Background: World Health Organization recommends the implementation of contact tracing and Leprosy Post Exposure prophylaxis (LPEP) to interrupt the chain of transmission. To accelerate the uptake of this recommendati...Background: World Health Organization recommends the implementation of contact tracing and Leprosy Post Exposure prophylaxis (LPEP) to interrupt the chain of transmission. To accelerate the uptake of this recommendation, a cross-sectional study among contacts of leprosy patients was conducted to investigate the feasibility of integrating leprosy systematic contact tracing and post-exposure prophylaxis (PEP) into the routine leprosy control program. Methods: This was a mixed methods cross-sectional study. The study was implemented in Kumi, Ngora, Serere, Soroti, Budaka and Kibuku Districts. Results: The 45 enrolled index patients (97.8% of the registered) identified a total of 135 contacts, of which 134 (99·2%) consented and were screened. Among them, one new leprosy patient was identified and started on treatment with multidrug therapy (MDT). All the eligible contacts, received the prophylactic treatment with Single Dose Rifampicin (SDR). Overall, SDR was administered to 133(98.5% of the listed contacts) with no adverse event reported. Factors associated with successful contact investigation and management included: Involvement of index patients, health care workers during the contact screening and SDR A administration, counselling of the index patients and contacts by the health care works, LPEP being administered as Directly observed Therapy (DOT) among others. Results Interpretation: The integration of leprosy post-exposure prophylaxis with administration of SDR and contact tracing is feasible, generally accepted by the patient, their contacts and health workers and can be integrated into the National Leprosy control programmes with minimal additional efforts once contact tracing has been established. Therefore, we recommend integration of administration of SDR in to the routine leprosy control program.展开更多
Rifampicin-resistant tuberculosis (RR-TB) is a global public health problem caused by mycobacterium tuberculosis resistant to Rifampicin. Drug-induced peripheral neuropathy and neurotoxicity are well-known adverse eff...Rifampicin-resistant tuberculosis (RR-TB) is a global public health problem caused by mycobacterium tuberculosis resistant to Rifampicin. Drug-induced peripheral neuropathy and neurotoxicity are well-known adverse effects of treatment regimens that cause significant morbidity. Pyridoxine is often added to treatment regimens for the prevention and/or treatment of these side effects. The basis and effectiveness of this practice are unclear. We conducted a systematic review to evaluate the effectiveness of pyridoxine in preventing and/or treating neuropathy and neurotoxicity associated with RR-TB treatment. We included studies with patients with RR-TB who experienced neuropathy or neurotoxicity attributed to RR-TB regimens and were given pyridoxine. Our findings showed contradicting evidence on the use of pyridoxine for preventing or treating neurotoxicity due to cycloserine in the treatment of RR-TB. Moreover, pyridoxine did not have a protective effect against neuropathy and/or neurotoxicity caused by other RR-TB regimens that do not contain isoniazid. In conclusion, we found that withdrawing or withholding medications such as linezolid, cycloserine, thioamides, fluoroquinolones, and ethambutol, implicated in causing neuropathy or neurotoxicity was more effective than using pyridoxine to stop the progression of symptoms, and in some instances, led to their reversal over time.展开更多
A number of HPLC methods have been approved for the determination of rifampicin, but no references involved the assay of related substances of rifampicin. In the present paper, a reversed-phase liquid chromatographic ...A number of HPLC methods have been approved for the determination of rifampicin, but no references involved the assay of related substances of rifampicin. In the present paper, a reversed-phase liquid chromatographic method for the determination of related substances of rifampicin is developed and validated. Rifampicin and its related substances, including rifamycin SV, rifampicin N-oxide and 3-formylrifamycin SV were separated using a Zorbax Eclipse C8, 250×4.6 mm(i.d), 5 μm column by isocratic elution at a flow rate of 1 mL·min -1. The detector was set at 254 nm. The mobile phase is a mixture of methanol-acetonitrile -0.075 mol·L -1 monopotassium phosphate -1.0 mol·L -1 citric acid (31:31:35:3, v/v). The method validation included accuracy, precision, linearity, sensitivity and stability. All results are shown to be acceptable.展开更多
AIM： To evaluate the hepatoprotective effect of garlic on liver injury induced by isoniazid （INH） and rifarnpicin （RIF）. METHODS： Wistar rats weighing 150-200 g were treated orally with 50 mg/kg of INH and RIF d...AIM： To evaluate the hepatoprotective effect of garlic on liver injury induced by isoniazid （INH） and rifarnpicin （RIF）. METHODS： Wistar rats weighing 150-200 g were treated orally with 50 mg/kg of INH and RIF daily each for 28 d. For hepatoprotective studies, 0.25 g/kg per day of freshly prepared garlic hornogenate was administered orally half an hour before the INH＋RIF doses. Serum alanine arninotransferase （AIT）, aspartate aminotransferase （AST） and bilirubin were estimated on d 0, 14, 21, and 28 in all the rats. Histological analysis was carried out to assess the injury to the liver. Lipid peroxidation （1PO） as a marker of oxidative stress and non-protein thiols （glutathione） for antioxidant levels were measured in liver hornogenate. RESULTS： The treatment of rats with INH＋RIF （50 mg/kg per day each） induced hepatotoxicity in all the treated animals as judged by elevated serum ALT, AST, and bilirubin levels, presence of focal hepatocytic necrosis （6/8） and portal triaditis （8/8）. Garlic simultaneously administered at a dose of 0.25 g/kg per day prevented the induction of histopathological injuries in INH＋RIF co-treated animals, except in 4 animals, which showed only moderate portal triaditis. The histological changes correlated with oxidative stress in INH＋RIF treated animals. The group which received 0.25 g/kg per day garlic hornogenate along with INH＋RIF showed higher levels of glutathione （P〈0.05） and low levels of 1PO （P〈 0.05） as compared to INH＋RIF treated group. CONCLUSION： Freshly prepared garlic homogenate protects against INH＋RIF-induced liver injury in experimental animal model.展开更多
AIM To explore the protective effects and mechanisms of naringenin(NRG) on hepatic injury induced by isoniazid(INH) and rifampicin(RIF).METHODS Male mice were randomly divided into four groups and treated for 14 d as ...AIM To explore the protective effects and mechanisms of naringenin(NRG) on hepatic injury induced by isoniazid(INH) and rifampicin(RIF).METHODS Male mice were randomly divided into four groups and treated for 14 d as follows: normal control group was administered intragastrically with normal saline solution alone; model group was administered intragastrically with INH(100 mg/kg) and RIF(100 mg/kg); lowand high-dosage NRG pretreatment groups were administered intragastrically with different doses of NRG(50 or 100 mg/kg) 2 h before INH and RIF challenge. Mice were killed 16 h after the last dose of drug treatment to determine activity of serum transaminases. Oxidative stress was evaluated by measuring hepatic glutathione(GSH) and superoxide dismutase(SOD) and malondialdehyde(MDA) levels. Histopathological changes in hepatic tissue were observed under the optical microscope. Hepatocyte apoptosis was measured by TUNEL assay and caspase-3 activation. Expression of Bcl-2 and Bax in liver was determined by western blot.RESULTS Both low- and high-dosage NRG pretreatment obviously alleviated serum levels of alanine aminotransferase and aspartate aminotransferase, liver index, hepatic MDA content, and increased hepatic GSH content and SOD activity compared with the INH and RIF-treated group(44.71 ± 8.15 U/L, 38.22 ± 6.64 U/L vs 58.15 ± 10.54 U/L; 98.36 ± 14.78 U/L, 92.41 ± 13.59 U/L vs 133.05 ± 19.36 U/L; 5.34% ± 0.26%, 4.93% ± 0.25% vs 5.71% ± 0.28%; 2.76 ± 0.67 nmol/mgprot, 2.64 ± 0.64 nmol/mgprot vs 4.49 ± 1.12 nmol/mgprot; 5.91 ± 1.31 mg/gprot, 6.42 ± 1.42 mg/gprot vs 3.11 ± 0.73 mg/gprot; 137.31 ± 24.62 U/mgprot, 148.83 ± 26.75 U/mgprot vs 102.34 ± 19.22 U/mgprot; all P < 0.01 or 0.05). Histopathological evaluation showed obvious necrosis and inflammatory cell infiltration in liver of mice administered INH and RIF; however, mice pretreated with NRG showed minor hepatic injury. In addition, INH and RIF resulted in hepatocyte apoptosis, and NRG pretreatment dramatically suppressed INHand RIF-induced hepatocytes apoptosis. Furthermore, NRG-mediated anti-apoptotic effects seemed to be in connection with its regulation of Bax and Bcl-2 protein expression in hepatic tissue.CONCLUSION NRG might attenuate INH- and RIF-induced hepatic injury via suppression of oxidative stress and hepatocyte apoptosis.展开更多
