RESUMO
BACKGROUND: Thyroid hormones are essential for the maturation and functions of the central nervous system. Pain sensitivity is related to the thyroid status. However, information on how thyroid hormones affect pain processing and synaptic transmission in the anterior cingulate cortex (ACC) is limited. Nociceptive threshold and synaptic transmission in the ACC were detected in the experimental hypothyroidism (HT) mice. RESULTS: HT was induced by methimazole and potassium perchlorate in distilled drinking water for 4 weeks. The threshold of pain perception to hot insults, but not mechanical ones, decreased in hypothyroid mice. After treatment with tri-iodothyronine (T3) or thyroxine (T4) for 2 weeks, thermal pain threshold recovered. Electrophysiological recordings revealed enhanced glutamatergic synaptic transmission and reduced GABAergic synaptic transmission in the ACC. Supplementation with T3 or T4 significantly rescued this synaptic transmission imbalance. In the same model, HT caused the up-regulation of the GluR1 subunit of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor and NR2B-containing N-methyl-D-aspartate receptors, but it down-regulated γ-aminobutyric acid A receptors in the ACC. Supplementation with T3 or T4 notably recovered the levels of above proteins. CONCLUSIONS: These results suggest that HT promotes hypersensitivity to noxious thermal, and that supplementation with T3 or T4 rescues the imbalance between excitatory and inhibitory transmission in the ACC.
Assuntos
Giro do Cíngulo/fisiopatologia , Hipotireoidismo/patologia , Limiar da Dor/fisiologia , Transmissão Sináptica/fisiologia , Animais , Modelos Animais de Doenças , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/fisiologia , Giro do Cíngulo/efeitos dos fármacos , Hiperalgesia/tratamento farmacológico , Hiperalgesia/etiologia , Hipotireoidismo/sangue , Hipotireoidismo/complicações , Hipotireoidismo/etiologia , Técnicas In Vitro , Masculino , Metimazol/toxicidade , Camundongos , Camundongos Endogâmicos C57BL , Limiar da Dor/efeitos dos fármacos , Percloratos/toxicidade , Compostos de Potássio/toxicidade , Receptores de AMPA/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Transmissão Sináptica/efeitos dos fármacos , Tiroxina/sangue , Tiroxina/farmacologia , Tri-Iodotironina/sangue , Tri-Iodotironina/farmacologia , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/fisiologiaRESUMO
Doxorubicin (DOX) is a broad-spectrum antitumor drug used in the clinic. However, it can cause serious heart toxicity. To increase the therapeutic index of DOX and to attenuate its toxicity toward normal tissues, we conjugated DOX with either α-linolenic acid (LNA) or palmitic acid (PA) by a hydrazone or an amide bond to produce DOX-hyd-LNA, DOX-ami-LNA, DOX-hyd-PA, and DOX-ami-PA. The cytotoxicity of DOX-hyd-LNA on HepG2, MCF-7, and MDA-231 cells was higher compared to that of DOX, DOX-ami-LNA, DOX-hyd-PA, and DOX-ami-PA. The cytotoxicity of DOX-hyd-LNA on HUVECs was lower than that of DOX. DOX-hyd-LNA released significantly more DOX in pH 5.0 medium than it did in pH 7.4 medium. DOX-hyd-LNA induced more apoptosis in MCF-7 and HepG2 cells than DOX or DOX-ami-LNA. Significantly more DOX was released from DOX-hyd-LNA in both MCF-7 and HepG2 cells compared with DOX-ami-LNA. Compared to free DOX, a biodistribution study showed that DOX-hyd-LNA greatly increased the content of DOX in tumor tissue and decreased the content of DOX in heart tissue after it was intravenously administered. DOX-hyd-LNA improved the survival rate, prolonged the life span, and slowed the growth of the tumor in tumor-bearing nude mice. These results indicate that DOX-hyd-LNA improved the therapeutic index of DOX. Therefore, DOX-hyd-LNA is a potential compound for use as a cancer-targeting therapy.
