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Article ; Online: Adropin's Role in Energy Homeostasis and Metabolic Disorders.

Ali, Ifrah Ismail / D'Souza, Crystal / Singh, Jaipaul / Adeghate, Ernest

International journal of molecular sciences

2022 Volume 23, Issue 15

Abstract: Adropin is a novel 76-amino acid-peptide that is expressed in different tissues and cells including the liver, pancreas, heart and vascular tissues, kidney, milk, serum, plasma and many parts of the brain. Adropin, encoded by ... ...

Abstract	Adropin is a novel 76-amino acid-peptide that is expressed in different tissues and cells including the liver, pancreas, heart and vascular tissues, kidney, milk, serum, plasma and many parts of the brain. Adropin, encoded by the
MeSH term(s)	Animals ; Blood Proteins/genetics ; Cholesterol ; Glucose/metabolism ; Homeostasis ; Intercellular Signaling Peptides and Proteins/genetics ; Metabolic Diseases ; Mice
Chemical Substances	Blood Proteins ; Intercellular Signaling Peptides and Proteins ; Cholesterol (97C5T2UQ7J) ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2022-07-28
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23158318
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Article ; Online: Early (5-Day) Onset of Diabetes Mellitus Causes Degeneration of Photoreceptor Cells, Overexpression of Incretins, and Increased Cellular Bioenergetics in Rat Retina.

Adeghate, Jennifer O / D'Souza, Crystal / Kántor, Orsolya / Tariq, Saeed / Souid, Abdul-Kader / Adeghate, Ernest

Cells

2021 Volume 10, Issue 8

Abstract: The effects of early (5-day) onset of diabetes mellitus (DM) on retina ultrastructure and cellular bioenergetics were examined. The retinas of streptozotocin-induced diabetic rats were compared to those of non-diabetic rats using light and transmission ... ...

Abstract	The effects of early (5-day) onset of diabetes mellitus (DM) on retina ultrastructure and cellular bioenergetics were examined. The retinas of streptozotocin-induced diabetic rats were compared to those of non-diabetic rats using light and transmission electron microscopy. Tissue localization of glucagon-like-peptide-1 (GLP-1), exendin-4 (EXE-4), and catalase (CAT) in non-diabetic and diabetic rat retinas was conducted using immunohistochemistry, while the retinal and plasma concentration of GLP-1, EXE-4, and CAT were measured with ELISA. Lipid profiles and kidney and liver function markers were measured from the blood of non-diabetic and diabetic rats with an automated biochemical analyzer. Oxygen consumption was monitored using a phosphorescence analyzer, and the adenosine triphosphate (ATP) level was determined using the Enliten ATP assay kit. Blood glucose and cholesterol levels were significantly higher in diabetic rats compared to control. The number of degenerated photoreceptor cells was significantly higher in the diabetic rat retina. Tissue levels of EXE-4, GLP-1 and CAT were significantly (
MeSH term(s)	Adenosine Triphosphate/metabolism ; Animals ; Biomarkers/blood ; Blood Glucose/analysis ; Catalase/blood ; Catalase/metabolism ; Diabetes Mellitus, Experimental/metabolism ; Diabetes Mellitus, Experimental/pathology ; Glucagon-Like Peptide 1/blood ; Glucagon-Like Peptide 1/metabolism ; Incretins/blood ; Incretins/genetics ; Incretins/metabolism ; Male ; Microscopy, Electron, Transmission ; Oxygen Consumption ; Photoreceptor Cells/cytology ; Photoreceptor Cells/metabolism ; Rats ; Rats, Wistar ; Retina/metabolism ; Retina/pathology ; Retina/ultrastructure
Chemical Substances	Biomarkers ; Blood Glucose ; Incretins ; Glucagon-Like Peptide 1 (89750-14-1) ; Adenosine Triphosphate (8L70Q75FXE) ; Catalase (EC 1.11.1.6)
Language	English
Publishing date	2021-08-04
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells10081981
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Article ; Online: Exogenous Ghrelin Increases Plasma Insulin Level in Diabetic Rats.

