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1.
Microb Pathog ; 104: 125-132, 2017 Mar.
Article in English | MEDLINE | ID: mdl-28089949

ABSTRACT

Candida infection is an important cause of morbidity and mortality on immunosuppressed patients. This growing trend has been associated with resistance to the antimicrobial therapy and the ability of microorganism to form biofilms. TTO oil is used as antimicrobial which shows antibiofilm activity against Candida species. However, it presents problems due to its poor solubility and high volatility. The present study aimed to evaluate in vitro antibiofilm activity of TTO nanoparticles against many Candida species. It was performed the characterization of the oil and nanoparticles. The levels of exopolysaccharides, proteins, and the biomass of biofilms were measured. The chromatographic profile demonstrated that the TTO oil is in accordance with ISO 4730 with major constituents of 41.9% Terpinen-4-ol, 20.1% of γ-Terpinene, 9,8% of α-Terpinene, and 6,0% of 1,8-Cineole. The TTO nanoparticles showed pH of 6.3, mean diameter of 158.2 ± 2 nm, polydispersion index of 0.213 ± 0.017, and zeta potential of -8.69 ± 0.80 mV. The addition of TTO and its nanoparticles represented a significant reduction of biofilm formed by all Candida species, as well as a reduction of proteins and exopolysaccharides levels. It was possible to visualize the reduction of biofilm in presence of TTO nanoparticles by Calcofluor White method.


Subject(s)
Antifungal Agents/administration & dosage , Biofilms/drug effects , Candida/drug effects , Candida/physiology , Melaleuca/chemistry , Nanoparticles/administration & dosage , Plant Extracts/administration & dosage , Antifungal Agents/chemistry , Bacterial Proteins/metabolism , Biomass , Candida/ultrastructure , Microbial Sensitivity Tests , Nanoparticles/chemistry , Plant Extracts/chemistry , Plant Oils/administration & dosage , Plant Oils/chemistry
2.
J Helminthol ; 90(3): 377-82, 2016 May.
Article in English | MEDLINE | ID: mdl-26096177

ABSTRACT

Haemonchus contortus is one of the major gastrointestinal nematodes responsible for significant economic and production losses of sheep. Diseases caused by this species lack effective anthelmintic products, and the search for new compounds to replace synthetic anthelmintics has been extensive. The present investigation assesses the in vitro activity of the essential oil of melaleuca (Melaleuca alternifolia), both free (TTO) and nanostructured (nanoTTO), and terpinen-4-ol (terp-4-ol) on eggs and larvae of H. contortus. Tests of egg hatching (EHT) and inhibition of larval migration (LMIT) were used to assess the in vitro efficacy of TTO, nanoTTO and terp-4-ol. Using EHT, at a concentration of 3.5 mg/ml, 100% inhibition occurred using TTO and terp-4-ol, with LC50 values of 0.43 and 0.63 mg/ml, and LC90 values of 1.75 mg/ml and 3.12 mg/ml, respectively. NanoTTO had lower activity, with 82.6% inhibition at the same concentration. Using LMIT, TTO and nanoTTO had a similar activity with 88.0% and 84.8% inhibition, respectively, at a concentration of 56 mg/ml. Terp-4-ol had a greater effect on larvae, with 85.7% inhibition at a concentration of 56 mg/ml and 82.4% at 3.5 mg/ml, demonstrating high activity at the lowest concentration tested. Therefore, the results indicate that all substances tested showed ovicidal and larvicidal activity against H. contortus. TTO, terp-4-ol and, mainly, nanoTTO may be targeted in in vivo studies, besides being a promising line of research into the control and treatment of veterinary important helminths.


Subject(s)
Anthelmintics/pharmacology , Haemonchus/drug effects , Melaleuca/chemistry , Oils, Volatile/pharmacology , Terpenes/pharmacology , Zygote/drug effects , Animals , Anthelmintics/isolation & purification , Biological Assay , Haemonchus/growth & development , Larva/drug effects , Locomotion/drug effects , Oils, Volatile/isolation & purification , Survival Analysis , Terpenes/isolation & purification
3.
R. bras. Ci. avíc. ; 18(1): 41-46, jan.-mar. 2016. tab, graf
Article in English | VETINDEX | ID: vti-341403

