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Article: Basic aspects of the pharmacodynamics of tolperisone, a widely applicable centrally acting muscle relaxant.

Tekes, Kornelia

2014 Volume 8, Page(s) 17–22

Abstract: Tolperisone (2-methyl-1-(4-methylphenyl)-3-piperidin-1-ylpropan-1-one hydro-chloride) was introduced in the clinical practice more than forty years ago and is still evaluated as a widely applicable compound in pathologically elevated skeletal muscle tone ...

Abstract	Tolperisone (2-methyl-1-(4-methylphenyl)-3-piperidin-1-ylpropan-1-one hydro-chloride) was introduced in the clinical practice more than forty years ago and is still evaluated as a widely applicable compound in pathologically elevated skeletal muscle tone (spasticity) and related pains of different origin. In the present review, basic pharmacodynamic effects measured on whole animals, analyses of its actions on cell and tissue preparations and molecular mechanism of action on sodium and calcium channels are summarized as recently significantly new data were reported.
Language	English
Publishing date	2014-07-11
Publishing country	United Arab Emirates
Document type	Journal Article
ZDB-ID	2395968-X
ISSN	1874-1045
ISSN	1874-1045
DOI	10.2174/1874104501408010017
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Article ; Online: An Update on the Molecular and Cellular Basis of Pharmacotherapy in Type 2 Diabetes Mellitus.

Mahgoub, Mohamed Omer / Ali, Ifrah Ismail / Adeghate, Jennifer O / Tekes, Kornélia / Kalász, Huba / Adeghate, Ernest A

International journal of molecular sciences

2023 Volume 24, Issue 11

Abstract: Diabetes mellitus (DM) is a chronic illness with an increasing global prevalence. More than 537 million cases of diabetes were reported worldwide in 2021, and the number is steadily increasing. The worldwide number of people suffering from DM is ... ...

Abstract	Diabetes mellitus (DM) is a chronic illness with an increasing global prevalence. More than 537 million cases of diabetes were reported worldwide in 2021, and the number is steadily increasing. The worldwide number of people suffering from DM is projected to reach 783 million in 2045. In 2021 alone, more than USD 966 billion was spent on the management of DM. Reduced physical activity due to urbanization is believed to be the major cause of the increase in the incidence of the disease, as it is associated with higher rates of obesity. Diabetes poses a risk for chronic complications such as nephropathy, angiopathy, neuropathy and retinopathy. Hence, the successful management of blood glucose is the cornerstone of DM therapy. The effective management of the hyperglycemia associated with type 2 diabetes includes physical exercise, diet and therapeutic interventions (insulin, biguanides, second generation sulfonylureas, glucagon-like peptide 1 agonists, dipeptidyl-peptidase 4 inhibitors, thiazolidinediones, amylin mimetics, meglitinides, α-glucosidase inhibitors, sodium-glucose cotransporter-2 inhibitors and bile acid sequestrants). The optimal and timely treatment of DM improves the quality of life and reduces the severe burden of the disease for patients. Genetic testing, examining the roles of different genes involved in the pathogenesis of DM, may also help to achieve optimal DM management in the future by reducing the incidence of DM and by enhancing the use of individualized treatment regimens.
MeSH term(s)	Humans ; Diabetes Mellitus, Type 2/complications ; Hypoglycemic Agents/therapeutic use ; Hypoglycemic Agents/pharmacology ; Quality of Life ; Sodium-Glucose Transporter 2 Inhibitors/therapeutic use ; Dipeptidyl-Peptidase IV Inhibitors/pharmacology ; Dipeptidyl-Peptidase IV Inhibitors/therapeutic use
Chemical Substances	Hypoglycemic Agents ; Sodium-Glucose Transporter 2 Inhibitors ; Dipeptidyl-Peptidase IV Inhibitors
Language	English
Publishing date	2023-05-26
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/ijms24119328
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Article ; Online: Pharmacokinetics of Two Chlorine-Substituted Bis-Pyridinium Mono-Aldoximes with Regenerating Effect on Butyrylcholinesterase.

Kalász, Huba / Szimrók, Zoltán / Karvaly, Gellért / Adeghate, Jennifer / Tekes, Kornélia

Molecules (Basel, Switzerland)

2020 Volume 25, Issue 5

Abstract: Our aim was to find chlorine-substituted antidotes against organophosphate poisoning and compare their pharmacokinetics to their parent compound, K-203. White male Wistar rats were intramuscularly injected with K-203, K-867 or K-870. Serum, brain, ... ...

