Assuntos
Acidose Respiratória/etiologia , Hipercapnia/etiologia , Pneumopatias/complicações , Respiração Artificial/métodos , Acidose Respiratória/diagnóstico , Acidose Respiratória/terapia , Gasometria , Broncoscopia , Diagnóstico Diferencial , Evolução Fatal , Humanos , Hipercapnia/diagnóstico , Hipercapnia/terapia , Pneumopatias/diagnóstico , Pneumopatias/terapia , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios XRESUMO
The objective of this study was to determine the effects of enrichment with n-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on the differentiation of 3T3-L1 preadipocytes. Enrichment with DHA but not EPA significantly increased the differentiation markers compared to control differentiated cells. DHA compared to EPA treatment led to a greater increase in adiponectin secretion and, conditioned media collected from DHA treated cells inhibited monocyte migration. Moreover, DHA treatment resulted in inhibition of pro-inflammatory signaling pathways. DHA treated cells predominantly accumulated DHA in phospholipids whereas EPA treatment led to accumulation of both EPA and its elongation product docosapentaenoic acid (DPA), an n-3 fatty acid. Of note, adding DPA to DHA inhibited DHA-induced differentiation. The differential effects of EPA and DHA on preadipocyte differentiation may be due, in part, to differences in their intracellular modification which could impact the type of n-3 fatty acids incorporated into the cells.
Assuntos
Adipócitos/metabolismo , Diferenciação Celular/efeitos dos fármacos , Ácidos Docosa-Hexaenoicos/farmacologia , Ácido Eicosapentaenoico/farmacologia , Células 3T3-L1 , Adipócitos/citologia , Animais , CamundongosRESUMO
OBJECTIVE: Adipose tissue (AT)-specific inflammation is considered to mediate the pathological consequences of obesity and macrophages are known to activate inflammatory pathways in obese AT. Because cyclooxygenases play a central role in regulating the inflammatory processes, we sought to determine the role of hematopoietic cyclooxygenase-1 (COX-1) in modulating AT inflammation in obesity. MATERIALS/METHODS: Bone marrow transplantation was performed to delete COX-1 in hematopoietic cells. Briefly, female wild type (wt) mice were lethally irradiated and injected with bone marrow (BM) cells collected from wild type (COX-1+/+) or COX-1 knock-out (COX-1-/-) donor mice. The mice were fed a high fat diet for 16 weeks. RESULTS: The mice that received COX-1-/- bone marrow (BM-COX-1-/-) exhibited a significant increase in fasting glucose, total cholesterol and triglycerides in the circulation compared to control (BM-COX-1+/+) mice. Markers of AT-inflammation were increased and were associated with increased leptin and decreased adiponectin in plasma. Hepatic inflammation was reduced with a concomitant reduction in TXB2 levels. The hepatic mRNA expression of genes involved in lipogenesis and lipid transport was increased while expression of genes involved in regulating hepatic glucose output was reduced in BM-COX-1-/- mice. Finally, renal inflammation and markers of renal glucose release were increased in BM-COX-1-/- mice. CONCLUSION: Hematopoietic COX-1 deletion results in impairments in metabolic homeostasis which may be partly due to increased AT inflammation and dysregulated adipokine profile. An increase in renal glucose release and hepatic lipogenesis/lipid transport may also play a role, at least in part, in mediating hyperglycemia and dyslipidemia, respectively.