ABSTRACT

The aim of this study was to evaluate the in vitro bioactivity of tea tree (Melaleuca alternifolia) essential oil against larvae and adult forms of lesser mealworms (Alphitobius diaperinus) and its influence on the soil fauna. Tests were performed in triplicate using pure tea tree oil (TTO; 1, 5, 10, 25, 50, and 100%), TTO nanoparticles (1, 3, and 7.5%), or terpinen-4-ol, the main compound of the tea tree oil, at the same concentrations of TTO. Larvae and adult mortality occurred at concentrations up to 10 and 50% of TTO, respectively. No larvicidal or insecticidal effect of TTO nanoparticles was observed. Terpinen-4-ol showed insecticidal and larvicidal effect at concentrations higher than 25%. The evaluation of TTO effect on soil organisms was performed by standard ecotoxicological tests (ISO) with the springtail species Folsomia candida. Only TTO was used for ecotoxicological tests in doses of 1, 5, 10, 25, 50, and 100 mg kg-1 of soil. TTO had no negative effects on F. candida survival or reproduction. Therefore, it was concluded that M. alternifolia oil may be a new alternative for control of the lesser mealworm.(AU)


Subject(s)
Tea Tree Oil/analysis , Tea Tree Oil/pharmacokinetics , Pest Control, Biological/methods , Fauna/adverse effects , In Vitro Techniques , In Vitro Techniques/veterinary
4.
Rev. bras. ciênc. avic ; 18(1): 41-46, jan.-mar. 2016. tab, graf
Article in English | VETINDEX | ID: biblio-1490228

ABSTRACT

The aim of this study was to evaluate the in vitro bioactivity of tea tree (Melaleuca alternifolia) essential oil against larvae and adult forms of lesser mealworms (Alphitobius diaperinus) and its influence on the soil fauna. Tests were performed in triplicate using pure tea tree oil (TTO; 1, 5, 10, 25, 50, and 100%), TTO nanoparticles (1, 3, and 7.5%), or terpinen-4-ol, the main compound of the tea tree oil, at the same concentrations of TTO. Larvae and adult mortality occurred at concentrations up to 10 and 50% of TTO, respectively. No larvicidal or insecticidal effect of TTO nanoparticles was observed. Terpinen-4-ol showed insecticidal and larvicidal effect at concentrations higher than 25%. The evaluation of TTO effect on soil organisms was performed by standard ecotoxicological tests (ISO) with the springtail species Folsomia candida. Only TTO was used for ecotoxicological tests in doses of 1, 5, 10, 25, 50, and 100 mg kg-1 of soil. TTO had no negative effects on F. candida survival or reproduction. Therefore, it was concluded that M. alternifolia oil may be a new alternative for control of the lesser mealworm.


Subject(s)
Pest Control, Biological/methods , Fauna/adverse effects , Tea Tree Oil/analysis , Tea Tree Oil/pharmacokinetics , In Vitro Techniques , In Vitro Techniques/veterinary
5.
R. bras. Reprod. Anim. ; 38(3): 170-175, Jul-Set. 2014. tab
Article in Portuguese | VETINDEX | ID: vti-28257

ABSTRACT

Este estudo objetivou caracterizar o sêmen de Prochilodus brevis e avaliar os efeitos de diferentescrioproterores e taxas de diluição sobre a cinética e a morfologia do sêmen criopreservado. Inicialmente,amostras seminais de P. brevis (n = 40) foram analisadas quanto ao volume, pH, osmolaridade, concentração,motilidade e morfologia espermáticas. Para a criopreservação, o material coletado foi distribuído em 10 pools desêmen (n = 10), submetidos a seis tratamentos compostos pela combinação de glicose 5%, dois crioprotetores(DMSO ou MG) e três taxas de diluição (1:3, 1:6 ou 1:9 sêmen:diluidor). As amostras, in natura e pósdescongeladas,foram analisadas quanto à sua morfologia e cinética espermática utilizando o CASA. O sêmen deP. brevis apresentou características semelhantes a demais espécies de Prochilodus. O sêmen congelado comglicose e MG apresentou resultados significativamente superiores (P < 0,05) comparado àquele congeladoutilizando DMSO. As diluições 1:3 e 1:6 apresentaram melhores resultados para glicose + MG, enquanto 1:9 foimelhor para glicose + DMSO. Portanto, a associação glicose + MG, numa taxa de diluição de 1:3 ou 1:6, é amais indicada para a criopreservação do sêmen de Prochilodus brevis.(AU)