Abstract	Our aim was to find chlorine-substituted antidotes against organophosphate poisoning and compare their pharmacokinetics to their parent compound, K-203. White male Wistar rats were intramuscularly injected with K-203, K-867 or K-870. Serum, brain, kidneys, liver, lung, eyes, and testes tissues were taken after 5, 15, 30, 60, and 120 min and analyzed using reversed-phase high-performance liquid chromatography. K-203, K-867, or K-870 was present in every tissue that was analyzed, including the serum, the eyes, testes, liver, kidneys, lungs, and the brain. The serum levels of K-867 and K-870 (chlorine-substituted derivatives of K-203) were nearly constant between 15 and 30 min, while their parent compound (K-203) showed peak level at 15 min after the administration of 30 µmol/rat. Neither K-203, nor K-867 or K-870 were toxic at a dose of 100 µmol/200 g in rats. Chlorine-substitution of K-867 and K-870 produced limited absorbance and distribution compared to their parent compound, K203.
MeSH term(s)	Animals ; Antidotes/metabolism ; Butyrylcholinesterase/metabolism ; Chlorine ; Male ; Organophosphate Poisoning/drug therapy ; Oximes/pharmacokinetics ; Pyridinium Compounds/pharmacokinetics ; Rats ; Rats, Wistar
Chemical Substances	Antidotes ; Oximes ; Pyridinium Compounds ; Chlorine (4R7X1O2820) ; Butyrylcholinesterase (EC 3.1.1.8)
Language	English
Publishing date	2020-03-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules25051250
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Article: HPLC determination of serotonin and its metabolites from human platelet-rich plasma; shift to 5-hydroxytryptophol formation following alcohol consumption.

Tekes, Kornélia

Journal of chromatographic science

2008 Volume 46, Issue 2, Page(s) 169–173

Abstract: A sensitive, simple, and reliable high-performance liquid chromatographic method with electrochemical detection is developed for the measurement of four natural products, the serotonin-related indols from human platelet-rich plasma (PRP) using N- ... ...

Abstract	A sensitive, simple, and reliable high-performance liquid chromatographic method with electrochemical detection is developed for the measurement of four natural products, the serotonin-related indols from human platelet-rich plasma (PRP) using N-methylserotonin as internal standard. Separation of serotonin (5HT), 5-hydroxytryptophan (5HTP), 5-hydroxytryptophol (5HTOL), and 5-hydroxyindole-acetic acid (5HIAA) is carried out on Supelcosil LC-18DB stationary phase. A mixture of 48 mM citric acid, 28 mM sodium phosphate dibasic, 0.027 mM Na2EDTA, and 3% methanol (pH 3.18) serves as the mobile phase. Measurements are carried out at 25 degrees C at Eox=0.65 V. The calibration curves are linear through the range of 10-200 pg/mL. Method validation is performed according to internationally accepted criteria. Blood is collected from healthy controls and schizophrenic subjects. Significantly higher PRP serotonin is measured in schizophrenics; patients with recent alcohol consumption could be characterized with significantly elevated 5HTOL/5HIAA ratio.
MeSH term(s)	5-Hydroxytryptophan/blood ; Adult ; Alcohol Drinking/metabolism ; Chromatography, High Pressure Liquid ; Female ; Humans ; Hydroxyindoleacetic Acid/blood ; Hydroxytryptophol/blood ; Hydroxytryptophol/metabolism ; Male ; Middle Aged ; Platelet-Rich Plasma/chemistry ; Schizophrenia/metabolism ; Serotonin/analogs & derivatives ; Serotonin/blood ; Serotonin/metabolism ; Statistics, Nonparametric
Chemical Substances	N-methylserotonin (1134-01-6) ; Hydroxytryptophol (154-02-9) ; Serotonin (333DO1RDJY) ; Hydroxyindoleacetic Acid (54-16-0) ; 5-Hydroxytryptophan (C1LJO185Q9)
Language	English
Publishing date	2008-03-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80141-0
ISSN	1945-239X ; 0021-9665
ISSN (online)	1945-239X
ISSN	0021-9665
DOI	10.1093/chromsci/46.2.169
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Article ; Online: Tackling type 2 diabetes-associated cardiovascular and renal comorbidities: a key challenge for drug development.

Adeghate, Ernest A / Kalász, Huba / Al Jaberi, Saeeda / Adeghate, Jennifer / Tekes, Kornelia

Expert opinion on investigational drugs

2020 Volume 30, Issue 2, Page(s) 85–93

MeSH term(s)	Animals ; Cardiovascular Diseases/prevention & control ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/drug therapy ; Diabetic Nephropathies/prevention & control ; Drug Development ; Humans ; Hypoglycemic Agents/therapeutic use
Chemical Substances	Hypoglycemic Agents
Language	English
Publishing date	2020-12-28
Publishing country	England
Document type	Editorial
ZDB-ID	1182884-5
ISSN	1744-7658 ; 0967-8298 ; 1354-3784
ISSN (online)	1744-7658
ISSN	0967-8298 ; 1354-3784
DOI	10.1080/13543784.2021.1865914
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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: 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: Circulating nociceptin and CGRP in medication-overuse headache.

Munksgaard, Signe B / Ertsey, Csaba / Frandsen, Erik / Bendtsen, Lars / Tekes, Kornelia / Jensen, Rigmor H

Acta neurologica Scandinavica

2018 Volume 139, Issue 3, Page(s) 269–275

Abstract: Background: Previous studies found low serum levels of nociceptin in migraine patients but high serum levels of calcitonin gene-related peptide (CGRP). CGRP can elicit migraine-like headache. Medication-Overuse Headache (MOH) often has migraine features ...