Assuntos
Antineoplásicos/química , Antineoplásicos/uso terapêutico , Doxorrubicina/química , Doxorrubicina/uso terapêutico , Ácido alfa-Linolênico/química , Animais , Antineoplásicos/administração & dosagem , Linhagem Celular , Linhagem Celular Tumoral , Doxorrubicina/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Feminino , Células Hep G2 , Humanos , Hidrazonas/química , Concentração de Íons de Hidrogênio , Neoplasias Hepáticas/tratamento farmacológico , Camundongos , Camundongos Nus , Ácido Palmítico/química , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
1. We have shown previously that 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid pentyl methyl ester (MN9202), a new 1,4-dihydropyridine Ca(2+) channel modulator, has significant hypotensive effects and favourable pharmacokinetic characteristics. As a chiral molecule, MN9202 has two optical isomers. The aim of the present study was to evaluate the pharmacological properties of the two enantiomers. 2. The two enantiomers, S-(-)- and R-(+)-MN9202, were obtained by HPLC. At 1 micromol/L, both racemic MN9202 and S-(-)-MN9202 decreased the contractility of rat ventricular myocytes by 54.0 and 64.4%, respectively, compared with control, whereas R-(+)-MN9202 enhanced cell shortening by 10.1%. At 1 micromol/L, racemic MN9202 markedly reduced calcium transient (CaT) and L-type Ca(2+) channel current (I(Ca,L)) by 60.0 and 50.7%, respectively, whereas the reductions in CaT and I(Ca,L) produced by 1 micromol/L S-(-)-MN9202 were greater still (62.2 and 65.7%, respectively). In contrast, 1 micromol/L R-(+)-MN9202 increased CaT and I(Ca,L) by 11.4 and 10.6%, respectively. Furthermore, findings from kinetics studies of I(Ca,L) revealed that the steady state inactivation curve of I(Ca,L) was shifted towards a hyperpolarizing potential by S-(-)-MN9202, but towards a depolarizing potential by R-(+)-MN9202. These results demonstrate different effects of R-(+)-MN9202 and S-(-)-MN9202. 3. In conclusion, the findings of the present study suggest that the chirality of MN9202 results in opposing pharmacological properties of its two enantiomers: S-(-)-MN9202 may be responsible for the therapeutic effects of racemic MN9202, whereas R-(+)-MN9202 contributes to it unwanted effects. The findings of the present study also indicate that MN9202 may be used as a new probe with which to investigate the structure-function relationships of Ca(2+) channels.
Assuntos
Bloqueadores dos Canais de Cálcio/farmacologia , Di-Hidropiridinas/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Nitrobenzenos/farmacologia , Algoritmos , Animais , Bloqueadores dos Canais de Cálcio/química , Canais de Cálcio Tipo L/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Di-Hidropiridinas/química , Eletrofisiologia , Técnicas In Vitro , Cinética , Masculino , Contração Miocárdica/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Nitrobenzenos/química , Técnicas de Patch-Clamp , Ratos , Ratos Sprague-Dawley , Estereoisomerismo , Relação Estrutura-AtividadeRESUMO
The prototype 1,4-dihydropyridine (1,4-DHP) nifedipine, indicated for the management of hypertension and angina pectoris, has disadvantages including photodegradation and a short half-life. Several newer 1,4-DHPs, including m-nifedipine and its analogs at the C3, C5 position such as MN9201, MN9202 and MN9203, have been designed to offset these problems. The aim of this study was to investigate the pharmacokinetic characteristics of these derivatives to provide reference for their further evaluation and modification. Derivatives were intravenously bolus administered to beagle dogs. The drug concentration in the plasma was determined by the HPLC method. The pharmacokinetic parameters were calculated by the non-compartmental method. The analysis of variance (ANOVA) was used to compare the pharmacokinetic parameters of the derivatives. The results showed that the area under the curve from time zero to the last sampling time (AUC(0-t)) of m-nifedipine, MN9201, MN9202 and MN9203 was 45.1 +/- 13.6, 51.7 +/- 15.2, 70 +/- 16 and 62 +/- 12.4 micromol/l*min, respectively. The elimination half-life (t(1/2)) was 98 +/- 24, 129 +/- 55, 190 +/- 21 and 92 +/- 25 min, respectively. The t(1/2) of MN9202 was significantly longer than those of the others (p<0.05 or p<0.01). These results suggest that the length of the carbon chain at the C3 or C5 position in the derivatives had a marked effect on its metabolism, and M9202 is a promising new drug candidate worth further evaluation.