This study aimed to characterize Prochilodus brevis sperm and evaluate the effects of different diluentsand dilution ratios on kinetics and morphology of cryopreserved sperm. Initially, sperm samples of P. brevis(n = 40) were assessed for volume, pH, osmolality, spermatic concentration, motility and morphology. Forcryopreservation, the collected material was distributed in ten pools of semen (n = 10), submitted to sixtreatments composed by a combination of glucose 5% with two cryoprotectants (DMSO or MG) and threedilution ratios (1:3, 1:6 or 1:9 - sperm:diluent). In natura and post-thawed samples were assessed for spermaticmorphology and kinetics using CASA. The sperm of P. brevis showed similar characteristics to otherProchilodus species. Sperm cryopreserved in glucose plus MG presented significantly higher results (P < 0.05)compared to sperm frozen in DMSO. The dilution ratios of 1:3 and 1:6 yielded better results for glucose + MG,while 1:9 was the best dilution for glucose + DMSO. In conclusion, the association of glucose + MG, in adilution ratio of 1:3 or 1:6, is the most indicated for Prochilodus brevis sperm cryopreservation.(AU)


Subject(s)
Animals , Male , Cryopreservation , Cryoprotective Agents , Characiformes
6.
Rev. bras. reprod. anim ; 38(3): 170-175, Jul-Set. 2014. tab
Article in Portuguese | VETINDEX | ID: biblio-1492120

ABSTRACT

Este estudo objetivou caracterizar o sêmen de Prochilodus brevis e avaliar os efeitos de diferentescrioproterores e taxas de diluição sobre a cinética e a morfologia do sêmen criopreservado. Inicialmente,amostras seminais de P. brevis (n = 40) foram analisadas quanto ao volume, pH, osmolaridade, concentração,motilidade e morfologia espermáticas. Para a criopreservação, o material coletado foi distribuído em 10 pools desêmen (n = 10), submetidos a seis tratamentos compostos pela combinação de glicose 5%, dois crioprotetores(DMSO ou MG) e três taxas de diluição (1:3, 1:6 ou 1:9 – sêmen:diluidor). As amostras, in natura e pósdescongeladas,foram analisadas quanto à sua morfologia e cinética espermática utilizando o CASA. O sêmen deP. brevis apresentou características semelhantes a demais espécies de Prochilodus. O sêmen congelado comglicose e MG apresentou resultados significativamente superiores (P < 0,05) comparado àquele congeladoutilizando DMSO. As diluições 1:3 e 1:6 apresentaram melhores resultados para glicose + MG, enquanto 1:9 foimelhor para glicose + DMSO. Portanto, a associação glicose + MG, numa taxa de diluição de 1:3 ou 1:6, é amais indicada para a criopreservação do sêmen de Prochilodus brevis.


This study aimed to characterize Prochilodus brevis sperm and evaluate the effects of different diluentsand dilution ratios on kinetics and morphology of cryopreserved sperm. Initially, sperm samples of P. brevis(n = 40) were assessed for volume, pH, osmolality, spermatic concentration, motility and morphology. Forcryopreservation, the collected material was distributed in ten pools of semen (n = 10), submitted to sixtreatments composed by a combination of glucose 5% with two cryoprotectants (DMSO or MG) and threedilution ratios (1:3, 1:6 or 1:9 - sperm:diluent). In natura and post-thawed samples were assessed for spermaticmorphology and kinetics using CASA. The sperm of P. brevis showed similar characteristics to otherProchilodus species. Sperm cryopreserved in glucose plus MG presented significantly higher results (P < 0.05)compared to sperm frozen in DMSO. The dilution ratios of 1:3 and 1:6 yielded better results for glucose + MG,while 1:9 was the best dilution for glucose + DMSO. In conclusion, the association of glucose + MG, in adilution ratio of 1:3 or 1:6, is the most indicated for Prochilodus brevis sperm cryopreservation.


Subject(s)
Male , Animals , Characiformes , Cryopreservation , Cryoprotective Agents
7.
Rev. ciênc. farm. básica apl ; Rev. ciênc. farm. básica apl;31(3)set.-dez. 2010.
Article in Portuguese | LILACS | ID: lil-570162