Objective:To evaluate luciferase reporter phage(LRP)phAE85 in rapid detection of rifampicin resistance in a region where TB is endemic.Methods:One hundred and ninety primary isolates on Lowenstein-Jensen medium were t...Objective:To evaluate luciferase reporter phage(LRP)phAE85 in rapid detection of rifampicin resistance in a region where TB is endemic.Methods:One hundred and ninety primary isolates on Lowenstein-Jensen medium were tested.Middlebrook 7H9 complete medium with and without rifampicin at 2μg/mL was inoculated with standard inoculum from suspensions of the clinical isolate.After incubation for 72 h,LRP was added.Following 4 h of further incubation,light output from both control and test was measured as relative light units.Strains exhibiting a reduction of less than 50%relative light units in the drug containing vial compared to control were classified as resistant.Results were compared with the conventional minimum inhibitory concentration method(MIC)of drug susceptibility testing.Results:The two methods showed high level of agreement of 97%(CI 0.94,0.99)and P value was 0.000 1.The sensitivity and specificity of LRP assay for detection of rifampicin resistance were 91%h(CI 0.75,0.98)and 99ct(CI0.95,1.00)respectively.Time to detection of resistance by LRP assay was 3 d in comparison with 28 d by the minimum inhibitory concentration method.Conclusions:LRP assay with phAE85 is 99%specific,91%sensitive and is highly reproducible.Thus the assay offers a simple procedure for drug sensitivity testing,within die scope of semi-automation.展开更多
BACKGROUND： Rifampicin inhibits the formation of a-synuclein multimer and protects against 1-methyl-4-phenyl-1,2, 3, 6-tetrahydropyritine （MPTP）-induced PC12 cell apoptosis. OBJECTIVE： To compare the effect of rif...BACKGROUND： Rifampicin inhibits the formation of a-synuclein multimer and protects against 1-methyl-4-phenyl-1,2, 3, 6-tetrahydropyritine （MPTP）-induced PC12 cell apoptosis. OBJECTIVE： To compare the effect of rifampicin pre- and post-treatment on tyrosine hydroxylase and α-synuclein expression in substantia nigra pars compacta in a rat model of Parkinson＇s disease. DESIGN, TIME AND SE＇B＇ING： A randomized, controlled experiment was performed at the Experimental Animal Center of Sun Yat-sen University North Campus （China） from November 2006 to October 2008. MATERIALS： Rifampicin was purchased from MD, USA; rotenone was purchased from Sigma, USA; mouse anti-rat α-synuclein monoclonal antibody was purchased from B＆D, USA; and rabbit anti-rat tyrosine hydroxylase monoclonal antibody was purchased from Chemicon, USA. METHODS： A total of 72 male, Sprague Dawley rats, aged 8 weeks, were randomly assigned to 5 groups： blank control （n = 12）, rifampicin （n = 12）, rotenone （n = 16）, rifampicin pre-treatment （n = 16）, and rifampicin post-treatment （n = 16）. Parkinson＇s disease model rats were established via a subcutaneous injection of rotenone （1.5 mg/kg per day） in the three treatment groups, once a day for 3 successive weeks. Rifampicin （30 mg/kg per day） was intragastrically administered in the rifampicin pre-treatment group 3 days prior to rotenone induction and in the rifampicin post-treatment group 7 days after rotenone induction. Rats were treated with a subcutaneous injection of 1 mL/kg per day sunflower oil in the blank control group and an intragastric injection of 30 mg/kg per day rifampicin in the rifampicin group, once a day for 3 successive weeks in total. MAIN OUTCOME MEASURES： Prior to treatment and in the end of the 3^rd week after treatment, the rats were evaluated using the modified neurological severity score. The substantia nigra from the rats was extracted for hematoxylin-eosin staining. Western blot analysis was performed to determine tyrosine hydroxylase and α-synuclein expression. RESULTS： Hematoxylin-eosin staining revealed a significant reduction in the number of substantia nigral neurons in the rotenone group, in addition to neurodegradation, hypopigmentation, and pyknosis. In the rifampicin pre-treatment and post-treatment groups, the number of dopaminergic neurons was significantly increased compared with the rotenone group （P 〈 0.01）, with slight neuronal damage. Compared with the rotenone group, substantia nigral tyrosine hydroxylase expression was significantly increased in the rifampicin pre-treatment and post-treatment groups （P 〈 0.01）, but α-synuclein expression and modified neurological severity scores were significantly decreased （P 〈 0.01）. In addition, the effect of rifampicin in the pre-treatment group was superior to the post-treatment group. There was no significant difference in tyrosine hydroxylase and α-synuclein expression, or in the modified neurological severity scores, between the blank control and rifampicin groups （P 〉 0.05）. CONCLUSION： Rifampicin significantly attenuated neuropathological and behavioral motor deficits induced by rotenone. Moreover, rifampicin enhanced tyrosine hydroxylase expression, but inhibited α-synuclein expression. The effect of rifampicin pre-treatment was superior to rifampicin post-treatment.展开更多
The prognosis of patients with previously treated tuberculosis (TB) was suggested to be dependent on whether the initial treatment was in compliance with the established guidelines. The aim of this retrospective multi...The prognosis of patients with previously treated tuberculosis (TB) was suggested to be dependent on whether the initial treatment was in compliance with the established guidelines. The aim of this retrospective multicenter study was to determine the proportion of new TB patients who received standard doses of rifampicin in multiple provinces of China, and the relationship between low doses of rifampicin and frequency of rifampicin-resistance as well as treatment outcomes. A total of 713 new TB patients were treated with either once-daily dose of bulk anti-TB drugs (group I) or every other day combination blister packs of anti-TB drugs containing rifampicin (group II) at more than 30 TB treatment centers/hospitals in China. Treatment history, therapeutic doses of rifampicin, and information about patients were extracted from their medical records and analyzed, and rifampicin-resistance of isolates collected from patients following the treatment as well as treatment outcomes were compared between two treatment groups. Among 522 patients in treatment group I, 154 (29.5%) received standard and 363 (69.5%) received low doses of rifampicin;238 (45.6%) isolates were rifampicin-resistant, and 243 (46.6%) were successfully treated. Among 191 patients in treatment group II, 175 (91.6%) received standard and 15 (7.9%) received low doses of rifampicin;72 (37.7%) isolates were rifampicin-resistant, and 105 (55%) were successfully treated. When patients who received low doses of rifampicin were compared to others within the same treatment group, increased rates for rifampicin-resistance and treatment failure were observed. Results from this study showed that most new TB patients in treatment group I (69.5%) received low doses of rifampicin, and their treatment outcomes were worse than those in treatment group II, indicating that low doses of rifampicin used for the initial treatment of new TB patients were correlated to increased frequency of rifampicin-resistance and poorer treatment outcomes.展开更多
BACKGROUND： Previous studies have shown that rifampicin exhibits neuroprotective effects, but the precise mechanisms remain unclear. Rifampicin is thought to exert the neuroprotective effect as a hydroxyl free radica...BACKGROUND： Previous studies have shown that rifampicin exhibits neuroprotective effects, but the precise mechanisms remain unclear. Rifampicin is thought to exert the neuroprotective effect as a hydroxyl free radical scavenger. OBJECTIVE： To investigate the protective effects of rifampicin pretreatment on rotenone-induced mitochondrial oxidative stress in differentiated PC12 cells.DESIGN, TIME AND SETrlNG： A repeated measure, cell-based study was performed at the Department of Neurology, Second Affiliated Hospital, Sun Yat-sen University, China between December 2007 and November 2008. MATERIALS： PC12 cells were a kind gift from the Physiology Laboratory of Zhongshan Medical School, Sun Yat-sen University, China. Rotenone and rifampicin were purchased from Sigma, USA. METHODS： PC12 cells were differentiated by culturing with 100 ng/mL 7S nerve growth factor for 9 days in Dulbecco＇s modified Eagle＇s medium/Nutrient Mix F12 （DMEM/F12） supplemented with 10% fetal bovine serum. The cells were assigned to six groups according to various treatment conditions： control, cultured with normal media; rifampicin group, treated with 300 pmol/L rotenone for 26 hours; rotenone group, treated with 2.5 pmol/L rotenone for 24 hours; rifampicin pretreatment groups, pretreated with 100, 200, and 300 pmol/L rifampicin for 2 hours, respectively, followed by 2.5 μmol/L rotenone for 24 hours.MAIN OUTCOME MEASURES： Mitochondrial membrane potential was measured by fluorescence microscopy and flow cytometry, respectively, using rhodamine123 staining. Intracellular reactive oxygen species formation was analyzed by flow cytometry using 2＇, 7＇-dichlorofluorescin-diacetate staining, and intracellular reduced glutathione was measured with a microplate reader. Cell viability was determined by 3-（4, 5-dimethylthiazol-2-yl）-2, 5-diphenyltetrazolium bromide assay. Cell apoptosis was detected by Hoechst 33342 staining and flow cytometry. RESULTS： Increased apoptosis in rotenone-induced, differentiated, PC12 cells was accompanied by the loss of mitochondrial transmembrane potential, the formation of reactive oxygen species, and reduced glutathione depletion （P 〈 0.01）. Rotenone-induced mitochondrial dysfunction was blocked in a dose-dependent manner by rifampicin （P 〈 0.05 or P 〈 0.01）, CONCLUSION： Pretreatment of differentiated PC12 cells with rifampicin blocked rotenone-induced apoptosis by ameliorating mitochondrial dysfunction and oxidative stress.展开更多
