NAT2＊6A, a haplotype of the N-acetyltransferase 2 gene, is an important biomarker for risk of anti-tuberculosis drug-induced hepatotoxicity in Japanese patients with tuberculosis

AIM: To investigate an association between N -acetyltransferase 2 (NAT2 )-haplotypes/diplotypes and adverse effects in Japanese pulmonary tuberculosis patients. METHODS: We studied 100 patients with pulmonary TB treated with anti-TB drugs including INH. The frequencies and distributions of single nucleotide polymorphisms, haplotypes, and diplotypes of NAT2 were determined by the PCR-restriction fragment length polymorphism method, and the results were compared between TB patients with and without adverse effect, using multivariate logistic regression analysis.RESULTS: Statistical analysis revealed that the frequency of a variant haplotype, NAT2*6A , was signifi cantly increased in TB patients with hepatotoxicity, compared with those without hepatotoxicity [P = 0.001, odds ratio (OR) = 3.535]. By contrast, the frequency of a wild-type (major) haplotype, "NAT2*4", was signif icantly lower in TB patients with hepatotoxicity than those without hepatotoxicity (P < 0.001, OR = 0.265). There was no association between NAT2-haplotypes and skin rash or eosinophilia. CONCLUSION: The present study shows that NAT2 is one of the determinants of anti-TB drug-induced hepatotoxicity. Moreover, the haplotypes, NAT2*4 and NAT2*6A, are useful new biomarkers for predicting anti- TB drug-induced hepatotoxicity.

Colonoscopy evaluation after short-term anti-tuberculosis treatment in nonspecific ulcers on the ileocecal area

AIM: To evaluate the eff icacy of colonoscopy follow-up after short-term anti-tuberculosis treatment in patients with nonspecific ulcers on ileocecal areas being suspicious of tuberculous colitis. METHODS: We prospectively analyzed the colonoscopic fi ndings before and after short term anti- tuberculosis treatment in 18 patients with nonspecifi c ulcers on the ileocecal area and compared them with 7 patients of confi rmed tuberculous colitis by acid-fast bacilli or caseating granuloma on colonic biopsy. RESULTS: Mean duration for short-term follow- up was 107.3 d with combined chemotherapy containing isoniazid, rifampicin, ethambutol and pyrazinamide. Seven patients with tuberculous colitis showed complete healing of active ulcers after short- term medication. After short-term anti-tuberculosis treatment, follow-up colonoscopy findings devided 18 patients with nonspecific ulcers into two groups by ulcer state. One is the "suspicious tuberculous colitis group" showing healing of ulcers and erosions and another is the "suspicious inflammatory bowel disease group" showing active ulcers with or without aggravation of the lesion. Finally, all 9 of the "suspicious tuberculous colitis group" were diagnosed as tuberculous colitis showing no recurrence of ulcers after termination of 9 mo of anti-tuberculosis medication. Patients of the "suspicious inflammatorybowel disease group" were f inally diagnosed as Crohn's disease or nonspecifi c colonic ulcers during long-term follow up. CONCLUSION: Follow-up colonoscopy shows a healing stage ulcer or scarring change without an active ulcer with just 2 mo to 3 mo of medication in patients with tuberculous colitis. Colonoscopy follow-up after short term anti-tuberculosis trial in patients with nonspecif ic ulcers on the ileocecal area is valuable in making early differential diagnosis of tuberculous colitis.

Pyrrolidine dithiocarbamate alleviates the anti-tuberculosis drug-induced liver injury through JAK2/STAT3 signaling pathway:An experimental study

