RESUMO
BACKGROUND: In severe acute pancreatitis (AP), intravenous glutamine has been shown to reduce the rate of complications, hospital stay, and mortality. In the present randomized trial, we aimed to evaluate the effect of enteral glutamine supplementation on clinical outcomes, gut permeability, systemic inflammation, oxidative stress, and plasma glutamine levels in patients with severe and predicted severe AP. METHODS: Patients with AP admitted within 72 h of onset of symptoms were included. The primary outcome measure was development of infected pancreatic and peri-pancreatic necrosis and in-hospital mortality. High-sensitivity C-reactive protein (HS-CRP) and interleukin-6 (IL-6) were evaluated as markers of inflammation; plasma thiobarbituric acid reactive substances (TBARS) and activities of serum superoxide dismutase and glutathione peroxidase were determined to evaluate oxidative stress; serum polyethylene glycol (PEG) was tested for intestinal permeability; subjective global assessment (SGA) was used for nutritional assessment, and an improvement in organ function was measured by the Modified Marshall score. Intention-to-treat analysis was used. A p-value of < 0.05 was considered statistically significant. RESULTS: After power calculation, we enrolled 18 patients in the glutamine and 22 in the control arm. There was no significant improvement in the development of infected necrosis and in-hospital mortality between the groups. Improvement in Modified Marshall score was observed in a higher proportion of patients receiving glutamine (15 [83.3%] vs. 12 [54.5%]; p = 0.05). Plasma glutamine levels improved more in glutamine-treated group (432.72 ± 307.83 vs. 618.06 ± 543.29 µM/L; p = 0.004), while it was lower in controls (576.90 ± 477.97 vs. 528.20 ± 410.45 µM/L; p = 0.003). PEG level was lower after glutamine supplementation (39.91 ± 11.97 vs. 32.30 ± 7.39 ng/mL; p = 0.02). Statistically significant reduction in IL-6 concentration was observed in the glutamine group at the end of treatment (87.44 ± 7.1 vs. 63.42 ± 33.7 µM/L; p = 0.02). CONCLUSIONS: Despite absence of improvement in infected necrosis and in-hospital mortality, enteral glutamine supplementation showed improvement in gut permeability, oxidative stress, and a trend towards improvement in organ function as depicted by improvement in the Modified Marshall score. TRIAL REGISTRATION: NCT01503320.
Assuntos
Suplementos Nutricionais , Nutrição Enteral/métodos , Glutamina/farmacocinética , Mucosa Intestinal/metabolismo , Pancreatite/terapia , Doença Aguda , Adulto , Biomarcadores/sangue , Feminino , Glutamina/sangue , Humanos , Inflamação , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/efeitos dos fármacos , Pancreatite/metabolismo , Permeabilidade/efeitos dos fármacos , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
The objective of the present work is to investigate the role of different grain sizes produced by equal channel angular pressing (ECAP) on the degradation behavior of magnesium alloy using in vitro and in vivo studies. Commercially available AZ31 magnesium alloy was selected and processed by ECAP at 300°C for up to four passes using route Bc. Grain refinement from a starting size of 46µm to a grain size distribution of 1-5µm was successfully achieved after the 4th pass. Wettability of ECAPed samples assessed by contact angle measurements was found to increase due to the fine grain structure. In vitro degradation and bioactivity of the samples studied by immersing in super saturated simulated body fluid (SBF 5×) showed rapid mineralization within 24h due to the increased wettability in fine grained AZ31 Mg alloy. Corrosion behavior of the samples assessed by weight loss and electrochemical tests conducted in SBF 5× clearly showed the prominent role of enhanced mineral deposition on ECAPed AZ31 Mg in controlling the abnormal degradation. Cytotoxicity studies by MTT colorimetric assay showed that all the samples are viable. Additionally, cell adhesion was excellent for ECAPed samples particularly for the 3rd and 4th pass samples. In vivo experiments conducted using New Zealand White rabbits clearly showed lower degradation rate for ECAPed sample compared with annealed AZ31 Mg alloy and all the samples showed biocompatibility and no health abnormalities were noticed in the animals after 60days of in vivo studies. These results suggest that the grain size plays an important role in degradation management of magnesium alloys and ECAP technique can be adopted to achieve fine grain structures for developing degradable magnesium alloys for biomedical applications.
