RESUMEN
Over 5% of the world's population has varying degrees of hearing loss. Mutations in GJB2 are the most common cause of autosomal recessive non-syndromic hearing loss (ARNHL) in many populations. The frequency and type of mutations are influenced by ethnicity. Guatemala is a multi-ethnic country with four major populations: Maya, Ladino, Xinca, and Garifuna. To determine the mutation profile of GJB2 in a ARNHL population from Guatemala, we sequenced both exons of GJB2 in 133 unrelated families. A total of six pathogenic variants were detected. The most frequent pathogenic variant is c.131G>A (p.Trp44*) detected in 21 of 266 alleles. We show that c.131G>A is associated with a conserved haplotype in Guatemala suggesting a single founder. The majority of Mayan population lives in the west region of the country from where all c.131G>A carriers originated. Further analysis of genome-wide variation of individuals carrying the c.131G>A mutation compared with those of Native American, European, and African populations shows a close match with the Mayan population.
RESUMEN
We aimed to evaluate the effects of aerobic exercise training (4 days) and metformin exposure on acute glucose intolerance after dexamethasone treatment in rats. Forty-two adult male Wistar rats (8 weeks old) were divided randomly into four groups: sedentary control (SCT), sedentary dexamethasone-treated (SDX), training dexamethasone-treated (DPE), and dexamethasone and metformin treated group (DMT). Glucose tolerance tests and in situ liver perfusion were undertaken on fasting rats to obtain glucose profiles. The DPE group displayed a significant decrease in glucose values compared with the SDX group. Average glucose levels in the DPE group did not differ from those of the DMT group, so we suggest that exercise training corrects dexamethasone-induced glucose intolerance and improves glucose profiles in a similar manner to that observed with metformin. These data suggest that exercise may prevent the development of glucose intolerance induced by dexamethasone in rats to a similar magnitude to that observed after metformin treatment.
Asunto(s)
Animales , Masculino , Intolerancia a la Glucosa/prevención & control , Hipoglucemiantes/uso terapéutico , Metformina/uso terapéutico , Condicionamiento Físico Animal/fisiología , Glucemia/análisis , Dexametasona/farmacología , Ayuno/sangre , Prueba de Tolerancia a la Glucosa , Glucocorticoides/farmacología , Intolerancia a la Glucosa/inducido químicamente , Glucosa/análisis , Hiperglucemia/terapia , Hígado/química , Perfusión , Distribución Aleatoria , Ratas Wistar , NataciónRESUMEN
We aimed to evaluate the effects of aerobic exercise training (4 days) and metformin exposure on acute glucose intolerance after dexamethasone treatment in rats. Forty-two adult male Wistar rats (8 weeks old) were divided randomly into four groups: sedentary control (SCT), sedentary dexamethasone-treated (SDX), training dexamethasone-treated (DPE), and dexamethasone and metformin treated group (DMT). Glucose tolerance tests and in situ liver perfusion were undertaken on fasting rats to obtain glucose profiles. The DPE group displayed a significant decrease in glucose values compared with the SDX group. Average glucose levels in the DPE group did not differ from those of the DMT group, so we suggest that exercise training corrects dexamethasone-induced glucose intolerance and improves glucose profiles in a similar manner to that observed with metformin. These data suggest that exercise may prevent the development of glucose intolerance induced by dexamethasone in rats to a similar magnitude to that observed after metformin treatment.