Objective:To study the effect of pyrrolidine dithiocarbamate(PDTC) on the anti-tuberculosis drug-induced liver injury and the molecular mechanism. Methods:Clean male SD rats were selected as experimental animals and randomly divided into normal group,model group,PDTC group and AG490 group. Animal model of anti-tuberculosis drug-induced liver injury was established by intragastric administration isoniazid + rifampicin. PDTC group received intraperitoneal injection of PDTC,and AG490 group received intraperitoneal injection of AG490. Twenty-eight days after intervention,the rats were executed,and the liver injury indexes,inflammation indexes and oxidative stress indexes in serum as well as JAK2/STAT3 expression,liver injury indexes,inflammation indexes and oxidative stress indexes in liver tissue were determined. Results:p-JAK2,p-STAT3,TNF-α,IL-1β,IL-6,ROS,8-OHdG and MDA expression in liver tissue as well as TBIL,ALT,AST,γ-GT,TNF-α,IL-1β,IL-6,ROS,8-OHdG and MDA levels in serum of model group were significantly higher than those of normal group while p-JAK2,p-STAT3,TNF-α,IL-1β,IL-6,ROS,8-OHdG and MDA expression in liver tissu as well as TBIL,ALT,AST,γ-GT,TNF-α,IL-1β,IL-6,ROS,8-OHdG and MDA levels in serum of PDTC group and AG490 group were significantly lower than those of model group. Conclusions:PDTC can inhibit the inflammation and oxidative stress mediated by JAK2/STAT3 signaling pathway to alleviate the anti-tuberculosis drug-induced liver injury.

Effect of anti-tuberculosis therapy on liver function of pulmonary tuberculosis patients infected with hepatitis B virus

AIM: To observe the effect of anti-tuberculosis therapy on liver function of pulmonary tuberculosis patients with hepatitis B virus (HBV) infection, and to compare the differences of liver function by two treatments of antituberculosis.METHODS: Forty-seven TB patients with HBV infection and 170 TB patients without HBV infection were divided into HPBE(S) and HLAMKO treatment groups. Liver function tests before and after the treatments were performed once in 2 wk or monthly, and their clinical manifestations were recorded.RESULTS: The rate of hepatotoxicity occurred in 26 (59%)TB patients with HBV during anti-TB treatment, higher than that in 40 (24%) TB patients without HBV. Hepatotoxicity occurred in 66 out of 217 patients, and the incidence of liver dysfunction was 46.1% in HPBE(S) group, significantly higher than that in HLAMKO group (12.7%) (P＜0.01).CONCLUSION: TB patients with HBV should choose HLAMKO treatment because of fewer hepatotoxicity.

Pancreatic tuberculosis mimicking pancreatic carcinoma during anti-tuberculosis therapy:A case report

Pancreatic tuberculosis(TB) is a rare condition,even in immunocompetent hosts.A case is presented of pancreatic TB that mimicked pancreatic head carcinoma in a 40-year-old immunocompetent male patient.The patient was admitted to our hospital after suffering for nine days from epigastralgia and obstructive jaundice.Computed tomography revealed a pancreatic mass that mimicked a pancreatic head carcinoma.The patient had undergone an operation four months prior for thoracic TB and was undergoing anti-TB therapy.A previous abdominal ultrasound was unremarkable with the exception of gallbladder steroid deposits.The patient underwent surgery due to the progressive discomfort of the upper abdomen and a mass that resembled a pancreatic malignancy.A biopsy of the pancreas and lymph nodes was performed,revealing TB infection.The patient received a cholecystostomy tube and recovered after being administered standard anti-TB therapy for 15 mo.This case is reported to emphasize the rarecontribution of pancreatic TB to pancreatic masses and obstructive jaundice.

Evaluation of <i>In-Vitro</i>Anti-Tuberculosis Activity of <i>Tetrapleura tetraptera</i>Crude and Fractions on Multidrug Resistant <i>Mycobacterium tuberculosis</i>