Assuntos
Ligas , Implantes Experimentais , Magnésio , Teste de Materiais , Ligas/química , Ligas/farmacologia , Animais , Corrosão , Temperatura Alta , Magnésio/química , Magnésio/farmacologia , CoelhosRESUMO
Wistar of the National Institute of Nutrition obese (WNIN/Ob) is a unique rat strain isolated and established at NIN, Hyderabad, India, in 1996, from its existing stock of Wistar rat colony (WNIN). This animal model exhibits all traits of metabolic syndrome and has a remarkably reduced lifespan (1.5 years as compared to 3 years in parental WNIN rats), albeit, the factors associated with premature aging are not well understood. Considering that oxidative stress and DNA damage are crucial players associated with senescence, we analyzed oxidative stress markers like lipid peroxidation and protein oxidation; DNA damage in terms of both single-stranded and double-stranded breaks and the activity of antioxidant enzymes: superoxide dismutase and catalase in brain regions of these animals. Our study revealed that the magnitude of oxidative stress and DNA damage in the neocortex and hippocampus of 3-month-old WNIN/Ob obese rats is as high as that seen in 15-month-old parental WNIN control rats. Concurrently, the antioxidant enzyme activity was significantly decreased. From these results, it can be concluded that increased oxidative stress-induced damage of macromolecules, probably due to reduced activity of antioxidant enzymes, is associated with premature aging in WNIN/Ob obese rats.
Assuntos
Senilidade Prematura/fisiopatologia , Hipocampo/fisiopatologia , Neocórtex/fisiopatologia , Estresse Oxidativo/fisiologia , Fatores Etários , Animais , Catalase/metabolismo , Dano ao DNA/fisiologia , Modelos Animais de Doenças , Peroxidação de Lipídeos/fisiologia , Masculino , Obesidade/fisiopatologia , Ratos , Superóxido Dismutase/metabolismoRESUMO
Polysaccharides are frequently incorporated into scaffolds for tissue engineering applications to improve mechanical and biological properties. We evaluated the influence of a Ficoll® scaffold on collagen films, a scaffold that is extensively used for soft and hard tissue repair. To avoid cytotoxicity issues associated with chemical reagents, the influence of genipin, a naturally occurring crosslinking agent, was assessed. Ultra-structural level collagen films formed with and without Ficoll showed a fine fibrillar structure whereas genipin crosslinked films showed a coarse fibrillar and partially nodular structure. In contrast, glutaraldehyde crosslinked films lost their fibrillar pattern. Crosslinking significantly increased denaturation temperature (p < 0.001), stress (p < 0.0001) and force (p < 0.0001) at break. Collagen/Ficoll and collagen/Ficoll/genipin films showed the highest WI38 fibroblast attachment than any other scaffold (p < 0.003) and significantly greater WI38 fibroblast metabolic activity than other scaffolds (p < 0.001). By day 6. collagen/Ficoll/genipin films also induced higher and more aligned fibronectin matrix deposition than other scaffolds. Overall, this study indicates the suitability of collagen/Ficoll/genipin for tissue engineering applications.
Assuntos
Colágeno/química , Ficoll/química , Iridoides/química , Alicerces Teciduais/química , Tendão do Calcâneo/patologia , Animais , Materiais Biocompatíveis/química , Adesão Celular , Linhagem Celular , Reagentes de Ligações Cruzadas/química , Fibroblastos/citologia , Fibroblastos/metabolismo , Glutaral/química , Humanos , Imuno-Histoquímica , Microscopia de Contraste de Fase , Estresse Mecânico , Suínos , Engenharia Tecidual/instrumentação , Engenharia Tecidual/métodosRESUMO
Phytochemicals protect against oxidative stress which in turn helps in maintaining the balance between oxidants and antioxidants. In recent times natural antioxidants are gaining considerable interest among nutritionists, food manufacturers, and consumers because of their perceived safety, potential therapeutic value, and long shelf life. Plant foods are known to protect against degenerative diseases and ageing due to their antioxidant activity (AOA) attributed to their high polyphenolic content (PC). Data on AOA and PC of Indian plant foods is scanty. Therefore we have determined the antioxidant activity in 107 commonly consumed Indian plant foods and assessed their relation to their PC. Antioxidant activity is presented as the range of values for each of the food groups. The foods studied had good amounts of PC and AOA although they belonged to different food groups. Interestingly, significant correlation was observed between AOA (DPPH and FRAP) and PC in most of the foods, corroborating the literature that polyphenols are potent antioxidants and that they may be important contributors to the AOA of the plant foods. We have also observed that common domestic methods of processing may not affect the PC and AOA of the foods studied in general. To the best of our knowledge, these are the first results of the kind in commonly consumed Indian plant foods.