AIM, To study the role of N-acetylcysteine （NAC） as a protective agent in rifampicin （RMP）-induced oxidative hepatic injury of young rats. METHODS： Hepatic injury was produced by giving 50mg/kg body weight/day of...AIM, To study the role of N-acetylcysteine （NAC） as a protective agent in rifampicin （RMP）-induced oxidative hepatic injury of young rats. METHODS： Hepatic injury was produced by giving 50mg/kg body weight/day of RMP for 3 wk. A dose of NAC （100mg/kg body weight/day） was given in combination with RMP intraperitoneally. Analysis of lipid peroxidation, thiol levels, cytochrome P4se, superoxide dismutase （SOD）, catalase, glutathione peroxidase, reductase and transferase were estimated in liver along with the body weight, liver weight and histological observations. RESULTS： RMP exposure resulted in no change in body and liver weight while antioxidative enzymes were altered but the non protein thiol （GSH） status was well preserved. Cytochrome P450 system and peroxidation of lipids were induced by RMP exposure. Partial protection was observed with NAC against RMP-induced changes in liver, which was evidenced from the prevention of increase in lipid peroxidation and the reduction in SOD and catalase enzyme levels. CONCLUSION. NAC protects young rats against RMP- induced oxidative hepatic injury.展开更多
AIM： To investigate overlapping regions of the rpoB gene previously involved with rifamycin resistance in M. tuberculosis and seek correlation between rpoB mutations in dinical MAP strains with susceptibility to RIF ...AIM： To investigate overlapping regions of the rpoB gene previously involved with rifamycin resistance in M. tuberculosis and seek correlation between rpoB mutations in dinical MAP strains with susceptibility to RIF and RFB. METHODS： We designed a molecular-based PCR method for the evaluation of rifabutin （RFB） and rifampicin （RIF） resistance based on probable determinant regions within the rpoB gene of MAP, including the 81 bp variable site located between nucleotides 1363 and 1443. The minimum inhibitory concentration （MIC） for RIF was also determined against 11 MAP isolates in attempt to seek correlation with rpoB sequences. RESULTS： We determined that MAP strain 18 had an MIC of 〉 30 mg/L and ≤ 5 mg/L for RIF and RFB respectively, and a significant and novel rpoB mutation C1367T, compared to an MIC of ≤ 1.0 mg/L for both drugs in the wild type MAP. The 30-fold increase in the MIC was a direct result of the rpoB mutation C1367T, which caused an amino acid change Thr456 to Ile456 in the drug＇s binding site. In addition, MAP strain 185 contained five silent rpoB mutations and exhibited an MIC comparable to the wild-type. Moreover, our in vitro selected mutation in MAP strain UCF5 resulted in the generation of a new resistant strain （UCF5-RIF16r） that possessed T1442C rpoB mutation and an MIC 〉 30 mg/L and 〉 10 mg/L for RIF and RFB respectively. Sequencing of the entire rpoB gene in MAP strains UCF4, 18, and UCF5-RIF16r revealed an rpoB mutation A2284C further downstream of the 81 bp variable region in UCF4, accounting for observed slight increase in MIC. In addition, no other significant mutations were found in strains 18 and UCF-RIF16r. CONCLUSION： The data clearly illustrates that clinical and in vitro-selected MAP mutants with rpoB mutations result in resistance to RIF and RFB, and that a single amino acid change in the beta subunit may have a significant impact on RIF resistance. Unconventional drug susceptibility testing such as our molecular approach will be beneficial for evaluation of antibiotic effectiveness. This molecular approach may also serve as a model for other drugs used for treatment of MAP infections.展开更多
AIM: To evaluate and compare the hepatoprotective and immunomodulatory effects of Curcuma longa (CL), Ocimum sanctum (OS), Tinospora cordifolia (TC) and Zizyphus mauritiana (ZM) on liver injury and immunosuppression i...AIM: To evaluate and compare the hepatoprotective and immunomodulatory effects of Curcuma longa (CL), Ocimum sanctum (OS), Tinospora cordifolia (TC) and Zizyphus mauritiana (ZM) on liver injury and immunosuppression induced by Isoniazid (INH), Rifampicin (RIF) and Pyrazinamide (PZA). METHODS: Duncan Hartley guinea pigs, weighing 700-1050 g, were treated orally with 50 mg/kg of INH, 100 mg/kg of RIF and 300 mg/Kg of PZA for 21-d. 200 mg/kg (bw) of each herb crude extract was administered to the herb control group and 2-h previous to INH + RIF + PZA (AKT) doses to the Herb + AKT groups. Serum alanine aminotransferase (ALT), aspertate aminotransferase (AST) bilirubin and Alkaline Phosphatase (ALP) were assessed on d 0 and 21 in all the groups. Phagocytic % (P%), Phagocytic Index (PI) and Chemotactic Index (CI) were also measured as immunologic parameters. Histological analysis was carried out to assess injury to the liver. RESULTS: The AKT treated control group showed hepatotoxicity as judged by elevated serum AST 5-fold, AST/ALT ratio 4-fold, ALP 2-fold and hepatological changes, such as focal necrosis, portal triaditis and steatosis. Immune function was suppressed as judged by decreased P% (51.67 ?1.68 vs 40.61 ?1.28, P < 0.01), PI (2.0725±0.05 vs 0.61±0.05, P < 0.001) and CI (1.8525±0.04 vs 0.695±0.07, P < 0.001). All four herb treated groups showed normal liver histology, enzyme levels and increased P%, while PI and CI were enhanced in the TC and ZM treated groups, respectively. CL + AKT, TC + AKT and ZM + AKT showed nearly normal histology with minimal inflammation and microvesicular steatosis, while OS + AKT showed partial protection. Hepatotoxicity was prevented by restricting the rise of AST by 2-fold in CL + AKT and TC + AKT groups and by 3-fold in OS + AKT and ZM + AKT groups, AST/ALT by 2-fold and ALP to normal levels in all four groups. All four herb + AKT groups showed normal to enhanced neutrophil function. CONCLUSION: All four herbs showed hepatoprotective potential and prevented immunosuppression. CL and TC showed the highest hepatoprotective activity, while TC and ZM showed strong immunostimulatory activity.展开更多
The aim of the present work is to develop rifampicin loaded phospholipid lipospheres containing sulfphobutyl etherβ-cyclodextrin and Vitamin C for inhalation to test their potential for deep lung delivery.The finding...The aim of the present work is to develop rifampicin loaded phospholipid lipospheres containing sulfphobutyl etherβ-cyclodextrin and Vitamin C for inhalation to test their potential for deep lung delivery.The findings of the solid state characterization revealed the amorphous nature of the lipospheres.These exhibited a better flowability,an aerodynamic diameter in the range of 1.76 to 3.99μm.Moreover,the fine particle fraction and emitted dose was found in the range of 68.84–83.73% and 80–93%,respectively.Moreover,lipospheres exhibited enhanced/equivalent efficacy in vitro in H37Rv strain.Hence,the results show the potential of lipospheres for pulmonary delivery of rifampicin.展开更多
BACKGROUND The drug interaction between warfarin and rifampicin is widely known,but there are still some difficulties in managing the combination of the two drugs.CASE SUMMARY A patient with brucellosis received stric...BACKGROUND The drug interaction between warfarin and rifampicin is widely known,but there are still some difficulties in managing the combination of the two drugs.CASE SUMMARY A patient with brucellosis received strict monitoring from a Chinese pharmacist team during combination of warfarin and rifampicin.The dose of warfarin was increased to 350%in 3 mo before reaching the lower international normalized ratio treatment window.No obvious adverse reaction occurred during the drugadjustment period.This is the first case report of long-term combined use of rifampicin and warfarin in patients with brucellosis and valve replacement in China based on the Chinese lower warfarin dose and international normalized ratio range.CONCLUSION Anticoagulation for valve replacement in Chinese patients differs from that in other races.Establishment of a pharmacist clinic provides vital assistance in warfarin dose adjustment.展开更多