The management, control and elimination of tuberculosis (TB) have been difficult with the advent of HIV and cases of multidrug resistant (MDR-TB) tuberculosis. The cases of multidrug resistance to rifampicin and isoniazid pose greater challenges on first line and second line drugs to eliminate TB. The study is aimed at establishing anti-tuberculosis activity of Tetrapleura tetraptera against Mycobacterium tuberculosis and MDR-TB and the phytochemical present. The leaves of Tetrapleura tetraptera were collected, weighed, dried and pulverized to powder. The pulverized leaves of Tetrapleura tetraptera were subjected to 70% methanol extraction and screened for phytochemical. The crude extract was further purified into fractions using silica gel and thin layer chromatography techniques. M. tuberculosis and MDR-TB were obtained from positive acid fast bacilli sputa of TB patients and confirmed using GeneXpert to differentiate genotypic drug susceptible M. tuberculosis and MDR-TB. The sputa were digested using sodium hydroxide-cysteine technique and cultured in Middlebrook 7H9. The crude extract and fractions were screened for anti-tuberculosis activity using tetrazolium microtitre plate assay. The results showed that Tetrapleura tetraptera crude had activities against M. tuberculosis at 7.4 ± 0 mg/ml and 27.5 ± 0 mg/ml for MDR-TB. One of the fractions inhibited the growth of M. tuberculosis at 0.24 ± 0 mg/ml and MDR-TB at 0.89 ± 0 mg/ml. The phytochemical screened includes tannins, alkaloids, saponins, flavonoids, phenols and resins. T. tetraptra possesses anti-tuberculosis potential at low concentration on MDR-TB and can be a lead compound in drug development for the treatment of tuberculosis and multidrug resistant tuberculosis.

First Line Anti-Tuberculosis Drugs Resistance Patterns of <i>Mycobacterium tuberculosis</i>Isolates from Newly Diagnosed Cases of Tuberculosis

Introduction: Tuberculosis is a major cause of mortality and morbidity world-wide. Anti-tuberculosis drugs have been used for many decades but resistance to them is now widespread. Globally 5% of tuberculosis cases and in India 3% among new TB cases. This study was planned to know the pattern of first line anti-tuberculosis drug resistance in south Gujarat, Surat region in newly diagnosed patients of tuberculosis. Material and Methods: 350 samples were processed for homogenisation and concentration using 4% NAOH-2.9% trisodium citrate. Processed samples were inoculated in liquid medium that is MGIT (Mycobacterial growth indicator tube). Positive samples for M. tbwere processed further for first line anti-tuberculosis drugs sensitivity testing (DST). Reading was taken by using MicroMGIT system. Result: Out of 350 samples 59 (17%) were positive samples, of which 48 (13%) were M. tb and 11 (3%) were non tuberculous mycobacteria. Out of 48 samples 2% (1 isolate) was resistant to isoniazid and Rifampicin while 2% were monoresistant to isoniazide, 2% monoresistant to streptomycin. No rifampicin monoresistant was detected. Conclusion: Such study may help in control of tuberculosis at regional and national level which would in turn help in planning of measures to control Multi-drug resistance tuberculosis. Continuous surveillance should be applied to know the periodic changing patterns and trend in Drug resistant tuberculosis.

Use of Cost Effective Semi-Automated (Mannual/Micro) MGIT System over BACTEC 960 to Perform First Line Anti-Tuberculosis Drugs Sensitivity Testing

Introduction: Multi-drug resistant tuberculosis (MDR-TB) that is the tuberculosis that is resistant to at least 2 of the first line anti-tuberculosis drugs is fatal infectious disease. Cases of MDR-TB are now increasing with 30,000 cases of MDR-TB reported in 2013 by national TB programme. Rapid diagnosis of MDR-TB is extremely important for rapid treatment of patient and to prevent spread of MDR-TB to other. BACTEC 960 system helps in rapid diagnosis but purchase of expensive instrument for the same is the limitation. However, the same purpose can be solved by use of semi-automated MGIT system. Aims and Objectives: Aim of this study is to do drug sensitivity testing of the first line anti-tuberculosis drugs with the use of semi-automated MGIT systems. 350 newly registered and suspected cases of tuberculosis in tertiary care hospital were included. Samples were processed for digestion and decontamination and inoculated in MGIT tubes and also on LJ medium. Reading was taken using semi-automated MGIT system. Positive tubes were confirmed by rapid test for M. tuberculosis and then drug sensitivity was performed. Result: Out of 350 samples, 62% were sputum;33% were pleural fluid and rest 5% were lymph node, Ascetic fluid, CSF, pus. Average day of positivity by MGIT was 13 - 20 days as compared to 25 - 37 days by solid medium, which was statistically significant with p value Conclusion: Manual MGIT System is a simple, efficient, safe to use diagnostic system. It does not require any expensive/special instrumentation other than the UV lamp for detection of fluorescence. The rapidity by which mycobacteria are detected is the most important advantage of the Manual MGIT. In areas with limited resources where purchase of expensive instruments such as the MGIT960 is out of scope, the use of manual MGIT for rapid susceptibility testing for MDR-TB could be a possibility.