Asunto(s)
Intolerancia a la Glucosa/prevención & control , Hipoglucemiantes/uso terapéutico , Metformina/uso terapéutico , Condicionamiento Físico Animal/fisiología , Animales , Glucemia/análisis , Dexametasona/farmacología , Ayuno/sangre , Glucocorticoides/farmacología , Glucosa/análisis , Intolerancia a la Glucosa/inducido químicamente , Prueba de Tolerancia a la Glucosa , Hiperglucemia/terapia , Hígado/química , Masculino , Perfusión , Distribución Aleatoria , Ratas Wistar , NataciónRESUMEN
Acinetobacter baumannii is a major cause of healthcare-associated infection, often affecting critically ill patients. The purpose of the study was to examine the associations of carbapenem resistance with mortality, length of hospital stay and hospital costs among patients infected with A. baumannii in intensive-care units (ICUs) in Colombia. A prospective, multicentre cohort study was conducted among 165 patients with A. baumannii infection admitted to ICUs between April 2006 and April 2010. Patients with carbapenem-resistant A. baumannii had higher risk of 30-day mortality than patients with carbapenem-susceptible A. baumannii in the univariate analysis (unadjusted hazard ratio = 2.12; 95% CI 1.14-3.95; p 0.018). However, carbapenem resistance was not significantly associated with risk of mortality (adjusted hazard ratio = 1.45; 95% CI 0.74-2.87; p 0.28) after adjusting for APACHE II score and other confounding factors. We did not find a significant difference in length of stay in ICU after the onset of infection between the two groups in the multivariate analysis (adjusted mean = 13.1 days versus 10.5 days; p 0.14). The average total cost of hospitalization among patients with carbapenem-resistant A. baumannii was significantly higher than that among patients with carbapenem-susceptible A. baumannii in the multivariate analysis (adjusted cost; US$ 11 359 versus US$ 7049; p <0.001). Carbapenem resistance was not significantly associated with mortality, though we are unable to rule out an increased risk due to the limited sample size. Carbapenem resistance was associated with an additional cost of hospitalization.
Asunto(s)
Infecciones por Acinetobacter/economía , Infecciones por Acinetobacter/microbiología , Acinetobacter baumannii/efectos de los fármacos , Carbapenémicos/farmacología , Costos de la Atención en Salud , Resistencia betalactámica , Infecciones por Acinetobacter/mortalidad , Acinetobacter baumannii/aislamiento & purificación , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Colombia , Infección Hospitalaria/economía , Infección Hospitalaria/microbiología , Infección Hospitalaria/mortalidad , Femenino , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
Coriandrum sativum L. (Umbelliferae), conhecido popularmente por coentro, é uma planta doméstica cultivada nas diversas partes do mundo, inclusive no Brasil. As folhas e frutos do coentro são utilizados como condimento em culinária e na medicina popular como analgésica, antirreumática, carminativa e colagoga. O objetivo deste estudo foi avaliar o efeito do tratamento com o óleo essencial (OEC) e o extrato hidroalcóolico (EHC) do coentro em modelos experimentais de inflamação em roedores. A atividade antiinflamatória do coentro foi avaliada por meio dos testes de pleurisia em ratos e formação do edema de orelha em camundongos. A pleurisia foi induzida pela carragenina em animais tratados ou não com EHC. O edema de orelha induzido pela aplicação tópica de óleo de cróton e a atividade da mieloperoxidase foi avaliada em camundongos tratados ou não com OEC ou EHC. No teste da pleurisia o tratamento com EHC promoveu significativa diminuição no edema pleural, mas não sobre a migração leucocitária. Além disso, diferentemente ao observado com o tratamento com OEC, o uso tópico de EHC diminui significativamente o edema de orelha e a migração celular induzidos pela aplicação do óleo de cróton. Os dados indicam que EHC apresenta atividade antiinflamatória quando administrado pelas via oral e tópica, enquanto que OEC não apresenta atividade antiinflamatória tópica.
Commonly known as coriander, Coriandrum sativum L. (Umbelliferae) is a home plant grown in several parts of the world, including Brazil. Its leaves and fruits have been used as condiment in cooking and in folk medicine as analgesic, antirheumatic, carminative and cholagogue. The aim of this study was to evaluate the effect of essential oil (EO) and hydroalcoholic extract (HE) from coriander on experimental inflammation models in rodents. Coriander anti-inflammatory activity was evaluated by pleurisy tests in rats and ear edema formation in mice. Pleurisy was induced by carrageenan in HE-treated or non-treated animals. The ear edema was induced by topical application of croton oil and the myeloperoxidase activity was evaluated in EO-treated and HE-treated or non-treated mice. In the pleurisy test, HE treatment significantly decreased pleural edema but not the leukocyte migration. Furthermore, differently from EO, the topical use of HE significantly decreased ear edema and cell migration induced by croton oil application. The results indicate that HE had anti-inflammatory activity when orally and topically administered, whereas EO did not present topical anti-inflammatory activity.