Assuntos
Nifedipino/análogos & derivados , Animais , Área Sob a Curva , Cães , Masculino , Estrutura Molecular , Nifedipino/sangue , Nifedipino/química , Nifedipino/farmacocinética , Reprodutibilidade dos TestesRESUMO
AIM: To study the biliary excretion of genistein and its metabolite at different doses in rats. METHODS: Suspended in 0.5% CMC-Na solution, genistein was orally administered to rats at the dose of 6.25, 12.5 and 50 mg x kg(-1), separately. At various time intervals, the bile was collected. The bile was treated with beta-glucuronidase. The genistein in bile was extracted twice by vortexing with 2.0 mL mixture of methyl tert-tubtyl ether and pentane (8:2). The organic phase was removed into the tubes and then evaporated in ventilation cabinet. The residue was dissolved in 50 microL of methanol. Twenty microL solution was drawn and detected by high-performance liquid chromatography. RESULTS: The accumulative biliary excretion of genistein was (42.56 +/- 6.54) , (75.17 +/- 18.87) and (126.60 +/- 34.78) microg at the dose of 6.25, 12.5 and 50 mg x kg(-1), respectively. The total drug (genistein plus glucuronidated genistein) excreted from bile was (108.46 +/- 35.23), (423.46 +/- 158.31) and ( 853.74 +/- 320. 84) microg, and the ratio of glucuronidated genistein was 60.76% , 82.25% and 85.17% at the dose of 6.25, 12.5 and 50 mg x kg(-1), respectively. CONCLUSION: The genistein was excreted mainly in the form of glucuronidated genistein in rat bile. The genistein and glucuronidated genistein were excreted in a nonlinear dose-dependent manner.
Assuntos
Bile/metabolismo , Genisteína/metabolismo , Genisteína/farmacocinética , Administração Oral , Animais , Relação Dose-Resposta a Droga , Feminino , Genisteína/química , Masculino , Estrutura Molecular , Fitoestrógenos/administração & dosagem , Fitoestrógenos/metabolismo , Fitoestrógenos/farmacocinética , Ratos , Ratos Sprague-DawleyRESUMO
AIM: To study the metabolic kinetics of MN9202 in Beagle dog liver microsome. METHODS: Beagle dog liver microsomes were prepared by using ultracentrifuge method. After incubating 0.4 micromol x L(-1) MN9202 with 1 g x L(-1) microsomes for 30 min at 37 degrees C, the reaction was terminated by adding 0.5 mL alkalization. The RP-HPLC was used to determine the drug in the incubation mixture. The Michaelis-Menten parameters Km, and Vmax in Beagle dog liver microsomes were initially estimated by analyzing Lineweave-Brurk plot. Various selective CYP inhibitors were used to investigate their inhibitory effect on the metabolism of MN9202. RESULTS: The Km, Vmax and CLint of MN9202 were (22.6 +/- 8.0) micromol x L(-1), (0.54 +/- 0.17) micromol x g(-1) x min(-1) and (0.0242 +/- 0.0009) L x g(-1) x min(-1), respectively. The metabolism of MN9202 was significantly inhibited by ketoconazole (Ket) and troleandomycin (Tro) in Beagle dog liver microsomes. Tranylcypromine (Tra) could inhibit the metabolism of drug as well. While other inhibitors showed little inhibitory effect on the metabolism of MN9202. CONCLUSION: It was shown that CYP3A and CYP2C19 were involved in MN9202 metabolism. The inhibitors of human CYP3A and CYP2C19 may have potential interaction with MN9202, and this can reduce the metabolism rate and increase the toxicity of MN9202.