Assuntos
Tecido Adiposo/enzimologia , Tecido Adiposo/patologia , Células da Medula Óssea/enzimologia , Transplante de Medula Óssea , Ciclo-Oxigenase 1/deficiência , Macrófagos , Obesidade/complicações , Adiponectina/sangue , Animais , Biomarcadores/sangue , Biomarcadores/metabolismo , Western Blotting , Ciclo-Oxigenase 1/sangue , Ciclo-Oxigenase 1/genética , Dieta Hiperlipídica , Ingestão de Alimentos , Feminino , Imunofluorescência , Inflamação/metabolismo , Rim/metabolismo , Rim/patologia , Leptina/sangue , Fígado/metabolismo , Fígado/patologia , Camundongos , Camundongos Knockout , Obesidade/enzimologia , Obesidade/etiologia , Reação em Cadeia da Polimerase em Tempo Real , Aumento de PesoRESUMO
Fish oil (FO) is a potent anti-inflammatory and lipid-lowering agent. Because inflammation can modulate lipid metabolism and vice versa, we hypothesized that combining FO with cyclooxygenase inhibitors (COXIBs), well-known anti-inflammatory drugs, can enhance the anti-inflammatory and lipid-lowering effect of FO. LDLR(-/-) mice were fed a high-fat diet supplemented with 6% olive oil or FO for 12 wk in the presence or absence of indomethacin (Indo, 6 mg/l drinking water). FO reduced plasma total cholesterol by 30% but, in combination with Indo, exerted a greater decrease (44%). The reduction of liver cholesterol ester (CE) and triglycerides (TG) by FO (63% and 41%, respectively) was enhanced by Indo (80% in CE and 64% in TG). FO + Indo greatly increased the expression of genes modulating lipid metabolism and reduced the expression of inflammatory genes compared with control. The mRNA and/or protein expression of pregnane X receptor (PXR) and cytochrome P450 isoforms that alter inflammation and/or lipid metabolism are increased to a greater extent in mice that received FO + Indo. Moroever, the nuclear level of PXR is significantly increased in FO + Indo group. Combining FO with COXIBs may exert their beneficial effects on inflammation and lipid metabolism via PXR and cytochrome P450.
Assuntos
Anti-Inflamatórios/farmacologia , Dislipidemias/metabolismo , Fígado Gorduroso/metabolismo , Óleos de Peixe/farmacologia , Hipolipemiantes/farmacologia , Indometacina/farmacologia , Receptores de LDL/genética , Animais , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Dislipidemias/tratamento farmacológico , Feminino , Fígado/metabolismo , Fígado/patologia , Camundongos , Receptor de Pregnano X , RNA Mensageiro/metabolismo , Receptores de LDL/metabolismo , Receptores de Esteroides/genética , Receptores de Esteroides/metabolismoRESUMO
Obstructive apneas produce high negative intrathoracic pressure that imposes an afterload burden on the left ventricle. Such episodes might produce structural changes in the left ventricle over time. Doppler echocardiograms were obtained within 2 months of attended polysomnography. Patients were grouped according to apnea-hypopnea index (AHI): mild/no obstructive sleep apnea (OSA; AHI <15) and moderate/severe OSA (AHI ≥15). Mitral valve tenting height and area, left ventricular (LV) long and short axes, and LV end-diastolic volume were measured in addition to tissue Doppler parameters. Comparisons of measurements at baseline and follow-up between and within groups were obtained; correlations between absolute changes (Δ) in echocardiographic parameters were also performed. After a mean follow-up of 240 days mitral valve tenting height increased significantly (1.17 ± 0.12 to 1.28 ± 0.17 cm, p = 0.001) in moderate/severe OSA as did tenting area (2.30 ± 0.41 to 2.66 ± 0.60 cm(2), p = 0.0002); Δtenting height correlated with ΔLV end-diastolic volume (rho 0.43, p = 0.01) and Δtenting area (rho 0.35, p = 0.04). In patients with mild/no OSA there was no significant change in tenting height; there was a borderline significant increase in tenting area (2.20 ± 0.44 to 2.31 ± 0.43 cm(2), p = 0.05). Septal tissue Doppler early diastolic wave decreased (8.04 ± 2.49 to 7.10 ± 1.83 cm/s, p = 0.005) in subjects with moderate/severe OSA but not in in those with mild/no OSA. In conclusion, in patients with moderate/severe OSA, mitral valve tenting height and tenting area increase significantly over time. This appears to be related, at least in part, to changes in LV geometry.