Asunto(s)
Animales , Masculino , Adulto Joven , Ratones , Ratas , Antiinflamatorios , Coriandrum , Análisis de Varianza , Oído , Edema , Inflamación , Plantas Medicinales , Pleuresia/prevención & controlRESUMEN
Neste trabalho foram comparados os efeitos da farinha de linhaça dourada e farinha de linhaça marrom sobre o perfil lipídico e evolução ponderal em ratos Wistar. Os animais foram divididos aleatoriamente em três grupos, Grupo Controle (GC); Grupo suplementado com Farinha de Linhaça Marrom (LM) e Grupo Suplementado com Farinha de Linhaça Dourada (LD). Os animais foram submetidos à avaliação ponderal em dias alternados até o dia do sacrifício, no 36º dia, quando amostras de sangue foram coletadas para avaliação do perfil lipídico. O uso da farinha de linhaça como suplemento dietético de ratos Wistar, no período de 35 dias, promoveu redução significativa dos níveis de triglicérides séricos e da razão CT/HDL-c, com concomitante aumento dos níveis séricos de HDL-c, demonstrando assim efeito cardioprotetor. Os efeitos sobre o incremento de massa corporal dos animais durante o período do experimento sugerem importante ação preventiva no desenvolvimento da obesidade para a farinha de linhaça.
In this work, the effects of brown and golden flax flour were compared based on lipid profile and weight gain in Wistar rats. The animals were randomly divided into three groups: control group (CG); group supplemented with brown flax flour (BF); and group supplemented with golden flax flour (GF). The animals were subjected to weight assessment on alternate days until sacrifice at the 36th day, when blood samples were collected for lipid profile evaluation. The use of flax flour as dietary supplement to Wistar rats, in a 35-day period, led to a significant decrease in the serum levels of triglycerides and TC:HDL-C ratio, with concomitant increase in HDL-C serum levels, demonstrating thus a cardioprotective effect. The effects on rat weight gain over the experimental period suggest an important preventive action of flax flour on the obesity development.
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Animales , Masculino , Adulto , Ratas , /estadística & datos numéricos , Evolución Biológica , Lino , Harina , Trastornos del Metabolismo de los Lípidos , Ratas Wistar , Suplementos Dietéticos/análisis , Peso por Estatura , Análisis de Varianza , Enfermedades MetabólicasRESUMEN
Leishmanicide potential of Calophyllum brasiliense leaves on promastigote and amastigote of Leishmania (Leishmania) amazonensis is evaluated. The LD(50) of dichloromethane extract and hexane fraction for promastigotes was respectively 40 microg/ml and 20 microg/ml. In mouse peritoneal macrophages infected with Leishmania amastigotes the Infection Index decreased respectively 100% and 84.2% in 80 microg/ml and 40 microg/ml concentrations of dichloromethane extract. Hexane fraction decreased infection index respectively by 98.7% and 91.3% within the same concentrations. It was found that pretreatment with dichloromethane extract or with hexane fraction of experimentally infected BALB/c mice decrease the volume of the lesions by L. (L.) amazonensis. Moreover, animals treated topically also revealed healing lesions. Besides, the parasite load in the animals' popliteal lymph nodes was significantly reduced in treated animals, showing that plant components actually control infection. Results show that crude extract and hexane fraction of C. brasiliense reveal a significant in vitro and in vivo leishmanicide activity.
Asunto(s)
Antiparasitarios/uso terapéutico , Calophyllum/química , Leishmania/efectos de los fármacos , Leishmaniasis/tratamiento farmacológico , Macrófagos Peritoneales/efectos de los fármacos , Fitoterapia , Extractos Vegetales/uso terapéutico , Animales , Antiparasitarios/farmacología , Femenino , Leishmaniasis/patología , Ganglios Linfáticos/parasitología , Macrófagos Peritoneales/parasitología , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Extractos Vegetales/química , Extractos Vegetales/farmacología , Hojas de la PlantaRESUMEN
Rosmarinus officinalis L. (Family Lamiaceae), popularly named rosemary, is a common household plant grown in many parts of the world, including Brazil. Rosemary leaves are used for food flavoring and have been used in folk medicine for many conditions; they have antispasmodic, analgesic, antirheumatic, carminative, cholagogue, diuretic, expectorant, and antiepileptic effects. The objective of this study was to evaluate the effects of rosemary essential oil (REO) on experimental models of nociception and inflammation in animals. The anti-inflammatory effect of REO was evaluated by inflammatory exudate volume and leukocyte migration in carrageenan-induced pleurisy and carrageenan-induced paw edema tests in rats. Antinociception was evaluated using the acetic acid-induced writhing and hot plate tests in mice. REO (500 mg/kg) significantly reduced the volume of pleural exudate and slightly decreased the number of cells that had migrated compared with the control animals. At doses of 250, 500, and 750 mg/kg, REO significantly inhibited carrageenan-induced edema 1-4 hours after injection of the phlogistic agent. In the hot plate test, REO administration (125, 250, and 500 mg/kg) showed unremarkable effects on response latency, whereas control injection of meperidine induced significant antinociceptive effects. REO at doses of 70, 125, and 250 mg/kg had a significant antinociceptive effect in the acetic acid-induced abdominal writhing test compared with control animals. These data suggest that REO possesses anti-inflammatory and peripheral antinociceptive activity.