Assuntos
Bloqueadores dos Canais de Cálcio/farmacocinética , Di-Hidropiridinas/farmacocinética , Microssomos Hepáticos/metabolismo , Nitrobenzenos/farmacocinética , Animais , Hidrocarboneto de Aril Hidroxilases/antagonistas & inibidores , Bloqueadores dos Canais de Cálcio/metabolismo , Citocromo P-450 CYP2C19 , Inibidores do Citocromo P-450 CYP3A , Di-Hidropiridinas/metabolismo , Cães , Cetoconazol/farmacologia , Oxigenases de Função Mista/antagonistas & inibidores , Nitrobenzenos/metabolismo , Tranilcipromina/farmacologia , Troleandomicina/farmacologiaRESUMO
AIM: To study the pharmacokinetics of genistein at different doses in Beagle dogs. METHODS: Suspended in 0.5% CMC-Na solution, genistein was orally administered to Beagle dogs at doses of 2.67, 5.34 and 10.68 mg.kg(-1). At various time intervals, 1.5 mL of blood was drawn from the femoral vein of dogs in their front legs. The plasma was treated with beta-glucuronidase. The genistein in plasma was extracted twice by vortexing with 2.0 mL mixture of methyl tert-tubtyl ether and pentane (v/v = 8:2). The organic phase was removed into the tubes and then evaporated in ventilation cabinet. The residue was dissolved in 50 microL of methanol. 20 microL solution was drawn and detected by high-performance liquid chromatography. The pharmacokinetic parameters were calculated by 3P97 software. RESULTS: The plasma drug concentration-time data were fitted to the two-compartment model. When the dose was 2.67 mg.kg(-1), the MRT and AUC of parent compound were 52.9 min and 6.7 mg.min. L(-1), respectively. When the dose rose to 5.34 mg.kg(-1), the MRT and AUC of parent compound became 224.8 min and 26.1 mg.min.L(-1), respectively. However, when the dose increased to 10.68 mg .kg(-1), the MRT and AUC of parent compound increased to 267.7 min and 33.2 mg.min L(-1), respectively. The AUC of glucuronidated genistein was 33.9, 70.1 and 140.5 mg.min.L(-1) at the dose of 2.67, 5.34 and 10.68 mg.kg(-1), respectively. CONCLUSION: Due to significant first pass metabolism, the drug was mainly existed in the form of glucuronidated genistein in the plasma. With the increase of dose, the absorption of genistein became saturated and the half life prolonged.
Assuntos
Anticarcinógenos/farmacocinética , Genisteína/farmacocinética , Animais , Anticarcinógenos/administração & dosagem , Anticarcinógenos/sangue , Área Sob a Curva , Cães , Relação Dose-Resposta a Droga , Feminino , Genisteína/administração & dosagem , Genisteína/sangue , Glucuronídeos/sangue , Glucuronídeos/farmacocinética , MasculinoRESUMO
AIM: To study the pharmacokinetics of m-nifedipine (m-Nif) in Beagle dogs. METHODS: The Beagle dogs were divided into two groups. m-Nif was intravenously administered to the Beagle dogs in group 1 at the dose of 0. 288 mg x kg(-1), and it was orally administered to the Beagle dogs in group 2, 3 and 4 at the dose of 1.152, 3.456 and 10.370 mg x kg(-1), respectively. m-Nif in plasma was detected by reversed phase high performance liquid chromatography. The pharmacokinetic parameters were calculated by 3P97 software. RESULTS: When m-Nif was intravenously administered, the plasma concentration-time curve was fit to a two-compartment model and T1/2beta was 117 min. When m-Nif was orally administered, the plasma concentration-time curve was fit to a one-compartment model. T1/2 (Ke) and Cmax were 147 min and 20 microg x L(-1); at the low dose of 1.152 mg x kg(-1). T1/2 (Ke) was 122 min and Cmax was 36 microg x L(-1) at the middle dose of 3.456 mg x kg(-1). T1/2 (Ke) was 144 min and Cmax was 69 microg x L(-1) at the high dose of 10.37 mg x kg(-1), respectively. CONCLUSION: It was showed that the speed of elimination of m-Nif was high in Beagle dogs. The absolute bioavailability of m-Nif given orally was very low.