<b><span style="font-family:Verdana;">Objective:</span></b><span style="font-family:Verdana;"> To investigate the clinical effect of rifapentine and rifampicin in the ...<b><span style="font-family:Verdana;">Objective:</span></b><span style="font-family:Verdana;"> To investigate the clinical effect of rifapentine and rifampicin in the treatment of pulmonary tuberculosis.</span><b> </b><span style="font-family:Verdana;"><b></b></span><b><b><span style="font-family:Verdana;">Methods:</span></b><span style="font-family:Verdana;"></span></b><b> </b><span style="font-family:Verdana;">Seventy-two cases of patients with initial treatment of pulmonary tuberculosis who attended the First Hos</span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">pital Affiliated to Hebei North </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">University</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> from February 2017 to August 2019 we</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">re </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">selected. They were randomly divided into observation group and control gro</span></span></span><span><span><span style="font-family:;" "=""><span style="font-family:Verdana;">up, with 36 cases in each group. The observation group was treated with isoniazid + rifapentine + ethambutol, while the control group was treated with isoniazid + rifampicin + ethambutol. The symptom relief, image absorption and adverse reactions were compared between the two groups. <b></b></span><b><b><span style="font-family:Verdana;">Results:</span></b><span style="font-family:Verdana;"></span></b><span style="font-family:Verdana;"> The rate of symp</span></span></span></span><span><span><span style="font-family:;" "=""><span style="font-family:Verdana;">tom relief was 86.11% in the observation group and 94.44% in the control</span><span><span style="font-family:Verdana;"> group, P < 0.05, which was statistically significant. Rifampin was more helpful than rifapentine in relieving clinical symptoms</span><span style="font-family:Verdana;">. The lesion absorption rate was 77.79% in the observation group and 88.89% in the control group, P < 0.05, and the difference was statistically significant. Rifampin was more beneficial to the absorption of TB lesions than rifapentine. The incidence of adverse reactions in the observation group was 16.67% much lower than that in the control group, which was 38.89%, indicating that the adverse reactions of rifapentine were less. <b></b></span><b><b><span style="font-family:Verdana;">Conclusion:</span></b><span style="font-family:Verdana;"></span></b></span><b> </b><span style="font-family:Verdana;">Rifampicin is superior to rifapentine in clinical symptom relief and lesion absorption, but the incidence of adverse reactions is high.</span></span></span></span>展开更多
Vaccinations for coronavirus disease-2019(COVID-19)have begun more than a year before,yet without specific treatments available.Rifampicin,critically important for human medicine(World Health Organization’s list of e...Vaccinations for coronavirus disease-2019(COVID-19)have begun more than a year before,yet without specific treatments available.Rifampicin,critically important for human medicine(World Health Organization’s list of essential medicines),may prove pharmacologically effective for treatment and chemoprophylaxis of healthcare personnel and those at higher risk.It has been known since 1969 that rifampicin has a direct selective antiviral effect on viruses which have their own RNA polymerase(severe acute respiratory syndrome coronavirus 2),like the main mechanism of action of remdesivir.This involves inhibition of late viral protein synthesis,the virion assembly,and the viral polymerase itself.This antiviral effect is dependent on the administration route,with local application resulting in higher drug concentrations at the site of viral replication.This would suggest also trying lung administration of rifampicin by nebulization to increase the drug’s concentration at infection sites while minimizing systemic side effects.Recent in silico studies with a computer-aided approach,found rifampicin among the most promising existing drugs that could be repurposed for the treatment of COVID-19.展开更多
Background: To explore the hepatoprotective effect of Yigan mingmu oral liquid (YGMM) on isoniazid-rifampicin induced liver injury in rats. Methods: Total 38 SD rats were randomly divided into 6 groups including contr...Background: To explore the hepatoprotective effect of Yigan mingmu oral liquid (YGMM) on isoniazid-rifampicin induced liver injury in rats. Methods: Total 38 SD rats were randomly divided into 6 groups including control group, model group, silymarin positive control group, and three YGMM treatment groups. Model group was administered intragastrically with INH (100 mg/kg) and RIF (100 mg/kg) for 14 days. Silymarin group and YGMM treatment groups were administered intragastrically with silymarin (100 mg/kg) and different doses of YGMM (1, 2.5, 5 mg/kg) 2 hours before INH and RIF administration from day 4 to day 14.?Results: Rats were sacrificed 16 hours after the last day treatment to determine the activities of serum alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP), as well as total bilirubin (TB) content. Oxidative stress was evaluated by measuring total superoxide dismutase (T-SOD) and malondialdehyde (MDA) levels. Histopathological changes in liver tissues were observed under an optical microscope by using hematoxylin and eosin staining. The mice?in model groups showed significantly (p < 0.05) increased levels in AST, ALT, ALP, TB and MDA compared to their control groups;and showed significantly (p < 0.05) decreased level in T-SOD. These changes were significantly (p < 0.05) reversed by the YGMM treatments in a dose-dependent manner. Hepatic pathological changes were attenuated or even reversed by silymarin or YGMM treatments. Conclusions: YGMM has a good hepatoprotective activity on isoniazid-rifampicin induced liver injuries in rats.展开更多
Objective:To investigate the cellular toxicity of isoniazid together with rifampicin and the metabolites of isoniazid on cultured QSG-7701 cells lines.Methods:Isoniazid,rifampicin, mixture of rifampicin and isoniazid,...Objective:To investigate the cellular toxicity of isoniazid together with rifampicin and the metabolites of isoniazid on cultured QSG-7701 cells lines.Methods:Isoniazid,rifampicin, mixture of rifampicin and isoniazid,acetylhydrazine,hydrazine were added in cultural media of QSG-7701 cells and cultured for 48 hours.The survival rate of cells was determined by MTT method.The cultural media and cells were collected and the activity of lactate dehydrogenase was detected by chromatometry.Results:Compared with control group,the survival rate decreased significantly and the lactate dehydrogenase released from cell increased significantly in cells treated with isoniazid,rifampicin,acetylhydrazine,hydrazine.Hydrazine,the metabolite of isoniazid produced significant damage on hepatocytes in low concentration.Conclusions: Rifampicin together with rifampicin and metabolites of isoniazid produce cellular toxic effects and hydrazine may be the most toxiferous metabolite.展开更多
AIM:To determine the histopathological changes of rifampicin applied intravitreally on retinal ganglion cells by means of stereological and histopathological methods.METHODS:For this study twenty-four New Zealand adul...AIM:To determine the histopathological changes of rifampicin applied intravitreally on retinal ganglion cells by means of stereological and histopathological methods.METHODS:For this study twenty-four New Zealand adult rabbits were divided into four groups(n=6 for each group).50μg/0.1mL(group 1),100μg/0.1mL(group 2),150μg/0.1mL(group 3) and 200μg/0.1mL(group 4),rifampicin were injected into the vitreous of the right eyes of animals,their left eyes were used as control(group 5).After the 28thday of application,animals were anesthetised with xylazine(8mg/kg,IM) and then their eyes were enucleated immediately.Patterns were taken away and eyes were prepared for both stereological and electromicroscopic observation.RESULTS:Depending on the high dose of rifampicin,some histopathological changes such as cytoplasmic dilatation and damaged membrane were observed on the electromicroscopic level.Using quantitative examination,which was done at the light microscopic level,it was shown that the number of neurons decreased linearly as rifampicin dose increased when compared with the control group.CONCLUSION:Based on these findings,low-dose rifampicin(50μg/0.1mL) may be useful for treatment of the ocular diseases.展开更多
SLCO1B1 and NAT2 polymorphisms have been associated with the variability of Rifampicin and Isoniazid pharmacokinetic (PK). The objective of this study was to identify in African patients with tuberculosis (TB) or TB/H...SLCO1B1 and NAT2 polymorphisms have been associated with the variability of Rifampicin and Isoniazid pharmacokinetic (PK). The objective of this study was to identify in African patients with tuberculosis (TB) or TB/HIV co-infection, the SLCO1B1 and NAT2 polymorphisms, associated with the variability of Rifampicin and Isoniazid pharmacokinetic. TB or TB/HIV co-infected patients from Benin, Guinea, Senegal, and South Africa were included in this study. The blood samples collected were stored at -80˚C until DNA extractions. The DNA extracts were then frozen at -80˚C after quality control. Double stranded DNA of the samples were quantified using a fluorimetric method to select suitable samples for the preparation of 96-well microplates, containing 100 μl of DNA extract per well at the concentration of 20 ng/μl. Illumina HumanOmniExpress-24 v1.2 microarray genotyping was performed by an external vendor. The genotyping data were analyzed and the polymorphisms with a call rate < 95% or presenting a departure from the Hardy-Weinberg Equilibrium (HWE) were excluded. The correlation between significant genetic polymorphisms, the clearance, and the AUC were tested by a multiple linear regression model using the PLINK2 software. Out of 385 samples, five (05) were excluded after quality controls. After the frequency test, 384,586 SNPs failed the Hardy-Weinberg Equilibrium. Finally, 378 samples and 318,751 SNPs were included in the genetic analyses. The SLCO1B1 and NAT2 polymorphisms were associated with the variability of Rifampicin and Isoniazid PK parameters. There are SLCO1B1 and NAT2 polymorphisms carriers among TB and TB/HIV co-infected patients from Sub-Saharan Africa.展开更多
