International open trial of uniform multidrug therapy regimen for leprosy patients: Findings & implications for national leprosy programmes.

BACKGROUND & OBJECTIVES: Uniform therapy for all leprosy patients will simplify leprosy treatment. In this context, we evaluated six-month multidrug therapy (MDT) currently recommended for multibacillary (MB) patients as uniform MDT (U-MDT) in a single-arm open trial under programme conditions. Primary objective was to determine efficacy to prevent five-year cumulative five per cent relapse. Secondary objectives were to assess acceptability, safety and compliance. METHODS: Newly detected, treatment-naive leprosy patients were enrolled in India (six sites) and P. R. China (two sites). Primary outcome was clinically confirmed relapse of occurrence of one or more new skin patches consistent with leprosy, without evidence of reactions post-treatment. Event rates per 100 person years as well as five-year cumulative risk of relapse, were calculated. RESULTS: A total of 2091 paucibacillary (PB) and 1298 MB leprosy patients were recruited from the 3437 patients screened. Among PB, two relapsed (rate=0.023; risk=0.11%), eight had suspected adverse drug reactions (ADRs) (rate=0.79) and rate of new lesions due toreactions was 0.24 (n=23). Rates of neuritis, type 1 and type 2 reactions were 0.39 (n=37), 0.54 (n=51) and 0.03 (n=3), respectively. Among MB, four relapsed (rate=0.07; risk=0.37%) and 16 had suspected ADR (rate=2.64). Rate of new lesions due to reactions among MB was 1.34 (n=76) and rates of neuritis, type 1 and type 2 reactions were 1.37 (n=78), 2.01 (n=114) and 0.49 (n=28), respectively. Compliance to U-MDT was 99 per cent. Skin pigmentation due to clofazimine was of short duration and acceptable. INTERPRETATION & CONCLUSIONS: We observed low relapse, minimal ADR and other adverse clinical events. Clofazimine-related pigmentation was acceptable. Evidence supports introduction of U-MDT in national leprosy programmes. [CTRI No: 2012/ 05/ 002696].

International open trial of uniform multi-drug therapy regimen for 6 months for all types of leprosy patients: rationale, design and preliminary results.

OBJECTIVE: To describe the rationale, design and preliminary results of an open trial of 6 months uniform multi-drug therapy (U-MDT) for all types of leprosy patients assuming a cumulative relapse rate not exceeding 5% over 5 years of follow-up. METHODS: We intended to recruit 2500 patients each in multi-bacillary (MB) and pauci-bacillary (PB) groups from India (five centres) and China (two centres). Standardized clinical criteria were used to assess skin lesions in the field. RESULTS: A total of 2912 patients enrolled from November 2003 to May 2007 (India, 2746; China, 166). MB patients constituted 39% and 3% had grade 2 disability. During follow-up, 27 patients (0.9%) developed new lesions. Of these, 78% were on account of reactions. Six patients had clinically confirmed relapse. Clofazimine-related skin pigmentation was short-lived and was acceptable to patients. We analysed data for clinical status of skin lesions. About 2.9% of patients were lost to follow-up; 85.9% completed treatment, of whom 19% had inactive skin lesions. PB patients responded better than MB patients (27%vs. 6%; P < 0.001). At the end of the first (n = 2013) and second year (n = 807) of follow-up post-U-MDT, in 49% and 46% patients, lesions were inactive, respectively (59% and 57% in PB, 37% and 28% in MB; P < 0.001). CONCLUSION: U-MDT appears to be promising with respect to clinical status of skin lesions.

