reported that they would like more education on antimicrobial use and resistance. The medical students in this study showed knowledge of antimicrobial resistance, but lacked comprehension of components of antimicrobial stewardship, including prevention of inappropriate use and classes of antibiotics. Therefore, steps need to be taken to prepare medical students for antimicrobial resistance and stewardship initiatives effectively.

Action of Essential Oils Obtained from Baccharis coridifolia D.C.(Asteraceae-Astereae)on the Activity of Antibiotics

The aim of this study was to investigate the effects of Baccharis coridifolia essential oil on the Activity of Antibiotics. Assays were performed with ampicillin (10 μg), cephalothin (30 μg), chloramphenicol (30 μg), gentamicin (10 μg) and tetracycline (30 μg) alone and in combination with the essential oil (4% v/v) through the disk diffusion susceptibility test. The results showed the effects of essential oil on the activity of the antibiotics tested. Zones of inhibition of bacterial growth with different diameters were observed surrounding the antibiotic disks, whether or not they were impregnated with the essential oil. The occurrence of the synergistic or antagonistic effect was observed in both bacterial strains assessed—Staphylococcus aureus (ATCC-25923) and Escherichia coli (ATCC-25922). These results show that the use of products derived from plants can, in some cases, interfere with the effectiveness of antibiotics during clinical therapy.

不同药物对鸡沙门氏菌病治疗的研究

[目的]为比较研究临床上常用药物对鸡沙门氏菌病的治疗效果,筛选出合理治疗药物,避免抗生素的盲目使用。[方法]将具有清热解毒和一定抗菌消炎的复方中药组方优化后与硫酸卡那霉素、恩诺沙星、氯霉素、磺胺甲恶唑进行药敏试验和治疗比较试验。[结果]磺胺甲恶唑,高敏感株占比达86.6%,治愈率达86%;复方中药高敏感株占比73.4%,治愈率76%;硫酸卡那霉素、氯霉素高敏感株占比分别为80%、76.7%,略高于复方中药,治愈率分别为64%、66%,低于复方中药组;恩诺沙星高敏感株占比为56.7%,治愈率为58%,效果较差。[结论]复方中药对沙门氏菌有一定的抑菌和抗菌作用,中西药结合对疾病有很好的治疗和预防作用。

Controversies regarding transplantation of mesenchymal stem cells

Mesenchymal stem cells(MSCs)have tantalized regenerative medicine with their therapeutic potential,yet a cloud of controversies looms over their clinical tran-splantation.This comprehensive review navigates the intricate landscape of MSC controversies,drawing upon 15 years of clinical experience and research.We delve into the fundamental properties of MSCs,exploring their unique immuno-modulatory capabilities and surface markers.The heart of our inquiry lies in the controversial applications of MSC transplantation,including the perennial debate between autologous and allogeneic sources,concerns about efficacy,and lingering safety apprehensions.Moreover,we unravel the enigmatic mechanisms surro-unding MSC transplantation,such as homing,integration,and the delicate balance between differentiation and paracrine effects.We also assess the current status of clinical trials and the ever-evolving regulatory landscape.As we peer into the future,we examine emerging trends,envisioning personalized medicine and innovative delivery methods.Our review provides a balanced and informed perspective on the controversies,offering readers a clear understanding of the complexities,challenges,and potential solutions in MSC transplantation.

抗生素降阶梯方案对48例重症肺炎患者的疗效分析

目的探讨重症肺炎患者接受抗生素降阶梯方案治疗的效果。方法选择2020年1月—2022年12月兖矿新里程总医院收治的重症肺炎患者96例,根据随机盲选的方式将其分为对照组与试验组,各48例。所有患者在入院后均接受常规基础治疗,对照组在治疗期间给予传统抗生素治疗,试验组则给予抗生素阶梯方案治疗。对比2组的治疗效果、抗生素使用时间、肺啰音消失时间、感染控制时间、住院时间及2组治疗前后的炎症因子水平。结果对照组的总有效率为72.92%,试验组的总有效率为91.67%,差异有统计学意义(P<0.05)。观察组的抗生素使用时间为(10.13±3.22)d,肺啰音消失时间为(12.31±1.89)d,感染控制时间为(11.16±2.08)d,住院时间为(14.32±2.73)d,明显低于对照组的(17.05±4.36)d、(15.70±2.65)d、(19.33±1.39)d、(19.91±3.38)d,差异有统计学意义(P<0.05)。治疗前,2组的降钙素原(procalcitonin,PCT)、D-二聚体(D-Dimer,D-D)、C反应蛋白(C-reactive protein,CRP)等水平相比,差异无统计学意义(P>0.05);治疗后,试验组的PCT为(2.09±0.43)ng/L、D-D为(0.65±0.17)μg/L、CRP为(5.61±1.06)mg/L,明显低于对照组的(3.12±0.76)ng/L、(1.41±0.29)μg/L、(8.57±1.43)mg/L,差异有统计学意义(P<0.05)。结论在重症肺炎的治疗中,采用抗生素降阶梯方案治疗效果确切,能快速改善其症状,促进其病情康复,还能降低炎症因子水平。

How antibiotic resistances could change Helicobacter pylori treatment:A matter of geography?