文摘Background: World Health Organization recommends the implementation of contact tracing and Leprosy Post Exposure prophylaxis (LPEP) to interrupt the chain of transmission. To accelerate the uptake of this recommendation, a cross-sectional study among contacts of leprosy patients was conducted to investigate the feasibility of integrating leprosy systematic contact tracing and post-exposure prophylaxis (PEP) into the routine leprosy control program. Methods: This was a mixed methods cross-sectional study. The study was implemented in Kumi, Ngora, Serere, Soroti, Budaka and Kibuku Districts. Results: The 45 enrolled index patients (97.8% of the registered) identified a total of 135 contacts, of which 134 (99·2%) consented and were screened. Among them, one new leprosy patient was identified and started on treatment with multidrug therapy (MDT). All the eligible contacts, received the prophylactic treatment with Single Dose Rifampicin (SDR). Overall, SDR was administered to 133(98.5% of the listed contacts) with no adverse event reported. Factors associated with successful contact investigation and management included: Involvement of index patients, health care workers during the contact screening and SDR A administration, counselling of the index patients and contacts by the health care works, LPEP being administered as Directly observed Therapy (DOT) among others. Results Interpretation: The integration of leprosy post-exposure prophylaxis with administration of SDR and contact tracing is feasible, generally accepted by the patient, their contacts and health workers and can be integrated into the National Leprosy control programmes with minimal additional efforts once contact tracing has been established. Therefore, we recommend integration of administration of SDR in to the routine leprosy control program.
文摘Rifampicin-resistant tuberculosis (RR-TB) is a global public health problem caused by mycobacterium tuberculosis resistant to Rifampicin. Drug-induced peripheral neuropathy and neurotoxicity are well-known adverse effects of treatment regimens that cause significant morbidity. Pyridoxine is often added to treatment regimens for the prevention and/or treatment of these side effects. The basis and effectiveness of this practice are unclear. We conducted a systematic review to evaluate the effectiveness of pyridoxine in preventing and/or treating neuropathy and neurotoxicity associated with RR-TB treatment. We included studies with patients with RR-TB who experienced neuropathy or neurotoxicity attributed to RR-TB regimens and were given pyridoxine. Our findings showed contradicting evidence on the use of pyridoxine for preventing or treating neurotoxicity due to cycloserine in the treatment of RR-TB. Moreover, pyridoxine did not have a protective effect against neuropathy and/or neurotoxicity caused by other RR-TB regimens that do not contain isoniazid. In conclusion, we found that withdrawing or withholding medications such as linezolid, cycloserine, thioamides, fluoroquinolones, and ethambutol, implicated in causing neuropathy or neurotoxicity was more effective than using pyridoxine to stop the progression of symptoms, and in some instances, led to their reversal over time.
文摘A number of HPLC methods have been approved for the determination of rifampicin, but no references involved the assay of related substances of rifampicin. In the present paper, a reversed-phase liquid chromatographic method for the determination of related substances of rifampicin is developed and validated. Rifampicin and its related substances, including rifamycin SV, rifampicin N-oxide and 3-formylrifamycin SV were separated using a Zorbax Eclipse C8, 250×4.6 mm(i.d), 5 μm column by isocratic elution at a flow rate of 1 mL·min -1. The detector was set at 254 nm. The mobile phase is a mixture of methanol-acetonitrile -0.075 mol·L -1 monopotassium phosphate -1.0 mol·L -1 citric acid (31:31:35:3, v/v). The method validation included accuracy, precision, linearity, sensitivity and stability. All results are shown to be acceptable.
基金Supported by the Indian Council of Medical Research,New Delhi,India,No.45/39/2002-PHA/BMS
文摘AIM： To evaluate the hepatoprotective effect of garlic on liver injury induced by isoniazid （INH） and rifarnpicin （RIF）. METHODS： Wistar rats weighing 150-200 g were treated orally with 50 mg/kg of INH and RIF daily each for 28 d. For hepatoprotective studies, 0.25 g/kg per day of freshly prepared garlic hornogenate was administered orally half an hour before the INH＋RIF doses. Serum alanine arninotransferase （AIT）, aspartate aminotransferase （AST） and bilirubin were estimated on d 0, 14, 21, and 28 in all the rats. Histological analysis was carried out to assess the injury to the liver. Lipid peroxidation （1PO） as a marker of oxidative stress and non-protein thiols （glutathione） for antioxidant levels were measured in liver hornogenate. RESULTS： The treatment of rats with INH＋RIF （50 mg/kg per day each） induced hepatotoxicity in all the treated animals as judged by elevated serum ALT, AST, and bilirubin levels, presence of focal hepatocytic necrosis （6/8） and portal triaditis （8/8）. Garlic simultaneously administered at a dose of 0.25 g/kg per day prevented the induction of histopathological injuries in INH＋RIF co-treated animals, except in 4 animals, which showed only moderate portal triaditis. The histological changes correlated with oxidative stress in INH＋RIF treated animals. The group which received 0.25 g/kg per day garlic hornogenate along with INH＋RIF showed higher levels of glutathione （P〈0.05） and low levels of 1PO （P〈 0.05） as compared to INH＋RIF treated group. CONCLUSION： Freshly prepared garlic homogenate protects against INH＋RIF-induced liver injury in experimental animal model.
基金Supported by National Natural Science Foundation of China,No.31502059Education Department of Hubei Province,No.B2016039+1 种基金Medical School of Yangtze University,No.YXYQ201406Clinical and Molecular Immunology Research Center of Yangtze University
文摘AIM To explore the protective effects and mechanisms of naringenin(NRG) on hepatic injury induced by isoniazid(INH) and rifampicin(RIF).METHODS Male mice were randomly divided into four groups and treated for 14 d as follows: normal control group was administered intragastrically with normal saline solution alone; model group was administered intragastrically with INH(100 mg/kg) and RIF(100 mg/kg); lowand high-dosage NRG pretreatment groups were administered intragastrically with different doses of NRG(50 or 100 mg/kg) 2 h before INH and RIF challenge. Mice were killed 16 h after the last dose of drug treatment to determine activity of serum transaminases. Oxidative stress was evaluated by measuring hepatic glutathione(GSH) and superoxide dismutase(SOD) and malondialdehyde(MDA) levels. Histopathological changes in hepatic tissue were observed under the optical microscope. Hepatocyte apoptosis was measured by TUNEL assay and caspase-3 activation. Expression of Bcl-2 and Bax in liver was determined by western blot.RESULTS Both low- and high-dosage NRG pretreatment obviously alleviated serum levels of alanine aminotransferase and aspartate aminotransferase, liver index, hepatic MDA content, and increased hepatic GSH content and SOD activity compared with the INH and RIF-treated group(44.71 ± 8.15 U/L, 38.22 ± 6.64 U/L vs 58.15 ± 10.54 U/L; 98.36 ± 14.78 U/L, 92.41 ± 13.59 U/L vs 133.05 ± 19.36 U/L; 5.34% ± 0.26%, 4.93% ± 0.25% vs 5.71% ± 0.28%; 2.76 ± 0.67 nmol/mgprot, 2.64 ± 0.64 nmol/mgprot vs 4.49 ± 1.12 nmol/mgprot; 5.91 ± 1.31 mg/gprot, 6.42 ± 1.42 mg/gprot vs 3.11 ± 0.73 mg/gprot; 137.31 ± 24.62 U/mgprot, 148.83 ± 26.75 U/mgprot vs 102.34 ± 19.22 U/mgprot; all P < 0.01 or 0.05). Histopathological evaluation showed obvious necrosis and inflammatory cell infiltration in liver of mice administered INH and RIF; however, mice pretreated with NRG showed minor hepatic injury. In addition, INH and RIF resulted in hepatocyte apoptosis, and NRG pretreatment dramatically suppressed INHand RIF-induced hepatocytes apoptosis. Furthermore, NRG-mediated anti-apoptotic effects seemed to be in connection with its regulation of Bax and Bcl-2 protein expression in hepatic tissue.CONCLUSION NRG might attenuate INH- and RIF-induced hepatic injury via suppression of oxidative stress and hepatocyte apoptosis.