SARS-COV-2 Infection and Anti-Tuberculosis Immunity: Temporal Association or Real Protective Role?

Introduction: According to the literature consulted to date, there is epidemiological heterogeneity of Covid-19 between countries depending on their vaccination policy, in particular BCG vaccination. These findings have led to several hypotheses, including the protective role of immunity induced by the BCG tuberculosis vaccine against Covid-19 infection. The immunity induced by the BCG vaccine significantly increases the secretion of pro-inflammatory cytokines, in particular IL-1B, which has been shown to play an essential role in antiviral immunity. This cross-immunity, although not specific, if highlighted, is a real providence that must be taken advantage of in the face of this pandemic. The main objective of this study is to rule out or confirm that anti-tuberculosis immunity protects against SARS-COV-2 in our context. Material and Methods: Two groups will be compared: cases infected with the virus and controls who have never been infected with the virus. Both case and control groups will undergo a tuberculin skin test: the intra dermal tuberculin reaction (IDR). Results: We found that our control group had a high IDR immunity value, with an IDR tuberculin positive percentage of 67.2%. This suggests that immunity to IDR is a protective factor against coronavirus disease. Conclusion: The hypothesis of nonspecific anti-tuberculosis protection deserves further verification studies;it would have large positive repercussions for developing countries.

In Vitro Anti-tuberculosis Activity of Total Crude Extract of Echinops Amplexicaulis against Multi-drug Resistant Mycobacterium Tuberculosis

Background： TB （Tuberculosis） is the second leading killer infectious disease after HIV （human immunodeficiency virus）. Its incidence is worsened by development of multi-drag resistant and extensive drug resistant TB stxains. Available treatment regimens are expensive, toxic and lengtjy resulting to problems of non-adherence and inadequate response. Medicinal plants on the other hand may offer hope for developing alternative medicine for treatment of TB. This study evaluated the anti-tuberculosis activity of Echinops amplexicaulis. Materials and methods： Total crude extracts ofE. amplexicaulis were tested for activity against a wild strain resistant to Rifampicin and Isoniazid （MDR）, a fully susceptible laboratory strain （H37Rv） and Mycobacwrium boris （BCG strain） using disk diffusion method. MIC （minimum inhibitory concentration） was determined using Middlebrook 7H9 broil1. The strains were sub-cultured on Middlebrook 7H10 medium and MBC （minimum bactericidal concentration） determined. Susceptibility was evaluated by measuring zones of inhibition; MIC was obtained as the lowest concentration with no significant growth as shown by clog formation ofMTB （Mycobacwria tuberculosis） cells on the walls of the macro broth tube and MBC was obtained as the lowest concentration that inhibited growth of MTB colonies on Middlebrook 7H10 medium. Results： The extract showed a significant effect at a concentration of 50 mg/mL against all the three test strains F （2, 18） = 437.7, p = 0.00. It exhibited a MIC of 0.0488 mg/mL against MDR-TB and M. boris. Its MBC was the same at 0.0977 mg/mL against both MDR TB and M. boris. The MIC was much lower （0.0122 mg/mL） for the H37Rv strain. Terpenoids, alkaloids and tannins were present in large amount in the extract while saponins were present in small amounts. Flavonoids were not detected in the extract. Conclusion： E. amplexicaulis has the potential to be developed into new anti-TB drug and outcome of tile study supports the folkloric claims of anti-tuberculosis activity of tile plant.