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Analgésicos/farmacología , Antiinflamatorios/farmacología , Inflamación/tratamiento farmacológico , Aceites Volátiles/farmacología , Dolor/tratamiento farmacológico , Fitoterapia , Rosmarinus , Analgésicos/química , Analgésicos/toxicidad , Animales , Antiinflamatorios/química , Antiinflamatorios/toxicidad , Carragenina , Edema/inducido químicamente , Edema/tratamiento farmacológico , Femenino , Inflamación/inducido químicamente , Masculino , Ratones , Monoterpenos/análisis , Aceites Volátiles/química , Aceites Volátiles/toxicidad , Dolor/inducido químicamente , Rosmarinus/química , Rosmarinus/toxicidadRESUMEN
OBJECTIVE AND DESIGN: Knowing that hyperglycemia is a hallmark of vascular dysfunction in diabetes and that neonatal streptozotocin-induced diabetic rats (n-STZ) present reduced inflammatory response, we decided to evaluate the effect of chlorpropamide-lowered blood glucose levels on carrageenan-induced rat paw edema and pleural exudate in n-STZ. MATERIALS: Diabetes was induced by STZ injection (160 mg/kg, ip) in neonates (2-day-old) Wistar rats. TREATMENT: n-STZ diabetic rats were treated with chlorpropamide (200mg/kg, 15d, by gavage) 8 weeks after STZ injection. METHODS: Carrageenan-induced paw edema and pleural exudate volumes were assessed concomitantly with peripheral and exudate leukocyte count. We also evaluated the expression of inducible nitric oxide synthase (iNOS) in lungs of all experimental groups. RESULTS: Chlorpropamide treatment improved glucose tolerance, beta-cell function (assessed by HOMA-beta), corrected paw edema, and pleural exudate volume in n-STZ. Neither leukocyte count nor iNOS expression were affected by diabetes or by chlorpropamide treatment. CONCLUSION: Chlorpropamide treatment by restoring beta-cell function, reducing blood sugar levels, and improving glucose tolerance might be contributing to the correction of the reduced inflammatory response tested as paw edema and pleural exudate in n-STZ diabetic rats.
Asunto(s)
Clorpropamida/uso terapéutico , Diabetes Mellitus Experimental/tratamiento farmacológico , Edema/etiología , Hipoglucemiantes/uso terapéutico , Pleuresia/etiología , Animales , Glucemia/análisis , Carragenina , Diabetes Mellitus Experimental/fisiopatología , Edema/fisiopatología , Células Secretoras de Insulina/efectos de los fármacos , Células Secretoras de Insulina/fisiología , Masculino , Óxido Nítrico Sintasa de Tipo II/genética , Pleuresia/fisiopatología , ARN Mensajero/análisis , Ratas , Ratas Wistar , EstreptozocinaRESUMEN
Leaves of Piper ovatum are known in folk medicine as "joão burandi" or "anestésica" and in traditional Brazilian medicine are used to treat inflammatory disease. The hydroalcoholic extract, fractions, and a mixture of piperovatine (1) and piperlonguminine (2) in a proportion of 2:3 obtained from Piper ovatum were assayed for anti-inflammatory activity by means of carrageenan-induced pleurisy in rats and croton oil-induced ear edema in mice. The hydroalcoholic extract was analyzed by high-performance liquid chromatography. Fraction constituents were evaluated by phytochemical screening, and the mixture of amides (1 and 2) was identified by analyses of spectral data of (1)H and (13)C nuclear magnetic resonance. Acute toxicity of the extract also was evaluated. At 500mg/kg, the hydroalcoholic extract of Piper ovatum leaves did not reduce the volume of inflammatory pleural exudates compared with control animals. However, the hydroalcoholic extract and fractions F1-F3 at doses of 5.0mg/ear and a mixture of piperovatine (1) and piperlonguminine (2) at doses of 2.5, 1.25, and 0.625mg/ear significantly reduced the degree of ear edema. Taken together, the results indicate that the amide fractions piperovatine and piperlonguminine showed the greatest inhibitory activity of topical inflammation induced by croton oil.
