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.

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

ＩＮＴＲＯＤＵＣＴＩＯＮＨｅｐａｔｏｌｅｎｔｉｃｕｌａｒｄｅｇｅｎｅｒａｔｉｏｎ（ＨＬＤ）ｉｓａｎａｕｔｏｓｏｍａｌｒｅｃｅｓｉｖｅｄｉｓｏｒｄｅｒｔｈａｔｃａｕｓｅｓｃｈａｎｇｅｓｉｎｔｈｅｂａｓａｌｇａｎｇｌｉａａｎｄｌｉｖｅｒｔｈａｔｒｅｓｐｅ...

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

Ｆｕｎｃｔｉｏｎａｌｄｙｓｐｅｐｓｉａｏｆｕｌｃｅｒｄｙｓｍｏｔｉｌｉｔｙｔｙｐｅ：ｃｌｉｎｉｃａｌｉｎｃｉｄｅｎｃｅａｎｄｔｈｅｒａｐｅｕｔｉｃｓｔｒａｔｅｇｙＷＡＮＧＸｉａｏＺｈｏｎｇａｎｄＬＩＮＧｕＺｈｅｎＳｕｂｊｅｃｔｈｅａａｄｉｎｇｓ...

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.

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.

Combination of "low-dose" ribavirin and interferon alfa-2a therapy followed by interferon alfa-2a monotherapy in chronic HCV-infected nonresponders and relapsers after interferon alfa-2a monotherapy

AIM To report on the efficacy, safety and tolerability of interferon alfa-2a combined with a "low dose" of ribavirin for relapsers and non responders to alpha interferon monotherapy.METHODS Thirty-four chronic hepatitis C virus-infected non-responders to interferon alfa2a monotherapy (a course of at least 3 months treatment) and 13 relapsers to interferon alfa 2a monotherapy (a dose of 3 to 6 million units three times per week for at least 20 weeks but not more than 18 months) were treated with the same dose of interferon alfa-2a used before (3 to 6 million units three times per week) and ribavirin (10 mg/ kg daily) for 6 months. In complete responders, interferon alfa-2a was administered for further 6 months at the same dose used before as monotherapy.RESULTS Seven (20.6%) of 34 non-responders stopped the combined therapy due to adverse events, including two patients with histological and clinical Child A cirrhosis. In 17/27 (63%)non-responders, the combined therapy was stopped after three months because of non-response. Ten of the 27 non-responders completed the 1;2-month treatment course. At a mean follow up of 28 months (16- 37 months)after the treatment, 4/10 (15%) previous non-responders still remained complete responders,All 13 previous relapsers completed the 12-month treatment course. At a mean follow up of 22months (9 - 36 months) after treatment, 6/13(46%) the previous relapsers were stillsustained complete responders.CONCLUSION Our treatment schedule of the combined therapy for 6 months of interferon alfa2a with a low dose of ribavirin (10 mg/kg/day)followed by 6 months of interferon alfa-2amonotherapy is able to induce a sustainedcomplete response rate in 15% of non-responders and 46% of relapsers with chronic hepatitis C virus-related liver diseases comparable to those obtained with the standarddoses of ribavirin 1000 - 1200 mg/day.Randomized prospective controlled trials using lower total amounts of ribavirin in combination with interferon should be performed.

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.

Patient education improves adherence to peg-interferon and ribavirin in chronic genotype 2 or 3 hepatitis C virus infection:A prospective,real-life,observational study

AIM: To evaluate the impact of therapeutic education on adherence to antiviral treatment and sustained virological response (SVR) in a real-life setting in genotype 2/3 hepatitis C,as there are few adherence data in genotype 2/3 infection,even from randomized trials.METHODS: This prospective survey included genotype 2/3 patients who received peg-interferon alfa-2b and ribavirin.There was no intervention.Adherence was self-reported over the past 4 wk (peg-interferon) or 7 d (ribavirin).Adherence to bitherapy was defined as adherence to the two drugs for ≥ 20 wk.SVR was defined as undetectable RNA ≥ 12 wk after the end of treatment.RESULTS: 370/674 patients received education during the first 3 mo of treatment.After 6 mo,adherence to bitherapy was higher in educated patients (61% vs 47%,P = 0.01).Adherence to peg-interferon was 78% vs 69% (P = 0.06).Adherence to ribavirin was 70% vs 56% (P = 0.006).The SVR (77% vs 70%,P = 0.05) and relapse (10% vs 16%,P = 0.09) rates tended to be improved.After adjustment for baseline differences,education improved adherence [Odds ratio (OR) 1.58,P = 0.04] but not the SVR (OR 1.54,P = 0.06).CONCLUSION: In genotype 2/3 patients,therapeutic education helped maintain real-life adherence to bitherapy.

