RESUMO
Polygonum capitatum Buch.-Ham. ex D. Don is traditionally used by Hmong for the treatment of urinary tract infections and pyelonephritis. Information regarding the pharmacokinetic behavior of the extract in the condition of pyelonephritis is lacking. In the present study, we aimed to compare the pharmacokinetic properties of gallic acid (GA), protocatechuic acid (PCA), and quercitrin (QR)-the main bioactive constituents in the herb-in normal and pyelonephritis rats. The plasma samples were collected at various time points after administration of a single dose of Polygonum capitatum extract. The plasma level of GA, PCA, and QR at the designed time points was determined by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and drug concentration versus time plots were constructed to estimate the pharmacokinetic parameters. The AUC(0-t), AUC(0-∞), MRT(0-t), and CL of GA, PCA, and QR in pyelonephritis rats was significantly different from those of the normal rats. The results indicated that the three constituents have higher rate of uptake and slower rate of elimination in the rats with pyelonephritis, suggesting altered rate and extent of drug metabolism.
Assuntos
Ácido Gálico/farmacocinética , Hidroxibenzoatos/farmacocinética , Extratos Vegetais/uso terapêutico , Polygonum/química , Quercetina/análogos & derivados , Animais , Medicamentos de Ervas Chinesas/uso terapêutico , Feminino , Pielonefrite/tratamento farmacológico , Pielonefrite/metabolismo , Quercetina/farmacocinética , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: Here we report the serum carnitine ester profile during and after 1g iv/day L-carnitine supplementation in haemodialysis patients. MATERIALS AND METHODS: Seven patients were studied over 29 weeks. After a control day, 12 weeks of replacement therapy was introduced followed by 17 weeks of washout period. The serum acylcarnitine concentrations were determined by isotope dilution ESI MS/MS technique. RESULTS: At baseline significantly decreased free carnitine (48%, p < 0.01) and a 1.5-16-fold elevation of 16 out of 27 acylcarnitines were detected in HD patients compared with the controls. On the last day of L-carnitine supplementation a 1.6-4.8-fold increase was observed in the acylcarnitine levels compared with day 0; the increase-profile was achieved in four different patterns. The increase rate was rapid and early saturable for C5, C5OH, C6DC, C8:1, C10DC and C18:2 esters, slower for C2, C4, C6, C18 and C18:1 esters, it was slowest and reached a late plateau for C3, C8DC, C14:2, C16 and C16:1, and finally almost gradual increase was seen for 11 acylcarnitines. Three months after the cessation of carnitine treatment marked concentration drops were found for almost all acylcarnitines (by 11-74 % of week 12, p < 0.05); the values further decreased over the five remaining weeks of the observation period. CONCLUSION: Carnitine administration affected the levels of circulating esters in different dynamics and kinetics suggesting a regulated, non-random adaptive reallocation of nutrients. A considerable washout was achieved 3 months after discontinuation of the supplementation; however, the profile still was suggestive for presence of rest of accumulated supplement.
Assuntos
Carnitina/administração & dosagem , Suplementos Nutricionais , Glomerulonefrite/terapia , Nefrocalcinose/terapia , Pielonefrite/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carnitina/sangue , Carnitina/farmacocinética , Estudos de Casos e Controles , Feminino , Glomerulonefrite/metabolismo , Humanos , Pessoa de Meia-Idade , Nefrocalcinose/metabolismo , Estudos Prospectivos , Pielonefrite/metabolismo , Diálise Renal , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
Clinical studies were made in 117 patients with chronic pyelonephritis at the stage of sanatorium-and-health-resort treatment using hyperbaric oxygenation. Supplementing the "traditional" naftusya-based balneotherapy with hyperbaric oxygenation has been shown to potentiate the effect of the water on the course of the illness, functional condition of the urinary organs, to strengthen the potential of those systems res responsible for homeostasis of the peroxide oxygenation of lipids in the body, which fact validates a high efficiency of their combined use.
