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Biomedical subjects

B Ji

Publications and source records attributed to B Ji.

At least 73 records · Page 4Linked to original sources
PubMed1994

Further study of the effectiveness of single doses of clarithromycin and minocycline against Mycobacterium leprae in mice.

The anti-Mycobacterium leprae activities of single doses of rifampin (RMP), clarithromycin (CLARI), or minocycline (MINO) alone, and various combinations of CLARI + MINO were determined in immunocompetent mice by the kinetic method. A single dose of RMP 10 mg/kg, CLARI 100 mg/kg or 200 mg/kg, MINO 25 mg/kg or 50 mg/kg alone, or various combinations of CLARI & MINO were active. RMP was more active than the other treatments; the activity of CLARI 100 mg/kg was greater than that of 50 mg/kg, but did not differ significantly from that of 200 mg/kg; MINO 50 mg/kg was more active than 25 mg/kg; and none of the combinations of CLARI + MINO was more active than any of the stronger components administered alone. Therefore, both CLARI and MINO may be applied, either alone or in combination, as components of monthly administered, fully supervised, multidrug regimens for the treatment of multibacillary leprosy. Taking into account the effectiveness of the drugs and the comparative pharmacokinetic data, we propose that the optimal dosage in human trials is CLARI 1000 mg per month or MINO 200 mg per month.

Animals↗
PubMed1993

Powerful bactericidal activities of clarithromycin and minocycline against Mycobacterium leprae in lepromatous leprosy.

Thirty-six patients with newly diagnosed lepromatous leprosy were allocated randomly to three groups and treated for 56 days with minocycline (100 mg daily), clarithromycin (500 mg daily), or clarithromycin (500 mg) plus minocycline (100 mg daily). All groups had rapid and remarkable clinical improvement and significant decline of the bacterial and morphologic indices in skin smears during treatment. More than 99% and > 99.9% of the viable Mycobacterium leprae had been killed by 28 and 56 days of treatment, respectively, as measured by inoculation of organisms recovered from skin samples, taken before and during treatment, into the footpads of immunocompetent and nude mice. Clinical improvement and bactericidal activity did not differ significantly among the three groups. Adverse reactions were rare and mild, and no laboratory abnormality was detected during the trial. Both clarithromycin and minocycline displayed powerful bactericidal activities against M. leprae in leprosy patients and may be considered important components of new multidrug regimens for the treatment of multibacillary leprosy.

Adolescent↗
PubMed1993

Powerful bactericidal activity of sparfloxacin (AT-4140) against Mycobacterium tuberculosis in mice.

The bactericidal activities of various monotherapies and combined regimens were compared in mice at different stages after infection with Mycobacterium tuberculosis. These therapies mimicked the initial and continuation phases of chemotherapy for human tuberculosis. As monotherapy, the bactericidal activity of sparfloxacin (SPFX) was dose related; the activity of SPFX at 100 mg/kg of body weight was comparable to that of rifampin (RMP) and was significantly greater than those of isoniazid (INH), pyrazinamide (PZA), or ofloxacin (OFLO) during both the initial and continuation phases of chemotherapy. During the initial phase, the addition of SPFX did not enhance or diminish the activities of the combinations INH-RMP-PZA or RMP-PZA; the combinations SPFX-PZA-streptomycin (SM) and SPFX-PZA-kanamycin (KANA) displayed powerful bactericidal activity. Because the area under the plasma concentration-time curve of SPFX (100 mg/kg) in mice is similar to that of SPFX (400 mg) in humans, the promising bactericidal activity displayed by SPFX in mice might be achieved in humans by administration of the drug in a clinically tolerated dosage. In addition, the combinations SPFX-PZA-SM and SPFX-PZA-KANA may be useful for the treatment of multidrug-resistant tuberculosis.

Animals↗
PubMed1993

Effectiveness of rifampin, rifabutin, and rifapentine for preventive therapy of tuberculosis in mice.