Evaluation of Clinical Efficacy of Shengmaisan Granules in Inhibiting Myocardial Fibrosis in Patients with Chronic Heart Failure with Qi-Yin Deficiency Syndrome Based on CMR / 中国实验方剂学杂志

ObjectiveTo evaluate the effect of Shengmaisan granules on myocardial fibrosis in chronic heart failure patients with Qi-Yin deficiency syndrome by cardiac magnetic resonance （CMR） imaging and serological indicators. MethodSixty-six chronic heart failure patients with Qi-Yin deficiency syndrome who visited the Affiliated Hospital of Integrated Traditional Chinese and Western Medicine， Nanjing University of Chinese Medicine from October 2021 to January 2023 were selected. The patients were assigned into a control group （33 cases） and an observation group （33 cases） by the minimization random method. Both groups received standardized Western medicine treatment for heart failure. In addition， the control group was treated with placebo granules， and the observation group with Shengmaisan granules for a course of 6 months. The baseline data， clinical efficacy， TCM symptom scores， serological indicators ［high-sensitivity C-reactive protein （hs-CRP）， soluble growth stimulation expressed gene 2 protein （sST2）， pro-collagen Ⅲ N-terminal peptide （PⅢNP）， interleukin （IL）-6， IL-11， transforming growth factor-β1 （TGF-β1）］， echocardiography ［Left atrial diameter （LAD）， left ventricular end systolic diameter （LVEDs）， left ventricular end diastolic diameter （LVEDd）］ and CMR indicators ［left ventricular ejection fraction （LVEF）， myocardial extracellular volume fraction （ECV）， and longitudinal relaxation time （T1）］ were compared between the two groups. ResultFinally， 31 patients in the control group and 30 patients in the observation group were included. There was no significant difference in baseline data or indicators between the two groups before treatment. Compared with those before treatment， the scores of TCM symptoms （shortness of breath， fatigue， palpitations， spontaneous or night sweats， thirst/dry throat， feverish feeling in palms and soles， and edema in lower limbs）， total score of TCM symptoms， ECV， T1， inflammation/fibrosis indicators （hs-CRP， sST2， PⅢNP， IL-6， IL-11， and TGF-β1） in observation group decreased （P<0.05， P<0.01）， and the scores of TCM symptoms （except feverish feeling in palms and soles）， T1， and inflammation/fibrosis indicators in the control group decreased （P<0.05， P<0.01）. After treatment， the observation group had lower scores of TCM symptoms （except feverish feeling in palms and soles and edema in lower limbs）， ECV， T1， and inflammation/fibrosis indicators than the control group （P<0.05， P<0.01）. After treatment， the total response rate in the observation group was 93.33% （28/30）， which was higher than that （80.65%， 25/31） in the control group （Z=2.976， P<0.01）. There was no significant difference in adverse reactions between the two groups during treatment. ConclusionFor patients with chronic heart failure with Qi-Yin deficiency syndrome， Shengmaisan Granules can alleviate the TCM symptoms， reduce inflammation， and inhibit myocardial fibrosis by regulating the TGF-β1/IL-11 signaling axis.

Clinical Effect of Bushen Shengxue Prescription on Chronic Aplastic Anemia and Its Effect on T Cell Subsets and Expression of T-bet and GATA3 / 中国实验方剂学杂志

