Propolis modulates cellular biochemistry, antioxidants, cytokine profile, histological and ultra-morphological status against antituberculosis drugs induced hepatic injury

To evaluate hepatic injury induced by antituberculosis drugs(ATDs) when administered orally for 2, 4, 6 and 8 weeks and the therapeutic potential of propolis(bee hive product) against ATDs induced hepatic injury. Methods: The ATDs were administered for 8 weeks as well as propolis extract at three different doses(100, 200, 400 mg/kg) conjointly for 8 weeks in rats. Silymarin(50 mg/kg) was given as positive control. Animals were euthanized after 8 weeks; blood and liver samples were collected to perform various biochemicals, serological and histopathological and ultramorphological studies. Results: Significant increase(P < 0.05) in aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, triglyceride and cholesterol along with reduction in glucose and albumin level were noted after ATDs induced hepatic injury. Significant increase(P < 0.05) in lipid peroxidation, triglyceride, cholesterol and CYP2E1 activity; decline in reduced glutathione, catalase, superoxide dismutase, glutathione reductase, glutathione peroxidase, glucose-6-phosphatase dehydrogenase activity were observed after ATDs intoxication. Due to presence of a wide range of flavonoids and polyphenols in propolis extract, its administration reduced hepatic injury and maintained biochemical indices towards control. Histopathological and electron microscopic observations indicated hepatoprotective potential of propolis at cellular level whereas, TNF-α, IL-6 and IGF-1 confirmed therapeutic potential of propolis at molecular level. Conclusions: It can be concluded that propolis possess hepatoprotective potential against ATDs induced hepatic injury that may prove itself as a clinically useful natural product in management of drug induced liver injury.

Antituberculosis Drug-Induced Liver Injury: An Ignored Fact, Assessment of Frequency, Patterns, Severity and Risk Factors

Background/Aims: Antituberculosis drug-induced liver injury (TB DILI) is a frequent medical problem in Pakistan. Critical understanding of various aspects of TB DILI is not only important to manage liver injury but may also prevent unnecessary discontinuation of antituberculosis treatment. The study is aimed to determine the frequency, types, severity and patterns of TB DILI. Study further evaluates various risk factors of TB DILI. Materials and Methods: This is a prospective cohort study of two seventy-eight patients with the diagnosis of tuberculosis, where patients were followed during tuberculosis treatment. TB DILI was defined in accordance to international DILI expert working group. Results: Out of two seventy eight-patients, ninety-five (34.14%) had TB DILI. The most common pattern of TB DILI was hepatocellular (63.15%) followed by mixed (23.15%) and Cholestatic (13.68%). Most of the patients had mild DILI (43.15%) followed by moderate (30.52%), severe (20.01%) and very severe (5.26%). Age > 35 years, concomitant hepatotoxic drugs, extrapulmonary TB and malnutrition are important risk factors for TB DILI. Conclusion: All patterns of TB DILI with varying severity were present. Age > 35 years, malnutrition, extrapulmonary TB and concomitant use of hepatotoxic drugs were risk factors for TB DILI.

New antituberculosis drugs targeting the respiratory chain

With the emergence of multidrug-resistant tuberculosis and extensive drug-resistant tuberculosis strains,there is an urgent need to develop novel drugs for the treatment of tuberculosis.The respiratory chain is a promising target for the development of newantimycobacterial agents,and a growing number of compounds have been reported and some have entered clinical trials.In this review,we summarize the main features and the electron transfer process of the mycobacterial respiratory chain,and the recent progress in the search for new small molecule inhibitors to rgeting the three main potential targets in the respiratory chain of Mycrobacterium tuberculosis.Our emphasis is on the optimization strategy of QcrB inhibitors and the challenges of developing QcrB inhibitors as antituberculosis drugs due to the alternate bd-type oxidase oxidative compensation pathway are discussed.

A narrative review on inhibitory effects of edible mushrooms against malaria and tuberculosis-the world’s deadliest diseases

The isolated secondary metabolites from 39 edible mushrooms are reported,among which 107 compounds were active,61 demonstrated antitubercular activities with IC_(50) range of 0.2-50μg/mL and 46 manifested antimalarial effects with IC_(50) range of 0.061-36μg/mL.While more than 2000 strains of edible mushrooms are identified,this review shows the paucity of research in these rich organisms featuring a vital culinary ingredient worldwide.A thorough search was conducted on basidiomycetes to discuss the chemistry and biology of the isolated compounds,structure activity relationships(SAR)as well as the cytotoxicity profiles of,primarily,the active anti-plasmodial and antitubercular molecules.With a safe cellular profile,lanostane triterpenoids were found to be the only molecules with combined activities against both diseases.SAR correlations reviewed here indicated the significance of 3β-and 7α-hydroxylation in the anti-tuberculosis activity and the terminal unsaturated moiety between C-4 and C-28 in the antimalarial activity in the same terpene skeleton.This review will attract the attention of medicinal chemists,and food scientists to optimize and rationalize the use of mushrooms both as unexploited sources of novel molecules and as nutraceuticals to treat two of the deadliest infectious diseases,malaria,and tuberculosis.