Assuntos
Ecocardiografia Doppler , Insuficiência da Valva Mitral/fisiopatologia , Valva Mitral/fisiopatologia , Polissonografia , Apneia Obstrutiva do Sono/fisiopatologia , Disfunção Ventricular Esquerda/fisiopatologia , Adulto , Algoritmos , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/diagnóstico por imagem , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de Doença , Apneia Obstrutiva do Sono/diagnóstico por imagem , Fatores de Tempo , Disfunção Ventricular Esquerda/diagnóstico por imagemRESUMO
It is quite apparent that the incidence of neurodegenerative diseases in both men and women increases in a logarithmic fashion with age and begins to rise much more rapidly after the age of 60. Brain aging is accompanied by structural and functional changes at cellular and tissue levels such as increase in free radical generation, lowered antioxidant defenses, decrease in number of neurons, decrease in the activities of enzymes, (g) decrease in impulse transmission. The present study was aimed to assess the neuromodulatory role of Glutathione monoester (GME) when administered intraperitoneally (12 mg/kg body weight) for 20 days on acetylcholine esterase (AchE) activity, levels of neurotransmitters such as dopamine, serotonin, norepinephrine and rotorod behavioral analysis in discrete brain regions of young and aged male albino Wistar rats. Age-related decrease (p<0.05) in acetylcholine esterase activity, neurotransmitter levels and also decrease in sensorimotor performance was observed. GME administration was effective in restoring these neuronal parameters in aged rat brain regions. Thus GME act as a neuromodulator in discrete brain regions of aged rats.
Assuntos
Envelhecimento/fisiologia , Química Encefálica , Encéfalo/metabolismo , Ésteres/metabolismo , Glutationa , Neurotransmissores , Acetilcolinesterase/metabolismo , Animais , Comportamento Animal/fisiologia , Feminino , Glutationa/química , Glutationa/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Neurotransmissores/química , Neurotransmissores/metabolismo , Estresse Oxidativo , Ratos , Ratos Wistar , Teste de Desempenho do Rota-RodRESUMO
An ever-increasing number of reports show the involvement of free radicals in the functional and structural changes occurring in the brain as a part of the normal aging process. This study aimed to assess the potential efficacy of glutathione monoester (GME) when administered intraperitoneally (12 mg/kg body weight) for 20 days on memory and the antioxidant defense system and lipid peroxidation in discrete brain regions such as cortex, striatum, and hippocampus of young and aged rats. Age-associated decline in memory and activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione, vitamin E, and vitamin C, and elevated levels of lipid peroxidation and oxidized glutathione, were observed in all the brain regions studied (p < .001). GME administration was effective in restoring the antioxidant status and in decreasing lipid peroxidation level in aged rat brain regions.
Assuntos
Envelhecimento/metabolismo , Antioxidantes/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Glutationa/análogos & derivados , Animais , Catalase/metabolismo , Glutationa/metabolismo , Glutationa/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/fisiologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Memória/efeitos dos fármacos , Memória/fisiologia , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismoRESUMO
Brain aging has become an area of intense research and a subject of much speculation fueled largely from the widely recognized fact that age is the biggest risk factor in most neurodegenerative diseases and age-related increase of reactive oxygen species is particularly detrimental to postmitotic tissues. In the present study, we have evaluated the possible role of glutathione monoester (GME), when administered intraperitoneally (12mg/kg body weight) for 20 days on age-associated changes in the levels of lipofuscin, Na+K+, Mg2+, Ca2+ ATPase activities and intracellular calcium levels in discrete brain regions of young and aged male albino Wistar rats. An age-associated increase in lipofuscin, intracellular calcium in cortex, striatum and hippocampus was observed and contradictorily, a decrease in the activities of membrane-bound enzyme activities was also observed. Supplementation of GME brought these changes to near normalcy. Thus, GME improves neuronal antioxidant status, thereby effectively attenuating any putative increase in oxidative stress with age.