Asunto(s)
Amidas/farmacología , Antiinflamatorios/uso terapéutico , Edema/tratamiento farmacológico , Fitoterapia , Piper/química , Extractos Vegetales/uso terapéutico , Amidas/uso terapéutico , Animales , Masculino , Ratones , Extractos Vegetales/química , Extractos Vegetales/toxicidad , Hojas de la Planta/química , Pleuresia/tratamiento farmacológico , Ratas , Pruebas de Toxicidad AgudaRESUMEN
UNLABELLED: The present study investigated the acute inflammatory response (increase in vascular permeability and leukocytes migration) in the pleura of spontaneously hypertensive rats (SHR) and normotensive rats (NTR), using two different stimulus: carrageenan and active anaphylaxis. In addition, the role of endogenous nitric oxide in these responses was investigated. RESULTS: The inflammatory response induced by intrapleural carrageenan injection in SHR developed similarly to that in NTR. Treatment with L-NAME, reduced the intensity of this response in both groups of rats. The inflammatory response induced by active anaphylaxis in SHR and NTR was different. The increase in vascular permeability occurred later in the SHR compared to NTR. The number of leukocyte present in inflammatory exudates was increased at 4 h in both groups of rats. L-NAME treatment did not inhibit exudation at the intervals under analysis, however, reduced the number of mononuclear cells in the inflammatory exudate of SHR. CONCLUSION: The development of the inflammatory response in SHR differs from that in NTR, depending on the nature of the inflammatory stimulus. Endogenous NO plays a clear role in carrageenan-induced inflamma-tion, but not in immunologically mediated inflammation in the analyzed period.
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Anafilaxia/complicaciones , Quimiotaxis de Leucocito , Hipertensión/metabolismo , Leucocitos/inmunología , Óxido Nítrico/metabolismo , Pleuresia/metabolismo , Anafilaxia/inducido químicamente , Anafilaxia/inmunología , Anafilaxia/metabolismo , Animales , Permeabilidad Capilar , Carragenina , Ensayos de Migración de Leucocitos , Quimiotaxis de Leucocito/efectos de los fármacos , Modelos Animales de Enfermedad , Inhibidores Enzimáticos/farmacología , Exudados y Transudados/citología , Exudados y Transudados/metabolismo , Hipertensión/inmunología , Leucocitos/efectos de los fármacos , Masculino , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico Sintasa/antagonistas & inhibidores , Óxido Nítrico Sintasa/metabolismo , Ovalbúmina , Pleuresia/inducido químicamente , Pleuresia/etiología , Pleuresia/inmunología , Ratas , Ratas Endogámicas SHR , Ratas WistarRESUMEN
This study was carried out to evaluate whether the anti-inflammatory response in rats to the whole extract of Harpagophytum procumbens is a consequence of adrenal corticosteroid release. Carrageenan-induced inflammatory responses in the hindpaws were evaluated in control, sham-operated and adrenalectomized rats. The extract was administered orally (by gavage) or intraperitoneally, 30min prior to injury stimulus. Blood samples were then collected, and the number of circulating leukocytes was estimated. Pretreatment with the whole extract of H. procumbens reduced the intensity of inflammatory response in normal, sham-operated and adrenalectomized animals. When administered orally, the extract was ineffective. The reduced number of circulating leukocytes observed following intraperitoneal injection of the extract characterized adrenal hyperactivity. The inhibitory effect of the whole extract of H. procumbens on acute inflammatory response in the rat, when administered intraperitoneally, does not depend on the release of adrenal corticosteroids.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Harpagophytum , Inflamación/prevención & control , Fitoterapia , Extractos Vegetales/farmacología , Administración Oral , Corticoesteroides/metabolismo , Glándulas Suprarrenales/efectos de los fármacos , Glándulas Suprarrenales/metabolismo , Animales , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/uso terapéutico , Carragenina , Inflamación/inducido químicamente , Inyecciones Intraperitoneales , Leucocitos/efectos de los fármacos , Masculino , Extractos Vegetales/administración & dosificación , Extractos Vegetales/uso terapéutico , Ratas , Ratas WistarRESUMEN