Assuntos
Antioxidantes/análise , Manipulação de Alimentos , Alimentos , Plantas/química , Índia , Fenóis/química , Polifenóis/análise , Espécies Reativas de Oxigênio/análiseRESUMO
A two-and-half-year-old cow was presented with a defect nonunion of the right metatarsal III/IV bone following a severely comminuted open fracture two months previously. The animal underwent open fixation using a 4.5 mm, broad, 10-hole, dynamic compression plate and autogenous cancellous bone graft collected from the contralateral iliac shaft. The animal started partial weight bearing after the third postoperative day and resumed complete weight bearing after the 10th day. Fracture healing was complete and the implants were removed after the 120th postoperative day. Stable fixation by means of a bone plate in conjunction with a cancellous bone graft facilitated complete healing and restoration of the bone column of the defect and the metatarsal fracture. The animal made a complete recovery.
Assuntos
Bovinos/lesões , Fixação Interna de Fraturas/veterinária , Fraturas Ósseas/veterinária , Fraturas não Consolidadas/veterinária , Ossos do Metatarso/lesões , Animais , Feminino , Fraturas Ósseas/cirurgia , Fraturas não Consolidadas/patologia , Fraturas não Consolidadas/cirurgiaRESUMO
Fetal growth is a complex process which depends both on the genetic makeup and intrauterine environment. Maternal nutrition during pregnancy is an important determinant of fetal growth. Adequate nutrient supply is required during pregnancy and lactation for the support of fetal/infant growth and development. Macro- and micronutrients are both important to sustain pregnancy and for appropriate growth of the fetus. While macronutrients provide energy and proteins for fetal growth, micronutrients play a major role in the metabolism of macronutrients, structural and cellular metabolism of the fetus. Discrepancies in maternal diet at different stages of foetal growth / offspring development can have pronounced influences on the health and well-being of the offspring. Indeed intrauterine growth restriction induced by nutrient insult can irreversibly modulate the endocrine/metabolic status of the fetus that leads to the development of adiposity and insulin resistance in its later life. Understanding the role of micronutrients during the development of fetus will provide insights into the probable underlying / associated mechanisms in the metabolic pathways of endocrine related complications. Keeping in view the modernized lifestyle and food habits that lead to the development of adiposity and world burden of obesity, this review focuses mainly on the role of maternal micronutrients in the foetal origins of adiposity.