Assuntos
Adenosina Trifosfatases/metabolismo , Envelhecimento/metabolismo , Encéfalo/metabolismo , Sinalização do Cálcio/fisiologia , Glutationa/análogos & derivados , Lipofuscina/metabolismo , Envelhecimento/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/fisiopatologia , ATPase de Ca(2+) e Mg(2+)/efeitos dos fármacos , ATPase de Ca(2+) e Mg(2+)/metabolismo , Sinalização do Cálcio/efeitos dos fármacos , ATPases Transportadoras de Cálcio/efeitos dos fármacos , ATPases Transportadoras de Cálcio/metabolismo , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Córtex Cerebral/fisiopatologia , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Corpo Estriado/fisiopatologia , Citoproteção/efeitos dos fármacos , Citoproteção/fisiologia , Glutationa/farmacologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/fisiopatologia , Injeções Intraperitoneais , Líquido Intracelular/efeitos dos fármacos , Líquido Intracelular/metabolismo , Membranas Intracelulares/efeitos dos fármacos , Membranas Intracelulares/metabolismo , Masculino , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Ratos , Ratos Wistar , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/fisiologiaRESUMO
The generation of reactive oxygen species (ROS) and resultant oxidative stress has been implicated in the mechanism of brain dysfunction due to age-related neurodegenerative diseases. We have evaluated the efficacy of glutathione monoester (GME) when administered intraperitoneally (12 mg/kg body weight) for 20 days on glutathione, ROS, superoxide anion production, lipid peroxidation (LPO), protein carbonyls, thiol status, oxidative DNA damage products such as 8-hydroxy deoxy guanosine and DNA protein cross-links in discrete brain regions of young and aged rats. An age associated increase in ROS, superoxide anion production, LPO, protein oxidation, and DNA damage products in cortex, striatum, and hippocampus was observed which was reversed by GME. Contradictorily, a decline in the levels of glutathione, total thiol, and nonprotein and protein thiols was observed which was also reversed upon GME administration. These findings suggest that GME administration inhibits free radical-induced oxidative macromolecular damage in aged rats and thereby protects the brain from ROS.
Assuntos
Envelhecimento/metabolismo , Encefalopatias Metabólicas/metabolismo , Encéfalo/metabolismo , Dano ao DNA/efeitos dos fármacos , DNA/metabolismo , Glutationa/análogos & derivados , Estresse Oxidativo/efeitos dos fármacos , 8-Hidroxi-2'-Desoxiguanosina , Animais , Biomarcadores/metabolismo , Encéfalo/efeitos dos fármacos , Encefalopatias Metabólicas/tratamento farmacológico , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Modelos Animais de Doenças , Glutationa/administração & dosagem , Glutationa/efeitos dos fármacos , Glutationa/metabolismo , Glutationa/uso terapêutico , Injeções Intraperitoneais , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Protetores contra Radiação/administração & dosagem , Protetores contra Radiação/uso terapêutico , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Espectrofotometria , Superóxidos/metabolismo , Resultado do TratamentoRESUMO
Aging is the accumulation of diverse deleterious changes in the cells and tissues leading to increased risk of diseases. Oxidative stress is considered as a major risk factor and contributes to age related increase in DNA oxidation and DNA protein cross-links in central nervous system during aging. In the present study, we have evaluated the salubrious role of grape seed extract on accumulation of oxidative DNA damage products such as 8-OHdG and DNA protein cross-links in aged rats. Male albino rats of Wistar strain were divided into four groups: Group I, young control rats; Group II, young rats treated with grape seed extract (100 mg/kg b.wt.) for 30 days; Group III, aged control rats; Group IV, aged rats supplemented with grape seed extract (100 mg/kg b.wt.) for 30 days. Our results, thus, revealed that grape seed extract has inhibiting effect on the accumulation of age-related oxidative DNA damages in spinal cord and in various brain regions such as cerebral cortex, striatum and hippocampus.