Elabadlah, Haba / Hameed, Rasheed / D'Souza, Crystal / Mohsin, Sahar / Adeghate, Ernest A

Biomolecules

2020 Volume 10, Issue 4

Abstract: Ghrelin, a 28-amino acid peptide, is a strong growth hormone secretagogue and a regulator of food intake. In addition, ghrelin is thought to play a role in insulin secretion and in glucose homeostasis. A lot of contradictory data have been reported in ... ...

Abstract	Ghrelin, a 28-amino acid peptide, is a strong growth hormone secretagogue and a regulator of food intake. In addition, ghrelin is thought to play a role in insulin secretion and in glucose homeostasis. A lot of contradictory data have been reported in the literature regarding the co-localization of ghrelin with other hormones in the islet of Langerhans, its role in insulin secretion and attenuation of type 2 diabetes mellitus. In this study, we investigate the effect of chronic ghrelin treatment on glucose, body weight and insulin level in normal and streptozotocin-induced diabetic male Wistar rats. We have also examined the distribution pattern and co-localization of ghrelin with insulin in pancreatic islet cells using immunohistochemistry and immune-electron microscopy and the ability of ghrelin to stimulate insulin release from the CRL11065 beta cell line. Control, non-diabetic groups received intraperitoneal injection of normal saline, while treated groups received intraperitoneal injection of 5 µg/kg body weight of ghrelin (amino acid chain 24-51) on a daily basis for a duration of four weeks. Our results show that the administration of ghrelin increases the number of insulin-secreting beta cells and serum insulin level in both normal and diabetic rats. We also demonstrated that ghrelin co-localizes with insulin in pancreatic islet cells and that the pattern of ghrelin distribution is altered after the onset of diabetes. Moreover, ghrelin at a dose of 10-6M and 10-12M increased insulin release from the CRL11065 beta cell line. In summary, ghrelin co-localizes with insulin in the secretory granules of pancreatic beta cells and enhances insulin production.
MeSH term(s)	Animals ; Blood Glucose/metabolism ; Body Weight/drug effects ; Diabetes Mellitus, Experimental/blood ; Fasting/blood ; Ghrelin/pharmacology ; Glucose Tolerance Test ; Insulin/blood ; Insulin Secretion/drug effects ; Insulin-Secreting Cells/drug effects ; Insulin-Secreting Cells/metabolism ; Insulin-Secreting Cells/ultrastructure ; Male ; Rats, Wistar ; Signal Transduction/drug effects
Chemical Substances	Blood Glucose ; Ghrelin ; Insulin
Language	English
Publishing date	2020-04-19
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2701262-1
ISSN	2218-273X ; 2218-273X
ISSN (online)	2218-273X
ISSN	2218-273X
DOI	10.3390/biom10040633
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Article ; Online: Activation of the subthalamic nucleus suppressed by high frequency stimulation: A c-Fos immunohistochemical study.

Shehab, Safa / D'souza, Crystal / Ljubisavljevic, Milos / Redgrave, Peter

Brain research

2018 Volume 1685, Page(s) 42–50

Abstract: Deep brain stimulation applied at high frequency (HFS) to the subthalamic nucleus (STN) is used to ameliorate the symptoms of Parkinson's disease. The mechanism by which this is achieved remains controversial. In particular, it is uncertain whether HFS ... ...