The present study evaluates the effects of methotrexate (MTX) and chloroquine (CQ), and of combined MTX + CQ treatment, on the inflammatory response and on plasma and liver phosphatase and transaminase activities, employing an adjuvant-induced arthritis model in rats. Arthritis was induced by the intradermal injection of a suspension of Mycobacterium tuberculosis in mineral oil into the plantar surface of the hind paws. Development of the inflammatory response was assessed over a 21-day period. Animal groups received either: (i) MTX, administered i.p., weekly, in 0.15, 1.5, 3, 6 or 12 mg/kg doses; (ii) CQ, given intragastrically, in daily 25 or 50 mg/kg doses; or (iii) MTX + CQ, administered in two combinations (MTX1.5 mg/kg + CQ50 mg/kg, or MTX6 mg/kg + CQ50 mg/kg). At the end of the experimental period, the animals were anesthetized and killed, blood and liver samples were collected and prepared for measurement of acid and alkaline phosphatase (AP, ALP), and aspartate (AST) and alanine aminotransferase (ALT) activities. MTX at 6 and 12 mg/kg reduced the inflammatory response while CQ had no effect. MTX6 mg/kg + CQ50 mg/kg reduced the inflammatory response similar to MTX12 mg/kg, without affecting the bone marrow. Plasma AP and liver ALP activities were very elevated in the arthritic rats. While MTX treatment partially reduced both plasma AP and liver ALP activities at all doses used in the arthritic rats, CQ treatment reduced plasma AP, but increased liver AP activity. MTX + CQ treatment decreased plasma AP and liver ALP activities in the arthritic rats to control values. Plasma and liver AST activities were unaltered in the arthritic rats, and were unaffected by treatment. However, plasma and liver ALT activities were significantly reduced in the arthritic rats. While MTX or CQ treatment did not alter plasma transaminase activity in the arthritic rats, after MTX + CQ treatment, plasma ALT activity returned to normal values. In conclusion, the present data suggest that MTX + CQ treatment provides more effective anti-inflammatory protection against adjuvant-induced arthritis than does MTX alone, reverting the alterations in enzyme activities induced by this inflammatory disease in rats.
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Artritis Experimental/tratamiento farmacológico , Cloroquina/administración & dosificación , Metotrexato/administración & dosificación , Fosfatasa Ácida/metabolismo , Alanina Transaminasa/metabolismo , Fosfatasa Alcalina/metabolismo , Animales , Artritis Experimental/enzimología , Aspartato Aminotransferasas/metabolismo , Peso Corporal/efectos de los fármacos , Quimioterapia Combinada , Hígado/enzimología , Masculino , RatasRESUMEN
This study investigates the action of Canova medication (CM) on experimental infection by Leishmania (Leishmania) amazonensis, utilizing in vitro and in vivo assays. For the in vitro tests, Balb/c mouse peritoneal macrophages (5x10(5) cells in 500 microl of culture medium, supplemented with 10% fetal calf serum, penicillin (100 U/ml) and streptomycin (0.1 mg/ml) (were distributed in 24-well plates and CM was added at concentrations of 20 or 40%. Twenty-four hours later, the macrophages were infected with Leishmania amastigotes in culture medium. The effect of CM on macrophages leishmanicidal activity in 24 and 48 h cultures was evaluated by determining infection index and measuring nitric oxide (NO) production. The in vivo tests were performed in mice infected with 10(7)L. (L.) amazonensis promastigotes injected in to the right hind footpad (25 microl in phosphate buffered saline). The progression of the lesions was examined over a 9-week period by measuring footpad swelling, and the parasite load in regional lymph nodes and spleen. The in vitro results showed that at 40% CM reduced the infection index, and induced NO production in the elicited macrophages, which suggests that the inhibitory effect on infection index may be mediated by NO. In the in vivo infection, when administered, orally or subcutaneously in mice, CM reduced infection by L. (L.) amazonensis in the paws, resulting in smaller lesions. CM treatment also decreased parasite load in the regional popliteal lymph nodes and in the spleen. These results suggest that CM modulates experimental infection by L. (L.) amazonensis, controlling infection progression and limiting dissemination.