克拉霉素联合抗痨药治疗老年人复治肺结核临床观察

目的观察克拉霉素联合氧氟沙星、力克肺疾和利福喷丁治疗老年人复治肺结核的临床疗效。方法选择住院60例老年人复治肺结核病人为研究对象,随机分为治疗组和对照组。治疗组采用克拉霉素和氧氟沙星联合力克肺疾、利福喷丁四联抗痨;对照组采用力克肺疾、利福喷丁、氧氟沙星三联抗痨。疗程均为6个月(强化期2个月,维持期4个月,维持期均以力克肺疾和利福喷丁治疗),6个月后随访所有患者的症状、复查肝肾功能及胸片。结果治疗组在胸片病灶吸收方面,较对照组有明显改善(P<0.05);但在药物不良反应方面两种方案无显著差异(P>0.05)。结论克拉霉素联合氧氟沙星、力克肺疾及利福喷丁比氧氟沙星联合力克肺疾、利福喷丁治疗老年人复治肺结核疗效好。

Delayed diagnosis and comprehensive treatment of cutaneous tuberculosis:A case report

BACKGROUND Tuberculosis(TB)is a widespread infectious disease,with an incidence that is increasing worldwide.Cutaneous TB(CTB)occurs rarely,accounting for less than 1%of all TB cases.Due to the clinical presentation and diagnostic difficulties,CTB is often clinically neglected and misdiagnosed.CASE SUMMARY A 32-year-old man underwent several debridement surgeries and skin flap transplantation after trauma.The wound remained unhealed,accompanied by sinus formation.According to empirical judgment,T-cell spot of TB test,and bacterial culture of pyogenic fluids,he was diagnosed with CTB due to infection with exogenous Mycobacterium tuberculosis.A comprehensive anti-TB regimen that included isoniazid,rifampicin,ethambutol,and pyrazinamide was applied.The sinus was filled with a hydrophilic fiber-containing silver dressing,and woundprotecting sponges were applied to part of the wound.The wound healed after 40 d.No ulceration was found within 2 mo after discharge;further follow-up will be conducted.CONCLUSION A non-healing wound may be caused by TB infection.Comprehensive treatment of CTB is effective.

Ameliorative effect of Pergularia daemia(Forssk.) Chiov. leaves extract against anti-tuberculosis drugs induced liver injury in rats

Objective:To evaluate therapeutic potential of hydroethanolic extract of Pergularia daemia(P.daemia) against anti-tuberculosis drugs(ATDs) induced liver injury.Methods:Wistar albino rats were divided into seven groups of six animal in each.The ATDs and P.daemia extract(100,200 and 400 mg/kg,p.o.) were conjointly administered for 8 weeks and various biochemical,histoarchitectural,ultrastructural studies were performed.Results:Administration of ATDs significantly increased aspartate aminotransferase,alanine aminotransferase,alkaline phosphatase,triglycerides,cholesterol,bilirubin and decreased glucose and albumin level.Increased lipid peroxidation and reduction in glutathione,superoxide dismutase,catalase,glutathione peroxidase,glutathione reductase and glucose-6-phosphate dehydrogenase were found after ATDs exposure.Administration of P.daemia extract maintained serum biochemical indices as well as antioxidant status similar to control and diminished oxidative stress in dose dependent manner.Histological and ultra-structural observations substantiated biochemical findings.Conclusions:P.daemia has therapeutic potential against ATDs induced liver injury and may be of clinical significance after extensive studies.

Effects of quadruple antituberculous drugs in combination with linezolid and moxifloxacin on CSF cytology, NSE, NGF and its receptors in patients with refractory tuberculous meningitis