Assuntos
Adipócitos/fisiologia , Adiposidade/fisiologia , Metabolismo dos Lipídeos/fisiologia , Micronutrientes/fisiologia , Adipogenia/fisiologia , Adipocinas/metabolismo , Adiposidade/genética , Adulto , Animais , Epigenômica , Feminino , Desenvolvimento Fetal/genética , Desenvolvimento Fetal/fisiologia , Humanos , Metabolismo dos Lipídeos/genética , Lipídeos/sangue , Fenômenos Fisiológicos da Nutrição Materna , Gravidez , Fenômenos Fisiológicos da Nutrição Pré-Natal , RatosAssuntos
Cloreto de Amônio/farmacologia , Cloreto de Amônio/uso terapêutico , Copépodes/efeitos dos fármacos , Doenças dos Peixes/terapia , Doenças Parasitárias em Animais/prevenção & controle , Lagoas , Quarentena/veterinária , Animais , Antiparasitários/farmacologia , Antiparasitários/uso terapêutico , Doenças dos Peixes/parasitologia , Peixes , Estágios do Ciclo de Vida/efeitos dos fármacos , Doenças Parasitárias em Animais/transmissão , Quarentena/métodosRESUMO
BACKGROUND/OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is considered an integral part of metabolic syndrome (MS). We aimed to explore the inter-relations of MS and dietary composition in subjects with and without hepatic steatosis and to identify the nutritional risk factors contributing to NAFLD. SUBJECTS/METHODS: In all 98 subjects with steatosis and 102 controls were selected for the study after screening 260 consecutive healthy individuals. Anthropometric and nutritional information, biochemical data and clinical profile were analyzed. Prevalence of MS was determined based on the consensus statement for diagnosis of MS for Asian Indians. Multiple logistic regression analysis was done to predict the dietary risk factors in NAFLD. RESULTS: Prevalence of MS was 44.9% among NAFLD cases and 25.5% among controls (P=0.003). Subjects with NAFLD had significantly higher values of body mass index (BMI), waist circumference (WC), percent body fat, total cholesterol, triglycerides and blood pressure than controls. The total calorie intake, percent of carbohydrate and fat intake of NAFLD cases was significantly higher than controls. Multiple logistic regression analysis showed BMI (odds ratio 6.03 (95% confidence interval 3.26-11.14)), WC (5.49 (2.59-11.57)) and percent dietary fat intake (2.51 (1.99-3.31)) as independent nutritional risk factors in NAFLD. CONCLUSIONS: In this study, there is a high prevalence of MS among subjects with steatosis and metabolic disorders were closely related to NAFLD. BMI, WC and percent fat intake are independent dietary risk factors in NAFLD. Decreased nutritional intake with restricted fat may constitute an important therapy in subjects with NAFLD.
Assuntos
Síndrome Metabólica/epidemiologia , Avaliação Nutricional , Tecido Adiposo/metabolismo , Adulto , Antropometria , Composição Corporal , Índice de Massa Corporal , Estudos de Casos e Controles , Colesterol/sangue , Dieta , Fígado Gorduroso/complicações , Fígado Gorduroso/epidemiologia , Comportamento Alimentar , Feminino , Humanos , Índia/epidemiologia , Masculino , Síndrome Metabólica/complicações , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica , Obesidade/diagnóstico , Obesidade/epidemiologia , Prevalência , Fatores de Risco , Triglicerídeos/sangue , Circunferência da CinturaRESUMO
Study was conducted to find out the comparative susceptibility of fingerlings of seven species of carps (Labeo fimbriatus, L. rohita, L. calbasu, Catla catla, Ctenopharyngodon idella, Cyprinus carpio and Hypophthamichthys molitrix) grown under both mono and polyculture to Lernaea cyprinacea infection. Under monoculture, C. carpio, L. rohita and L. calbasu, did not acquire Lernaea infection and were thus considered resistant, whereas C. idella, H. molitrix, C. catla and L. fimbriatus were susceptible. Even challenge with higher infective doses of copepodids under monoculture did not result in infection in the resistant fish species. The resistance of L. rohita and C. carpio to Lernaea infection under monoculture was not sustained when these two fish species were maintained in polyculture along with susceptible fish species. Labeo calbasu, even under polyculture, however, did not acquire Lernaea infection indicating that this fish species is the most resistant and least preferred host for this parasite. Similarly, C. carpio, L. rohita and L. calbasu when grown together in polyculture and exposed to a higher infective dose (120 copepodids/fish) also did not develop the infection. The possible reasons for differences in susceptibility shown by these carp species in monoculture and the loss of resistance by rohu and common carp while in polyculture with susceptible species are discussed. The ability of resistant fish species to prevent establishment of anchor worms on them under monoculture can be utilized to control this parasitic infection commonly encountered in culture ponds.