To identify alternative regimens for preventive therapy of tuberculosis, the pharmacokinetics and antimicrobial activities of rifampin (RMP), rifabutin (RBT), and rifapentine (RPT) were compared in BCG-vaccinated and M. tuberculosis-infected immunocompetent mice. RPT showed the highest serum peak level (Cmax) and the longest half-life (t1/2), whereas RBT displayed the lowest Cmax and the shortest t1/2. On weight-to-weight basis, both RPT and RBT were more bactericidal than RMP. The activity of RMP was significantly reduced when the frequency of administration was reduced from six to three times weekly, whereas significant bactericidal activity was still observed in mice treated with RPT, 10 mg/kg up to once fortnightly, or RBT, 10 mg/kg twice weekly. Because the bactericidal activity of RBT, 10 mg/kg six times/wk for 6 wk, or RPT, 10 mg/kg two times/wk for 12 wk, was comparable to that of RMP, 10 mg/kg six times/wk for 12 wk in mice, the two regimens are appropriate for clinical trials of preventive therapy of tuberculosis.

Animals↗
PubMed1992

Selection of resistant mutants of Mycobacterium avium in beige mice by clarithromycin monotherapy.

Beige mice were inoculated intravenously with 10(7.90) CFU of Mycobacterium avium 101. Among the untreated control mice, when the mean CFU per spleen increased to a level greater than 10(8), small numbers of organisms resistant to clarithromycin (CLARI) were isolated from some of the spleens; the frequency of CLARI-resistant mutants was estimated to be between 10(-8) and 10(-9). In mice treated with 200 mg of CLARI per kg of body weight six times weekly, however, CLARI-resistant organisms were isolated from the spleens of all mice examined after treatment for 8 weeks; the mean CFU per spleen and the frequency of resistant mutants were significantly greater than those of control mice and increased further after treatment for 16 weeks. The MICs of CLARI against the resistant organisms isolated from both control and treated mice were > or = 512 micrograms/ml.

Animals↗
PubMed1992

Antagonism between isoniazid and the combination pyrazinamide-rifampin against tuberculosis infection in mice.

Mice that had been inoculated intravenously with 6.30 log10 Mycobacterium tuberculosis H37Rv 14 days earlier were administered one of three combinations of drugs, i.e., isoniazid (INH)-rifampin (RMP)-pyrazinamide (PZA), INH-RMP, and RMP-PZA, during an initial 2-month period to mimic the initial phase of chemotherapy for human tuberculosis and during a later 4-month period to mimic the continuation phase of chemotherapy. At the end of the initial phase, all three combined regimens were found to have been highly effective in terms of the number of CFUs in the spleens of infected mice. The bactericidal activities of INH-RMP-PZA and INH-RMP were similar, whereas that of RMP-PZA was significantly greater. The spleens of all of the mice that had been treated initially with INH-RMP-PZA were culture negative by the end of 6 months of treatment, regardless of the regimen employed during the continuation phase. However, after an additional period of 6 months without treatment, the proportion of spleen culture positivity, or relapse rate, was significantly smaller in the subgroup treated with RMP-PZA during the continuation phase than in the subgroups treated with INH-RMP-PZA or INH-RMP; the relapse rate did not differ significantly between the latter two subgroups. These results suggest that antagonism occurs between INH and the combination RMP-PZA during both the initial and continuation phases of chemotherapy, compromising the benefit conferred by the addition of PZA to the combined regimen. The preliminary pharmacokinetic analysis suggested that the pharmacological interaction between INH and RMP was very likely to be involved in the mechanism of antagonism, as concomitant treatment with INH had significantly reduced the peak serum level and the area under the serum concentration-time curve of RMP in mice.

Animals↗
PubMed1992

Relapses in multibacillary leprosy patients after stopping treatment with rifampin-containing combined regimens. Marchoux Chemotherapy Study Group.