ObjectiveTo investigate the efficacy of Bushen Shengxue prescription and Yiqi Yangxue prescription in the treatment of chronic aplastic anemia and the effect on T cell subsets and the expression of T-box expressed in T cells （T-bet） and GATA binding protein 3 （GATA3）. MethodA total of 585 patients with chronic aplastic anemia who were treated in 19 hospitals in China from May 2018 to June 2021 were enrolled. With the prospective， double-blind and randomized control methods， the patients were randomized into three groups： kidney deficiency group， Qi and blood deficiency group， and control group. The three groups were respectively treated with Bushen Shengxue prescription granule， Yiqi Yangxue prescription granule， and Placebo （half the dose of Bushen Shengxue formula granules）. In addition， all of them were given oral cyclosporin and androgen. The treatment lasted 6 months， with 3 months as a course. The blood routine indexes， T cell subsets， and fusion genes T-bet and GATA3 before and after treatment were analyzed， and the safety indexes were monitored. ResultDuring the observation， a total of 75 cases dropped out and 18 were rejected. Finally， 161 cases in the kidney deficiency group， 164 in the Qi and blood deficiency group， and 167 in the control group were included. After 6 months of treatment， the total effective rate was 98.8% （159/161） in the kidney deficiency group， which was higher than the 79.9% （131/164） in the Qi and blood deficiency group （χ2=30.135， P<0.01） and the 61.7% （103/167） in the control group （χ2=70.126， P<0.01）. The total effective rate was higher in the Qi and blood deficiency group than in the control group （χ2=13.232， P<0.01）. After treatment， the hemoglobin （HGB） content increased significantly in three groups （P<0.05） as compared with that before treatment， particularly the kidney deficiency group （P<0.01）. After treatment， the white blood cell （WBC） count and platelet （PLT） count in the kidney deficiency group and the control group increased compared with those in the Qi and blood deficiency group （P<0.01）. There was no specific difference in neutrophils （ANC） after treatment among the three groups. At the same time point， the level of T helper type 1 （Th1） cells， Th1/Th2 ratio （P<0.05）， level of CD4+， and CD4+/CD8+ ratio （P<0.05） were significantly low in the kidney deficiency group among three groups. There was no significant difference in CD19-， HLA/DR+， and CD25+ between the kidney deficiency group and the other two groups， but the T-bet of the kidney deficiency group and the control group was lower than that of the Qi and blood deficiency group （P<0.05）. ConclusionBushen Shengxue prescription exerts therapeutic effect on the aplastic anemia by improving the immunoregulatory mechanism， inhibiting the activity of immune system， modulating T cell subsets， suppressing Th1 and CD4+， and promoting bone marrow hematopoiesis. Moreover， it is safe with little side effects， which is worthy of further promotion.

Analysis on the detection of new leprosy cases before, during and after the year of leprosy elimination campaigns.

To analyse the impact on of case finding of leprosy elimination campaigns (LECs), data on newly detected leprosy cases in a leprosy endemic area were collected before, during and after the year of LEC. The number of new leprosy cases detected during the year of LEC was significantly higher than previously. The number of newly detected cases after the year of LEC was similar to that of detected before the year of LEC in counties with persisting case finding activities. However, the number of newly detected cases after the year of LEC significantly decreased in counties without active case finding activities. The average distance from the homes of leprosy cases detected during LEC to the leprosy control unit at the count town was 62.8 km, which is farther than that of other leprosy cases detected before and after the year of LEC. The average time from disease onset to diagnosis of leprosy cases detected after the year of LEC shortened. The results also showed that carrying out LECs is unlikely to have a significant impact on the trend of case finding within a short time in local areas, but it may improve some indicators of leprosy patients and so promote leprosy control in local areas.

Trends in case detection influenced by leprosy elimination campaigns in certain areas of China.

LECs were carried out from 1998 to 2000 in eight counties of west China. The number of cases detected during the year of LECs was much higher than that detected by routine methods before the year of the LEC. However, the annual number of cases detected during the year after the LEC showed different patterns. One pattern is that the number of new cases detected in the year after the LEC declined to the level similar to that before the year of the LEC. The second pattern is that the number of new cases detected in the year after the LEC declined steeply to less than that detected before the year of the LEC. Following peak case-detection during the year of the LEC, a gradual decrease in the number of new cases was observed in the subsequent years. The repeat LEC brought a weakly rebounding peak case-detection during the year following the first LEC carried out 3 years earlier. The operational, epidemiological and technical factors influencing the trends of case-detection during the LECs are discussed.