Assuntos
Bloqueadores dos Canais de Cálcio/farmacocinética , Nifedipino/farmacocinética , Administração Oral , Animais , Área Sob a Curva , Disponibilidade Biológica , Bloqueadores dos Canais de Cálcio/administração & dosagem , Cães , Injeções Intravenosas , Isomerismo , Nifedipino/administração & dosagemRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: As a well-known traditional Chinese medicine the root bark of Aralia taibaiensis has multiple pharmacological activities, including relieving rheumatism, promoting blood circulation to arrest pain, inducing diuresis to reduce edema, and antidiabetic action. It has long been used as a folk medicine for the treatment of traumatic injury, rheumatic arthralgia, nephritis, edema, hepatitis and diabetes mellitus in China. AIM OF STUDY: To evaluate the antihyperglycemic, hypolipidemic and antioxidant activities of total saponins extracted from Aralia taibaiensis (SAT) in experimental type 2 diabetic mellitus (T2DM) rats. MATERIALS AND METHODS: Acute toxicity was studied in rats to determine the safe oral dose of SAT. Then, SAT was given orally to normal and streptozotocin-nicotinamide induced T2DM rats at 80, 160 and 320 mg/kg doses for a series of 28 days to determine the antihyperglycemic activity. Glibenclamide (600 µg/kg), a standard antidiabetic drug, was used as a positive control drug. At the end of treatment, biochemical parameters and antioxidant levels were measured to evaluate the hypolipidemic and antioxidant activities of SAT. RESULTS: Oral administration of SAT did not exhibit toxicity and death at a dose not more than 2000 mg/kg. SAT dose-dependently improved the symptoms of polydipsia, polyuria, polyphagia and weight loss in diabetic rats. Compared with diabetic control group, administration of 320 mg/kg SAT resulted in significant (P<0.05) fall in the levels of fasting blood glucose, glycosylated hemoglobin, creatinine, urea, alanine transarninase, aspartate aminotransferase, total cholesterol, triglycerides, low density lipoprotein cholesterol and malondialdehyde, but significant (P<0.05) increase in the levels of serum insulin, superoxide dismutase and reduced glutathione. However, SAT did not have any effect on the normal rats. CONCLUSIONS: SAT had excellent antihyperglycemic, hypolipidemic and antioxidant activities in T2DM rats and might be a promising drug in the therapy of diabetes mellitus and its complications.
Assuntos
Aralia/química , Hipoglicemiantes/farmacologia , Extratos Vegetais/farmacologia , Saponinas/farmacologia , Animais , Antioxidantes/administração & dosagem , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Glicemia/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/fisiopatologia , Relação Dose-Resposta a Droga , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/isolamento & purificação , Hipolipemiantes/administração & dosagem , Hipolipemiantes/isolamento & purificação , Hipolipemiantes/farmacologia , Lipídeos/sangue , Masculino , Niacinamida/toxicidade , Extratos Vegetais/administração & dosagem , Ratos , Ratos Wistar , Saponinas/administração & dosagem , Saponinas/isolamento & purificação , Estreptozocina/toxicidade , Testes de Toxicidade AgudaRESUMO
Pivalate-generating prodrugs have been suggested to cause clinically significant hypocarnitinaemia. Tenofovir dipivoxil, a novel ester prodrug of tenofovir, can be used for treatment for hepatitis B and HIV infection and it was necessary to evaluate the effect of its treatment on carnitine homeostasis. We sought to investigate the effect of Class 1 drug tenofovir dipivoxil on endogenous L-carnitine level during a 72-hr test in healthy Chinese volunteers and to establish a suitable dose of L-carnitine nutritional supplement for patients who were administered short-term tenofovir dipivoxil tablets for treatment for hepatitis B and herpes simplex virus infection. Tenofovir dipivoxil was administered in one of eight dosing regimens (single dose 150, 300 and 600 mg, multiple dose 300, 450, and 600 mg, multiple dose 450 (600) mg tenofovir dipivoxil and 0.5 g L-carnitine) to gender-balanced groups of 84 healthy Chinese volunteers. Plasma concentrations of L-carnitine were quantified before, during and after treatment. Plasma L-carnitine concentrations fell during tenofovir dipivoxil dosing. The nadir in L-carnitine concentration was dependent on the dose of tenofovir dipivoxil and it decreased from 6.1 ± 0.6 to 4.4 ± 0.8 µg/ml, 6.1 ± 1.8 to 3.3 ± 1.2 µg/ml, 6.2 ± 0.6 to 2.5 ± 0.5 µg/ml for single doses of 150, 300, 600 mg tenofovir dipivoxil tablets and from 6.0 ± 1.4 to 2.1 ± 1.5 µg/ml, 6.2 ± 0.4 to 0.9 ± 0.5 µg/ml for multiple doses of 450, 600 mg tenofovir dipivoxil tablets, respectively. Short-term administration of tenofovir dipivoxil results in hypocarnitinaemia and increased losses of carnitine in resulting of minor adverse events of decreased food appetite, nausea, abdominal distention and muscle weakness.