ABSTRACT

O objetivo deste trabalho é avaliar a eficácia e a segurança da dose de 20 mg/dia de sibutramina em voluntários obesos, com IMC superior a 35, e compará-las com a dose de 10 mg/dia e à mudança de estilo de vida de pacientes com IMC inferior a 35 (a avaliação e a comparação foram realizadas em um período de 24 semanas). Foram submetidos a um estudo transversal 54 voluntários, distribuídos em três grupos de observação: grupo sem tratamento farmacológico (GMEV), grupo com IMC inferior a 35 e uma dose de 10 mg/ dia de sibutramina (G1) e grupo com IMC superior a 35 e dose de 20 mg/ dia de sibutramina (G2). Os parâmetros avaliados foram peso, circunferência abdominal e perfil metabólico. Os grupos submetidos ao tratamento farmacológico demonstraram maior redução do peso (G1: redução média de 9,4% ; G2: redução média de 20,6%) quando comparados a indivíduos sem tratamento farmacológico (GMEV: redução de 3,9%), assim como da circunferência abdominal (redução de 7,1%, 12,8% e 3,1% em G1, G2 e GMEV, respectivamente). Em relação aos achados laboratoriais, foram observados redução da glicemia de jejum (14,8%, 22,9% e 5% em G1, G2 e GMEV, respectivamente), aumento do HDL colesterol (31,2%, 40% e 14,2% em G1, G2 e GMEV, respectivamente) e redução do colesterol total (29,0%, 32,8% e 13,7% em G1, G2 e GMEV, respectivamente). Os resultados deste estudo demonstram que a dose de 20 mg de sibutramina é uma indicação segura e eficaz em pacientes obesos com IMC superior a 35


The aim of this study is to assess the efficacy and safety of an oral daily dose of 20 mg sibutramine in obese volunteers (BMI > 35), in comparison with a dose of 10 mg/day and changed lifestyle in patients whose BMI is less than 35. The testing and comparison were performed over 24 weeks. The 54 volunteers were subjected to a cross-sectional study in three observation groups: a reference group without pharmacological treatment (GMEV), a group with BMI < 35, treated with 10 mg ?day sibutramine (G1), and another with BMI ? 35, on a dose of 20 mg? day (G2). The variables assessed were weight, abdominal circumference and metabolic profile. The groups subjected to the drug treatments exhibited greater weight losses (G1: -9.4% and G2: -20.6%) than the group that took no drugs (GMEV: -3.9%). The abdominal circumference was reduced by 7.1%, 12.8% and 3.1% in G1, G2 and GMEV, respectively. Regarding the biochemical variables, there was a reduction in fasting glucose levels (-14.8%, -22.9% and -5% in G1, G2 and GMEV, respectively); an increase in HDL cholesterol (+31.2%, +40% and +14.2% in G1, G2 and GMEV, respectively) and a reduction in total cholesterol (-29.0%, -32.8% and ?13.7% in G1, G2 and GMEV, respectively). The results of this study show that sibutramine, in doses of 20 mg/ day, is a safe and efficient drug for obesity treatment in patients whose BMI exceeds 35.


Subject(s)
Humans , Male , Female , Adolescent , Adult , Metabolism , Obesity/drug therapy , Weight Loss
8.
Transplant Proc ; 40(3): 771-3, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18455012

ABSTRACT

The objective of the present study was to analyze hepatic mitochondrial function in patients with familial amyloidotic polyneuropathy (FAP) undergoing cadaveric donor orthotopic liver transplantation. From February 2005 to May 2007, eight patients with FAP, ranging in age from 34 to 41 years and with Model for End-Stage Liver Disease scores ranging from 24 to 29. Underwent orthotopic transplantation using a liver from a deceased donor by the piggyback method. Immediately before beginning the recipient hepatectomy in a patient with FAP, a biopsy was obtained for analysis of mitochondrial function (FAP group). The control group consisted of 15 patients undergoing hepatic surgery to treat small tumors of the liver. Mitochondrial respiration was determined on the basis of oxygen consumption by energized mitochondria using a polarographic method. The membrane potential of the mitochondria was determined spectrofluorometrically. Data were analyzed statistically by the Mann-Whitney test, with the level of significance set at 5%. State 3 and 4 values, respiratory control ratio, and membrane potential were 47 +/- 8 versus 28 +/- 10 natoms O/min/mg protein (P < .05); 14 +/- 3 vs 17 +/- 7 nat.O/min/mg.prot.mit. (P > .05); 3.6 +/- .5 vs 1.7 +/- 0.7 (P < .05); and 135 +/- 5.2 vs 135 +/- 6 mV (P > .05) for control versus FAP patients, respectively, demonstrating a decreased energy status of the liver in FAP.


Subject(s)
Amyloid Neuropathies, Familial/metabolism , Amyloid Neuropathies, Familial/surgery , Liver Transplantation , Mitochondria, Liver/metabolism , Adult , Female , Hepatectomy , Humans , Male , Membrane Potentials , Oxygen Consumption
9.
Transplant Proc ; 40(3): 774-6, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18455013