Development and validation of an in vitro model of mycobacterial granuloma / 中华皮肤科杂志

Objective To establish an in vitro model of mycobacterial granuloma.Methods Mononuclear cells were isolated from peripheral blood of healthy human subjects,and stimulated to differentiate into macrophages,which were then classified into four groups to be cocultured with Mycobacterium marinum,Mycobacterium tuberculosis,Bacillus Calmette-Guérin,and Mycobacterium leprae,respectively,for five days followed by incubation with peripheral blood mononuclear cells (PBMCs) from the corresponding donors to establish an in vitro model of mycobacterial granuloma.The macrophages cocultured with PBMCs or mycobacteria alone served as the control.Microscopy was performed to dynamically visualize the formation of granuloma in vitro,flow cytometry to detect the expressions of cell surface antigens at different stages,real-time quantitative PCR and enzyme-linked immunosorbent assay (ELISA) to determine the mRNA expressions of important cytokines and their protein levels in the supernatant of macrophages,respectively.Results After 7-9 days of coculture with mycobacteria and PBMCs,the macrophages aggregated to form granuloma-like clumps,and some cells fused to form multinuclear giant cells,along with the expressions of some surface antigens such as CD14,CD68 and CD86 on these macrophages.The mRNA expressions of some important cytokines,including tumor necrosis factor-a,interferon-γ interleukin (IL)-1 β and IL-10,were detectable in the macrophages cocultured with mycobacteria and PBMCs,and the secretion of these cytokines was confirmed by ELISA in the supernatant of these cells.Conclusions An in vitro model of mycobacterial granuloma is basically established,which may facilitate the investigation into the formation of granuloma caused by and immune response to mycobacterial infection.

Comparative genomic and phylogeographic analysis of Mycobacterium leprae.

Reductive evolution and massive pseudogene formation have shaped the 3.31-Mb genome of Mycobacterium leprae, an unculturable obligate pathogen that causes leprosy in humans. The complete genome sequence of M. leprae strain Br4923 from Brazil was obtained by conventional methods (6x coverage), and Illumina resequencing technology was used to obtain the sequences of strains Thai53 (38x coverage) and NHDP63 (46x coverage) from Thailand and the United States, respectively. Whole-genome comparisons with the previously sequenced TN strain from India revealed that the four strains share 99.995% sequence identity and differ only in 215 polymorphic sites, mainly SNPs, and by 5 pseudogenes. Sixteen interrelated SNP subtypes were defined by genotyping both extant and extinct strains of M. leprae from around the world. The 16 SNP subtypes showed a strong geographical association that reflects the migration patterns of early humans and trade routes, with the Silk Road linking Europe to China having contributed to the spread of leprosy.

Epidemiological analysis on leprosy in China, 2001-2010 / 中华皮肤科杂志

ObjectiveTo study the epidemiological characteristics of leprosy in China,2001-2010.MethodsData were collected from the database of the national system of leprosy surveillance.A descriptive and comparative analysis was performed.ResultsTotally,15 507 new leprosy cases were detected from 2001 to 2010 with an average case detection rate of 0.118 per 100 000 population.Among these cases,2.7％ were children under 15 years,86.5％ multibacillary,and 22.5％ suffered from grade 2 disability.From 2001 to 2010,a total of 1506 relapse cases were detected,and relapse occurred after multi-drug therapy(MDT) in 464 of these cases.There were significant differences between low and high endemic areas in the proportion of children under 15 years,females,immigrant patients among newly detected patients as well as the proportion of cases of relapse after MDT among all the relapse cases.By the end of 2010,the registered leprosy cases were 6032 with a prevalence rate of 0.450 per 100 000 population,among whom 2886 were under MDT.ConclusionsThe leprosy case detection rate continued to decrease in China from 2001 to 2010 with an unequal distribution.The pocket areas were in Yunnan province,Guizhou province,Sichuan province,Guangdong province,Hunan province and Tibet Autonomous Region.It is warranted to enhance the control of leprosy and reduce the prevalence of disability due to leprosy.