Abstract	Deep brain stimulation applied at high frequency (HFS) to the subthalamic nucleus (STN) is used to ameliorate the symptoms of Parkinson's disease. The mechanism by which this is achieved remains controversial. In particular, it is uncertain whether HFS has a suppressive or excitatory action locally within the STN. Brief exposure of rats to ether anesthesia evokes pathological burst firing and associated expression of the immediate early gene c-Fos in STN neurons. We used this ether model of STN activation to test the effect of a range of HFS parameters on c-Fos expression evoked by the anesthetic. The elevated baseline of c-Fos expression afforded the possibility of detecting further excitatory, or suppressive effects of STN HFS. Four HFS protocols were examined; 130, 200 and 260 Hz with 60 µs, and 130 Hz with 90 µs pulse width (HFS intensity:150-300 µA). All HFS protocols were applied for 20 min while the animals were exposed to ether. Ether-evoked expression of c-Fos immunoreactivity was suppressed by HFS at 200 and 260 Hz with a pulse width of 60 µs, and by 130 Hz when the pulse width was increased to 90 µs. HFS at 130 Hz with the 60 µs pulse width had no significant effect and HFS alone caused negligible c-Fos expression in the STN. These findings suggest that HFS of the STN causes significant suppression of evoked neuronal activity. It remains to be determined whether this locally suppressive property of HFS is associated with the efficacy of STN deep brain stimulation to relieve the symptoms of Parkinson's disease.
MeSH term(s)	Action Potentials/physiology ; Animals ; Deep Brain Stimulation/methods ; Disease Models, Animal ; Electric Stimulation/methods ; Male ; Neurons/metabolism ; Parkinson Disease/metabolism ; Parkinson Disease/physiopathology ; Proto-Oncogene Proteins c-fos/metabolism ; Rats, Wistar ; Subthalamic Nucleus/drug effects ; Subthalamic Nucleus/physiopathology
Chemical Substances	Proto-Oncogene Proteins c-fos
Language	English
Publishing date	2018-02-05
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1200-2
ISSN	1872-6240 ; 0006-8993
ISSN (online)	1872-6240
ISSN	0006-8993
DOI	10.1016/j.brainres.2018.01.034
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Article: Nociceptin Increases Antioxidant Expression in the Kidney, Liver and Brain of Diabetic Rats.

Adeghate, Ernest / D'Souza, Crystal M / Saeed, Zulqarnain / Al Jaberi, Saeeda / Tariq, Saeed / Kalász, Huba / Tekes, Kornélia / Adeghate, Ernest A

Biology

2021 Volume 10, Issue 7

Abstract: Nociceptin (NC) consists of 17 amino acids (aa) and takes part in the processing of learning and memory. The role of NC in the induction of endogenous antioxidants in still unclear. We examined the effect of NC on the expression of endogenous ... ...

Abstract	Nociceptin (NC) consists of 17 amino acids (aa) and takes part in the processing of learning and memory. The role of NC in the induction of endogenous antioxidants in still unclear. We examined the effect of NC on the expression of endogenous antioxidants in kidney, liver, cerebral cortex (CC), and hippocampus after the onset of diabetes mellitus, using enzyme-linked immunosorbent assay and immunohistochemistry. Exogenous NC (aa chain 1-17; 10 µg/kg body weight) was given intraperitoneally to normal and diabetic rats for 5 days. Our results showed that catalase (CAT) is present in the proximal (PCT) and distal (DCT) convoluted tubules of kidney, hepatocytes, and neurons of CC and hippocampus. The expression of CAT was significantly (
Language	English
Publishing date	2021-07-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2661517-4
ISSN	2079-7737
ISSN	2079-7737
DOI	10.3390/biology10070621
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Article ; Online: Lipocalin-2: Structure, function, distribution and role in metabolic disorders.

Jaberi, Saeeda Al / Cohen, Athena / D'Souza, Crystal / Abdulrazzaq, Yousef M / Ojha, Shreesh / Bastaki, Salim / Adeghate, Ernest A

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

2021 Volume 142, Page(s) 112002

Abstract: Lipocalin-2 (LCN-2) is a novel, 198 amino acid adipocytokine also referred to as neutrophil gelatinase-associated lipocalin (NGAL). LCN-2 is a circulatory protein responsible for the transportation of small and hydrophobic molecules (steroid, free fatty ... ...

