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Article ; Online: Insights into antiviral mechanisms of remdesivir, lopinavir/ritonavir and chloroquine/hydroxychloroquine affecting the new SARS-CoV-2.

Uzunova, Katya / Filipova, Elena / Pavlova, Velichka / Vekov, Toni

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

2020 Volume 131, Page(s) 110668

Abstract: Coronavirus disease 2019 (COVID-19) is a kind of viral pneumonia with an unusual outbreak in Wuhan, China, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There is currently no licensed antiviral treatment available to ... ...

Abstract	Coronavirus disease 2019 (COVID-19) is a kind of viral pneumonia with an unusual outbreak in Wuhan, China, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There is currently no licensed antiviral treatment available to prevent human CoV infection. The widespread clinical use and existing knowledge on antiviral mechanisms of remdesivir, lopinavir/ritonavir and chloroquine/hydroxychloroquine in the treatment of previous epidemic diseases, namely, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), may be helpful in the combat with novel SARS-CoV-2 infection. Recent clinical evidence didn't confirm the beneficial role of lopinavir/ritonavir and chloroquine/hydroxychloroquine for COVID-19 patients and their use was reassessed. We provide an overview of the current evidence into the mechanisms of action of these available drugs which are repurposed for treatment of the new virus. Available data identifies remdesivir as an adenosine analogue that can target the RNA-dependent RNA polymerase and block viral RNA synthesis. It has been a promising antiviral drug against a wide array of RNA viruses. 3CLpro is a major CoV protease that cleaves the large replicase polyproteins during viral replication and can be targeted by the protease inhibitor lopinavir/ritonavir but the clinical effects are controversial. Chloroquine/Hydroxychloroquine could impair the replication of SARSCoV-2 by multiple mechanisms and their immunomodulatory properties could ameliorate clinical manifestations that are mediated by immune reactions of the host although its beneficial effects are under question and need to be proven at the clinical level. Existing in vitro and in vivo evidence delineate the molecular mechanisms of these drugs in CoV-infected cells. Numerous studies demonstrated the ability of remdesivir to inhibit SARS-CoV-2 replication but future research would be needed to understand the exact mode of action of lopinavir/ritonavir and chloroquine/hydroxychloroquine in SARS-CoV-2 infected cells and to use this knowledge in the treatment of the current COVID-19.
MeSH term(s)	Adenosine Monophosphate/analogs & derivatives ; Adenosine Monophosphate/pharmacology ; Alanine/analogs & derivatives ; Alanine/pharmacology ; Animals ; Antiviral Agents/pharmacology ; Betacoronavirus/drug effects ; Betacoronavirus/isolation & purification ; COVID-19 ; Chloroquine/pharmacology ; Coronavirus Infections/drug therapy ; Coronavirus Infections/virology ; Drug Combinations ; Humans ; Hydroxychloroquine/pharmacology ; Lopinavir/pharmacology ; Pandemics ; Pneumonia, Viral/drug therapy ; Pneumonia, Viral/virology ; Ritonavir/pharmacology ; SARS-CoV-2 ; COVID-19 Drug Treatment
Chemical Substances	Antiviral Agents ; Drug Combinations ; lopinavir-ritonavir drug combination ; Lopinavir (2494G1JF75) ; remdesivir (3QKI37EEHE) ; Adenosine Monophosphate (415SHH325A) ; Hydroxychloroquine (4QWG6N8QKH) ; Chloroquine (886U3H6UFF) ; Ritonavir (O3J8G9O825) ; Alanine (OF5P57N2ZX)
Keywords	covid19
Language	English
Publishing date	2020-08-24
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.2020.110668
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Article ; Online: Insights into antiviral mechanisms of remdesivir, lopinavir/ritonavir and chloroquine/hydroxychloroquine affecting the new SARS-CoV-2

Uzunova, Katya / Filipova, Elena / Pavlova, Velichka / Vekov, Toni

Biomedicine & Pharmacotherapy

2020 Volume 131, Page(s) 110668

Keywords	Pharmacology ; General Medicine ; covid19
Language	English
Publisher	Elsevier BV
Publishing country	us
Document type	Article ; Online
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.2020.110668
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Bosutinib: Valuable therapeutic option for the Bulgarian market.