Detection of drug-resistance associated mutations in patients with recurring or treatment-resistant leprosy during 2010-2011 / 中华皮肤科杂志

Objective To detect gene mutations associated with dapsone-,rifampicin-and ofloxacinresistance in lesions of patients with recurring or treatment-resistant leprosy collected from 2010 to 2011.Methods Clinical data and lesional specimens were collected during 2010-2011 from patients with recurring or treatment-resistant leprosy who were diagnosed and reported by provincial centers for leprosy control.Mycobacterium leprae DNA was extracted from the specimens and subjected to PCR for the amplification of folP1,rpoB and gyrA genes.The PCR products were directly sequenced and BLAST program was used to compare the sequence of isolated strains with the reference sequence in GenBank.Results Twenty-four patients were enrolled in this study,including 13 with recurring leprosy and 11 with treatment-resistant leprosy.Twenty-one patients showed positive PCR results in all the three regions.Of these PCR-positive specimens,3 from 1 patient with recurring and 2 patients with resistant leprosy harbored a point mutation,acc (threonine)→gcc (alanine),at codon 53 in the floP1 gene,1 from a patient with recurring leprosy harbored a missense mutation,gat (aspartic acid) → aac (asparagine),at codon 441 in the rpoB gene.Conclusions Mutations are detected in the folP1 and rpoB genes,which are associated with the resistance to dapsone and rifampicin respectively,but not in the ofloxacin resistance-associated gyrA gene,in Mycobacterium leprae isolates from patients with recurring or treatment-resistant leprosy.

Efficacy comparison of uniform versus routine multidrug therapy for the treatment of multi-bacillary leprosy patients based on bacterial index and leprosy reactions / 中华皮肤科杂志

Objective To compare the efficacy of uniform multi-drug therapy (UMDT) versus routine multi-drug therapy (RMDT) for the treatment of multi-bacillary (MB) leprosy patients based on bacterial index changes and frequencies of leprosy reaction.Methods This study recruited newly diagnosed leprosy patients after taking informed consent in three districts of Guizhou province as well as in one district of Yunnan province from November 2003 to June 2005.The patients received 6-month UMDT or 2-year RMDT.Clinical follow up and bacterial reexamination were carried out once a year.Changes of bacterial index (BI) and frequencies of leprosy reaction were compared between the patients receiving RMDT and UMDT.Results A total of 166 patients received UMDT and 170 received RMDT in this study.Among the UMDT-treated patients,114 were skin smear positive,and 83 had been followed up for 42 months; of the RMDT-treated patients,149 underwent all the bacterial examinations during a 48-month follow up.The mean bacterial index decreased from 2.84 before treatment to 0.33 at the end of the 42-month follow up in the 83 patients,and from 2.55 to 0.26 at the end of the 48-month follow up in the 149 patients,with no significant difference in the changes of bacterial index between the two groups (t =0.77,P ＞ 0.05).Bacterial index became negative in 73.5％ (61/83) of the UMDT-treated patients and in 77.2％ (115/149) of the RMDT-treated patients (x2 =0.40,P＞ 0.05)at the end of follow up.During the follow up peroid,the incidence of type Ⅰ leprosy reaction was 14.6％ (13/89) in the UMDT group,significantly higher than that in the RMDT group (3.4％ (5/149),x2 =10.08,P＜ 0.01 ).Conclusions There is no significant difference in mean bacterial index changes and bacterial clearance rate during the follow up peroid between UMDT- and RMDT-treated patients.The incidence of type Ⅰ leprosy reaction is higher in the UMDT group than in the RMDT group,and further investigation is needed to clarify the mechanisms underlying the phenomenon.

A 2-year follow-up study on 166 leprosy patients treated with uniform multidrug therapy / 中华皮肤科杂志