Assuntos
Adenina/análogos & derivados , Antivirais/farmacologia , Carnitina/metabolismo , Homeostase/efeitos dos fármacos , Organofosfonatos/farmacologia , Pró-Fármacos/farmacologia , Adenina/farmacologia , Adenina/uso terapêutico , Adulto , Antivirais/uso terapêutico , Carnitina/sangue , Relação Dose-Resposta a Droga , Feminino , Hepatite B/tratamento farmacológico , Herpes Simples/tratamento farmacológico , Humanos , Masculino , Organofosfonatos/uso terapêutico , TenofovirRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Safflower is a popular Traditional Chinese Medicine (TCM) to invigorate the blood and dispel 'blood stasis', which arises from poor blood circulation. The differences of pharmacokinetic properties between normal and blood stasis syndrome rats were seldom reported. AIM OF THE STUDY: The present study was conducted to evaluate the pharmacokinetics of hydroxysafflower yellow A (HSYA) following oral administration of hydroxysafflower yellow A and safflower extract with approximately the same dose of HSYA 100mg/kg in both normal and acute blood stasis rats. MATERIALS AND METHODS: The animals were orally administered with HYSA monomer and safflower extract. The blood samples were collected according to the time schedule. The concentrations of HSYA in rat plasma were determined by HPLC. Various pharmacokinetic parameters were estimated from the plasma concentration versus time data using non-compartmental methods. RESULTS: It was found that AUC(0-t), C(max), Vd and CL of HSYA in both HSYA monomer and safflower extract in acute blood stasis rats were with significant difference (P<0.05) comparing with that in normal rats. CONCLUSIONS: The results indicated that HSYA was with high uptake and eliminated slowly in the animals with blood stasis syndrome, suggesting that the rate and extent of drug metabolism was altered in acute blood stasis animals.
Assuntos
Circulação Sanguínea , Doenças Cardiovasculares/sangue , Carthamus tinctorius/química , Chalcona/análogos & derivados , Extratos Vegetais/farmacocinética , Quinonas/farmacocinética , Administração Oral , Animais , Área Sob a Curva , Chalcona/sangue , Chalcona/farmacocinética , Diagnóstico Diferencial , Flores , Masculino , Medicina Tradicional Chinesa , Taxa de Depuração Metabólica , Extratos Vegetais/sangue , Extratos Vegetais/química , Quinonas/sangue , Distribuição Aleatória , Ratos , Valores de ReferênciaRESUMO
BACKGROUND: Median sternotomy is considered the most usually performed procedure in cardiac operations. This study aimed to assess clinical effectiveness of bilateral pectoralis major muscle flaps (BPMMF) for management of sternal osteomyelitis and mediastinal infection following median sternotomy. METHODS: Clinical data were collected and retrospectively analyzed from twelve patients who underwent the BPMMF transposition for management of sternal osteomyelitis and mediastinal infection following median sternotomy from January 2006 to June 2009. Procedure consisted of rigorous debridement of necrotic tissues, dead space obliteration using the BPMMF, and placement of drainage tubes connected to a negative pressures generator for adequate drainage. RESULTS: No patients died of drainage, and all 12 patients had viable BPMMF when discharged from hospital. At 1 week post discharge, 2 patients presented with sternal infection but recovered following local debridement and medication. No patients showed infection recurrence during the follow-up period over 10 months. CONCLUSIONS: Sternal osteomyelitis and mediastinal infection following median sternotomy may be effectively managed through rigorous debridement of infected soft tissues, resection of the damaged sternal segment, transposition of the BPMMF to fill the damaged sternum resulting from debridement, and adequate postoperative drainage.