ABSTRACT

Pulmonary abnormalities are observed in chronic hepatopathy. The measurement of the maximum inspiratory and expiratory pressure may evaluate lung function and the risks associated with hepatic transplantation. Thus, the present work sought to evaluate the respiratory muscle strength of 29 patients between 17 and 63 years old who were enrolled for liver transplantation. The patients were classified according to Child-Turcotte-Pugh score as A, B, or C, and also according to a physiotherapeutic evaluation, which included measurement of respiratory muscle strength by means of a digital manovacuometer, which determines the maximum inspiratory pressure (MaxIP) and the maximum expiratory pressure (MaxEP). The tests were performed with seated individuals having their nostrils obstructed by a nasal clip. The MaxIP was measured during the effort initiated in the residual volume, whereas the MaxEP was measured during the effort initiated in the total pulmonary capacity, keeping pressures stable for at least 1 second. The statistical analysis was performed through using the Mann-Whitney test with a 5% level of significance. The MaxIP values of Child A 95.5 +/- 40.507 cm H(2)O (average +/- DP) and Child B 87.2 +/- 35.02 patients were higher than those for Child C patients (34.83 +/- 3.68; P < .05). Similar results were observed for the MaxEP of Child A and B groups (116.25 +/- 31.98 and 97.28 +/- 31.08, respectively; P < .05), versus the Child C group (48.16 +/- 22.60). Between groups A and B, the MaxEP were similar (P > .05). We concluded that Child C patients display muscle weakness significantly greater than that of subjects classified as Child A or B.


Subject(s)
Liver Transplantation/physiology , Muscle Strength/physiology , Respiratory Muscles/physiology , Adolescent , Adult , Aged , Aged, 80 and over , Exhalation/physiology , Female , Humans , Inhalation/physiology , Liver Transplantation/adverse effects , Male , Middle Aged
10.
Transplant Proc ; 39(2): 361-4, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17362730

ABSTRACT

To minimize bleeding during major liver resections or liver transplantation, surgical measures have been adopted that induce ischemia-reperfusion injury (I/R) which may significantly contribute to morbidity and mortality of partial liver resections. Several methods have sought to minimize I/R hepatic lesions. The present project assessed the protective role of ischemic preconditioning (IPC) in rat livers. The IPC was accomplished by clamping the hepatic pedicle for 5 minutes, followed by a 5-minute reperfusion (R) period before a 2-hour ischemia. Thereafter, reperfusions of 1, 3, and 24 hours were compared among IPC and control groups without IPC. Liver biopsy and blood samples were measured for mitochondrial respiratory control ratio (RCR), serum aspartate aminotransferase (AST), and alanine aminotransferase (ALT). IPC protected liver mitochondrial function. Serum aminotransferase levels were significantly lower among animals undergoing IPC compared with groups without IPC. Thus, we verified the effects of IPC for hepatocellular protection against I/R lesions.


Subject(s)
Ischemic Preconditioning/methods , Liver , Reperfusion Injury/epidemiology , Alanine Transaminase/blood , Animals , Aspartate Aminotransferases/blood , Kinetics , Liver Circulation/physiology , Male , Models, Animal , Rats , Rats, Wistar , Reperfusion Injury/prevention & control , Respiration
11.
Transplant Proc ; 38(6): 1947-52, 2006.
Article in English | MEDLINE | ID: mdl-16908331

ABSTRACT

Hyperbaric oxygen therapy is a treatment that has been gradually implemented for the treatment of several pathologic conditions. The present study evaluated the effect of hyperbaric oxygen therapy for hepatic regeneration and its relationship to mitochondrial function. Male Wistar rats underwent partial hepatectomy (70%) and subsequently underwent two sessions of hyperbaric oxygen (90 minutes each, at a pressure of 2 ATA). The animals were sacrificed at 24 and 48 hours after surgery. Hepatic regeneration was evaluated by the dry weight of the remaining liver, the hepatic regeneration rate, the hepatic DNA content, and the hepatocyte proliferation rate using the "proliferating cell nuclear antigen" (PCNA) content. Function of the mitochondria was evaluated by its oxygen consumption during respiratory states 3 and 4, its respiratory control ratio (RCR), its membrane potential, as well as its osmotic swelling. We also measured serum levels of aminotransferases. The results revealed an increased dry weight of the remaining liver, regeneration rate, and DNA content at 24 and 48 hours after hepatectomy. The hepatocyte proliferation rate was significantly higher among animals treated with hyperbaric oxygen therapy at 48 hours after surgery. There was no significant difference in aminotransferase levels. Mitochondrial respiration revealed reduced oxygen consumption in state 3 after 48 hours. These results demonstrated that hyperbaric oxygen stimulates hepatic regeneration at 24 and 48 hours after 70% hepatectomy. The effect of hyperbaric oxygen on hepatic tissue occurs without tissue damage and protects mitochondria after 48 hours.