During the decade between the mid 1970s and the mid-1980s, 12 rifampin (RMP)-containing combined regimens were tested among lepromatous leprosy patients in the Institut Marchoux. The 384 patients who were seen at least once during the period beginning 12 months after completion of treatment were considered eligible for analysis of the relapse rate. By the end of May 1991, relapse, manifested by a significant increase of the bacterial index (BI) and the appearance of new lesions with a BI greater than that of preexisting lesions, had been observed in 68 (17.7%) of these patients. Relapse was confirmed by the presence of viable Mycobacterium leprae in skin biopsy specimens obtained from 54 of the first 61 cases; virtually all of the isolated strains remained susceptible to RMP. The relapses occurred late, about 5 +/- 2 years after stopping treatment; the shorter the duration of RMP administration, the earlier the appearance of the relapse. The variations of the relapse rate among regimens were considerable: total relapse rate ranged from 2.9% to 27.8%, and the relapse rate per 100 patient-years of observation ranged from 0.8 to 6.9. Among the 12 regimens, only the WHO/MDT yielded an acceptable relapse rate (defined as a rate lower than 1.0 per 100 patient-years). However, because the mean duration of follow up was shortest among the patients treated with WHO/MDT, the relative low relapse rate among these patients must be interpreted with great caution.

Drug Therapy, Combination↗
PubMed1992

Short-term trial of clofazimine in previously untreated lepromatous leprosy.

Forty-five previously untreated lepromatous leprosy patients were allocated randomly to three groups and treated, respectively, with Regimen A, standard dosage of clofazimine (CLO) in multidrug therapy (MDT) regimen; Regimen B, CLO 600 mg once every 4 weeks; and Regimen C, CLO 1200 mg once every 4 weeks. The duration of the trial was 24 weeks. By the end of the trial, although a few patients in each group did not improve at all clinically, the majority of patients showed clinical amelioration but the responses were slow. While the mean morphological index dropped to the baseline after 24 weeks of treatment, the mean bacterial index did not change significantly. About 80% of the patients in each group remained nasal-smear positive at the end of the trial, but the bacterial loads steadily declined. No significant difference has been detected in these parameters among the three groups. The patients tolerated the regimens very well and the side effects were mild. The results of serial mouse foot pad inoculation demonstrated that the positivity rates of multiplication of Mycobacterium leprae in mice and the proportions of viable organisms reduced gradually in all groups. Because the positivity rate at week 24 in Group C did not differ significantly from Group A, but was significantly smaller than that of Group B, we conclude that Regimen C was as active as Regimen A and could be applied for monthly supervised treatment along with rifampin; Regimen B is less effective and should not be used for the treatment of leprosy.

Adolescent↗
PubMed1992

Bactericidal activities of single or multiple doses of various combinations of new antileprosy drugs and/or rifampin against M. leprae in mice.

The bactericidal activities against Mycobacterium leprae of single or multiple doses of various combinations of new antileprosy drugs [minocycline (MINO), clarithromycin (CLARI), ofloxacin (OFLO), and sparfloxacin (SPFX)] and/or rifampin (RMP) were titrated in immunocompetent mice by the proportional bactericidal method. Drugs were administered by gavage at the following dosages (mg/kg) per dose: RMP 10, MINO 25, CLARI 100, OFLO 150, and SPFX 50. All 15 regimens exerted significant bactericidal activities, at least 96% of viables were killed. The activity of a single dose MINO + CLARI was only slightly inferior to that of RMP, and the activities of a single dose OFLO/SPFX + MINO + CLARI were similar to that of RMP. This suggests that either MINO + CLARI or OFLO/SPFX + MINO + CLARI may be administered once monthly together with RMP 600 mg for the treatment of multibacillary (MB) leprosy, and monthly administration of MINO + CLARI or OFLO/SPFX + MINO + CLARI may also be employed for the treatment of RMP-resistant MB leprosy. Because the killing effects of multiple doses of the combinations were so powerful, comparison of the bactericidal activities of these regimens was beyond the sensitivity of the immunocompetent mouse model, and are being tested in the nude mouse model. Although SPFX is more active against M. leprae than OFLO on a weight-to-weight basis, when both drugs were administered in mice at dosages equivalent to clinically tolerated dosages in humans, SPFX did not show more superiority than OFLO, and its real advantage over OFLO in the treatment of leprosy remains unclear.

Animals↗
PubMed1991

In vitro and in vivo activities of sparfloxacin (AT-4140) against Mycobacterium tuberculosis.