Assuntos
Carpas , Copépodes , Ectoparasitoses/veterinária , Doenças dos Peixes/parasitologia , Predisposição Genética para Doença , Animais , Ectoparasitoses/genética , Doenças dos Peixes/genéticaRESUMO
BACKGROUND: Peripheral Arterial Disease (PAD) remains the least recognized form of atherosclerosis. The Ankle-Brachial Index (ABI) has emerged as one of the potent markers of diffuse atherosclerosis, cardiovascular (CV) risk, and overall survival in general public, especially in diabetics. The important reason for the lack of early diagnosis is the non-availability of a test that is easy to perform and less expensive, with no training required. OBJECTIVES: To evaluate the osillometric method of performing ABI with regard to its usefulness in detecting PAD cases and to correlate the signs and symptoms with ABI. MATERIALS AND METHODS: Two hundred diabetics of varying duration attending the clinic for a period of eight months, from August 2006 to April 2007, were evaluated for signs, symptoms, and risk factors. ABI was performed using the oscillometric method. The positives were confirmed by Doppler evaluation. An equal number of age- and sex-matched controls, which were ABI negative, were also assessed by Doppler. Sensitivity and Specificity were determined. RESULTS: There were 120 males and 80 females. Twelve males (10%) and six females (7.5%) were ABI positive. On Doppler, eleven males (91.5%) and three females (50%) were true positives. There were six false negatives from the controls (three each). The Sensitivity was 70% and Specificity was 75%. Symptoms and signs correlated well with ABI positives. Hypertension was the most important risk factor. CONCLUSIONS: In spite of the limitations, the oscillometric method of performing ABI is a simple procedure, easy to perform, does not require training and can be performed as an outpatient procedure not only by doctors, but also by the paramedical staff to detect more PAD cases.
RESUMO
Transglutaminases (TGases) constitute a family of enzymes that stabilize protein assemblies by gamma-glutamyl-epsilon-lysine crosslinks. The role of tissue transglutaminase (TGase 2) in several pathophysiologies, wound healing applications, biomaterials functionalization, and drug delivery systems provides grounds for its use in tissue engineering. Herein, we initially studied the endogenous TGase activity and expression under normal (skin, duodenum, colon, and small bowel) and pathophysiological (keloid scar) conditions on cadaveric human tissues. Successful inhibition was achieved using low concentrations of BOC-DON-QIV-OMe (0.1 mM and 1 mM for normal skin and keloid scar, respectively), iodoacetamide (0.1 mM and 1 mM for normal skin and keloid scar, respectively), and cystamine dihydrochloride (1 mM and 10 mM for normal skin and keloid scar, respectively), whilst di-BOC-cystamine was found ineffective even at 100 mM concentration. Secondly, the addition of exogenous guinea pig liver transglutaminase (gpTGase) onto the inhibited tissues and collagen scaffolds was studied, and results presented advocate its use as potential tissue adhesive and drug delivery tool. However, the investigation of its crosslinking extent using second harmonic generation microscopy and differentially scanning calorimetry revealed rather poor stabilization function. Overall, our study indicates that TGase 2 has a role as a biological glue to consolidate various micro-structural components of tissues and biomaterials.
Assuntos
Isoenzimas/metabolismo , Engenharia Tecidual/métodos , Transglutaminases/metabolismo , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/metabolismo , Bioensaio/instrumentação , Bioensaio/métodos , Colágeno/química , Colágeno/metabolismo , Portadores de Fármacos/química , Portadores de Fármacos/metabolismo , Glutamina/química , Glutamina/metabolismo , Humanos , Queloide/enzimologia , Lisina/química , Lisina/metabolismo , Teste de Materiais , Estrutura Molecular , Pele/enzimologia , Distribuição Tecidual , Alicerces Teciduais , Cicatrização/fisiologiaRESUMO
BACKGROUND AND PURPOSE: Fibrosis, a pathological accumulation of collagen in tissues, represents a major global disease burden. Effective characterization of potential antifibrotic drugs has been constrained by poor formation of the extracellular matrix in vitro, due to tardy procollagen processing by collagen C-proteinase/BMP-1, and difficulties in relating this matrix to cell numbers in experimental samples. EXPERIMENTAL APPROACH: The Scar-in-a-Jar model provided, in vitro, the complete biosynthetic cascade of collagen matrix formation including complete conversion of procollagen by C-proteinase/BMP-1, its subsequent extracellular deposition and lysyl oxidase-mediated cross-linking, achieved by applying the biophysical principle of macromolecular 'crowding'. Collagen matrix deposition, velocity and morphology can be controlled using negatively charged 'crowders' in a rapid (2 days) mode or a mixture of neutral 'crowders' in an accelerated (6 days) mode. Combined with quantitative optical bioimaging, this novel system allows for in situ assessment of the area of deposited collagen(s) per cell. KEY RESULTS: Optical evaluation of known and novel antifibrotic compounds effective at the epigenetic, post-transcriptional/translational/secretional level correlated excellently with corresponding biochemical analyses. Focusing on quantitation of deposited collagen, the Scar-in-a-Jar was most effective in assessing novel inhibitors that may have multiple targets, such as microRNA29c, found to be a promising antifibrotic agent. CONCLUSIONS AND IMPLICATIONS: This novel screening system supersedes current in vitro fibroplasia models, as a fast, quantitative and non-destructive technique. This method distinguishes a reduction in collagen I deposition, excluding collagen cross-linking, and allows full evaluation of inhibitors of C-proteinase/BMP-1 and other matrix metalloproteinases.