Subject(s)
Hyperbaric Oxygenation , Liver Regeneration/physiology , Mitochondria, Liver/physiology , Alanine Transaminase/blood , Animals , Aspartate Aminotransferases/blood , Bilirubin/blood , Hepatectomy/methods , L-Lactate Dehydrogenase/blood , Male , Models, Animal , Rats , Rats, Wistar , Serum Albumin/analysis
12.
Phytomedicine ; 12(5): 359-62, 2005 May.
Article in English | MEDLINE | ID: mdl-15957370

ABSTRACT

Some studies have indicated that mitochondria may be the target organelle of plants. We therefore decided to assess the effects of the aqueous extract of Hyptis pectinata leaves on liver mitochondrial respiratory function in vitro. Eight rat livers were subjected to isolation of mitochondria by differential centrifugation. In an adequate medium, the plant extract was added at different concentrations. The analyzed data were: state 3, state 4 and respiratory control ratio (RCR). H. pectinata extract caused a statistically significant decrease in state 3 (at 0.05, 0.1 and 0.2 mg/mg protein) and RCR (at 0.05, 0.1 and 0.2 mg/mg protein). Respiratory state 4 was not altered by the increasing concentrations. In conclusion, the aqueous extract of H. pectinata leaves may not injure the mitochondrial inner membrane but decreases significantly the oxidative phosphorylation.


Subject(s)
Hyptis , Mitochondria, Liver/drug effects , Phytotherapy , Plant Extracts/pharmacology , Animals , Cell Respiration/drug effects , Male , Plant Extracts/administration & dosage , Plant Extracts/therapeutic use , Plant Leaves , Rats , Rats, Wistar
13.
Acta Trop ; 61(3): 255-61, 1996 May.
Article in English | MEDLINE | ID: mdl-8790775

ABSTRACT

Salivary gland extract of Triatoma infestans prolonged thrombin time, prothrombin time, and activated partial thromboplastin time, while salivary gland extract of Panstrongylus megistus delayed thrombin time and activated partial thromboplastin time. However, saliva of P. megistus prolonged activated partial thromboplastin time and saliva of T. infestans delayed activated partial thromboplastin time and prothrombin time. T. infestans saliva interferes particularly with activity of factor VIII (intrinsic pathway) and factor V (common pathway), but also affects other factors. Saliva of the triatomine species studied presented distinct SDS-PAGE profiles. These results demonstrate that there are differences in anticoagulant activity and protein composition of triatomine saliva.


Subject(s)
Anticoagulants/pharmacology , Hemiptera/physiology , Saliva/physiology , Animals , Humans , Proteins/analysis , Saliva/chemistry
14.
Biochem Pharmacol ; 48(3): 535-41, 1994 Aug 03.
Article in English | MEDLINE | ID: mdl-8068040

ABSTRACT

The in vitro and in vivo effects of fluoxetine (and its active metabolite norfluoxetine) on mitochondrial respiration and F0F1-ATPase were studied, respectively, in mitochondria and submitochondrial particles isolated from rat liver. Fluoxetine in vitro inhibited state 3 mitochondrial respiration for alpha-ketoglutarate and succinate oxidations (50% of effect at 0.25 and 0.35 mM drug concentrations, respectively); stimulated state 4 for succinate; and induced a decrease in the respiratory control ratio (RCR) for both oxidizable substrates. The F0F1-ATPase activity was determined at various pH levels in the absence and presence of Triton X-100. The solubilized form was not affected markedly, but an inhibition, apparently non-competitive, was observed for the membrane-bound enzyme, with 50% of the effect at a 0.06 mM drug concentration in pH 7.4. These results suggest that fluoxetine in vitro acts on F0F1-ATPase through direct interaction with the membrane F0 component (similar to oligomycin), or first with mitochondrial membrane and then affecting F0. A very similar behavior concerning the respiratory parameters and F0F1-ATPase properties was observed with norfluoxetine. The in vivo studies with fluoxetine showed stimulation of mitochondrial respiration in state 4 for alpha-ketoglutarate or succinate oxidations in acute or prolonged treatments (1 hr after a single i.p. dose of 20 mg of drug/kg of body weight, and 22 hr after 12 days of treatment with a daily dose of 10 mg/kg of body weight, respectively), indicating uncoupling of oxidative phosphorylation. Pronounced changes were not observed in the K0.5 values of F0F1-ATPase catalytic sites, but the Vmax decreased during the prolonged treatment. The results show that fluoxetine (as well as norfluoxetine) has multiple effects on the energy metabolism of rat liver mitochondria, being potentially toxic in high doses. The drug effects seem to be a consequence of the drug and/or metabolite solubilization in the inner membrane of the mitochondria.