文摘Objective:To evaluate luciferase reporter phage(LRP)phAE85 in rapid detection of rifampicin resistance in a region where TB is endemic.Methods:One hundred and ninety primary isolates on Lowenstein-Jensen medium were tested.Middlebrook 7H9 complete medium with and without rifampicin at 2μg/mL was inoculated with standard inoculum from suspensions of the clinical isolate.After incubation for 72 h,LRP was added.Following 4 h of further incubation,light output from both control and test was measured as relative light units.Strains exhibiting a reduction of less than 50%relative light units in the drug containing vial compared to control were classified as resistant.Results were compared with the conventional minimum inhibitory concentration method(MIC)of drug susceptibility testing.Results:The two methods showed high level of agreement of 97%(CI 0.94,0.99)and P value was 0.000 1.The sensitivity and specificity of LRP assay for detection of rifampicin resistance were 91%h(CI 0.75,0.98)and 99ct(CI0.95,1.00)respectively.Time to detection of resistance by LRP assay was 3 d in comparison with 28 d by the minimum inhibitory concentration method.Conclusions:LRP assay with phAE85 is 99%specific,91%sensitive and is highly reproducible.Thus the assay offers a simple procedure for drug sensitivity testing,within die scope of semi-automation.
基金the Natural Science Foundation of Guangdong Province,No.04009355Science and Technology Planning Project of Guandong Province,China,05B33801003
文摘BACKGROUND： Rifampicin inhibits the formation of a-synuclein multimer and protects against 1-methyl-4-phenyl-1,2, 3, 6-tetrahydropyritine （MPTP）-induced PC12 cell apoptosis. OBJECTIVE： To compare the effect of rifampicin pre- and post-treatment on tyrosine hydroxylase and α-synuclein expression in substantia nigra pars compacta in a rat model of Parkinson＇s disease. DESIGN, TIME AND SE＇B＇ING： A randomized, controlled experiment was performed at the Experimental Animal Center of Sun Yat-sen University North Campus （China） from November 2006 to October 2008. MATERIALS： Rifampicin was purchased from MD, USA; rotenone was purchased from Sigma, USA; mouse anti-rat α-synuclein monoclonal antibody was purchased from B＆D, USA; and rabbit anti-rat tyrosine hydroxylase monoclonal antibody was purchased from Chemicon, USA. METHODS： A total of 72 male, Sprague Dawley rats, aged 8 weeks, were randomly assigned to 5 groups： blank control （n = 12）, rifampicin （n = 12）, rotenone （n = 16）, rifampicin pre-treatment （n = 16）, and rifampicin post-treatment （n = 16）. Parkinson＇s disease model rats were established via a subcutaneous injection of rotenone （1.5 mg/kg per day） in the three treatment groups, once a day for 3 successive weeks. Rifampicin （30 mg/kg per day） was intragastrically administered in the rifampicin pre-treatment group 3 days prior to rotenone induction and in the rifampicin post-treatment group 7 days after rotenone induction. Rats were treated with a subcutaneous injection of 1 mL/kg per day sunflower oil in the blank control group and an intragastric injection of 30 mg/kg per day rifampicin in the rifampicin group, once a day for 3 successive weeks in total. MAIN OUTCOME MEASURES： Prior to treatment and in the end of the 3^rd week after treatment, the rats were evaluated using the modified neurological severity score. The substantia nigra from the rats was extracted for hematoxylin-eosin staining. Western blot analysis was performed to determine tyrosine hydroxylase and α-synuclein expression. RESULTS： Hematoxylin-eosin staining revealed a significant reduction in the number of substantia nigral neurons in the rotenone group, in addition to neurodegradation, hypopigmentation, and pyknosis. In the rifampicin pre-treatment and post-treatment groups, the number of dopaminergic neurons was significantly increased compared with the rotenone group （P 〈 0.01）, with slight neuronal damage. Compared with the rotenone group, substantia nigral tyrosine hydroxylase expression was significantly increased in the rifampicin pre-treatment and post-treatment groups （P 〈 0.01）, but α-synuclein expression and modified neurological severity scores were significantly decreased （P 〈 0.01）. In addition, the effect of rifampicin in the pre-treatment group was superior to the post-treatment group. There was no significant difference in tyrosine hydroxylase and α-synuclein expression, or in the modified neurological severity scores, between the blank control and rifampicin groups （P 〉 0.05）. CONCLUSION： Rifampicin significantly attenuated neuropathological and behavioral motor deficits induced by rotenone. Moreover, rifampicin enhanced tyrosine hydroxylase expression, but inhibited α-synuclein expression. The effect of rifampicin pre-treatment was superior to rifampicin post-treatment.
文摘The prognosis of patients with previously treated tuberculosis (TB) was suggested to be dependent on whether the initial treatment was in compliance with the established guidelines. The aim of this retrospective multicenter study was to determine the proportion of new TB patients who received standard doses of rifampicin in multiple provinces of China, and the relationship between low doses of rifampicin and frequency of rifampicin-resistance as well as treatment outcomes. A total of 713 new TB patients were treated with either once-daily dose of bulk anti-TB drugs (group I) or every other day combination blister packs of anti-TB drugs containing rifampicin (group II) at more than 30 TB treatment centers/hospitals in China. Treatment history, therapeutic doses of rifampicin, and information about patients were extracted from their medical records and analyzed, and rifampicin-resistance of isolates collected from patients following the treatment as well as treatment outcomes were compared between two treatment groups. Among 522 patients in treatment group I, 154 (29.5%) received standard and 363 (69.5%) received low doses of rifampicin;238 (45.6%) isolates were rifampicin-resistant, and 243 (46.6%) were successfully treated. Among 191 patients in treatment group II, 175 (91.6%) received standard and 15 (7.9%) received low doses of rifampicin;72 (37.7%) isolates were rifampicin-resistant, and 105 (55%) were successfully treated. When patients who received low doses of rifampicin were compared to others within the same treatment group, increased rates for rifampicin-resistance and treatment failure were observed. Results from this study showed that most new TB patients in treatment group I (69.5%) received low doses of rifampicin, and their treatment outcomes were worse than those in treatment group II, indicating that low doses of rifampicin used for the initial treatment of new TB patients were correlated to increased frequency of rifampicin-resistance and poorer treatment outcomes.