Assuntos
Colágeno Tipo I/biossíntese , Avaliação Pré-Clínica de Medicamentos/métodos , Matriz Extracelular/metabolismo , Fibrose/tratamento farmacológico , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Colágeno Tipo I/genética , Eletroforese em Gel de Poliacrilamida , Epigênese Genética , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibrose/patologia , Humanos , Ácidos Hidroxâmicos/farmacologia , Imuno-Histoquímica , MicroRNAs/genética , Microscopia de FluorescênciaRESUMO
Plant foods are important due to their antioxidant activity (AOA) attributed to the phenolics which are known to protect organisms against harmful effects of oxygen radicals. However, information on antioxidant activity of Indian plant foods is scanty. Therefore, the present study evaluated the AOA of cereals, millets, pulses and legumes, commonly consumed in India and assessed the relationship with their total phenolic content (TPC). AOA was assessed by DPPH (2,2-Diphenyl-1-picryl hydrazyl) radical scavenging assay, ferric reducing antioxidant power (FRAP) assay and reducing power. DPPH scavenging activity ranged from 0.24 and 1.73 mg/g, whereas FRAP ranged from 16.21 to 471.71 micromoles/g. Finger millet (Eleusine cora cana) and Rajmah (Phaseolus vulgaris) had the highest FRAP 471.71, 372.76 and DPPH scavenging activity 1.73, 1.07. Similar trends were observed with reducing power. Among cereals and legumes, Finger millet (Ragi) and black gram dhal (Phaseolus mungo Roxb) had the highest TPC, the values being 373 and 418 mg/100 g respectively, while rice (Oryza sativa) and green gram dhal (Phaseolus aureus Roxb) showed the least (47.6 and 62.4 mg/100 g). In the present study, FRAP (r = 0.91) and reducing power (r = 0.90) showed significant correlation with TPC in cereals and millets, but not in pulses and legumes. The results suggest that TPC contributes significantly to the AOA of Indian cereals and millets.
Assuntos
Antioxidantes , Grão Comestível/química , Fabaceae/química , Alimentos , Panicum/química , Eleusine/química , Hidroxibenzoatos/análise , Índia , Oryza/química , Phaseolus/químicaRESUMO
Pulmonary fibrosis represents a fatal stage of interstitial lung diseases of known and idiopathic aetiology. No effective therapy is currently available. Based on an indication-discovery approach we present novel in vitro evidence that the histone deacetylases inhibitor suberoylanilide hydroxamic acid (SAHA), an FDA approved anti-cancer drug, has antifibrotic and anti-inflammatory potential. Human lung fibroblasts (fetal, adult and idiopathic adult pulmonary fibrosis) were treated with transforming growth factor (TGF)-beta 1 with or without SAHA. Collagen deposition, alpha-smooth muscle actin (alpha-SMA) expression, matrix metalloproteinase (MMP)1 activity, tissue inhibitor of MMP (TIMP)1 production, apoptosis and cell proliferation were assessed. Pro-inflammatory cytokines relevant to pulmonary fibrosis were assayed in SAHA-treated human peripheral blood mononuclear cells (PBMC) and its subpopulations. SAHA abrogated TGF-beta 1 effects on all the fibroblast lines by preventing their transdifferentiation into alpha-SMA positive myofibroblasts and increased collagen deposition without inducing apoptosis. However, MMP1 activity and TIMP1 production was modulated without a clear fibrolytic effect. SAHA also inhibited serum-induced proliferation of the fibroblast lines and caused hyperacetylation of alpha-tubulin and histone. Cytokine secretion was inhibited from PBMC and lymphocytes at nonapoptotic concentrations. Taken together, these data demonstrate combined antifibrotic and anti-inflammatory properties of SAHA, suggesting its therapeutic potential for pulmonary fibrosis.