Endogenous peroxynitrite activated fluorescent probe for revealing anti-tuberculosis drug induced hepatotoxicity

Py^(+)razinamide (PZA), isoniazid (INH) and rifampicin (RFP) are all commonly used anti-tuberculosis drugs in clinical practice, and long-term medication may cause severe liver damage and toxicity. The level of peroxynitrite (ONOO^(-)) generated in liver has long been regarded as a biomarker for the prediction and measurement of drug-induced liver injury (DILI). In this article, we constructed a BODIPY-based fluorescent probe (BDP-Py^(+)) that enabled quickly and sensitively detect and image ONOO^(-) in vivo. Utilizing this probe, we demonstrated the change of ONOO^(-) content in cells and mice model of DILI induced by acetaminophen (APAP), and for the first time revealed the mechanism of liver injury induced by antituberculosis drug PZA. Moreover, BDP-Py^(+) could be applied to screen out and evaluate the hepatotoxicity of different anti-tuberculosis drugs. Comparing with the existing serum enzymes detection and H&E staining, the probe could achieve early diagnosis of DILI before solid lesions in liver via monitoring the up-regulation of ONOO^(-) levels. Collectively, this work will promote the understanding of the pathogenesis of anti-tuberculosis drug induced liver injury (ATB-DILI), and provide a powerful tool for the early diagnosis and treatment of DILI.

Changes of Anti-tuberculosis Herbs Formula during Past Three Decades in Contrast to Ancient Ones

Objective:To investigate the evolution of herbal medicine in treating tuberculosis(TB)and encourage anti-TB drug discovery and development.Methods:In this study,477 ancient traditional Chinese medicine formulae were collected from the Dictionary of Traditional Chinese Medicine Prescriptions and 172 modern Chinese medicine formulae(from 1986 to 2016)were collected by searching 4 databases:Wan Fang Data Knowledge Service Platform,China National Knowledge Infrastructure Database(CNKI),China Science and Technology Journal Database(VIP)and Chinese Bio-medical Literature and Retrieval System(Sino Med)in Chinese.We restricted the search to publications in Chinese.Further data analysis was done using the Traditional Chinese Medicine Inheritance Support System version 2 Software.Results:There were 425 herbs in the 477 ancient formulae and 257 herbs in the 172 modern formulae.Half of the top 30 herbs were shared by both modern and ancient prescriptions.They are Radix Ophiopogonis,Astragalus membranaceus,Fritillaria cirrhosa,Dried rehmannia glutinosa,Poria cocos,Angelica sinensis,Prepared rehmannia glutinosa,Platycodon Root,Radix paeoniae alba,Schisandra chinensis,Bighead atractylodes rhizome,Rhizoma anemarrhenae,Cortex lycii radicis and Radix Scutellariae.Only two groups of herbs with a high correlation coefficient were found in both modern and ancient prescriptions,the Dried rehmannia glutinosa with Radix ophiopogonis,and Radix ophiopogonis with Prepared rehmannia glutinosa.There were 9 and 15 core herb combinations in modern and ancient prescriptions,respectively,but no one was found simutaniously in both modern and ancient prescriptions.Conclusions:Although there were wide variations in the herb groups and herb combinations in the formulae,half of the top 30 herbs were found in both modern and ancient prescriptions.The core herb combinations in modern and ancient prescriptions could help us to improve the priscription for treatment of TB.

Time of Liver Function Abnormal Identification on Prediction of the Risk of Anti-tuberculosis-induced Liver Injury

Background and Aims:Anti-tuberculosis(anti-TB)druginduced liver injury(AT-DILI)is the most common side effect in patients who received anti-TB therapy.AT-DILI management includes monitoring liver function until symptoms arise in patients without high-risk factors for liver damage.The present study aimed to investigate the effect of liver function test(LFT)abnormal identification on the risk of DILI,including liver failure and anti-TB drug resistance in patients without high-risk factors.Methods:A total of 399 patients without high-risk factors for liver damage at baseline and who experienced LFT abnormal during the 6 months of first-line anti-TB treatment were enrolled.The Roussel Uclaf Causal Relationship Assessment Method(RUCAM,2016)was applied in suspected DILI.The correlations between the time of LFT abnormal identification and DILI,liver failure,and anti-TB drug resistance were analyzed by smooth curve fitting and multivariable logistic regression models.Results:Among all study patients,131 met the criteria for DILI with a mean RUCAM causality score of 8.86±0.63.26/131 and 105/131 were in the probable grading and highly probable grading,respectively.The time of abnormal LFT identification was an independent predictor of DILI,liver failure,and anti-TB drug resistance in the crude model and after adjusting for other risk patient factors.The time of abnormal LFT identification was positively correlated with DILI,liver failure,and anti-TB drug resistance.The late identification group(>8 weeks)had the highest risk of DILI,followed by liver failure compared with the other two groups.Conclusions:The time to identification of LFT was positively correlated with DILI,liver failure,and anti-TB drug resistance.The risk of DILI and liver failure was significantly increased in the late identification group with abnormal LFT identified after 8 weeks compared with 4 and 8 weeks.Early monitoring of LFT is recommended for patients without the high-risk factor of DILI after anti-TB treatment is initiated.