基金the Guangdong Province Science and Technology Program Funded Projects,No.2005B33801003
文摘BACKGROUND： Previous studies have shown that rifampicin exhibits neuroprotective effects, but the precise mechanisms remain unclear. Rifampicin is thought to exert the neuroprotective effect as a hydroxyl free radical scavenger. OBJECTIVE： To investigate the protective effects of rifampicin pretreatment on rotenone-induced mitochondrial oxidative stress in differentiated PC12 cells.DESIGN, TIME AND SETrlNG： A repeated measure, cell-based study was performed at the Department of Neurology, Second Affiliated Hospital, Sun Yat-sen University, China between December 2007 and November 2008. MATERIALS： PC12 cells were a kind gift from the Physiology Laboratory of Zhongshan Medical School, Sun Yat-sen University, China. Rotenone and rifampicin were purchased from Sigma, USA. METHODS： PC12 cells were differentiated by culturing with 100 ng/mL 7S nerve growth factor for 9 days in Dulbecco＇s modified Eagle＇s medium/Nutrient Mix F12 （DMEM/F12） supplemented with 10% fetal bovine serum. The cells were assigned to six groups according to various treatment conditions： control, cultured with normal media; rifampicin group, treated with 300 pmol/L rotenone for 26 hours; rotenone group, treated with 2.5 pmol/L rotenone for 24 hours; rifampicin pretreatment groups, pretreated with 100, 200, and 300 pmol/L rifampicin for 2 hours, respectively, followed by 2.5 μmol/L rotenone for 24 hours.MAIN OUTCOME MEASURES： Mitochondrial membrane potential was measured by fluorescence microscopy and flow cytometry, respectively, using rhodamine123 staining. Intracellular reactive oxygen species formation was analyzed by flow cytometry using 2＇, 7＇-dichlorofluorescin-diacetate staining, and intracellular reduced glutathione was measured with a microplate reader. Cell viability was determined by 3-（4, 5-dimethylthiazol-2-yl）-2, 5-diphenyltetrazolium bromide assay. Cell apoptosis was detected by Hoechst 33342 staining and flow cytometry. RESULTS： Increased apoptosis in rotenone-induced, differentiated, PC12 cells was accompanied by the loss of mitochondrial transmembrane potential, the formation of reactive oxygen species, and reduced glutathione depletion （P 〈 0.01）. Rotenone-induced mitochondrial dysfunction was blocked in a dose-dependent manner by rifampicin （P 〈 0.05 or P 〈 0.01）, CONCLUSION： Pretreatment of differentiated PC12 cells with rifampicin blocked rotenone-induced apoptosis by ameliorating mitochondrial dysfunction and oxidative stress.
基金Supported ty Department of Science and Technology,Changdigarh, India
文摘AIM, To study the role of N-acetylcysteine （NAC） as a protective agent in rifampicin （RMP）-induced oxidative hepatic injury of young rats. METHODS： Hepatic injury was produced by giving 50mg/kg body weight/day of RMP for 3 wk. A dose of NAC （100mg/kg body weight/day） was given in combination with RMP intraperitoneally. Analysis of lipid peroxidation, thiol levels, cytochrome P4se, superoxide dismutase （SOD）, catalase, glutathione peroxidase, reductase and transferase were estimated in liver along with the body weight, liver weight and histological observations. RESULTS： RMP exposure resulted in no change in body and liver weight while antioxidative enzymes were altered but the non protein thiol （GSH） status was well preserved. Cytochrome P450 system and peroxidation of lipids were induced by RMP exposure. Partial protection was observed with NAC against RMP-induced changes in liver, which was evidenced from the prevention of increase in lipid peroxidation and the reduction in SOD and catalase enzyme levels. CONCLUSION. NAC protects young rats against RMP- induced oxidative hepatic injury.
基金Supported by Grant RO1-AI51251-01 from NIH-NIAID
文摘AIM： To investigate overlapping regions of the rpoB gene previously involved with rifamycin resistance in M. tuberculosis and seek correlation between rpoB mutations in dinical MAP strains with susceptibility to RIF and RFB. METHODS： We designed a molecular-based PCR method for the evaluation of rifabutin （RFB） and rifampicin （RIF） resistance based on probable determinant regions within the rpoB gene of MAP, including the 81 bp variable site located between nucleotides 1363 and 1443. The minimum inhibitory concentration （MIC） for RIF was also determined against 11 MAP isolates in attempt to seek correlation with rpoB sequences. RESULTS： We determined that MAP strain 18 had an MIC of 〉 30 mg/L and ≤ 5 mg/L for RIF and RFB respectively, and a significant and novel rpoB mutation C1367T, compared to an MIC of ≤ 1.0 mg/L for both drugs in the wild type MAP. The 30-fold increase in the MIC was a direct result of the rpoB mutation C1367T, which caused an amino acid change Thr456 to Ile456 in the drug＇s binding site. In addition, MAP strain 185 contained five silent rpoB mutations and exhibited an MIC comparable to the wild-type. Moreover, our in vitro selected mutation in MAP strain UCF5 resulted in the generation of a new resistant strain （UCF5-RIF16r） that possessed T1442C rpoB mutation and an MIC 〉 30 mg/L and 〉 10 mg/L for RIF and RFB respectively. Sequencing of the entire rpoB gene in MAP strains UCF4, 18, and UCF5-RIF16r revealed an rpoB mutation A2284C further downstream of the 81 bp variable region in UCF4, accounting for observed slight increase in MIC. In addition, no other significant mutations were found in strains 18 and UCF-RIF16r. CONCLUSION： The data clearly illustrates that clinical and in vitro-selected MAP mutants with rpoB mutations result in resistance to RIF and RFB, and that a single amino acid change in the beta subunit may have a significant impact on RIF resistance. Unconventional drug susceptibility testing such as our molecular approach will be beneficial for evaluation of antibiotic effectiveness. This molecular approach may also serve as a model for other drugs used for treatment of MAP infections.
文摘AIM: To evaluate and compare the hepatoprotective and immunomodulatory effects of Curcuma longa (CL), Ocimum sanctum (OS), Tinospora cordifolia (TC) and Zizyphus mauritiana (ZM) on liver injury and immunosuppression induced by Isoniazid (INH), Rifampicin (RIF) and Pyrazinamide (PZA). METHODS: Duncan Hartley guinea pigs, weighing 700-1050 g, were treated orally with 50 mg/kg of INH, 100 mg/kg of RIF and 300 mg/Kg of PZA for 21-d. 200 mg/kg (bw) of each herb crude extract was administered to the herb control group and 2-h previous to INH + RIF + PZA (AKT) doses to the Herb + AKT groups. Serum alanine aminotransferase (ALT), aspertate aminotransferase (AST) bilirubin and Alkaline Phosphatase (ALP) were assessed on d 0 and 21 in all the groups. Phagocytic % (P%), Phagocytic Index (PI) and Chemotactic Index (CI) were also measured as immunologic parameters. Histological analysis was carried out to assess injury to the liver. RESULTS: The AKT treated control group showed hepatotoxicity as judged by elevated serum AST 5-fold, AST/ALT ratio 4-fold, ALP 2-fold and hepatological changes, such as focal necrosis, portal triaditis and steatosis. Immune function was suppressed as judged by decreased P% (51.67 ?1.68 vs 40.61 ?1.28, P < 0.01), PI (2.0725±0.05 vs 0.61±0.05, P < 0.001) and CI (1.8525±0.04 vs 0.695±0.07, P < 0.001). All four herb treated groups showed normal liver histology, enzyme levels and increased P%, while PI and CI were enhanced in the TC and ZM treated groups, respectively. CL + AKT, TC + AKT and ZM + AKT showed nearly normal histology with minimal inflammation and microvesicular steatosis, while OS + AKT showed partial protection. Hepatotoxicity was prevented by restricting the rise of AST by 2-fold in CL + AKT and TC + AKT groups and by 3-fold in OS + AKT and ZM + AKT groups, AST/ALT by 2-fold and ALP to normal levels in all four groups. All four herb + AKT groups showed normal to enhanced neutrophil function. CONCLUSION: All four herbs showed hepatoprotective potential and prevented immunosuppression. CL and TC showed the highest hepatoprotective activity, while TC and ZM showed strong immunostimulatory activity.
文摘The aim of the present work is to develop rifampicin loaded phospholipid lipospheres containing sulfphobutyl etherβ-cyclodextrin and Vitamin C for inhalation to test their potential for deep lung delivery.The findings of the solid state characterization revealed the amorphous nature of the lipospheres.These exhibited a better flowability,an aerodynamic diameter in the range of 1.76 to 3.99μm.Moreover,the fine particle fraction and emitted dose was found in the range of 68.84–83.73% and 80–93%,respectively.Moreover,lipospheres exhibited enhanced/equivalent efficacy in vitro in H37Rv strain.Hence,the results show the potential of lipospheres for pulmonary delivery of rifampicin.
文摘BACKGROUND The drug interaction between warfarin and rifampicin is widely known,but there are still some difficulties in managing the combination of the two drugs.CASE SUMMARY A patient with brucellosis received strict monitoring from a Chinese pharmacist team during combination of warfarin and rifampicin.The dose of warfarin was increased to 350%in 3 mo before reaching the lower international normalized ratio treatment window.No obvious adverse reaction occurred during the drugadjustment period.This is the first case report of long-term combined use of rifampicin and warfarin in patients with brucellosis and valve replacement in China based on the Chinese lower warfarin dose and international normalized ratio range.CONCLUSION Anticoagulation for valve replacement in Chinese patients differs from that in other races.Establishment of a pharmacist clinic provides vital assistance in warfarin dose adjustment.