Assuntos
Oxigenoterapia Hiperbárica/métodos , Pielonefrite/terapia , Adulto , Balneologia/métodos , Doença Crônica , Diurese/fisiologia , Estâncias para Tratamento de Saúde , Humanos , Testes de Função Renal , Peroxidação de Lipídeos/fisiologia , Peróxidos Lipídicos/sangue , Malondialdeído/sangue , Pessoa de Meia-Idade , Pielonefrite/metabolismo , Pielonefrite/fisiopatologia , Superóxido Dismutase/sangueAssuntos
Águas Minerais/administração & dosagem , Pielonefrite/reabilitação , Adolescente , Formação de Anticorpos , Criança , Doença Crônica , Ritmo Circadiano , Estâncias para Tratamento de Saúde , Humanos , Imunidade Celular , Imunidade Inata , Fagocitose , Pielonefrite/imunologia , Pielonefrite/metabolismoRESUMO
We compared the efficacies of fluconazole (Flu), amphotericin B (AmB), and 5-fluorocytosine (5FC) monotherapies with the combination of Flu plus 5FC and Flu plus AmB in a rabbit model of Candida albicans endocarditis, endophthalmitis, and pyelonephritis. The dose of Flu used was that which resulted in an area under the concentration-time curve in rabbits equivalent to that seen in humans who receive Flu at 1,600 mg/day, the highest dose not associated with central nervous system toxicity in humans. Quantitative cultures of heart valve vegetations, the choroid-retina, vitreous humor, and kidney were conducted after 1, 5, 14, and 21 days of therapy. All untreated controls died within 6 days of infection; animals treated with 5FC monotherapy all died within 18 days. In contrast, 93% of animals in the other treatment groups appeared well and survived until they were sacrificed. At day 5, the relative decreases in CFU per gram in the vitreous humor were greater in groups that received Flu alone and in combination with 5FC or AmB than in groups receiving AmB or 5FC monotherapies (P < 0. 005) but were similar thereafter. In the choroid-retina, 5FC was the least-active drug. However, there were no differences in choroidal fungal densities between the other treatment groups. On days 5 and 14 of therapy, fungal densities in kidneys of AmB recipients were lower than those resulting from the other therapies (P < 0.001 and P < or = 0.038, respectively) and AmB-plus-Flu therapy was antagonistic; however, all therapies for fungal pyelonephritis were similar by treatment day 21. While fungal counts in cardiac valves of Flu recipients were similar to those of controls on day 5 of therapy and did not change from days 1 to 21, AmB therapy significantly decreased valvular CFUs versus Flu at days 5, 14, and 21 (P < 0.005 at each time point). 5FC plus Flu demonstrated enhanced killing in cardiac vegetations compared with Flu or 5FC as monotherapies (P < 0. 03). Similarly, the combination of AmB and Flu was more active than Flu in reducing the fungal density in cardiac vegetations (P < 0.03). However, as in the kidney, AmB plus Flu demonstrated antagonism versus AmB monotherapy in the treatment of C. albicans endocarditis (P < 0.05, P = 0.036, and P < 0.008 on days 5, 14, and 21, respectively).