Asunto(s)
Venenos de Crotálidos/farmacología , Homeopatía , Factores Inmunológicos/fisiología , Leishmania mexicana/efectos de los fármacos , Leishmaniasis Cutánea/tratamiento farmacológico , Leishmaniasis Cutánea/inmunología , Extractos Vegetales/farmacología , Animales , Venenos de Crotálidos/uso terapéutico , Progresión de la Enfermedad , Formularios Homeopáticos como Asunto , Leishmania mexicana/inmunología , Leishmaniasis Cutánea/parasitología , Ganglios Linfáticos/parasitología , Macrófagos Peritoneales/parasitología , Macrófagos Peritoneales/fisiología , Masculino , Ratones , Ratones Endogámicos BALB C , Óxido Nítrico/análisis , Óxido Nítrico/biosíntesis , Parásitos/aislamiento & purificación , Extractos Vegetales/uso terapéutico , Bazo/parasitologíaRESUMEN
The inflammatory response is decreased in diabetic animals. After adrenals removal this impaired response in type 2 diabetic rats evaluated by pleurisy and vascular permeability tests was restored. Our studies demonstrate that endogenous corticosteroids play a partial role in the impaired inflammatory response in type 2 streptozotocin diabetic rats.
Asunto(s)
Corticoesteroides/fisiología , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patología , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patología , Mediadores de Inflamación/fisiología , Animales , Masculino , Ratas , Ratas WistarRESUMEN
OBJECTIVES AND DESIGN: To verify whether the inflammatory responses in animals with type 2 diabetes are altered to an extent similar to that in type 1 diabetes. MATERIALS: Male newborn (2 days old) Wistar rats were made diabetic by streptozotocin (160 mg/kg, i.p.) and used 8-10 weeks later (10 rats/group). METHODS: The inflammatory responses were evaluated using paw edema (induced by local injection of carrageenan or dextran), pleurisy (by pleural injection of carrageenan), increases in vascular permeability (induced by intradermal injection of histamine, serotonin and bradykinin) and leukocyte counts in peripheral blood and pleural exudate. RESULTS: Diabetic animals showed reduced inflammatory responses to carrageenan but not to dextran. The increase in vascular permeability induced by serotonin and bradykinin was reduced whereas that to histamine was not altered in diabetic compared to control rats. Although the pleural exudate was reduced, leukocyte counts were similar in diabetic and control rats. Insulin (2 IU, 4 h before), though effective in reducing blood sugar levels, did not restore the altered responses in diabetic rats. In contrast to that in rats with type 1 diabetes, in rats with type 2 diabetes, removal of the adrenal glands restored the reduced inflammatory responses. CONCLUSIONS: Insulin resistance in type 2 diabetic rats led to reduced inflammatory responses, which were partially corrected by adrenalectomy.
Asunto(s)
Diabetes Mellitus Experimental/patología , Diabetes Mellitus Tipo 2/patología , Inflamación/patología , Adrenalectomía , Animales , Animales Recién Nacidos , Permeabilidad Capilar/efectos de los fármacos , Carragenina , Edema/inducido químicamente , Edema/prevención & control , Prueba de Tolerancia a la Glucosa , Hipoglucemiantes/farmacología , Insulina/farmacología , Resistencia a la Insulina/fisiología , Recuento de Leucocitos , Masculino , Pleuresia/inducido químicamente , Pleuresia/prevención & control , Ratas , Ratas WistarRESUMEN
The aim of the present study was to evaluate the changes caused by adjuvant-induced arthritis in liver mitochondria and to investigate the effects of the nonsteroidal anti-inflammatory drug nimesulide. The main alterations observed in liver mitochondria from arthritic rats were: higher rates of state IV and state III respiration with beta-hydroxybutyrate as substrate; reduced respiratory control ratio and impaired capacity for swelling dependent on beta-hydroxybutyrate oxidation. No alterations were found in the activities of NADH oxidase and ATPase. Nimesulide produced: (1) stimulation of state IV respiration; (2) decrease in the ADP/O ratio and in the respiratory control ratio; (3) stimulation of ATPase activity of intact mitochondria; (4) inhibition of swelling driven by the oxidation of beta-hydroxybutyrate; (5) induction of passive swelling due to NH(3)/NH(4)+ redistribution. The activity of NADH oxidase was insensitive to nimesulide. Mitochondria from arthritic rats showed higher sensitivity to nimesulide regarding respiratory activity. The results of this work allow us to conclude that adjuvant-induced arthritis leads to quantitative changes in some mitochondrial functions and in the sensitivity to nimesulide. Direct evidence that nimesulide acts as an uncoupler was also presented. Since nimesulide was active in liver mitochondria at therapeutic levels, the impairment of energy metabolism could lead to disturbances in the liver responses to inflammation, a fact that should be considered in therapeutic intervention.