文摘<b><span style="font-family:Verdana;">Objective:</span></b><span style="font-family:Verdana;"> To investigate the clinical effect of rifapentine and rifampicin in the treatment of pulmonary tuberculosis.</span><b> </b><span style="font-family:Verdana;"><b></b></span><b><b><span style="font-family:Verdana;">Methods:</span></b><span style="font-family:Verdana;"></span></b><b> </b><span style="font-family:Verdana;">Seventy-two cases of patients with initial treatment of pulmonary tuberculosis who attended the First Hos</span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">pital Affiliated to Hebei North </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">University</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> from February 2017 to August 2019 we</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">re </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">selected. They were randomly divided into observation group and control gro</span></span></span><span><span><span style="font-family:;" "=""><span style="font-family:Verdana;">up, with 36 cases in each group. The observation group was treated with isoniazid + rifapentine + ethambutol, while the control group was treated with isoniazid + rifampicin + ethambutol. The symptom relief, image absorption and adverse reactions were compared between the two groups. <b></b></span><b><b><span style="font-family:Verdana;">Results:</span></b><span style="font-family:Verdana;"></span></b><span style="font-family:Verdana;"> The rate of symp</span></span></span></span><span><span><span style="font-family:;" "=""><span style="font-family:Verdana;">tom relief was 86.11% in the observation group and 94.44% in the control</span><span><span style="font-family:Verdana;"> group, P < 0.05, which was statistically significant. Rifampin was more helpful than rifapentine in relieving clinical symptoms</span><span style="font-family:Verdana;">. The lesion absorption rate was 77.79% in the observation group and 88.89% in the control group, P < 0.05, and the difference was statistically significant. Rifampin was more beneficial to the absorption of TB lesions than rifapentine. The incidence of adverse reactions in the observation group was 16.67% much lower than that in the control group, which was 38.89%, indicating that the adverse reactions of rifapentine were less. <b></b></span><b><b><span style="font-family:Verdana;">Conclusion:</span></b><span style="font-family:Verdana;"></span></b></span><b> </b><span style="font-family:Verdana;">Rifampicin is superior to rifapentine in clinical symptom relief and lesion absorption, but the incidence of adverse reactions is high.</span></span></span></span>
文摘Vaccinations for coronavirus disease-2019(COVID-19)have begun more than a year before,yet without specific treatments available.Rifampicin,critically important for human medicine(World Health Organization’s list of essential medicines),may prove pharmacologically effective for treatment and chemoprophylaxis of healthcare personnel and those at higher risk.It has been known since 1969 that rifampicin has a direct selective antiviral effect on viruses which have their own RNA polymerase(severe acute respiratory syndrome coronavirus 2),like the main mechanism of action of remdesivir.This involves inhibition of late viral protein synthesis,the virion assembly,and the viral polymerase itself.This antiviral effect is dependent on the administration route,with local application resulting in higher drug concentrations at the site of viral replication.This would suggest also trying lung administration of rifampicin by nebulization to increase the drug’s concentration at infection sites while minimizing systemic side effects.Recent in silico studies with a computer-aided approach,found rifampicin among the most promising existing drugs that could be repurposed for the treatment of COVID-19.
文摘Background: To explore the hepatoprotective effect of Yigan mingmu oral liquid (YGMM) on isoniazid-rifampicin induced liver injury in rats. Methods: Total 38 SD rats were randomly divided into 6 groups including control group, model group, silymarin positive control group, and three YGMM treatment groups. Model group was administered intragastrically with INH (100 mg/kg) and RIF (100 mg/kg) for 14 days. Silymarin group and YGMM treatment groups were administered intragastrically with silymarin (100 mg/kg) and different doses of YGMM (1, 2.5, 5 mg/kg) 2 hours before INH and RIF administration from day 4 to day 14.?Results: Rats were sacrificed 16 hours after the last day treatment to determine the activities of serum alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP), as well as total bilirubin (TB) content. Oxidative stress was evaluated by measuring total superoxide dismutase (T-SOD) and malondialdehyde (MDA) levels. Histopathological changes in liver tissues were observed under an optical microscope by using hematoxylin and eosin staining. The mice?in model groups showed significantly (p < 0.05) increased levels in AST, ALT, ALP, TB and MDA compared to their control groups;and showed significantly (p < 0.05) decreased level in T-SOD. These changes were significantly (p < 0.05) reversed by the YGMM treatments in a dose-dependent manner. Hepatic pathological changes were attenuated or even reversed by silymarin or YGMM treatments. Conclusions: YGMM has a good hepatoprotective activity on isoniazid-rifampicin induced liver injuries in rats.
文摘Objective:To investigate the cellular toxicity of isoniazid together with rifampicin and the metabolites of isoniazid on cultured QSG-7701 cells lines.Methods:Isoniazid,rifampicin, mixture of rifampicin and isoniazid,acetylhydrazine,hydrazine were added in cultural media of QSG-7701 cells and cultured for 48 hours.The survival rate of cells was determined by MTT method.The cultural media and cells were collected and the activity of lactate dehydrogenase was detected by chromatometry.Results:Compared with control group,the survival rate decreased significantly and the lactate dehydrogenase released from cell increased significantly in cells treated with isoniazid,rifampicin,acetylhydrazine,hydrazine.Hydrazine,the metabolite of isoniazid produced significant damage on hepatocytes in low concentration.Conclusions: Rifampicin together with rifampicin and metabolites of isoniazid produce cellular toxic effects and hydrazine may be the most toxiferous metabolite.
文摘AIM:To determine the histopathological changes of rifampicin applied intravitreally on retinal ganglion cells by means of stereological and histopathological methods.METHODS:For this study twenty-four New Zealand adult rabbits were divided into four groups(n=6 for each group).50μg/0.1mL(group 1),100μg/0.1mL(group 2),150μg/0.1mL(group 3) and 200μg/0.1mL(group 4),rifampicin were injected into the vitreous of the right eyes of animals,their left eyes were used as control(group 5).After the 28thday of application,animals were anesthetised with xylazine(8mg/kg,IM) and then their eyes were enucleated immediately.Patterns were taken away and eyes were prepared for both stereological and electromicroscopic observation.RESULTS:Depending on the high dose of rifampicin,some histopathological changes such as cytoplasmic dilatation and damaged membrane were observed on the electromicroscopic level.Using quantitative examination,which was done at the light microscopic level,it was shown that the number of neurons decreased linearly as rifampicin dose increased when compared with the control group.CONCLUSION:Based on these findings,low-dose rifampicin(50μg/0.1mL) may be useful for treatment of the ocular diseases.
文摘SLCO1B1 and NAT2 polymorphisms have been associated with the variability of Rifampicin and Isoniazid pharmacokinetic (PK). The objective of this study was to identify in African patients with tuberculosis (TB) or TB/HIV co-infection, the SLCO1B1 and NAT2 polymorphisms, associated with the variability of Rifampicin and Isoniazid pharmacokinetic. TB or TB/HIV co-infected patients from Benin, Guinea, Senegal, and South Africa were included in this study. The blood samples collected were stored at -80˚C until DNA extractions. The DNA extracts were then frozen at -80˚C after quality control. Double stranded DNA of the samples were quantified using a fluorimetric method to select suitable samples for the preparation of 96-well microplates, containing 100 μl of DNA extract per well at the concentration of 20 ng/μl. Illumina HumanOmniExpress-24 v1.2 microarray genotyping was performed by an external vendor. The genotyping data were analyzed and the polymorphisms with a call rate < 95% or presenting a departure from the Hardy-Weinberg Equilibrium (HWE) were excluded. The correlation between significant genetic polymorphisms, the clearance, and the AUC were tested by a multiple linear regression model using the PLINK2 software. Out of 385 samples, five (05) were excluded after quality controls. After the frequency test, 384,586 SNPs failed the Hardy-Weinberg Equilibrium. Finally, 378 samples and 318,751 SNPs were included in the genetic analyses. The SLCO1B1 and NAT2 polymorphisms were associated with the variability of Rifampicin and Isoniazid PK parameters. There are SLCO1B1 and NAT2 polymorphisms carriers among TB and TB/HIV co-infected patients from Sub-Saharan Africa.