Chemical constituents and anti-tuberculosis activity of ink extracts of cuttlefish, Sepiella inermis

Objective:To study the chemical constituents and the anti-tuberculosis activity of methanol and chloroform ink extracts of Sepiella inermis.Methods:Pulverized ink powder was extracted separately with chloroform and methanol.Chemical analysis was carried out by UV-VIS spectrophotometer,FT-IR and GC-MS.Crude extracts were tested in vitro for their activity against Mycobacterium tuberculosis using Lowenstein Jensen(L-J)medium.Activity in L-J medium was assessed by mean reduction in number of colonies on extract containing bottles as compared to extract free controls.Results:GC-MS of methanol extract revealed four compounds viz.hexadecanoic acid,9,12-octadecadienoic acid,9-octadecenoic acid and octadecanoic acid.The chloroform extract containing fourteen compounds.The methanol extract exhibited anti-tuberculosis activity in L-J medium at 64μg/mL with the observed inhibition of 14 CFU.Chloroform extract displayed a weak activity against Mycobacterium tuberculosis.Conclusions:This investigation showed the methanol extract exhibited significant activity against Mycobacterium tuberculosis than chloroform extract.Since ink of sepia is available abundantly as a waste material,further studies aimed at isolation and efficacy of active substances pave the way for new anti-tuberculosis drugs.

Effects of Yigan Capsule on the expression of HMGB1,RAGE and NF-κB protein in rats with drug-induced liver injury

Objective:To study the effect of Yigan capsule on the expression of high mobility group protein B1(HMGB1),nuclear factor-B(NF-κB)and receptor for advanced glycation end products(RAGE)in anti-tuberculosis drug-induced liver injury(ATB-DILI),and to explore its protective effect and mechanism on ATB-DILI,so as to provide experimental basis for the clinical application of Yigan capsule.Methods:Twenty-four rats were divided into two groups.Except for the blank group(n=6),the other 18 rats were given isoniazid(INH)+rifampicin(RFP)(50 mg/kg.d)for 4 weeks.Then 18 rats were randomly divided into three groups(model group,low dose group of Yigan capsule and high dose group of Yigan capsule)according to 6 rats in each group.The blank group and the model group were given 0.9%sodium chloride solution by intragastric administration.The low dose group of Yigan capsule was 0.468 g/kg,and the high dose group of Yigan capsule was 1.872 g/kg[1].After 4 weeks,the pathological changes of liver were observed by HE staining.The contents of ALT,AST,ALP,γ-GT and TBIL were detected.The expression of HMGB1,NF-κBp65 and RAGE protein was detected by IHC.The expression levels of HMGB1,NF-κBp65,RAGE,TNF-αand IL-1βwere detected by WB.Result:HE staining showed that the structure of the liver in the model group was disordered,the liver cells showed swelling and fusion,the number of inflammatory cells increased and accompanied by punctate necrosis,while the above pathological changes in each treatment group of Yigan capsule were significantly improved.The contents of ALT,AST,ALP,γ-GT and TBIL in the model group were higher than those in the blank group(P<0.05).The contents of ALT,AST,ALP,γ-GT and TBIL in each treatment group were significantly lower than those in the model group(P<0.05).Compared with the blank group,the expression levels of TNF-αand IL-1βin the model group were increased(P<0.05),and the expression levels of HMGB1,NF-κBp65 and RAGE were increased(P<0.05).Compared with the model group,the expression levels of TNF-αand IL-1βin each treatment group of Yigan capsule decreased(P<0.05),and the expression of HMGB1,NF-κBp65 and RAGE decreased(P<0.05).Conclusion:Yigan capsule may inhibit the secretion of inflammatory factors through HMGB1/RAGE/NF-κBp65 signaling pathway,thus protecting ATB-DILI.