Assuntos
Epigênese Genética , Fibrose/tratamento farmacológico , Fibrose/genética , Ácidos Hidroxâmicos/uso terapêutico , Pulmão/patologia , Actinas/metabolismo , Anti-Inflamatórios/farmacologia , Linhagem Celular , Proliferação de Células , Colágeno/metabolismo , Fibroblastos/efeitos dos fármacos , Humanos , Imuno-Histoquímica/métodos , Pulmão/efeitos dos fármacos , Metaloproteinase 1 da Matriz/metabolismo , Músculo Liso/metabolismo , Inibidor Tecidual de Metaloproteinase-1/biossíntese , VorinostatRESUMO
Epidemiological evidence indicates that poor early growth is associated with increased susceptibility to visceral obesity, insulin resistance and associated diseases in adulthood. Studies in experimental animals have demonstrated a robust association between nutrient imbalance during foetal life and disease prevalence in their later life specially of those involving macronutrient metabolism. There is very little data on the role of maternal micronutrient deficiencies widely prevalent in India. This review focuses on different animal models of micronutrient restriction, mimicking human situations during pregnancy and lactation that cause aberrations in macronutrient metabolism in the offspring. These aberrations consist of altered body composition, dyslipidaemia and altered insulin sensitivity associated with modulated insulin production. These phenotypic changes were associated with altered lipid profile, fatty acid synthesis / transport, oxidative stress, glucose tolerance / tissue uptake. Further, these were also associated with altered myogenesis and insulin expression and secretion from pancreatic beta-islets. While these changes during in utero or early postnatal life serve as essential adaptations to overcome adverse conditions, these become maladaptive subsequently and set the stage for obesity and type 2 diabetes.
Assuntos
Desnutrição/complicações , Desnutrição/metabolismo , Complicações na Gravidez/metabolismo , Tecido Adiposo/metabolismo , Animais , Composição Corporal , Metabolismo dos Carboidratos , Modelos Animais de Doenças , Epigênese Genética , Feminino , Crescimento e Desenvolvimento , Humanos , Hidrocortisona/metabolismo , Lactação/metabolismo , Metabolismo dos Lipídeos , Desnutrição/genética , Fenômenos Fisiológicos da Nutrição Materna , Músculos/metabolismo , Estresse Oxidativo , Gravidez , Complicações na Gravidez/genética , Efeitos Tardios da Exposição Pré-Natal/genética , Efeitos Tardios da Exposição Pré-Natal/metabolismoRESUMO
Collagen is the main component of the extra-cellular matrix and has been utilised for numerous clinical applications in many forms and products. However, since collagen remains a natural animal-derived biopolymer, variation between batches should be addressed and minimised to ensure reproducibility of the fabrication process. Recently, electro-spinning of collagen has been introduced as a leading technique for the production of bio-mimetic nano-scale scaffolds for tissue-engineering applications. However, no protocols are available that would allow comparisons of the quality of different collagen raw materials prior to the electro-spinning process. In order to bridge this gap we assessed the solubility of various freeze-dried collagens in 0.5 M acetic acid and analysed the solved collagen by gel electrophoresis. We show that raw material of limited solubility in acetic acid will not render high quality electro-spun nano-fibres using hexafluoropropanol. In particular, insoluble collagen directly failed to produce nano-fibres, collagen of reduced solubility produced fused nano-fibres with limited inter-nano-fibre space, whilst purified type-I collagen of high solubility produced smooth, reproducible nano-fibres. Gel electrophoresis confirmed the amount of solubility, as well as qualitative differences in terms of collagen cross-links and collagen types. We recommend this simple and fast step to save costs and to enhance control over the electro-spinning process of collagen. Furthermore, we believe that the solubility test should be introduced prior to any collagenous matrix preparation in order to ensure reproducibility and accuracy.