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Artritis Experimental/metabolismo , Metabolismo Energético/efectos de los fármacos , Mitocondrias Hepáticas/efectos de los fármacos , Sulfonamidas/farmacología , Adenosina Trifosfatasas/efectos de los fármacos , Adenosina Trifosfatasas/metabolismo , Adenosina Trifosfato/metabolismo , Animales , Artritis Experimental/inducido químicamente , Técnicas In Vitro , Masculino , Proteínas de la Membrana/efectos de los fármacos , Proteínas de la Membrana/metabolismo , Mitocondrias Hepáticas/metabolismo , Complejos Multienzimáticos/efectos de los fármacos , Complejos Multienzimáticos/metabolismo , NADH NADPH Oxidorreductasas/efectos de los fármacos , NADH NADPH Oxidorreductasas/metabolismo , Fosforilación Oxidativa/efectos de los fármacos , Consumo de Oxígeno/efectos de los fármacos , Polarografía , Ratas , Ratas Wistar , Desacopladores/metabolismoRESUMEN
The antiulcer activity of Maytenus aquifolium spray dried extract was studied in rats. Ulcers were induced by means of three experimental models: acidified-ethanol, indomethacin and acute stress. The extract was found to have significant antiulcer activity against all the models studied. These results show that preparation of the extract by means of the spray dried technique does not alter the biological activity of Maytenus aquifolium.
Asunto(s)
Antiulcerosos/uso terapéutico , Fitoterapia , Rosales/uso terapéutico , Úlcera Gástrica/prevención & control , Animales , Modelos Animales de Enfermedad , Etanol/toxicidad , Indometacina/toxicidad , Masculino , Extractos Vegetales/uso terapéutico , Hojas de la Planta/química , Ratas , Ratas Wistar , Estrés FisiológicoRESUMEN
This study explored the interference by Maytenus aquifolium leaves hydroalcoholic (MALHE) extract, administered orally, on the pharmacokinetic and antiinflammatory activity of piroxicam in rats. The results showed no significant difference in piroxicam bioavailability with simultaneous application of MALHE. MALHE also had no effect on the inhibitory effect of piroxicam on inflammatory processes induced by carrageenan and complete Freund adjuvant.
Asunto(s)
Artritis Experimental/tratamiento farmacológico , Piroxicam/farmacocinética , Piroxicam/uso terapéutico , Extractos Vegetales/farmacología , Plantas Medicinales , Animales , Antiinflamatorios no Esteroideos/farmacocinética , Antiinflamatorios no Esteroideos/uso terapéutico , Brasil , Masculino , Medicina Tradicional , Mycobacterium tuberculosis , Hojas de la Planta , Ratas , Ratas Sprague-Dawley , Ratas WistarRESUMEN
OBJECTIVE AND DESIGN: Glycolysis and the glucose phosphorylation capacity of livers from arthritic rats were studied because alterations in these parameters are suggested by some studies. SUBJECTS: Arthritis was induced in male albino rats (Wistar; 180-220 g). TREATMENT: The animals were injected with 100 microl heat inactivated Mycobacterium tuberculosis suspended in mineral oil at a concentration of 0.5% (w/v). Animals showing lesions after 14 to 21 days were selected. METHODS: Glucose phosphorylation was measured in the high speed supernatant fraction of liver homogenates and glycolysis in the isolated perfused liver. RESULTS: The glucose concentration for half-maximal rates was reduced from 18.32+/-5.69 in normal to 9.84+/-3.15 mM in arthritic rats (p = 0.024). Vmax was increased from 8.77+/-0.27 in normal to 11.49+/-0.29 nmol min(-1) mg protein(-1) in arthritic rats (p = 0.001). Perfused livers from arthritic rats showed a 2.43-fold higher rate of glycolysis. CONCLUSIONS: Livers from arthritic rats present a higher glucose phosphorylation capacity. Possibly this phenomenon is caused by circulating inflammatory mediators produced during adjuvant-induced arthritis.