High-intensity focused ultrasound extracorporeal ablation of liver tissuesin rabbits

ＨｉｇｈｉｎｔｅｎｓｉｔｙｆｏｃｕｓｅｄｕｌｔｒａｓｏｕｎｄｅｘｔｒａｃｏｒｐｏｒｅａｌａｂｌａｔｉｏｎｏｆｌｉｖｅｒｔｉｓｓｕｅｓｉｎｒａｂｂｉｔｓＣＨＥＮＧＳｈｕＱｕｎ１，ＺＨＯＵＸｉｎＤａ１，ＴＡＮＧＺｈａｏＹｏｕ１，ＹＵＹａｏ１，Ｂ...

Liver decompensation predicts ribavirin overexposure in hepatitis C virus patients treated with direct-acting antivirals

AIM To determine whether ribavirin(RBV) concentrations differ according to cirrhosis stage among cirrhotic patients treated with interferon-free regimens. METHODS We included patients with hepatitis C virus and cirrhosis [Child-Pugh(CP) A or B], Glomerular Filtration Rate ≥ 60 mL/min, who started therapy with DAAs and weightbased RBV between October 2014 and February 2016. RBV plasma levels were assessed during the treatment. We focused our analysis on the first 8 wk of therapy. RESULTS We studied 68 patients: 54 with compensated(CP-B) and 14 with decompensated(CP-A) cirrhosis. Patients withdecompensated cirrhosis displayed significantly higher RBV concentrations than those with compensated cirrhosis at week 1, 2, 4 and 8(P < 0.035). RBV levels were positively correlated with Hb loss over the treatment(P < 0.04). Majority(71%) of CP-B patients required a RBV dosage reduction during the treatment. After adjustment for confounders, Child-Pugh class remained significantly associated(95%CI: 35, 348, P = 0.017) to RBV levels, independently from baseline per-Kg RBV dosage. CONCLUSION Liver decompensation might affect RBV clearance leading to an overexposure and increased related toxicities in decompensated cirrhosis. Our findings underscore the importance of an early ribavirin therapeutic drug monitoring and suggest that an initial lower RBV dose, rather than weight-based, might be considered in those with advanced liver disease(CP-B) treated with directacting antivirals.

The role of drug utilization evaluation in medical sciences

Background:Drug utilization evaluation(DUE)is defined by the World Health Organization(WHO)and focuses on the medical,social,and economic consequences of pharmaceutical marketing,distribution,prescribing,and usage in society.The WHO recommends a physician to every 1000 people.According to the recent data from the Health Ministry in 2019,in which 1.16 million doctors are of active population with just 80%,or 0.9 million,practicing.As a result,a ratio of 0.68 doctors for every 1000 people,which is much below as per the WHO reports.This article describes history,types,WHO guidelines,need and purpose of DUE.Objective:The main aim of this paper is to provide information about the rational use of medication in outpa­tient and inpatient department with special emphasis of DUEs.It also provides awareness directly to healthcare professionals,researchers,academicians,pharmacist and nurses to reduce the irrationality of medicines.Methods:The method used to compile this review information gathered from websites,Google scholar,PubMed,Research gate,and studies published on DUE from July 20 to Oct 22 were included as source of information.Results:We studied more than 35 published study on DUE,that reveals most of the physicians prescribed branded drugs not generic drugs,but WHO prescribing indicator allows to prescribe generic drugs in the hospital pharmacy to maintain better inventory control.It may also help to prevent pharmacist misunderstanding during dispensing.Conclusion:The use of generic prescription names avoids the possibility of medication product duplication and lowers patient costs.It is important to remember that incorrect medication prescriptions have impact on both patients and their family members.WHO indicators identify irrational prescribing behaviours to make therapy more rational and cost-effective.

USE OF CELL-BASED BIOASSAY FOR THE QUALITY CONTROL OF BOTANICAL THERAPEUTICS

The single most important factor in modernization efforts of traditional oriental medicines is the limited understanding of active compounds responsible for claimed therapeutic effects.Indeed,the unknown identity of biologically active molecules generates major difficulties associated with botanical therapeutics in general.This includes management of raw materials,poor understanding of

小剂量干扰素α-2b递增方案联合利巴韦林治疗失代偿期丙型肝炎肝硬化的疗效观察

目的:观察应用干扰素α-2b小剂量开始逐渐加量,联合利巴韦林方案治疗失代偿期丙型肝炎肝硬化的临床疗效。方法:18例失代偿期丙型肝炎肝硬化患者采用干扰素α-2b(IFNα-2b)治疗。初始剂量为200万U/次,皮下注射,每周3次,加利巴韦林600mg/d,分3次口服,治疗1～3个月后,根据病情逐步将IFNα-2b剂量增加至300～500万U/次肌注及利巴韦林800～1000mg/d,分3次口服,治疗48周,观察疗效。结果:18例患者有17例耐受较好并完成IFN疗程,而1例无法耐受利巴韦林治疗提前终止。与治疗前比较,17例患者治疗后的ALT、AST、TBil、Alb、CHE、PTA、HCVRNA,肝纤维化指标(HA、LN、PCⅢ,C-Ⅳ)均有明显改善(P<0.05)。结论:小剂量IFNα-2b开始逐渐加量联合利巴韦林方案可治疗失代偿期丙型肝炎肝硬化患者,但治疗的远期疗效还有待进一步观察。