Assuntos
Colágeno/química , Nanoestruturas/química , Ácido Acético/química , Animais , Bovinos , Colágeno/isolamento & purificação , Custos e Análise de Custo , Eletricidade , Eletroforese em Gel de Poliacrilamida , Congelamento , Controle de Qualidade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Solubilidade , Fatores de TempoRESUMO
Efficacy of doramectin administered via oral and parenteral routes against experimentally induced and natural infections of the copepod parasite Lernaea cyprinacea in carps was studied. Administration of doramectin incorporated in feed at 1mg/kg b.wt. of fish for 10 days effectively controlled experimentally induced Lernaea infection in Labeo fimbriatus fingerlings within an average of 19 days of post-treatment as compared to the normal course of 41 days. Similarly, doramectin given through feed at 1mg/kgb.wt. of fish for 10 days was equally effective in controlling natural infection of this parasite in the underyearlings of Catla catla and L. fimbriatus. Intramuscular administration of doramectin at 200microg/kgb.wt. of fish effectively removed adult Lernaea infection in L. fimbriatus as early as 18 days of treatment as compared to the time period of 43 days taken by the untreated fish to get rid of the infection. Single intramuscular administration of the drug was more effective against the parasite than its administration in multiple divided doses. In all cases, doramectin did not cause any noticeable adverse reactions or toxicity to the fish host. In view of the handling associated stress and other operational difficulties involved, a single intramuscular administration of the drug at 200microg/kgb.wt. is suggested for treatment of heavily infected adults and brood stock of carps. Doramectin incorporated in feed at 1mg/kgb.wt. of fish is best suited for treatment of Lernaea infection in young fish including fingerlings. However, detailed studies on the toxicity and pharmacokinetics of doramectin upon its administration to aquatic organisms and the environmental impact of its usage are required to be undertaken before finally recommending the safe use of this drug for control of parasitic infections of aquatic organisms.
Assuntos
Carpas/parasitologia , Copépodes/efeitos dos fármacos , Ectoparasitoses/veterinária , Doenças dos Peixes/tratamento farmacológico , Ivermectina/análogos & derivados , Animais , Anti-Infecciosos/uso terapêutico , Relação Dose-Resposta a Droga , Ectoparasitoses/tratamento farmacológico , Ivermectina/uso terapêuticoRESUMO
Iodine deficiency disorders affect reproductive performance in the afflicted populations. Environmental iodine deficiency (ID) and goitrogens are important in their aetiology. We observed earlier that chronic maternal dietary ID but not goitrogen feeding altered the blood-brain barrier nutrient transport in adult rats. Whether similar differences exist in their effects on reproduction of dams and postnatal performance of the offspring has been assessed. Inbred, female, weaning WNIN rats were rendered hypothyroid by feeding for 8-12 weeks, a low iodine test diet or a control diet with added potassium thiocyanate (KSCN) (@ 25 mg/rat/day). Following mating with control males, they continued on their respective diets till their pups were weaned. Indices of reproductive performance such as percentage of conception, mortality of dams during pregnancy and parturition, litter size, and survival of pups till weaning were affected markedly by ID but not thiocyanate feeding. Neither ID nor thiocyanate feeding from conception or parturition affected their reproductive performance. Nevertheless, postnatal weight gain of pups was less in all the three ID groups but not thiocyanate fed dams. Rehabilitation of chronically ID pregnant dams from conception or parturition did not improve their pregnancy weight gain, litter size or birth weight of pups but decreased abortion and mortality of mothers during pregnancy and parturition. Rehabilitation improved the pups' postnatal weight gain but the effect was only moderate. Based on the results of the present study it may be suggested that maternal ID but not thiocyanate feeding affects reproductive performance and postnatal performance of their offspring.