Objective To assess the efficacy of 6-month uniform multidrug therapy in various types of leprosy. Methods A field trial was conducted among 166 patients with different types of leprosy. All patients were treated with uniform multidrug therapy for 6 months, then followed up for 2 years. Clinical and bacterio-logical improvements were evaluated. Results Among the 166 patients, 31 dropped out due to various reasons,and 135 completed the 6-month treatment and 2-year follow-up. Among the 135 patients, 45 (33.3%) were skin smear negative, and the other smear-positive 90 had an average bacterial index (BI) of 2.91±1.45 (range: 0.1-6.0) before treatment. At the end of the 2-year follow-up, the 45 skin smear-negative patients showed 93.3% improvement in skin lesions and 80.0% improvement in nerve impairments, and the smear-posi-tive 90 patients showed 95.6% improvements in skin lesions and 77.8% improvement in nerve impairments.Skin smear turned negative in 49 (54.4%) out of the smear-positive 90 patients with the average BI declining to 0.66±0.99. The annual decrease in BI reached 0.9 during the first 2.5 years after the beginning of treat-ment. Twenty-five patients developed leprosy reaction during the follow-up, including 13 cases of type Ⅰ leprosy reaction and 12 cases of type Ⅱ leprosy reaction. Relapse was noted in 1 patient with muhibacillary leprosy 13 months after the termination of treatment. Conclusions The short-term efficacy of uniform multidrug therapy is similar to that of 2-year treatment with routine multidrug therapy. However, further studies are required to survey the incidence of leprosy reaction and relapse in patients treated with uniform multidrug therapy.

Expression and clinical significance of multidrug resistance gene in epithelial ovarian cancer / 中国基层医药

Objective To study the expression of muhidrug resistance( MDR1 ) ,and clinical significance of MDR1 gone expression in EOC. Methods Reverse transcription polymerase chain reaction was used to determine the expression of MDR1 in 27 cases of epithelial ovarian cancer,38 cases of benign tumor and 20 cases of normal ovarian tissue. The expression rate of MDR1 and the clinical significance was explored. Results The expression rate of MDR1 gone in malignant,benign tumor and normal tissue of ovary was74.1%, 15.7 % and 0 % respectively. The levd of MDR1 gone expression in EOC was obviously higher than that in benign tumor(P<0.01 ). The non-respond-era to combination chemotherapy exhibited higher ratio of MDR1 expression than the respondera( P<0.05 ). Conclu-sion The expression of MDR1 is higher in EOC than that in normal ovary tissue and benign tumor. The expression of MDR1 is closely related to the tumor response to chemotherapy.

Pharmacokinetics study of astragaloside Ⅳ by intravenous administration with intermittent blood sampling in intact rats / 中国临床药理学与治疗学

AIM: To establish a sensitive method for quantitative determination of astragaloside Ⅳ (AGS-Ⅳ) in plasma and a preliminary evaluation of its pharmacokinetics parameters in intact rats. METHODS: A liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) was applied for determining AGS-Ⅳ in plasma by using digoxin as the internal standard (I.S.). Six rats were given AGS-Ⅳ 2.0 mg/kg by intravenous infusion for 5 min. Blood samples were drawn intermittently with each intact rat from left femoral artery at 0.025, 0.05, 0.1, 0.25, 0.5, 1, 2, 4, 6, 10, 14 and 24 h after medication. The samples were prepared by solid phase extraction and analyzed through a triple quadrupole mass spectrometer equipped with an electrospary probe. The samples were monitored in selected ion recording (SIR) mode of positive ions by using target ions at m/z 807.5 for AS- Ⅳand at m/z 803.5 for I.S. RESULTS: Calibration curves were linear over the ranges 1-1 000 ng/mL for AGS-Ⅳ (r=0.9992). The intra-and inter-day assay variability values were less than 6% and 8%, respectively. Extraction recoveries from plasma were 92.8%-98.4% for AGS-Ⅳ and 80.0%-90.9% for digoxin, respectively. The lower limit of quantitation (LLOQ) for AGS-Ⅳ was 0.5 ng/mL. The concentration-time curves of AGS-Ⅳ for each rat were fitted to an open two-compartment model by CAPP program. The pharmacokinetics parameters of AGS-Ⅳ were as following: the elimination half-life (t1/2β), clearance rate (CL), distribution volume at steady state (Vss), and AUC0-∞ were (3.46±0.52) h, (0.47±0.02) L/h, (0.76±0.16) L/kg and (4.27±0.19) μg·mL-1·h, respectively. CONCLUSION: These results show that this method is satisfied for the measurements of pharmacokinetics study for AGS-Ⅳ.