Objective: To investigate the effects of linezolid and moxifloxacin combined with quadruple antituberculosis drugs on CSF cytology, NSE (neuronal specific enolase), NGF(nerve growth facor) and its receptors, endothelin and its receptors and CRP (C reaction protein) in patients with refractory tuberculous meningitis. Method: A total of 56 patients were selected with tuberculous meningitis in our hospital from February 2014 to December 2017,randomly divided them into 2 groups, each group was 28 cases, set as the observation group and the control group, both groups were treated with quadruple antituberculosis drugs, the observation group was given ilinezolid on this basis, and the control group was combined with moxifloxacin, The course of treatment was 4 weeks, compared the levels of CSF cytology, NSE, NGF and NGF receptors, endothelin and endothelin receptors, and CRP after treatment in the two groups. Result:The CSF cytology, NSE, NGF and NGF receptors, endothelin and endothelin receptor, and CRP levels remained unchanged before treatment, the difference was not statistically significant. After treatment, the chloride and glucose levels in the observation group were higher than those before treatment and that of the control group, the protein, white blood cell count, and cerebrospinal fluid pressure levels were lower than before treatment and that of the control group, the difference was statistically significant;The NSE level in the observation group after treatment was lower than before treatment and that of the control group, the difference was statistically significant;After treatment, the levels of NGF and its receptors in the observation group were higher than those before treatment and that of the control group, and the levels of endothelin, and its receptor, CRP were lower than those before treatment and that of the control group, the difference was statistically significant. Conclusion:The use of linezolid in combination with quadruple antituberculosis drugs to treat refractory tuberculous meningitis has better clinical effect, effectively improve cerebrospinal fluid cytology, regulate cerebrospinal fluid NSE levels, restore NGF, endothelin and its receptor function, reduce inflammatory response, recommended for clinical promotion and application.

Primary Prostatic Tuberculosis: A Rare Entity

Objectives: To clarify the clinical, histological and therapeutic features of prostatic tuberculosis. Methods: We conducted a single-centre retrospective descriptive study of all patients presenting with prostatic tuberculosis between January 2002 and December 2020. Patients who were lost to follow-up, could not be reached by telephone or whose records were not usable were excluded from this study. Results: 240 patients were treated for urogenital tuberculosis, including 13 for isolated prostatic tuberculosis. The average age of the patients was 75 years. None of our patients had a history of tuberculosis. The average of international prostate symptom score (IPSS) was 27. Lower urinary tract symptoms in the filling phase were predominant. The digital rectal examination was suspicious in only one patient. The mean preoperative PSA was 9.24 ng/ml. 46.15% of patients underwent transurethral resection of the prostate and 53.85% underwent ultrasound-guided prostate biopsy. Histological examination showed epithelioid gigantocellular granuloma with isolated caseous necrosis in 61.53% of patients and associated adenomyomatous hyperplasia in 38.47% of patients. Antituberculosis treatment was given for 6 months. The average of follow up was 15 months. All patients reported an improvement in clinical signs with a mean post operative IPSS score of 17 and a normalisation of PSA levels. Conclusion: Isolated prostatic tuberculosis is a rare entity, it can simulate a cancer. In front of the symptoms of the lower urinary tract, the clinicians must think of it especially in the developing countries where tuberculosis still prevails in an endemic state.

抗结核药物致肝损害124例临床报告

目的：探讨抗结核药物致肝损害的致病机理。方法：对我院收住124例肺结核患者发生肝损害的临床资料进行回顾分析。结果：停用抗结核药物，卧床休息，一般保肝药物治疗，皆于1mo内肝功能恢复正常，无导致慢性肝炎病例。结论：异烟肼可在体内转化成有毒代谢产物，生成自由基，亲电子基，异烟肼在肝内经乙酰化合分解为异菸酸和乙酰肼。乙酰肼与肝细胞膜关键分子共价结合，破坏其功能而产生坏死。人体对异烟肼的代谢分快灭活及慢灭活二类，快灭活者产生乙酰肼多，易引起肝损害，慢灭活者产生乙酰肼少，很少发生肝损害。利福平能诱导肝药酯，抑制酶的活性，降低药物活性，使药物代谢迟缓，致肝细胞内质网增生，对肝脏的毒性增加。

Biosafety materials for tuberculosis treatment

Tuberculosis(TB)is among the deadliest infectious diseases worldwide.Although the existing antituberculosis(anti-TB)drugs remain to be effective,the administration of these complex anti-TB drug combinations with obvious toxicity often leads to patients’nonadherence.This may contribute toward the emergence of drug-resistant strains as well as lead to treatment failure and relapse.Therefore,in the past half century,the main focus of anti-TB drug research was to reduce the frequency of administration and toxicity and improve patients’compliance and drug sensitivity.Following these principles,the development of engineered biosafety materials is one of the most effective and promising methods in resolving these challenges.Compared with traditional drugs,biosafety materials provide a viable platform for treating TB,which are beneficial in reducing the frequency of drug administration and systemic toxicity,improving patients’compliance and drug sensitivity,and enhancing drug targeting.In this review,we summarized the application of biosafety materials in treatment of TB in recent years and discussed the challenges faced when developing a safe,more effective,and economical pharmacotherapy against TB.