Uzunova, Katya Hristova / Filipova, Elena Pavlova / Vekov, Toni Yonkov

Journal of cancer research and therapeutics

2018 Volume 14, Issue 5, Page(s) 909–915

Abstract: Aim of study: This review aims to highlight that bosutinib represents a valuable alternative for patients already treated unsuccessfully with one or more other tyrosine kinase inhibitors (TKIs). Chronic myelogenous leukemia (CML) is a myeloproliferative ...

Abstract	Aim of study: This review aims to highlight that bosutinib represents a valuable alternative for patients already treated unsuccessfully with one or more other tyrosine kinase inhibitors (TKIs). Chronic myelogenous leukemia (CML) is a myeloproliferative neoplasm associated with a specific genetic abnormality resulting in a fusion protein with an active tyrosine kinase region. Therefore, TKIs were developed as a suitable treatment option. Methods: Full-text articles, abstracts, and meta-analysis comparing the efficacy and safety of the five TKIs were included in the review. Efficacy of these enhanced therapies is estimated on the basis of achievement of a complete cytogenetic response (CCyR) and this outcome is an important goal as a surrogate marker for improved survival. Results: Bosutinib's efficacy is comparable to that of imatinib in the first-line setting and with dasatinib and nilotinib as second-line therapy, while its safety profile is distinctly different. Most therapeutic guidelines for CML recommend an initiation of therapy with imatinib and application of dasatinib and nilotinib as subsequent lines. Conclusion: Bosutinib is generally not recommended despite its demonstrated efficacy and manageable toxicity. However, resistance, intolerance, specific mutations, as well as disease progression are often the reasons for the lack of sufficient response to therapy registered by the lower rates or complete absence of CCyR. Treatment options are limited for these patients.
MeSH term(s)	Aniline Compounds/adverse effects ; Aniline Compounds/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Bulgaria/epidemiology ; Dasatinib/therapeutic use ; Drug Resistance, Neoplasm/drug effects ; Humans ; Imatinib Mesylate/therapeutic use ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/epidemiology ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology ; Nitriles/adverse effects ; Nitriles/therapeutic use ; Protein Kinase Inhibitors/therapeutic use ; Quinolines/adverse effects ; Quinolines/therapeutic use ; Treatment Outcome
Chemical Substances	Aniline Compounds ; Nitriles ; Protein Kinase Inhibitors ; Quinolines ; bosutinib (5018V4AEZ0) ; Imatinib Mesylate (8A1O1M485B) ; Dasatinib (RBZ1571X5H)
Language	English
Publishing date	2018-07-18
Publishing country	India
Document type	Journal Article ; Review
ZDB-ID	2187633-2
ISSN	1998-4138 ; 0973-1482
ISSN (online)	1998-4138
ISSN	0973-1482
DOI	10.4103/jcrt.JCRT_604_16
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Article: Insights into antiviral mechanisms of remdesivir, lopinavir/ritonavir and chloroquine/hydroxychloroquine affecting the new SARS-CoV-2

Uzunova, Katya / Filipova, Elena / Pavlova, Velichka / Vekov, Toni

Biomed Pharmacother

Abstract	Coronavirus disease 2019 (COVID-19) is a kind of viral pneumonia with an unusual outbreak in Wuhan, China, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There is currently no licensed antiviral treatment available to prevent human CoV infection. The widespread clinical use and existing knowledge on antiviral mechanisms of remdesivir, lopinavir/ritonavir and chloroquine/hydroxychloroquine in the treatment of previous epidemic diseases, namely, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), may be helpful in the combat with novel SARS-CoV-2 infection. Recent clinical evidence didn't confirm the beneficial role of lopinavir/ritonavir and chloroquine/hydroxychloroquine for COVID-19 patients and their use was reassessed. We provide an overview of the current evidence into the mechanisms of action of these available drugs which are repurposed for treatment of the new virus. Available data identifies remdesivir as an adenosine analogue that can target the RNA-dependent RNA polymerase and block viral RNA synthesis. It has been a promising antiviral drug against a wide array of RNA viruses. 3CLpro is a major CoV protease that cleaves the large replicase polyproteins during viral replication and can be targeted by the protease inhibitor lopinavir/ritonavir but the clinical effects are controversial. Chloroquine/Hydroxychloroquine could impair the replication of SARSCoV-2 by multiple mechanisms and their immunomodulatory properties could ameliorate clinical manifestations that are mediated by immune reactions of the host although its beneficial effects are under question and need to be proven at the clinical level. Existing in vitro and in vivo evidence delineate the molecular mechanisms of these drugs in CoV-infected cells. Numerous studies demonstrated the ability of remdesivir to inhibit SARS-CoV-2 replication but future research would be needed to understand the exact mode of action of lopinavir/ritonavir and chloroquine/hydroxychloroquine in SARS-CoV-2 infected cells and to use this knowledge in the treatment of the current COVID-19.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #726409
Database	COVID19