The in vitro and in vivo activities of sparfloxacin (AT-4140) against M. tuberculosis are reported. The MICs of sparfloxacin for 50% and 90% of 18 clinical isolates were, respectively, 0.25 and 0.5 mg/l, one or two dilutions lower than that of ciprofloxacin and ofloxacin. In mice infected intravenously with 0.1 mg M. tuberculosis H37Rv strain, the minimal effective dosage of sparfloxacin, as assessed by survival rate, spleen enlargement and gross lung lesions, was 12.5 mg/kg. The activities of various regimens were in the following rank order: INH 25 mg/kg = sparfloxacin 50-100 mg/kg greater than ofloxacin 300 mg/kg greater than (or =) sparfloxacin 25 mg/kg greater than sparfloxacin 12.5 mg/kg greater than (or =) ofloxacin 200 mg/kg greater than ofloxacin 100 mg/kg greater than (or =) negative control. Therefore, on a weight to weight basis, sparfloxacin was six to eight-fold more active against M. tuberculosis infection in mice than ofloxacin. In addition, WIN 57273, a new broad-spectrum fluoroquinolone, at a dosage of 100 mg/kg daily, was inactive against M. tuberculosis infection.

Animals↗
PubMed1991

Activities of pefloxacin and ofloxacin against mycobacteria: in vitro and mouse experiments.

The minimal inhibitory concentrations for 90% of strains (MIC90) of ofloxacin against Mycobacterium tuberculosis and Mycobacterium xenopi was 2 mg/l. This was three dilutions lower than that of pefloxacin and was well within the range of drug concentrations achievable in man. The antituberculosis activities of both quinolones were independent of resistance of the strains to other antimycobacterial agents. Mycobacterium avium-intracellulare was resistant to both compounds with MIC90s greater than 16 mg/l. The maximum serum levels (Cmax) of both compounds increased proportionally with increasing dose size. The terminal elimination half-life (T1/2) of pefloxacin was longer than that of ofloxacin, but the T1/2 of both compounds in mice were much shorter than in man. The area under the concentration curve (AUC) of pefloxacin was double than that of ofloxacin. In the mouse, pefloxacin at doses up to 150 mg/kg daily was inactive against M. tuberculosis infection: in terms of survival rate the minimal effective dose of ofloxacin against M. tuberculosis infection was 150 mg/kg daily when given by gavage or by incorporation into the mouse diet at a concentration of 0.1%, but in terms of cfu counts, ofloxacin 150 mg/kg daily only displayed a moderate degree of activity similar to ethambutol 100 mg/kg daily. The therapeutic effects of ofloxacin against M. tuberculosis infection were dose-related: 300 mg/kg daily by gavage or 0.4% in mouse diet displayed much better therapeutic effects than lower dosages. Since the AUC in mice treated with ofloxacin 150 mg/kg daily is close to that in man treated with a clinically tolerated dose--600 mg daily--such a dosage may be only moderately effective against human tuberculosis.

Animals↗
PubMed1991

Effectiveness of clarithromycin and minocycline alone and in combination against experimental Mycobacterium leprae infection in mice.

As determined by the proportional bactericide method, clarithromycin had strong bactericidal activity against Mycobacterium leprae. Clarithromycin was administered to mice by gavage as 20 daily doses at dosages of 12.5 to 50 mg/kg of body weight. At a dosage of 25 mg/kg, minocycline was more active than clarithromycin at a dosage of 50 mg/kg. Additive effects were displayed with the combination of clarithromycin (50 mg/kg) and minocycline (25 mg/kg), both of which were administered daily by gavage, and of clarithromycin and minocycline, both of which were administered daily by gavage at dosages of 25 mg/kg each, with rifampin at a single oral dose of 10 mg/kg.

Animals↗
PubMed1991

Effect of pH on the in vitro potency of clarithromycin against Mycobacterium avium complex.

Employing 7H11 agar medium at pH 6.6, the MICs of clarithromycin for 50% (MIC50) and 90% (MIC90) of 19 strains of Mycobacterium avium complex were 8 and 16 micrograms/ml, respectively. However, the MICs were 2 to 3 log2 dilutions lower in the 7H11 medium adjusted to pH 7.4, and the MICs on 10% OADC (oleic acid-albumin-dextrose-catalase)-enriched Mueller-Hinton agar at pH 7.3 were also 2 log2 dilutions lower than those measured on 7H11 agar at pH 6.6. Therefore, clarithromycin is more active at a physiologic than at an acidic pH.