One-stage total hip arthroplasty for advanced hip tuberculosis combined with developmental dysplasia of the hip:A case report

BACKGROUND A patient with advanced tuberculosis of the hip joint combined with Crowe type IV developmental dysplasia of the hip(DDH)and a drainage sinus is a rare condition.There are no previous reports of this condition,and it is a complex challenge for surgeons to develop a treatment scheme.CASE SUMMARY We report a 73-year-old male patient with severe hip pain and drainage sinus of the left hip for one month.Approximately 40 years ago,a drainage sinus occurred at the lateral left hip was healed at the local hospital with anti-infectious therapy.After the sinus healed,gradual pain occurred in the left hip for 40 years.Approximately one month prior,hip pain was sharply aggravated,and a drainage sinus reoccurred in the left hip.The X-ray and computed tomography examinations showed destruction of the head and neck of the left femur,as well as an acetabular deformity.The results of Mycobacterium tuberculosis antibody and Xpert were positive.Therefore,the patient was diagnosed with advanced TH combined with Crowe type IV DDH.After 22 d of treatment with anti-tuberculosis chemotherapy,the sinus healed,and the patient underwent one-stage total hip arthroplasty(THA)surgery consisting of debridement,osteotomy,and joint replacement.After surgery,the patient received anti-tuberculosis chemotherapy drugs for nine months,with no recurrent infection.After one year of follow-up,the Harris score of the patient increased from 21 pre-THA to 86.CONCLUSION Although drainage sinuses are a contraindication to one-stage THA,one-stage THA is still an effective and safe surgical method after the sinus heals.

Clinical Study on Ganbi Decoction (肝痹汤) in Treating Antituberculotic Agent-Caused Liver Injury

Objective： To study the effect and mechanism of Ganbi decoction （GBD, 肝痹汤 ） in treating patients with antituberculotic agent caused liver injury （ATB-LI）. Methods： One hundred and twenty-eight patients with ATB-LI were randomly assigned to the treated group （ n = 66） and the control group （ n = 62） with the envelop method. Meanwhile, 60 healthy persons were selected as the healthy control group. The treated group was treated by GBD one dose every day with the constituents modified depending on patients＇ symp- toms, and the control group was treated with glucuronolactone tablets and inosine injection. One week was taken as one treatment course. The changes of clinical syndromes, physical signs, T-lymphycyte sub-groups and serum level of nitric oxide （NO） were observed before and after treatment and the recovery time of liver function was recorded. The outcome was compared with that in the healthy control group. Results： In the treated group, 28 patients （42.4%） were cured, 30 （45.5%） improved and 8 （ 12.1% ） ineffectively cured, the total effective rate being 87.9% （58/66）. In the control group, 17 patients （27.4%） were cured, 24 （38.7%） improved, and21 （33.9%）ineffectively cured, the total effective rate being 66.1% （41/62）. The total effective rate in the treated group was significantly higher than that in the control group （ P〈0. 05）. Liver function was improved in both groups, recovery time in the treated group was 12.0±7.0 days, which was significantly shorter than that in the control group （16.0±8.0 days）, showing significant difference between the two groups （ P〈0.05）. The levels of CD3, CD4 and CD8 were significantly higher and level of NO significantly lower in the two groups of patients than those in the healthy control group （ P〈0. 05）, but these parameters were improved more significantly in the treated group after treatment, when compared with those before treatment or with those in the control group, all showing significant difference （P〈0.05）. Conclusion： GBD could prevent ATB-LI, and its mechanism could be by way of reducing NO production induced by endotoxin of macrophage and stimulating the proliferation of T-lymphycyte to elevate immunity.