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Article ; Online: Insights into antiviral mechanisms of remdesivir, lopinavir/ritonavir and chloroquine/hydroxychloroquine affecting the new SARS-CoV-2

Uzunova, Katya / Filipova, Elena / Pavlova, Velichka / Vekov, Toni

Biomedicine & pharmacotherapy, 131:110668

2020

Abstract	Coronavirus disease 2019 (COVID-19) is a kind of viral pneumonia with an unusual outbreak in Wuhan, China, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There is currently no licensed antiviral treatment available to prevent human CoV infection. The widespread clinical use and existing knowledge on antiviral mechanisms of remdesivir, lopinavir/ritonavir and chloroquine/hydroxychloroquine in the treatment of previous epidemic diseases, namely, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), may be helpful in the combat with novel SARS-CoV-2 infection. Recent clinical evidence didn’t confirm the beneficial role of lopinavir/ritonavir and chloroquine/hydroxychloroquine for COVID-19 patients and their use was reassessed. We provide an overview of the current evidence into the mechanisms of action of these available drugs which are repurposed for treatment of the new virus. Available data identifies remdesivir as an adenosine analogue that can target the RNA-dependent RNA polymerase and block viral RNA synthesis. It has been a promising antiviral drug against a wide array of RNA viruses. 3CLpro is a major CoV protease that cleaves the large replicase polyproteins during viral replication and can be targeted by the protease inhibitor lopinavir/ritonavir but the clinical effects are controversial. Chloroquine/Hydroxychloroquine could impair the replication of SARSCoV-2 by multiple mechanisms and their immunomodulatory properties could ameliorate clinical manifestations that are mediated by immune reactions of the host although its beneficial effects are under question and need to be proven at the clinical level. Existing in vitro and in vivo evidence delineate the molecular mechanisms of these drugs in CoV-infected cells. Numerous studies demonstrated the ability of remdesivir to inhibit SARS-CoV-2 replication but future research would be needed to understand the exact mode of action of lopinavir/ritonavir and chloroquine/hydroxychloroquine in SARS-CoV-2 infected cells and to use this knowledge in the treatment of the current COVID-19.
Keywords	COVID-19 ; Chloroquine/hydroxychloroquine ; Antiviral mechanism ; Remdesivir ; SARS-CoV-2 ; Lopinavir/ritonavir ; covid19
Language	English
Publishing country	de
Document type	Article ; Online
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Article ; Online: Network meta-analysis of efficacy and safety of chlorthalidone and hydrochlorothiazide in hypertensive patients.

Dineva, Stela / Uzunova, Katya / Pavlova, Velichka / Filipova, Elena / Kalinov, Krassimir / Vekov, Toni

Blood pressure monitoring

2020 Volume 26, Issue 2, Page(s) 160–168

Abstract: Hypertension is a chronic condition leading to increased stress on the heart and blood vessels, a critical risk factor for clinically significant events such as myocardial infarction heart failure, stroke and death. Chlorthalidone and hydrochlorothiazide ...