Abstract	Lipocalin-2 (LCN-2) is a novel, 198 amino acid adipocytokine also referred to as neutrophil gelatinase-associated lipocalin (NGAL). LCN-2 is a circulatory protein responsible for the transportation of small and hydrophobic molecules (steroid, free fatty acids, prostaglandins and hormones) to target organs after binding to megalin/glycoprotein and GP330 SLC22A17 or 24p3R LCN-2 receptors. LCN-2 has been used as a biomarker for acute and chronic renal injury. It is present in a large variety of cells including neutrophil, hepatocytes, lung, bone marrow, adipose tissue, macrophages, thymus, non-neoplastic breast duct, prostate, and renal cells. Different functions have been associated with LCN-2. These functions include antibacterial, anti-inflammatory, and protection against cell and tissue stress. Moreover, LCN-2 can increase the pool of matrix metalloproteinase 9 in human neutrophil granulocytes. Other reported functions of LCN-2 include its ability to destroy the extracellular matrix, which could enable cancer progression and spread of metastasis. Recent reports show that the tissue level of LCN-2 is increased in metabolic disorders such as obesity and type 2 diabetes, suggesting an association between LCN-2 and insulin sensitivity and glucose homeostasis. The precise role of LCN-2 in the modulation of insulin sensitivity, glucose and lipid metabolism is still unclear. This review explores the structure of LCN-2, tissue distribution, and its interaction with important metabolic pathways.
MeSH term(s)	Animals ; Diabetes Mellitus, Type 2/physiopathology ; Extracellular Matrix/metabolism ; Glucose/metabolism ; Humans ; Insulin Resistance ; Lipid Metabolism/physiology ; Lipocalin-2/chemistry ; Lipocalin-2/metabolism ; Metabolic Diseases/physiopathology ; Obesity/physiopathology
Chemical Substances	LCN2 protein, human ; Lipocalin-2 ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2021-08-27
Publishing country	France
Document type	Journal Article ; Review
ZDB-ID	392415-4
ISSN	1950-6007 ; 0753-3322 ; 0300-0893
ISSN (online)	1950-6007
ISSN	0753-3322 ; 0300-0893
DOI	10.1016/j.biopha.2021.112002
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Article: Nociceptin Increases Antioxidant Expression in the Kidney, Liver and Brain of Diabetic Rats

Adeghate, Ernest / D’Souza, Crystal M. / Saeed, Zulqarnain / Al Jaberi, Saeeda / Tariq, Saeed / Kalász, Huba / Tekes, Kornélia / Adeghate, Ernest A.

Biology. 2021 July 03, v. 10, no. 7

2021

Abstract	Nociceptin (NC) consists of 17 amino acids (aa) and takes part in the processing of learning and memory. The role of NC in the induction of endogenous antioxidants in still unclear. We examined the effect of NC on the expression of endogenous antioxidants in kidney, liver, cerebral cortex (CC), and hippocampus after the onset of diabetes mellitus, using enzyme-linked immunosorbent assay and immunohistochemistry. Exogenous NC (aa chain 1–17; 10 µg/kg body weight) was given intraperitoneally to normal and diabetic rats for 5 days. Our results showed that catalase (CAT) is present in the proximal (PCT) and distal (DCT) convoluted tubules of kidney, hepatocytes, and neurons of CC and hippocampus. The expression of CAT was significantly (p < 0.05) reduced in the kidney of normal and diabetic rats after treatment with NC. However, NC markedly (p < 0.001) increased the expression CAT in the liver and neurons of CC of diabetic rats. Superoxide dismutase (SOD) is widely distributed in the PCT and DCT of kidney, hepatocytes, and neurons of CC and hippocampus. NC significantly (p < 0.001) increased the expression of SOD in hepatocytes and neurons of CC and the hippocampus but not in the kidney. Glutathione reductase (GRED) was observed in kidney tubules, hepatocytes and neurons of the brain. NC markedly increased (p < 0.001) the expression of GRED in PCT and DCT cells of the kidney and hepatocytes of liver and neurons of CC. In conclusion, NC is a strong inducer of CAT, SOD, and GRED expression in the kidney, liver and brain of diabetic rats.
Keywords	antioxidants ; body weight ; catalase ; cerebral cortex ; diabetes mellitus ; enzyme-linked immunosorbent assay ; glutathione-disulfide reductase ; hepatocytes ; hippocampus ; immunohistochemistry ; liver ; memory ; superoxide dismutase
Language	English
Dates of publication	2021-0703
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2661517-4
ISSN	2079-7737
ISSN	2079-7737
DOI	10.3390/biology10070621
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Diabetes Mellitus Alters the Immuno-Expression of Neuronal Nitric Oxide Synthase in the Rat Pancreas.