Drug Resistance Pattern in Pulmonary Tuberculosis Patients and Risk Factors Associated with Multi-Drug Resistant Tuberculosis

Introduction: Anti-tuberculosis drug resistance is a major problem in tuberculosis (TB) control programme, particularly multi-drug resistance TB (MDR-TB) in Nepal. Drug resistance is difficult to treat due to its associated cost and side effects. The objective of this study was to assess the drug resistance pattern and assess risk factor associated with MDR-TB among pulmonary tuberculosis patients attending National Tuberculosis Center. Methodology: The comparative cross sectional study was conducted at National Tuberculosis Center during August 2015 to February 2015. Early morning sputum samples were collected from pulmonary tuberculosis suspected patients and subjected to Ziehl-Neelsen staining and fluorochrome staining and culture on Lowenstein-Jensen (LJ) medium. Drug Susceptibility test was performed on culture positive isolates by using proportion method. Univariate and multivariate analysis was computed to assess the risk factors of MDR-TB. Results: Out of 223 sputum samples, 105 were fluorochrome staining positive, 85 were ZN staining positive and 102 were culture positive. Out of 102 culture positive isolates, 37.2% were resistance to any four anti-TB drugs. 11 (28.9%) were initial drug resistance and 28 (43.7%) were acquired drug resistance. The overall prevalence of MDR-TB was 11.7%, of which 2 (5.3%) were initial MDR-TB and 10 (15.6%) were acquired MDR-TB. Univariate and multivariate analysis showed female were significantly associated (P = 0.05) with MDR-TB. Conclusion: Drug resistance TB particularly MDR-TB is high. The most common resistance pattern observed in this study was resistance to both isoniazid and rifampicin. Female were found to be associated with MDR-TB. Thus, early diagnosis of TB and provision of culture and DST are crucial in order to combat the threat of DR-TB.

Solitary splenic tuberculosis:A case report

BACKGROUND Solitary splenic tuberculosis(TB) is unusual and rarely reported.Whether splenic TB is best treated surgically is still controversial.We describe a 73-year-old man with solitary splenic TB and no extrapulmonary TB.CASE SUMMARY We report the case of a 73-year-old man with solitary splenic TB who complained of emaciation and fatigue.Abdominal computed tomography(CT) images suggested a splenic space-occupying lesion.We then performed a CT-guided splenic biopsy.The postoperative pathological examination revealed splenic TB.The patient took quadruple anti-TB medication.After 1 year,the patient recovered his normal weight and had no feeling of fatigue,and the splenic lesion had shrunk significantly.CONCLUSION If patients receive combined,appropriate,regular,full-time anti-TB treatment,solitary splenic TB may be cured.

Supercritical carbon dioxide extraction of Triognella foenum graecum Linn seeds:Determination of bioactive compounds and pharmacological analysis

Objective: To investigate the effect of temperature and pressure on supercritical CO_2 extraction of Triognella foenum graecum Linn seeds, to determine the optimal condition which leads to highest percentage of the accumulative yield and revealing the chemical composition of supercritical CO_2 extract.Methods: Temperatures in the range of 40–60C and pressures in the range of 10–25 MPa were used. FTIR and GC–MS analysis were used to detect the bioactive compounds present in the extract. The broth dilution method and slope method were used to evaluate the anti-microbial and anti-tuberculosis activities and the in vitro anti-malarial assay was carried out according to the micro assay protocol of Rieckmann and his coworkers.Results: The temperature was more affected than the pressure on the extraction performance and the highest yield of the extract(3.111%) was attained at 60C and 10 MPa.FTIR and GC–MS showed that the chemical composition of the extract included conjugated linoleic acid methyl ester as the major active principle(with concentration of72.28%), followed by saturated fatty acid methyl esters(16.03%), steroids(8.09%) and organic siloxane compound(3.61%). The extract showed moderate anti-bacterial activity with MIC values 100, 250, 125 mg/m L towards Escherichia coli, Staphylococcus aureus and Streptococcus pyogenus respectively. It exhibited high inhibition effect towards the fungi Candida albican with MFC value(250 mg/m L). The extract had low antituberculosis activity with MIC value(100 mg/m L) and comparable MIC value(0.29 mg/m L) towards Plasmodium flaciparum.Conclusions: Supercritical CO_2 extraction as alternate and green technology is performed successfully to extract the bioactive compounds from the seeds of T. foenum graecum Linn and it is concluded that this extract can be used as an alternate source of synthetic anti-biotic drugs.