Subject(s)
Fluoxetine/pharmacology , Mitochondria, Liver/drug effects , Animals , Dose-Response Relationship, Drug , Energy Metabolism , Fluoxetine/analogs & derivatives , Fluoxetine/metabolism , Ketoglutaric Acids/analysis , Male , Mitochondria, Liver/metabolism , Mitochondria, Liver/ultrastructure , Proton-Translocating ATPases/metabolism , Rats , Rats, Wistar , Succinates/analysis , Succinic Acid
15.
Sao Paulo Med J ; 112(2): 555-60, 1994.
Article in English | MEDLINE | ID: mdl-7610326

ABSTRACT

Previous reports have suggested the use of supraceliac aortic clamping in the surgical treatment of abdominal aortic aneurysm of difficult approach. The objective of the present report was to study the hepatic and renal metabolic changes of three groups of dogs submitted to temporary clamping (30 minutes) of the abdominal aorta at three different levels: below the renal arteries, infrarenal group (8 dogs); above the renal arteries, suprarenal group (9 dogs); above the celiac artery, supraceliac group (9 dogs). Blood bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea nitrogen, and creatinine levels were measured before clamping and 5 minutes and 24 hours after reperfusion of the aorta. Bilirubin levels remained unchanged 5 minutes and 24 hours after reperfusion in all three groups. Alkaline phosphatase levels were significantly increased in all three groups 24 hours after reperfusion. ALT levels increased significantly in the supraceliac group and AST levels increased significantly in the infrarenal and supraceliac groups 24 hours after reperfusion of the aorta. However, despite these significant increases after reperfusion, the levels of these hepatic enzymes were still within the normal range for dogs. Urea nitrogen and creatinine levels showed that renal function did not change in any of the three groups. We conclude that supraceliac, infrarenal or suprarenal aortic clamping for 30 minutes do not promote any important changes in the hepatic or renal function of dogs.


Subject(s)
Aortic Aneurysm, Abdominal/surgery , Alanine Transaminase/blood , Animals , Aspartate Aminotransferases/blood , Bilirubin/blood , Constriction , Creatinine/blood , Dogs , Female , Male , Urea/blood
16.
Braz J Med Biol Res ; 23(6-7): 515-8, 1990.
Article in English | MEDLINE | ID: mdl-1983169

ABSTRACT

Studies in the literature have shown the inhibitory action of bilirubin on serum gamma-glutamyl transpeptidase (GGT) activity. In spite of this, GGT is a sensitive diagnostic indicator, comparable to alkaline phosphatase for the diagnosis of chronic extrahepatic cholestasis (CEHC). To evaluate the relationship of bilirubin, alkaline phosphatase (AP) activity and GGT activity in CEHC we studied 30 patients with CEHC divided into two groups: A, 14 male and female subjects with serum bilirubin levels of 2 to 10 mg/dl, and B, 16 male and female subjects with serum bilirubin levels of 10.1 to 44 mg/dl. Serum GGT activity was measured by diluting serum samples 1:5 and 1:10. GGT values were equivalent in the two groups, there was no correlation between bilirubin and GGT (r = +0.179, P less than 0.01), and there was a significant correlation between GGT and AP (r = +0.627, P less than 0.01). The present results show that, if GGT inhibition by bilirubin did occur, this inhibition was not sufficient to prevent the increase in serum GGT levels and that the sensitivity of GGT as a marker for CEHC is similar to that of alkaline phosphatase.


Subject(s)
Alkaline Phosphatase/blood , Bilirubin/physiology , Cholestasis, Extrahepatic/blood , gamma-Glutamyltransferase/blood , Bilirubin/blood , Chronic Disease , Female , Humans , Male
17.
Braz J Med Biol Res ; 23(9): 801-3, 1990.
Article in English | MEDLINE | ID: mdl-1983192

ABSTRACT

Increased gamma-glutamyl transpeptidase (GGT) levels have been observed in patients with several types of liver diseases. However, since GGT activity can be inhibited or increased by several substances, the interpretation of these increased levels should be made with caution. The present study was designed to determine plasma GGT activity in blood samples obtained from 24 adult volunteers (13 males and 11 females aged 20 to 40 years) with the use of three different anticoagulants, i.e., ethylenediaminetetraacetic acid (EDTA), calcium fluoride and calcium citrate, and to compare it with GGT activity in serum obtained from the same blood samples. Serum GGT activity was significantly higher than plasma GGT activity (P less than 0.001) and significantly higher in men than in women (P less than 0.05), though plasma GGT activity was similar for both sexes.