Abstract	Hypertension is a chronic condition leading to increased stress on the heart and blood vessels, a critical risk factor for clinically significant events such as myocardial infarction heart failure, stroke and death. Chlorthalidone and hydrochlorothiazide are first-line antihypertensive agents for most patients with hypertension. The aim of our meta-analysis was to compare the efficacy and safety of both therapies in patients with hypertension. Searches of electronic databases PubMed, MEDLINE, Scopus, PsycInfo and eLIBRARY.ru, were performed. We used network meta-analysis to combine direct and indirect evidence. Forest plots and closed loops depict estimated results from studies included in our meta-analysis. Of 1289 identified sources, only 37 were included in our meta-analysis. Our analysis has demonstrated a slight superiority for chlorthalidone regarding SBP and not statistically significant differences regarding DBP. Simultaneously, hydrochlorothiazide seems to be a safer choice of therapy, as evidenced by the levels of serum potassium. The two diuretics can be used interchangeably.
MeSH term(s)	Antihypertensive Agents/adverse effects ; Blood Pressure ; Chlorthalidone/adverse effects ; Diuretics/adverse effects ; Humans ; Hydrochlorothiazide/adverse effects ; Hypertension/drug therapy ; Network Meta-Analysis ; Treatment Outcome
Chemical Substances	Antihypertensive Agents ; Diuretics ; Hydrochlorothiazide (0J48LPH2TH) ; Chlorthalidone (Q0MQD1073Q)
Language	English
Publishing date	2020-09-09
Publishing country	England
Document type	Journal Article ; Meta-Analysis
ZDB-ID	1324472-3
ISSN	1473-5725 ; 1359-5237
ISSN (online)	1473-5725
ISSN	1359-5237
DOI	10.1097/MBP.0000000000000486
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Combining angiotensin receptor blockers with chlorthalidone or hydrochlorothiazide - which is the better alternative? A meta-analysis.

Filipova, Elena / Dineva, Stela / Uzunova, Katya / Pavlova, Velichka / Kalinov, Krassimir / Vekov, Toni

Systematic reviews

2020 Volume 9, Issue 1, Page(s) 195

Abstract: Background: Hypertension is a disease with significant clinical and socio-economic consequences. The reduction in cardiovascular mortality and morbidity in patients treated for hypertension is directly related to the magnitude of blood pressure ... ...

Abstract	Background: Hypertension is a disease with significant clinical and socio-economic consequences. The reduction in cardiovascular mortality and morbidity in patients treated for hypertension is directly related to the magnitude of blood pressure reduction. Diuretics have proven useful for the prevention of cardiovascular complications in addition to a long history of safety and efficacy. The main aim for this meta-analysis is to compare the efficacy of the combination of angiotensin receptor blocker (ARB) and chlorthalidone (CTLD) to the combination of ARB and hydrochlorothiazide (HCTZ) in patients with hypertension. Methods: A comprehensive literature search was conducted through electronic databases PubMed, MEDLINE, Scopus, PsyInfo, Cochrane, eLIBRARY.ru, http://ClinicalTrials.gov and http://www.clinicaltrialsregister.eu in July 2020 to identify studies that investigate the effect of the combination of angiotensin receptor blocker with chlorthalidone or hydrochlorothiazide on the systolic and diastolic blood pressure in patients with hypertension. Changes in systolic and diastolic blood pressure (BP) expressed as a weighted mean difference (WMD) were our primary outcomes. The random-effects method was chosen as the primary analysis and results were presented with a 95% confidence interval (CI). Sensitivity analysis was performed and bias was assessed. Results: Our search returned 2745 titles. Of them, 51 full-text articles remained to be subjected to assessment. Comparisons of ARB/HCTZ versus ARB showed changes in BP of -6.89 (-8.09, -5.69) mmHg for systolic BP and - 3.67 (-4.15, -3.19) mmHg for diastolic BP. For the ARB/CTLD versus ARB/HCTZ comparison changes were - 6.30 (-7.30, -5.29) mmHg for systolic BP and - 3.57 (-4.17, 2.98) mmHg for diastolic BP. Conclusion: Our analysis suggests a small but significant favor for CTLD in blood pressure control when compared to HCTZ. We believe it should be considered as a valuable alternative for HCTZ and an option for fixed dose combinations with an ARB although further research is required.
MeSH term(s)	Angiotensin Receptor Antagonists/therapeutic use ; Angiotensin-Converting Enzyme Inhibitors/therapeutic use ; Antihypertensive Agents/therapeutic use ; Blood Pressure ; Chlorthalidone/pharmacology ; Chlorthalidone/therapeutic use ; Diuretics/therapeutic use ; Drug Therapy, Combination ; Humans ; Hydrochlorothiazide/pharmacology ; Hydrochlorothiazide/therapeutic use ; Hypertension/drug therapy ; Tetrazoles/pharmacology ; Tetrazoles/therapeutic use ; Treatment Outcome
Chemical Substances	Angiotensin Receptor Antagonists ; Angiotensin-Converting Enzyme Inhibitors ; Antihypertensive Agents ; Diuretics ; Tetrazoles ; Hydrochlorothiazide (0J48LPH2TH) ; Chlorthalidone (Q0MQD1073Q)
Language	English
Publishing date	2020-08-24
Publishing country	England
Document type	Journal Article ; Meta-Analysis ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2662257-9
ISSN	2046-4053 ; 2046-4053
ISSN (online)	2046-4053
ISSN	2046-4053
DOI	10.1186/s13643-020-01457-9
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Pioglitazone and the Risk of Bladder Cancer: A Meta-Analysis.