Emerald, Bright Starling / Mohsin, Sahar / D'Souza, Crystal / John, Annie / El-Hasasna, Hussain / Ojha, Shreesh / Raza, Haider / Al-Ramadi, Basel / Adeghate, Ernest

International journal of molecular sciences

2022 Volume 23, Issue 9

Abstract: Nitric oxide is generated from nitric oxide synthase following hyperglycemia-induced oxidative stress during the course of diabetes mellitus (DM). We examined the temporal immuno-expression of neuronal nitric oxide synthase (nNOS) in the pancreas of ... ...

Abstract	Nitric oxide is generated from nitric oxide synthase following hyperglycemia-induced oxidative stress during the course of diabetes mellitus (DM). We examined the temporal immuno-expression of neuronal nitric oxide synthase (nNOS) in the pancreas of diabetic and non-diabetic rats using immunohistochemical, immunofluorescence and western blot techniques 12 h, 24 h, 1 week, 2 weeks, 1, 8 and 15 months after induction of DM. nNOS co-localized with pancreatic beta cells but disappears 12 h after the onset of DM. In contrast, the nNOS content of pancreatic nerves increased significantly (p < 0.001) 24 h after the induction of DM, and decreased sharply thereafter. However, nNOS-positive ganglion cells were observed even 15 months post-diabetes. ROS increased by more than 100% two months after the onset of DM compared to non-diabetic control but was significantly (p < 0.000001) reduced at 9 months after the induction of DM. The pancreatic content of GSH increased significantly (p < 0.02) after 9 months of DM. Although, TBARS content was significantly (p < 0.009; p < 0.002) lower in aged (9 months) non-diabetic and DM rats, TBARS rate was markedly (p < 0.02) higher 9 months after the induction of DM when compared to younger age group. In conclusion, nNOS is present in pancreatic beta cell, but disappears 12 h after the onset of diabetes. In contrast, the tissue level of nNOS of pancreatic nerves increased in the first week of diabetes, followed by a sharp reduction. nNOS may play important roles in the metabolism of pancreatic beta cell.
MeSH term(s)	Animals ; Diabetes Mellitus/metabolism ; Diabetes Mellitus/pathology ; Nitric Oxide/metabolism ; Nitric Oxide Synthase/metabolism ; Nitric Oxide Synthase Type I/genetics ; Nitric Oxide Synthase Type I/metabolism ; Pancreas/metabolism ; Rats ; Thiobarbituric Acid Reactive Substances
Chemical Substances	Thiobarbituric Acid Reactive Substances ; Nitric Oxide (31C4KY9ESH) ; Nitric Oxide Synthase (EC 1.14.13.39) ; Nitric Oxide Synthase Type I (EC 1.14.13.39)
Language	English
Publishing date	2022-04-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23094974
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Article ; Online: Hypocretin/orexin modulates body weight and the metabolism of glucose and insulin.