Subject(s)
Calcium Fluoride/pharmacology , Calcium/pharmacology , Citrates/pharmacology , Edetic Acid/pharmacology , gamma-Glutamyltransferase/antagonists & inhibitors , Adult , Female , Humans , Male , Sex Factors , gamma-Glutamyltransferase/blood
18.
Braz J Med Biol Res ; 23(10): 995-7, 1990.
Article in English | MEDLINE | ID: mdl-2101066

ABSTRACT

Serum alanine aminotransferase (ALT) and serum aspartate aminotransferase (AST) levels are normal or discretely increased in rats with chronic extrahepatic cholestasis (CEHC). During the acute phase (first 72 h after biliary obstruction), however, serum transaminase values are quite elevated due to a mechanism not yet fully elucidated. Thus, this is a good experimental model, not involving hepatocellular necrosis, for the study of serum ALT and AST levels during the acute phase of CEHC. Male Wistar rats (250-350 g) were divided into two groups: group A (N = 60) was submitted to sham operation for bile duct ligation (BDL), and group B (N = 60) was submitted to BDL. Thirty and 120 min after BDL there was a 1.5-fold increase in both serum ALT and AST levels compared to sham-operated rats (P less than 0.05). Serum ALT levels were higher than AST levels as early as 30 min after BDL and the highest serum values for both transaminases were observed at 360 min which was also the last value measured. Serum AST levels increased 120 min after BDL, with no further significant increases thereafter.


Subject(s)
Alanine Transaminase/blood , Aspartate Aminotransferases/blood , Cholestasis, Extrahepatic/enzymology , Animals , Cholestasis, Extrahepatic/physiopathology , Chronic Disease , Male , Rats , Rats, Inbred Strains
19.
Rev. bras. pesqui. méd. biol ; Braz. j. med. biol. res;23(10): 995-7, 1990. ilus
Article in English | LILACS | ID: lil-91639

ABSTRACT

Serum alanine aminotransferase (ALT) and serum aspartate aminotransferase (AST) levels are normal or discretely increased in rats with chronic extrahepatic cholestasis (CEHC). During the acute phase (first 72 h after biliary obstruction), however, serum transminase values are quite elevated due to a mechanism not yet fully elucidated. Thus, this is a good experimental model, not involving hepatocellular necrosis, for the study of serum ALT and AST levels during the acute phase of CEHC. Male Wistar rats (250-350 g) were divided into two groups: group A(N = 60) was submitted to sham operation for bile duct ligation (BDL), and group B (N = 60) was submitted to BDL. Thirty and 120 min after BDL there was a 1.5-fold increase in both serum ALT and AST levels compared to sham-operated rats (P<0.05). Serum ALT levels were higher than AST levels as early as 30 min after BDL and the highest serum values for both transaminases were observed at 360 min which was also the last value measured. Serum AST levels increased 120 min after BDL, with no further significant increase thereafter


Subject(s)
Rats , Animals , Alanine Transaminase/blood , Aspartate Aminotransferases/blood , Cholestasis, Extrahepatic/blood , Cholestasis, Extrahepatic/physiopathology , Rats, Wistar
20.
Rev. bras. pesqui. méd. biol ; Braz. j. med. biol. res;23(6/7): 515-8, 1990.
Article in English | LILACS | ID: lil-92195

ABSTRACT

Studies in the literature have shown the inhibitory action action of bilirubin on serum gama-glutamyl transpeptidase (CGT) activity. In spite of this, CGT is a sensitive diagnostic indicator, comparable to alkaline phosphatase for the diagnosis of chronic extrahepatic cholestais (CEHC). To evaluate the relationship of bilirubin, alkaline phosphatase (AP) activity and GGT activity in CEHC we studied 30 patients with CEHC divided into two groups: A, 14 male and female subjects with bilirubin levels of 10.1 to 44 mg/dl. Serum GGT activity was meaured by diluting serum samples 1:5 and 1:10. GGT values were equivalent in the two groups, there was no correlation between bilirubin and GGT (r = +0.179, P > 0.01) and there was a significant correlation between GGT and AP(r = +0.627, P < 0.01). The present results show that, if GGT inhibition by bilirubin did occur, this inhibitions was not sufficient to prevent the increase in serum GGT levels and that the sensitivity of GGT as a marker for CEHC is simular to that of alkaline phosphatase


Subject(s)
Humans , Alkaline Phosphatase/blood , Bilirubin/physiology , Cholestasis, Extrahepatic/blood , gamma-Glutamyltransferase/blood , Bilirubin/blood , Chronic Disease
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