Assuntos
Envelhecimento/efeitos dos fármacos , Senescência Celular/efeitos dos fármacos , Sistema Nervoso Central/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Proantocianidinas/farmacologia , 8-Hidroxi-2'-Desoxiguanosina , Envelhecimento/metabolismo , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Senescência Celular/fisiologia , Sistema Nervoso Central/metabolismo , Sistema Nervoso Central/fisiopatologia , DNA/efeitos dos fármacos , Dano ao DNA/fisiologia , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Extrato de Sementes de Uva , Masculino , Estresse Oxidativo/fisiologia , Fenóis/farmacologia , Fenóis/uso terapêutico , Extratos Vegetais/uso terapêutico , Polifenóis , Proantocianidinas/uso terapêutico , Ratos , Ratos Wistar , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismo , Medula Espinal/fisiopatologia , Resultado do TratamentoRESUMO
Oxidative stress has been shown to play a major role in aging and in neurodegenerative disorders. Protein modification is one of the important consequences of oxidative stress. In the present study, we evaluated the role of grape seed extract on memory, reactive oxygen species production, protein carbonyls (PCO), and thiol status in discrete regions of central nervous system of young and aged rats. Male albino rats of Wistar strain were divided into four groups: Group I--control young rats, Group II--young rats treated with grape seed extract (100 mg/kg BW) for 30 days, Group III--aged control rats and Group IV-aged rats supplemented with grape seed extract (100 mg/kg BW) for 30 days. Memory loss was observed in the aged rats. Age associated increase in reactive oxygen species production and protein oxidation was observed in the spinal cord; cerebral cortex, striatum and the hippocampus regions of aged rats (Group III). The levels of total thiol, non-protein thiol, protein thiols were found to be significantly decreased in spinal cord and all the brain regions studied in aged rats when compared to young rats. Supplementation of aged rats with grape seed extract showed increased memory performance and declined reactive oxygen species production, decreased protein carbonyl levels and improved thiol levels. These findings demonstrated that grape seed extract enhanced the antioxidant status and decreased the incidence of free radical induced protein oxidation in aged rats thereby protecting the central nervous system from the reactive oxygen species.
Assuntos
Envelhecimento/efeitos dos fármacos , Antioxidantes/farmacologia , Sistema Nervoso Central/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Envelhecimento/metabolismo , Animais , Antioxidantes/uso terapêutico , Sistema Nervoso Central/fisiopatologia , Radicais Livres/antagonistas & inibidores , Radicais Livres/metabolismo , Masculino , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/fisiopatologia , Transtornos da Memória/prevenção & controle , Degeneração Neural/tratamento farmacológico , Degeneração Neural/fisiopatologia , Degeneração Neural/prevenção & controle , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Extratos Vegetais/uso terapêutico , Ratos , Ratos Wistar , Compostos de Sulfidrila/metabolismo , Resultado do Tratamento , Vitis/químicaRESUMO
STUDY OBJECTIVE: To evaluate the incidence of airway compromise, clinical presentation and morbidity of angiotensin-converting enzyme inhibitor (ACEI)-related angioedema (AE). METHOD: A retrospective chart review was conducted of all patients admitted to our hospital between 1996 and 2001 with the diagnosis of AE. RESULTS: A total of 70 charts on which a diagnosis of AE had been entered were reviewed. Of those, 45 patients (64%) had AE that was thought to be related to ACEI therapy. Of those 45 patients, 29 were women. The mean age was 62 years, and 41 (91%) were African-American. The duration of ACEI therapy before presentation varied from 1 day to 5 years postingestion. Twenty-one of 32 patients presented within 2 months of the initiation of therapy. The mean duration between the onset of symptoms and presentation to the hospital was 9 h. Lip and tongue swelling was seen in all patients. Pulmonary manifestations were noted in 17 of 45 patients (38%) [dyspnea 17 of 17 patients; stridor/respiratory failure, 5 of 17 patients; cough, 2 of 17 patients]. Dysphagia was noted in 9 of 45 patients, drooling of saliva in 8 of 45 patients, and pruritus in 6 of 45 patients. Ten of 45 patients had a history of AE. In five of those patients (50%), ACEI use was a presumed cause of the AE for the current hospital admission. Eighteen of 45 (40%) patients required ICU admission. The mean ICU length of stay was 2.2 days. Five of 45 patients required endotracheal intubation. The mean time spent receiving ventilation was 2.2 days. Discontinuation of the initiating agent and supportive care were the keys to therapy. All of our patients responded to supportive management, and there was no mortality. CONCLUSION: Sixty-four percent of patients in this series had AE due to receiving an ACEI. The majority of the patients were African-American women. Most patients presented within 2 months of starting to receive the drug, although longer durations of therapy were not uncommon. Lip and tongue swelling was the most common airway manifestation. Based on our observations, the discontinuation of ACEI therapy and supportive management are the recommended approaches to therapy to prevent an untoward outcome.