Filipova, Elena / Uzunova, Katya / Kalinov, Krassimir / Vekov, Toni

Diabetes therapy : research, treatment and education of diabetes and related disorders

2017 Volume 8, Issue 4, Page(s) 705–726

Abstract: People with type 2 diabetes are at increased risk of bladder cancer. Pioglitazone is said to increase it further, although published evidence is mixed. We conducted a meta-analysis to determine if any link between the use of pioglitazone and an increased ...

Abstract	People with type 2 diabetes are at increased risk of bladder cancer. Pioglitazone is said to increase it further, although published evidence is mixed. We conducted a meta-analysis to determine if any link between the use of pioglitazone and an increased risk of bladder cancer can be found. A comprehensive literature search was conducted through electronic databases as well as registries for data of clinical trials to identify studies that investigate the effect of pioglitazone on bladder cancer in diabetic patients. We used the risk ratio (RR) and the hazard ratio (HR) provided by the studies to illustrate the risk of occurrence of bladder cancer in the experimental group compared to that in the control group. Fourteen studies using RR and 12 studies using HR were included in the analysis. The overall RR was 1.13 with 95% CI (0.96-1.33) with low heterogeneity among the studies using RR, suggesting that no connection exists between use of pioglitazone and the risk of bladder malignancy. The summary HR was 1.07 (0.96-1.18) allowing us to affirm that there is no link between long-term use of pioglitazone and bladder cancer. Our results support the hypothesis of no difference in the incidence of bladder cancer among the pioglitazone group and the nonuser group. Our conclusion is that the explanation of hypothetically increased risk of bladder malignancy should be attributed to other factors. Funding: Tchaikapharma High Quality Medicines Inc.
Language	English
Publishing date	2017-06-16
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2566702-6
ISSN	1869-6961 ; 1869-6953
ISSN (online)	1869-6961
ISSN	1869-6953
DOI	10.1007/s13300-017-0273-4
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Effects of pioglitazone therapy on blood parameters, weight and BMI: a meta-analysis.

Filipova, Elena / Uzunova, Katya / Kalinov, Krassimir / Vekov, Toni

Diabetology & metabolic syndrome

2017 Volume 9, Page(s) 90

Abstract: Background: Type 2 diabetes mellitus (T2DM) is one of the most common diseases worldwide and insulin insufficiency and insulin resistance are two main metabolic issues connected with it. The dyslipidemia associated with insulin resistance and T2DM is ... ...