Protective effects of bendazac lysine against development of diabetic nephropathy / 中国临床药理学与治疗学

To investigate the protective effects of bendazac lysine (BDL) on diabetic nephropathy (DN) in vitro and in vivo experiments. METHODS: After rat mesangial cells were cultured in 3 concentrations of BDL for 36 h, the percentages of S phase of cells were determined by flowcytometry; the transforming growth factor β1 (TGF-β1) mRNA level was assayed by reverse transcription PCR; and two main components of extracellular matrix (ECM), collagen Ⅳ and laminin, were determined by radioimmunoassay. Streptozotocin (STZ) induced diabetic rats were administered BDL at doses of 100, 200, 400 mg/kg for 8 weeks. The physical behavior and HbAlC levels of rats were observed. RESULTS: In the presence of high glucose and H2O2, the percentages of S phase of cells were lowered, and TGF-β1 mRNA level, collagen Ⅳ and laminin level were significantly increased. When compared with those in the high glucose group, the percentages of S phase of cells were significantly raised, and the levels of TGF-β1 mRNA, collagen Ⅳ and laminin were statistically decreased. The physical behavior of high BDL treated rats restored to be vibrant, vigorous and weight gaining, and the HbAlC level was significantly reduced. CONCLUSION: BDL has the protective effects against damage caused by DN, and is a potential drug candidate worth further study in preventing and treating DN.

Pharmacokinetics and relative bioavailability of telmisartan in male healthy Chinese volunteers / 中国临床药理学与治疗学

AIM: To compare pharmacokinetics and relative bioavailability of telmisartan capsule (T) and telmisartan tablet(R). METHODS: 20 male healthy Chinese volunteers were enrolled in a randomized two-way crossover designs with a single-oral dose study(80 mg once per day for each preparation). The plasma telmisatan concentration was determined by HPLC- fluorescence detector. Plasma levels of telmisatan were followed up to 96 h. Area under the telmisartan concentration time curve was calculated by variance analysis and the bioequivalent was determined by two one-side t-test. RESULTS: A two-compartment model was adopted in telmisartan plasma concentration-time data analysis. The pharmacokinetic parameters of T and R in single-dose study including Cmax (μg·L-1), Tmax (h), T1/2β (h), MRT(h), AUC0-92(μg·h·L-1) were as following: 456±253 and 760±314, 1.61±0.71 and 1.08±0.36, 22.39±6.29 and 21.08±5.24, 27.02±6.23 and 24.27±5.79, 3454±1050 and 3635±1300, respectively. Statistically significant differences were observed between the parameter values of the two products in Cmax and Tmax; whereas there was no statistically significant difference between AUC0-∞μg·h·L-1 (3601±1095 and 3767±1399). The relative bioavailability for T was 97.28%±12.74%. CONCLUSION: The test telmisartan capsule is bioequivalent to the reference tablet.

The expression of hepatitis C virus truncated core and EGFP fusion gene in Sf9 cells / 临床检验杂志

Objective To construct recombinant baculovirus expression vector containing hepatitis C virus(HCV) truncated core gene and EGFP gene,and to study the antigenicity of the fusion protein expressed in Sf 9 cells.Methods PCR-amplified HCV truncated core gene and EGFP gene were cloned into the transposed vector pFastBac1 to construct a recombinant plasmid pFastCt-EGFP,by which E.coli DH10Bac was transformed to get the recombinant BacmidCt-EGFP.Insect Sf 9 cells were transfected with BacmidCt-EGFP and the expression of fusion protein Ct-EGFP was screened by SDS-PAGE and Western blotting.Results SDS-PAGE and Western blot analysis showed that fusion protein Ct-EGFP was expressed with the molecular mass of 40 kD.ELISA results showed that the fusion protein reacted with 15 of 28(54%) anti-HCV positive sera.Conclusion The fusion protein Ct-EGFP was expressed in insect Sf9 cells and showed partial antigenicity.