Clarithromycin↗
PubMed1991

Ofloxacin for the treatment of leprosy.

Among the major commercially available fluoroquinolones, ciprofloxacin was inactive against M. leprae in mice; pefloxacin was active, 50 mg/kg daily showed bacteriostatic activity but 150 mg/kg daily displayed bactericidal activity; ofloxacin was more active than pefloxacin, 50 mg/kg daily exerted the same level of bactericidal effect as pefloxacin 150 mg/kg daily, and ofloxacin 150 mg/kg displayed profound killing activity. Two clinical trials with 6 months of pefloxacin and/or ofloxacin in 31 previously untreated lepromatous patients have been completed. Pefloxacin 400 mg twice daily or 800 mg once daily or ofloxacin 400 mg once daily were equally effective; definite clinical improvement with drastically decrease of morphological index to the baseline were observed in all patients at 2 months after beginning of treatment; about 99.99%, or 4 "logs", of organisms viable on Day 0 were killed by 22 doses of either pefloxacin or ofloxacin. The side effects from the two trials were rare and mild, and the patients tolerated extremely well the combinations of pefloxacin/ofloxacin plus multidrug therapy (MDT) regimen for multibacillary leprosy recommended by WHO. The amount of rifampicin-resistant mutants in lepromatous patients before treatment are no more than 4 "logs", thus, all rifampicin-resistant mutants may be eliminated by 22 doses of either pefloxacin or ofloxacin. It is, therefore, possible that the combination of ofloxacin and rifampicin may considerably shorten the required duration of MDT.

Animals↗
PubMedDate not supplied

Cell culture and animal studies for intracerebral delivery of borocaptate in liposomal formulation.

The efficacy of a liposomal formulation for intracerebral delivery of borocaptate (BSH) to brain tumor cells has been investigated using cell culture to study BSH uptake and persistence and using tumor-bearing rats to determine BSH distribution in the brain. During a 16-hr incubation, cellular uptake of BSH solution or BSH liposomal formulation was similar. However, the cellular persistence of BSH greatly increased when BSH was present in liposome. The differences in cellular persistence for BSH solution and BSH-loaded liposomes were significant both in 12-hr and 24-hr incubation experiments (p < 0.05 and p < 0.01, respectively). For the studies involving tumor-bearing rats, BSH level in tumor tissue was significantly higher than that in normal brain tissue at 2 hr and 6 hr after intracerebral injection of BSH-loaded liposomes (p < 0.01). Our study indicated that the liposomal formulation enhanced cellular persistence of BSH in tumor cells and therefore favored the boron accumulation in the cells. With the prolonged physical retention of liposomes at the local injection site and the cellular retention of BSH enhanced by the liposomes, the intracerebral delivery of BSH using liposomal formulation may provide an effective boron delivery approach for boron neutron capture therapy of brain tumors.

Animals↗
PubMedDate not supplied

Cell culture studies of a carborane cholesteryl ester with conventional and PEG liposomes.

A new cholesterol-carborane conjugate (BCH) has been synthesized as a potential targeting agent for boron neutron capture therapy (BNCT) of cancers. The compound is extremely water insoluble and was formulated in two liposomal formulations to determine if the compound could be adequately taken up by 9L rat glioma cells in cell culture. Several factors potentially affecting the cellular uptake were evaluated, such as concentration of BCH in the incubation medium, incubation time, cell confluence, and the addition of polyethylene glycol (PEG) phospholipids to the liposomal formulation. The studies indicated that the cellular uptakes of BCH in the conventional and PEG liposomal formulations were 49.1 and 45.9 microg boron/g cells, respectively. Therefore, this compound, formulated in both liposomal formulations, delivered sufficient levels of boron to cancer cells in vitro, indicating that BCH is a promising approach for use in BNCT. The uptake appeared to depend upon BCH concentration in the media as well as the confluence of the cells. The greater boron uptake by nonconfluent cells indicated that active growth of cells was a factor in the uptake of this compound.

Animals↗