Abstract	Background: Previous studies found low serum levels of nociceptin in migraine patients but high serum levels of calcitonin gene-related peptide (CGRP). CGRP can elicit migraine-like headache. Medication-Overuse Headache (MOH) often has migraine features and can mimic chronic migraine. We therefore hypothesized that as in migraine, serum levels of nociceptin would be lower and CGRP serum levels higher in MOH patients compared with those in healthy volunteers. We hypothesized that the serum levels would normalize after detoxification. Methods: Seventeen MOH patients, hereof 70.6% with chronic migraine and MOH, and 30 sex and age matched headache-free controls were included. MOH patients underwent a 2-month outpatient detoxification program and after 6 months, 10 patients and 19 controls were retested. Blood samples were analyzed blinded. Results: We found no differences in the levels of nociceptin and CGRP between MOH patients and controls (P = 0.65 and P = 0.59). The mean headache frequency reduction was 43% and 70% of patients reverted to episodic headache after 6 months, but the levels of nociceptin and CGRP were unchanged (P = 0.71 and P = 0.82). Conclusion: In contrast to previous findings in migraine patients, we found normal serum levels of nociceptin and CGRP in MOH patients. Thus, we find no evidence that the increased headache frequency of MOH patients could be caused by altered nociceptin and CGRP levels. This underlines the importance of identifying medication overuse in chronic headache and treating the MOH.
MeSH term(s)	Adult ; Calcitonin Gene-Related Peptide/blood ; Female ; Headache Disorders, Secondary/blood ; Headache Disorders, Secondary/drug therapy ; Humans ; Male ; Middle Aged ; Opioid Peptides/blood ; Nociceptin
Chemical Substances	Opioid Peptides ; Calcitonin Gene-Related Peptide (JHB2QIZ69Z)
Language	English
Publishing date	2018-12-11
Publishing country	Denmark
Document type	Journal Article
ZDB-ID	90-5
ISSN	1600-0404 ; 0001-6314
ISSN (online)	1600-0404
ISSN	0001-6314
DOI	10.1111/ane.13053
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Article ; Online: HPLC analysis of blood-brain barrier penetration of 4-fluorodeprenyl.

Pöstényi, Zita / Tekes, Kornélia / Tóth-Molnár, Edit / Kalász, Huba

Journal of pharmaceutical and biomedical analysis

2015 Volume 102, Page(s) 529–534

Abstract: Validated HPLC analysis was developed in order to monitor the level of 4-fluorodeprenyl in rats. Male Wistar rats were intraperitoneally treated with 30 mg/kg of (-)-4-fluorodeprenyl. The rats were sacrificed after 5, 15, 30 and 60 min of treatment, and ... ...

Abstract	Validated HPLC analysis was developed in order to monitor the level of 4-fluorodeprenyl in rats. Male Wistar rats were intraperitoneally treated with 30 mg/kg of (-)-4-fluorodeprenyl. The rats were sacrificed after 5, 15, 30 and 60 min of treatment, and various tissues were isolated, such as serum, brain, CSF, liver, testis and lacrimal gland. Perchloric acid was given to aliquots, which were then homogenized, centrifuged and the supernatants were taken. The 4-fluorodeprenyl content was determined using reversed-phase HPLC, based on the comparison of the calibration line of the spiked samples. The level of 4-fluorodeprenyl was between 0.5 and 24 μg/g, showing maximum concentration in the brain and the liver after 5 min following its administration and in serum, CSF, testis, eyes and lacrimal gland after 15 min following its administration, while a relatively high concentration was found in the liver and the lacrimal gland.
MeSH term(s)	Animals ; Biological Transport/physiology ; Blood-Brain Barrier/drug effects ; Blood-Brain Barrier/metabolism ; Brain/drug effects ; Brain/metabolism ; Chemistry Techniques, Analytical/methods ; Chromatography, High Pressure Liquid/methods ; Male ; Rats ; Rats, Wistar ; Selegiline/analogs & derivatives ; Selegiline/analysis ; Selegiline/metabolism ; Selegiline/pharmacology
Chemical Substances	4-fluorodeprenyl (103596-43-6) ; Selegiline (2K1V7GP655)
Language	English
Publishing date	2015-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604917-5
ISSN	1873-264X ; 0731-7085
ISSN (online)	1873-264X
ISSN	0731-7085
DOI	10.1016/j.jpba.2014.09.035
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Article ; Online: An update on therapies for the treatment of diabetes-induced osteoporosis.

Mohsin, Sahar / Baniyas, May Myh / AlDarmaki, Reem Smh / Tekes, Kornélia / Kalász, Huba / Adeghate, Ernest A

Expert opinion on biological therapy

2019 Volume 19, Issue 9, Page(s) 937–948

Abstract: ... ...

Abstract	Introduction
MeSH term(s)	Animals ; Biological Products/therapeutic use ; Diabetes Complications/drug therapy ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/drug therapy ; Humans ; Osteoporosis/drug therapy ; Osteoporosis/etiology
Chemical Substances	Biological Products
Language	English
Publishing date	2019-05-27
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2052501-1
ISSN	1744-7682 ; 1471-2598
ISSN (online)	1744-7682
ISSN	1471-2598
DOI	10.1080/14712598.2019.1618266
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