Assuntos
Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Candidíase/tratamento farmacológico , Endocardite/tratamento farmacológico , Endoftalmite/tratamento farmacológico , Fluconazol/uso terapêutico , Flucitosina/uso terapêutico , Pielonefrite/tratamento farmacológico , Anfotericina B/farmacocinética , Animais , Antifúngicos/farmacocinética , Candida albicans/efeitos dos fármacos , Candidíase/metabolismo , Candidíase/microbiologia , Creatinina/sangue , Endocardite/metabolismo , Endocardite/microbiologia , Endoftalmite/metabolismo , Endoftalmite/microbiologia , Fluconazol/farmacocinética , Flucitosina/farmacocinética , Rim/metabolismo , Masculino , Testes de Sensibilidade Microbiana , Miocárdio/metabolismo , Pielonefrite/metabolismo , Pielonefrite/microbiologia , Coelhos , Análise de Sobrevida , Fatores de Tempo , Corpo Vítreo/metabolismoRESUMO
ABT-719 is a 2-pyridone antimicrobial which inhibits DNA gyrase activity. It has considerable subcutaneous (sc) and oral efficacy in the treatment of experimental pyelonephritis induced in carrageenan-treated mice by clinical isolates of Enterococcus faecalis, Enterococcus faecium, Escherichia coli, and Pseudomonas aeruginosa. Therapeutic ED50s, defined here as producing a 2 log10 reduction in kidney bacterial burden, provide a reliable end point for comparison of drug efficacy in this experimental infection. Therapeutic ED50s for ABT-719 against these infections were equal to or up to ten-fold lower than those for ciprofloxacin, used as a reference because of similarity in mode of action. Against E. faecalis, the therapeutic ED50s for ABT-719 were 4.5-13.6 mg/kg.day for sc administration and 6.8-8.9 mg/kg.day for oral administration. ABT-719 was more potent than ciprofloxacin and vancomycin against the E. faecalis strains, which showed ciprofloxacin and vancomycin resistance covering a range of MICs. Against E. faecium, the therapeutic ED50s for ABT-719 were 8.8 mg/kg.day (sc) and 9.4 mg/kg.day (oral). Against an isolate of E. faecium showing ciprofloxacin and vancomycin resistance the ED50 for ABT-719 to achieve a 1 log10 reduction in kidney bacterial burden was 17.9 mg/kg.day by sc administration. While ABT-719 had lower efficacy against this isolate than against others, ciprofloxacin and vancomycin failed to show efficacy. Against E. coli, the therapeutic ED50 for ABT-719 was 1.1 mg/kg.day (oral), and against P. aeruginosa, this value was 2.7 mg/kg.day (oral) with values against both of these pathogens similar to those for ciprofloxacin. ABT-719, which represents the new 2-pyridone compound class, has promise for the treatment of urinary tract infections, as suggested by the significant efficacy seen against experimental pyelonephritis caused by E. coli, P. aeruginosa and susceptible and resistant enterococci.
Assuntos
Antibacterianos/uso terapêutico , Enterococcus/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Pielonefrite/tratamento farmacológico , Animais , Antibacterianos/farmacocinética , Anti-Infecciosos/uso terapêutico , Avaliação Pré-Clínica de Medicamentos , Feminino , Fluoroquinolonas , Rim/efeitos dos fármacos , Rim/metabolismo , Camundongos , Camundongos Endogâmicos , Testes de Sensibilidade Microbiana , Pielonefrite/metabolismo , Pielonefrite/microbiologia , Piridonas/farmacocinética , Piridonas/uso terapêutico , Resultado do TratamentoRESUMO
30 patients were exposed to interference currents (IC) alone (group 1) versus 34 patients treated with IC plus iodobromine baths (group 2). After IC action on the region of the kidney projection patients of group 1 experienced positive changes in cellular and humoral immunity providing an antiinflammatory effect. In group 2, the improvement was seen in renal and urinary functions, 24-h urinary excretion of oxalates and calcium diminished. Interference current proved beneficial in chronic pyelonephritis patients with latent inflammation. The combined therapy was effective in patients at high risk of lithogenesis.
Assuntos
Banhos/métodos , Brometos/uso terapêutico , Terapia por Estimulação Elétrica/métodos , Iodetos/uso terapêutico , Pielonefrite/reabilitação , Adolescente , Adulto , Idoso , Formação de Anticorpos , Doença Crônica , Terapia Combinada , Estudos de Avaliação como Assunto , Humanos , Imunidade Celular , Pessoa de Meia-Idade , Pielonefrite/imunologia , Pielonefrite/metabolismoRESUMO
The importance of high intrarenal levels of gentamicin on the outcome of experimental pyelonephritis was studied in rats receiving either a short course (three days) of gentamicin (G) alone or combined with a longer course (14 days) of ampicillin (A), cephalothin (C), or trimethoprim (T), or two weeks of therapy with ampicillin, cephalothin, trimethoprim and gentamicin given alone. While ampicillin, cephalothin and trimethoprim were undetectable in the medulla within six hours of cessation of therapy, gentamicin was still detectable in levels six folds above the MIC up to six months after treatment had ceased. Six months after the end of treatment, the percentage of sterile left kidneys in animals treated with ampicillin (50%), cephalothin (15%), trimethoprim (20%) was lower than the percentage of animals receiving 14 days of gentamicin (100%), or the combinations AG:89%, CG:67% and TG:60%, P less than 0.01. Following three days of gentamicin, 50% of the left kidneys were sterilized. When compared to ampicillin, cephalothin or trimethoprim alone, combined therapies significantly reduced the number of CFU in the kidneys P less than 0.01. These combinations were almost as effective as two weeks of therapy with gentamicin. Short-term therapy (three days) with an aminoglycoside which concentrates in the renal parenchyma, combined with an antibiotic which will accumulate in other parts of the nephron, may result in "pharmacological synergy". This new approach to therapy of pyelonephritis may be promising.
