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.

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.

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.

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.

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.

Research progress on the drug action and resistance mechanism in Mycobacterium tuberculosis

Tuberculosis(TB)is a chronic infectious disease caused by Mycobacterium Tuberculosis(MTB).It is the second largest single cause of death besides novel coronavirus pneumonia.Along with the abuse of antibiotics and extensive use of anti-tuberculosis drugs,multidrug-resistant(MDR)TB,drug-resistant(XDR)TB and totally drug-resistant(TDR)TB became obstacles to the tuberculosis eradication worldwide.According to the World Health Organization(WHO)statistics,China is not only a high burden tuberculosis country in the world,but also a country with a serious epidemic of MDR.Traditional drugs fail to meet the needs of tuberculosis control.Therefore,it is urgent to find new targets of anti-tuberculosis drugs and develop new anti-tuberculosis drugs.Hence,this paper systematically summarizes the mechanism of traditional and newly developed anti-tuberculosis drugs,in which stressing the research progress of drug resistance mechanisms.This work provides us with new insights of new anti-tuberculosis drug developments,and may contribute to a reduction in the harm that tuberculosis brings to society.

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.

Unilateral adrenal tuberculosis whose computed tomography imaging characteristics mimic a malignant tumor:A case report

BACKGROUND Adrenal tuberculosis usually presents with bilateral involvement.It has special characteristics in computed tomography(CT)images,such as small size,low attenuation in the center,and peripheral rim enhancement,which differ from those of primary tumors.CASE SUMMARY A 42-year-old female presented to the hospital with low back pain.She had been diagnosed with hypertension as well as pulmonary and cerebral tuberculosis but denied having any fever,fatigue,anorexia,night sweats,cough,or weight loss.Abdominal CT revealed an irregular 6.0 cm×4.5 cm mass with uneven density in the right adrenal gland,while the left adrenal gland was normal.No abnormalities were observed in plasma total cortisol(8 am),adrenocorticotropic hormone,aldosterone/renin ratio,blood catecholamines,or urine catecholamines.A fineneedle aspiration biopsy of the right adrenal gland provided evidence of tuberculosis.After three years of anti-tuberculosis treatments,the large mass in the right adrenal gland was reduced to a slight enlargement.CONCLUSION This is a case of unilateral adrenal tuberculosis with CT imaging characteristics mimicking those of a malignant tumor.Extended anti-tuberculosis therapy is recommended in such cases.

Clinical Response to Treatment of Central Nervous System Tuberculosis in Non-Human Immunodeficiency Virus-Infected Adolescents and Adults

Introduction: More than half of patients with central nervous system tuberculosis (CNS TB) die or are left with severe neurological deficits despite receiving anti-TB treatment. Aims of the study: This study examined risk factors associated with poor response to initial treatment with four anti-TB drug regimens or three drug regimens with steroids as adjuvant therapy. Methods: This study analyzed medical records from two tertiary hospitals in Busan, Korea, between January 2009 and March 2012. The subjects were non-human immunodeficiency virus (HIV)-infected patients aged ≥16 years with clinical CNS TB. The subjects were divided into two groups according to response to treatment. Results: In totally, 52 patients with CNS TB were included. Of these, 14 (26%) and 38 (73%) showed poor and good responses, respectively. Of the patients with poor response, nine had stage III disease (64.3%) according to the British Medical Research Council (BMRC) staging system. A significantly higher proportion was seen in the good response group (p < 0.05). Patients with positive cerebrospinal fluid (CSF) acid-fast bacillus (AFB) culture, positive sputum AFB culture, positive CSF TB polymerase chain reaction (PCR) results, and brain tuberculoma had poorer responses (p < 0.05). Multivariate analysis to determine risk factors associated with poor response to anti-TB therapy revealed that a poor response was associated with stage III clinical signs upon diagnosis (odds ratio [OR] 32.122;95% confidence interval [CI] 2.221 - 464.605), positive sputum AFB culture (OR 13.624;95% CI 1.066 - 174.149), and tuberculoma on brain images (OR 45.714;95% CI 1.893 - 1104.018). Conclusions: The results demonstrate the importance of identifying the severity of CNS TB and promptly administering anti-TB drugs. It is necessary to perform drug susceptibility testing for anti-TB drugs. Further studies are needed to confirm the correlations between risk factors associated with poor response and anti-TB drug resistance and the other risk factors.

Isoniazid metabolism and hepatotoxicity

Isoniazid(INH) is highly effective for the management of tuberculosis.However,it can cause liver injury and even liver failure.INH metabolism has been thought to be associated with INH-induced liver injury.This review summarized the metabolic pathways of INH and discussed their associations with INH-induced liver injury.