Therapeutic management of Helicobacter pylori(H.pylori)remains an unsolved issue.Indeed,no therapeutic regimen is able to cure the infection in all treated patients,and in many the infection persists despite the administration of several consecutive standard therapies.Although antibiotic resistance reports describe alarming results,the outcome of therapeutic regimens does not seem to parallel this scenario in most cases,since a successful performance is often reached in more than 80%of cases.However,the phenomenon of increasing antibiotic resistance is being closely studied,and the results show controversial aspects even in the same geographic area.For the continents of Europe,America,Asia,Africa,and Oceania,minimal and maximal values of resistance to the main antibiotics(clarithromycin,amoxicillin,metronidazole,and levofloxacin)feature wide ranges in different countries.The real enigma is therefore linked to the several different therapeutic regimens,which show results that often do not parallel the in vitro findings even in the same areas.A first aspect to be emphasized is that some regimens are limited by their use in very small geographic districts.Moreover,not all therapeutic trials have considered bacterial and host factors affecting the therapeutic outcome.The additional use of probiotics may help to reduce adverse events,but their therapeutic impact is doubtful.In conclusion,the"ideal therapy",paradoxically,appears to be a"utopia",despite the unprecedented volume of studies in the field and the real breakthrough in medical practice made by the discovery and treatment of H.pylori.The ample discrepancies observed in the different areas do not encourage the development of therapeutic guidelines that could be valid worldwide.On these bases,one of the main challenges for the future might be identifying a successful solution to overcome antibiotic resistances.In this context,geography must be considered a relevant matter.

Clinacanthus nutans:a review of the medicinal uses,pharmacology and phytochemistry

Clinacanthus nutans Lindau is known as snake grass belonging to the Acanlhaceae family.This plant has diverse and potential medicinal uses in traditional herbal medicine for treating skin rashes,insects and snake bites,lesions caused by herpes simplex virus,diabetes,and gout in Malaysia.Indonesia.Thailand and China.Phylochemieal investigations documented the varied contents of bioaclive compounds from litis plant namely flavonoids,glycosides,glycoglyeerolipids.cerebrosides and monoacylmonogalatosylglycerol.The pharmacological experiment proved that various types of extracts and pure compounds from this species exhibited a broad range of biological properties such as anti-inflammatory,antiviral,antioxidant,and anti-diabetic activities.The lindings of toxicity study showed that extracts from this plant did not show any toxicity thus it can be used as strong therapeutic agents for specific diseased conditions.However,further experiments on chemical components and their mode of action showing biological activities are required to elucidate the complete phytochemical profile and assess to confirm their suitability tor future drugs.This review summarizes the medicinal uses,phytochemistry and pharmacology of this plant in order to explore its therapeutic potential and gaps necessitating for prospected research work.

Did the severe acute respiratory syndrome-coronavirus 2 pandemic cause an endemic Clostridium difficile infection?

BACKGROUND Clostridium difficile infection(CDI)has increased in prevalence during the last years.The coronavirus disease 2019(COVID-19)pandemic has negatively influenced patient outcomes.The majority of the severe acute respiratory syndrome-coronavirus 2(SARS-CoV-2)-infected patients received antibiotics during hospitalization.AIM To analyze the factors that influenced CDI development after SARS-CoV-2 infection.METHODS Between March 2020 to December 2020,we performed a prospective observational study including 447 patients diagnosed with CDI who were admitted to our tertiary referral university hospital.The diagnosis of CDI was based on the presence of diarrhea(≥3 watery stools within 24 h)associated with Clostridium difficile toxins A or B.We excluded patients with other etiology of acute diarrhea.RESULTS Among the total 447(12.5%)patients with CDI,most were male(54.3%)and mean age was 59.7±10.8 years.Seventy-six(17.0%)had history of COVID-19,most being elderly(COVID-19:62.6±14.6 years vs non-COVID-19:56.8±17.6 years,P=0.007),with history of alcohol consumption(43.4%vs 29.4%,P=0.017),previous hospitalizations(81.6%vs 54.9%,P<0.001)and antibiotic treatments(60.5%vs 35.5%,P<0.001),requiring higher doses of vancomycin and prone to recurrent disease(25.0%vs 13.1%,P=0.011).Age over 60 years[odds ratio(OR):2.591,95%confidence interval(CI):1.452-4.624,P=0.001],urban residence(OR:2.330,95%CI:1.286-4.221,P=0.005),previous antibiotic treatments(OR:1.909,95%CI:1.083-3.365,P=0.025),previous hospitalizations(OR:2.509,95%CI:1.263-4.986,P=0.009)and alcohol consumption(OR:2.550,95%CI:1.459-4.459,P=0.001)were risk factors of CDI in COVID-19.CONCLUSION CDI risk is unrelated to history of SARS-CoV-2 infection.However,previous COVID-19 may necessitate higher doses of vancomycin for CDI.

High-intensity focused ultrasound extracorporeal ablation of liver tissuesin rabbits

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