聚乙二醇干扰素联合利巴韦林治疗慢性丙型肝炎疗效观察及影响因素分析

目的:探讨聚乙二醇干扰素联合利巴韦林治疗慢性丙型肝炎的临床疗效及其影响因素。方法:收集慢性丙型肝炎患者142例,采用聚乙二醇干扰素联合利巴韦林作为抗病毒治疗方案,分别在治疗前、治疗第4周、第12周、第24周、第36周、第48周、治疗结束后24周检测HCVRNA载量。统计患者的持续病毒学应答率,同时对比不同临床资料患者的持续病毒学应答率以分析聚乙二醇干扰素联合利巴韦林治疗慢性丙型肝炎疗效的影响因素。结果:142例患者经过治疗后,快速病毒学应答率75.35%,治疗结束时病毒学应答率97.18%,持续病毒学应答率82.39%。对比不同临床资料患者的持续病毒学应答率,结果显示,年龄≤40岁、体质量<75kg、病程<10年患者的持续病毒学应答率显著高于年龄>40岁、体质量≥75kg、病程≥10年的患者(P<0.05);疗程越接近48周,聚乙二醇干扰素、利巴韦林累积用量越接近预计用量的患者,其持续病毒学应答率越高(P<0.05)。结论:聚乙二醇干扰素联合利巴韦林是慢性丙型肝炎较为理想的抗病毒方案,临床治疗中应尽量保证80%以上的疗程和80%以上的药物推荐剂量以获得更为理想的持续病毒学应答率。

痰热清联合利巴韦林治疗手足口病疗效观察

目的探讨痰热清联合利巴韦林治疗儿童手足口病的临床疗效。方法选取99例手足口病患儿随机分为治疗组和对照组,治疗组应用痰热清联合利巴韦林治疗,对照组单独采用利巴韦林治疗。结果治疗组有效率同对照组相比有显著差异(P<0.01)。结论痰热清注射液联合利巴韦林治疗儿童手足口病疗效确切,值得临床推广使用。

丹参注射液治疗特发性面神经麻痹临床研究

目的:观察丹参注射液治疗特发性面神经麻痹的临床疗效。方法:选择特发性面神经麻痹患者随机分为两组,治疗组及对照组各30例,治疗组采用西医常规对症治疗选用维生素B1 0.1 g及维生素B12 0.5 mg穴位注射,1次/d,14 d为1疗程;泼尼松片30 mg,1次/d,连用3 d后每隔日递减5 mg至停用;0.9%氯化钠注射液250 mL加利巴韦林0.3 g静脉滴注,1次/d,14d为1疗程,必要时应用抗生素眼膏保护角膜。治疗组在对照组药物治疗基础上给予丹参注射液,静脉滴注,1次/d,14 d为1疗程。结果:治疗组30例,痊愈16例,显效7例,痊愈显效率为76.67%;对照组30例,痊愈3例,显效10例,痊愈显效率为43.33%。治疗组疗效优于对照组(P<0.01)。结论:丹参注射液治疗特发性面神经麻痹疗效显著。

热毒宁联合利巴韦林治疗小儿疱疹性咽峡炎疗效观察

目的观察热毒宁联合利巴韦林治疗小儿疱疹性咽峡炎的临床疗效。方法将符合纳入标准的100例疱疹性咽峡炎患儿随机分成治疗组50例和对照组50例,治疗组给予热毒宁及利巴韦林静脉点滴,对照组给予静脉点滴利巴韦林,两组治疗5 d为1个疗程,观察两组患者体温下降、口腔疱疹及溃疡消退情况。结果从发热、口腔疱疹及溃疡消退情况观察,治疗组病程明显短于对照组,两者比较差异有显著性(P<0.01)。结论热毒宁联合利巴韦林治疗小儿疱疹性咽峡炎可以提高临床疗效,缩短疗程,值得临床推广。

病毒唑治疗成人麻疹临床疗效观察

目的 了解病毒唑治疗成人麻疹的效果及安全性。方法 随机对照试验。结果 治疗组退热时间较对照组缩短２天，有显著性差异（Ｐ＜０．０１），治疗组开始退疹时间较对照组缩短０．７天，差异有统计学意义（Ｐ＜０．０５），治疗组住院时间对照组缩短２天，无血液学、肾脏或肝脏方面的毒副反应。结论 病毒哇治疗成人麻疹有改善成人麻疹患者病情和缩短退热时间和病程的作用，且无毒副作用。