Activity of Home-made Ofloxacin Against M. leprae in Mice and its Clinical Trial in Multibacillary Leprosy / 中华皮肤科杂志

Seventy days after inoculation of 1. 0 ? 104 M. leprae to the foot--pads,the mice were treated with home-made ofloxacin 150mg/kg daily by gavage 5 times weekly for 63 days. The results showed that M. leprae multiplied well in the foot--pads of untreated mice,but no growth of M. lepare were found in the foot-pads of the mice treated with home-made ofloxacin, imported ofloxacin or rifampin until 12 months after infection of M. leprae. Eleven newly diagnosed and untreated BL/LL patients and 2 recently relapsed patients after dapsone monotherapy were treated with home--made ofloxacin 400mg daily 6 times weekly for 12 weeks. The results showed that the skin lesions of all patients markedly improved at the end of therapy. The mean morphological index(MI) in skin smear decreased from 11. 89% before therapy to 2. 59% at the end of 2 week treatment,and to 0% at the end of 4 week treatment. The mean bacteriological index(MI) decreased from 4. 28 before therapy to 3. 90 at the end of therapy. During the therapy, 4 patients developed type Ⅱ lepra reaction, but all patients tolerated the drug well. The study showed that the therapeutic effect of home-made ofloxacin is similar to that of imported one as reported in the literature. The home-made ofloxacin can be used in multidrug therapy for leprosy.

Evaluation of Effectiveness in implementing Leprosy Elimination Campaigns in High Leprosy- Epidemic Areas in Yunnan, Guizhou and Sichuan Provinces / 中华皮肤科杂志

Objective To evaluate the effectiveness of Leprosy Elimination Compaigns (LEC) integrated with routine case- finding of leprosy in the high leprosy- epidemic areas in Yunnan, Guizhou and Sichuan Provinces. Methods Extensive health education of leprosy in the community, training of paramedical workers on leprosy, clue survey and contact survey were carried out to make diagnosis and provide treatment. Results A total of 122 new leprosy cases were detected in 6 high leprosy- epidemic counties through LEC in 1999 with a detection rate of 3.7/100 000, but in contrast, the annual number of newly detected leprosy cases was 67 cases with an average detection rate of 2/100 000 during the period of 3 years before LEC. Among the newly detected leprosy cases, about 47％ were leprosy household contacts. Conclusion LEC combined with routine activities of case finding can improve the detection of the back- log cases in the communities. In the high epidemic areas, especially in the remote and difficult- to- access areas, majority of leprosy cases can be detected through combining active and passive case- finding methods, providing extensive health education, improving leprosy services in skin clinic, leprosy contact and clue surveys.

Epidemiological and Clinical Analyses of Leprosy in Children in China / 中华皮肤科杂志

Objective To study epidemiological and clinical patterns of leprosy in children in China. Methods The data of leprosy in children from 1989 to 1998 in China were analyzed in terms of gender, infection source, detection mode, skin lesion, nerve damage, leprosy reaction, clinical type and skin smear. Results A total of 22 437 leprosy cases were detected during 1989～ 1998, of which 912 (4.1％ ) were child cases (560 males and 352 females). Average delay in detection was 1.13 years (n=909). The main source of infection was close contact within families, accounting for 69.2％ , and majority of cases were detected through active modes. Among children with leprosy, 96.8％ were with skin lesions, 76.0％ with nerve damage, 4.7％ with leprosy reactions, 12.4％ with grade II disability and 41.2％ with positive skin smears. The average proportion of child cases was 4.2％ in Yunnan, Guizhou and Sichuan Provinces, and 1.3％ in Shandong, Jiangsu and Zhejiang Provinces. The proportion of child cases was stable in Guizhou and Sichuan Provinces during this period, whereas in 1998 it significantly increased to 11.6％ in Yunnan. Conclusion The present study suggests that proportion of children with leprosy is one of the sensitive indicators of leprosy endemicity. The sources of leprosy infection in children is predominately due to the contact with active cases within families.