Adeghate, Ernest / Lotfy, Mohamed / D'Souza, Crystal / Alseiari, Saleh Meqbel / Alsaadi, Abdulla Ali / Qahtan, Saif Abdo

Diabetes/metabolism research and reviews

2020 Volume 36, Issue 3, Page(s) e3229

Abstract: The hypocretin/orexin (Hcrt/orexin) unit affects the functions of the nervous, cardiovascular, gastrointestinal, and reproductive systems. Hcrt/orexin ligands and receptors have been localized to different parts of the central and peripheral nervous ... ...

Abstract	The hypocretin/orexin (Hcrt/orexin) unit affects the functions of the nervous, cardiovascular, gastrointestinal, and reproductive systems. Hcrt/orexin ligands and receptors have been localized to different parts of the central and peripheral nervous systems, cerebrospinal fluid and blood, exocrine (pancreas, salivary, lacrimal) as well as endocrine (pancreatic islets, pituitary, adrenal) glands. Several factors including stress, glucagon-like peptide-1 agonists, glutamate, nicotine, glucose, and hypoglycaemia stimulate the expression of Hcrt/orexin system, but it is inhibited by ageing, bone morphogenetic protein, hypoxia/hypercapnia, melanocortin receptor accessory protein 2, and glucagon. Literature reports show that Hcrt/orexin can significantly increase insulin secretion from normal and diabetic rat pancreata. Hcrt/orexin decreases blood glucose concentration and reduces insulin resistance partly via increased tissue expression of glucose transporter type 4. It reduces obesity by increasing browning of fat cells and energy expenditure. Taken together, Hcrt/orexin modulates obesity and the metabolism of glucose and insulin. The Hcrt/orexin system may thus be a target in the development of new therapies for the treatment of diabetes mellitus.
MeSH term(s)	Animals ; Body Weight/physiology ; Glucose/metabolism ; Humans ; Insulin/metabolism ; Insulin Secretion/physiology ; Islets of Langerhans/metabolism ; Neurons/metabolism ; Orexins/metabolism
Chemical Substances	Insulin ; Orexins ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2020-01-16
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1470192-3
ISSN	1520-7560 ; 1520-7552
ISSN (online)	1520-7560
ISSN	1520-7552
DOI	10.1002/dmrr.3229
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Article: Effects of yoga training and detraining on physical performance measures in prepubertal children--a randomized trial.

D'souza, Crystal / Avadhany, Sandhya T

Indian journal of physiology and pharmacology

2014 Volume 58, Issue 1, Page(s) 61–68

Abstract: Purpose of the study was to evaluate the effect of yoga training and detraining on physical performance measures in pre-pubertal (7-9 year old) school going children. Subjects were randomized to two groups - yoga group and Physical exercise (PE) group ... ...

Abstract	Purpose of the study was to evaluate the effect of yoga training and detraining on physical performance measures in pre-pubertal (7-9 year old) school going children. Subjects were randomized to two groups - yoga group and Physical exercise (PE) group after the baseline assessment. All the subjects were assessed for strength, endurance, whole body endurance through 20 meter shuttle and physical fitness, at 3 time points - Baseline, 3 months Post intervention and 3 months after detraining. The results suggest that the improvement in the physical performance is largely by the increase in the respiratory muscle strength in the yoga group. In conclusion, the study presents the efficacy of yoga to improve strength, endurance, whole body endurance and aerobic capacity with 3 months of training in the pediatric group. However, the effect of the training does not last after 3 months detraining.
MeSH term(s)	Child ; Female ; Forced Expiratory Volume ; Humans ; Male ; Muscle Strength ; Oxygen Consumption ; Physical Endurance ; Physical Fitness ; Yoga
Language	English
Publishing date	2014-01
Publishing country	India
Document type	Journal Article ; Randomized Controlled Trial
ZDB-ID	604352-5
ISSN	0019-5499
ISSN	0019-5499
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