Assuntos
Infecções por Escherichia coli/metabolismo , Gentamicinas/metabolismo , Rim/metabolismo , Pielonefrite/metabolismo , Doença Aguda , Ampicilina/metabolismo , Ampicilina/uso terapêutico , Animais , Cefalotina/metabolismo , Cefalotina/uso terapêutico , Avaliação Pré-Clínica de Medicamentos , Sinergismo Farmacológico , Quimioterapia Combinada , Infecções por Escherichia coli/tratamento farmacológico , Feminino , Gentamicinas/uso terapêutico , Pielonefrite/tratamento farmacológico , Ratos , Ratos Endogâmicos , Fatores de Tempo , Trimetoprima/metabolismo , Trimetoprima/uso terapêuticoRESUMO
To determine the optimal schemes of rational antibacterial therapy of pyelonephritis gravidarum with ampicillin and cephuroxim, assays of the patient urine and studies on the pharmacokinetics of the drugs were performed. The bacteriurea levels were estimated in 264 women with Gould's method in modification of Ryabinsky and Rodoman. The causative agents of the disease were isolated from the urine of 92 pregnant women. Sensitivity of the isolates to 9 antibiotics was tested with the use of standard paper disks and the method of serial dilutions in solid media. The pharmacokinetics of ampicillin and cephuroxim in the blood and urine of 97 patients was studied for 6-8 hours after parenteral administration of the antibiotics in doses of 500 mg. Comparative analysis of the pharmacokinetic parameters of the antibiotics in the blood and urine of the patients, the antibiotic MICs for the disease causative agents and the clinical course of the disease suggests that pyelonephritis gravidarum should be treated with ampicillin and cephuroxim on doses of 500 mg injected intramuscularly 4 and 3 times a day respectively for 7-8 days in combination with antiinflammatory therapy.
Assuntos
Complicações na Gravidez/tratamento farmacológico , Pielonefrite/tratamento farmacológico , Ampicilina/metabolismo , Ampicilina/uso terapêutico , Bacteriúria/microbiologia , Cefuroxima/metabolismo , Cefuroxima/uso terapêutico , Feminino , Humanos , Cinética , Testes de Sensibilidade Microbiana , Gravidez , Complicações na Gravidez/metabolismo , Complicações na Gravidez/microbiologia , Pielonefrite/metabolismo , Pielonefrite/microbiologia , Fatores de TempoAssuntos
Túbulos Renais/metabolismo , Fósforo/metabolismo , Pielonefrite/metabolismo , Absorção , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
In the Cornett strain of mice, water diuresis did not prevent hematogenous production of pyelonephritis by Staphylococcus aureus. Increased fluid intake did not affect the numbers of organisms deposited in the kidneys or the rate of growth during the first 4 hr after inoculation. Drinking the glucose solution did not enhance bacterial proliferation within the renal parenchyma. Subcutaneous injection of saline to supplement for interruption of drinking after inoculation reduced the numbers of organisms recovered in the kidneys but not sufficiently to prevent production of pyelonephritis. Incorporating penicillin as a marker indicated that fluids administered by subcutaneous injections were rapidly delivered to the kidneys. Combining diuresis with treatment did not influence the rapidity of delivery of antimicrobial to the kidneys or the length of time that it was present in the renal homogenate.