Abstract	Background: Type 2 diabetes mellitus (T2DM) is one of the most common diseases worldwide and insulin insufficiency and insulin resistance are two main metabolic issues connected with it. The dyslipidemia associated with insulin resistance and T2DM is characterized by higher triglycerides (TGs), higher very-low-density lipoprotein cholesterol and lower apo A1. Pioglitazone, a member of the thiazolidinedione class, with a proven antihyperglycemic effect, is known to positively influence insulin sensitivity and β-cell function and to have the potential to alter the lipid profile. Methods: The aim of our meta-analysis is to summarize and determine the influence of pioglitazone on the glycemic profile and lipoprotein metabolism as well as on weight and BMI in order to highlight the benefit of pioglitazone therapy in patients with T2DM. A comprehensive literature search was conducted through the electronic databases PubMed, MEDLINE, Scopus, PsyInfo, eLIBRARY.ru (from 2000 until February 2016) to identify studies that investigate the effect of pioglitazone on the glycemic and lipid profile and on the weight and BMI. We chose the random-effects method as the primary analysis. Forest plots depict estimated results from the studies included in the analysis and funnel plots are used to evaluate publication bias. Sensitivity analyses were performed in order to evaluate the degree of influence of the consequent elimination of each individual study on the final result. Results: Of the 1536 identified sources only 15 randomised trials were included in the meta-analysis. Pioglitazone treatment was associated with improvement in the glycemic profile. It reduced FPG levels by a mean of 1.1-2 mmol/l and HbA1c by a mean of 0.9-1.3%. Our results reaffirmed the hypothesis that pioglitazone has a positive influence on the lipid profile of T2DM patients with increase in TC and HDL, no significant changes in LDL and notable decrease in TGs. Results also showed that pioglitazone therapy led to increase in both weight and BMI (WMD 1.755, 95% CI 0.674 to 2.837 and 1.145, 95% CI 0.389 to 1.901 respectively). Conclusion: Our results prove that the PPAR γ agonist pioglitazone has the potential to be beneficial to patients with T2DM.
Language	English
Publishing date	2017-11-14
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2518786-7
ISSN	1758-5996
ISSN	1758-5996
DOI	10.1186/s13098-017-0290-5
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Article ; Online: Pioglitazone Therapy and Fractures: Systematic Review and Meta- Analysis.

Pavlova, Velichka / Filipova, Elena / Uzunova, Katya / Kalinov, Krassimir / Vekov, Toni

Endocrine, metabolic & immune disorders drug targets

2018 Volume 18, Issue 5, Page(s) 502–507

Abstract: Introduction: Thiazolidinediones are a group of synthetic medications used in type 2 diabetes treatment. Among available thiazolidinediones, pioglitazone is gaining increased attention due to its lower cardiovascular risk in type 2 diabetes mellitus ... ...

Abstract	Introduction: Thiazolidinediones are a group of synthetic medications used in type 2 diabetes treatment. Among available thiazolidinediones, pioglitazone is gaining increased attention due to its lower cardiovascular risk in type 2 diabetes mellitus sufferers and seems a promising future therapy. Accumulating evidence suggests that diabetic patients may exert bone fractures due to such treatments. Simultaneously, the female population is thought to be at greater risk. Still, the safety outcomes of pioglitazone treatment especially in terms of fractures are questionable and need to be clarified. Methods: We searched MEDLINE, Scopus, PsyInfo, eLIBRARY.ru electronic databases and clinical trial registries for studies reporting an association between pioglitazone and bone fractures in type 2 diabetes mellitus patients published before Feb 15, 2016. Among 1536 sources that were initially identified, six studies including 3172 patients proved relevant for further analysis. Result: Pooled analysis of the included studies demonstrated that after treatment with pioglitazone patients with type 2 diabetes mellitus had no significant increase in fracture risk [odds ratio (OR): 1.18, 95% confidence interval (CI): 0.82 to 1.71, p=0.38] compared to other antidiabetic drugs or placebo. Additionally, no association was found between the risk of fractures and pioglitazone therapy duration. The gender of the patients involved was not relevant to the risk of fractures, too. Conclusion: Pioglitazone treatment in diabetic patients does not increase the incidence of bone fractures. Moreover, there is no significant association between patients' fractures, their gender and the period of exposure to pioglitazone. Additional longitudinal studies need to be undertaken to obtain more detailed information on bone fragility and pioglitazone therapy.
MeSH term(s)	Diabetes Mellitus, Type 2/diagnosis ; Diabetes Mellitus, Type 2/drug therapy ; Diabetes Mellitus, Type 2/epidemiology ; Female ; Fractures, Bone/chemically induced ; Fractures, Bone/diagnosis ; Fractures, Bone/epidemiology ; Humans ; Hypoglycemic Agents/adverse effects ; Hypoglycemic Agents/therapeutic use ; Incidence ; Male ; Pioglitazone/adverse effects ; Pioglitazone/therapeutic use ; Risk Assessment ; Risk Factors ; Treatment Outcome
Chemical Substances	Hypoglycemic Agents ; Pioglitazone (X4OV71U42S)
Language	English
Publishing date	2018-05-07
Publishing country	United Arab Emirates
Document type	Journal Article ; Meta-Analysis ; Systematic Review
ZDB-ID	2228325-0
ISSN	2212-3873 ; 1871-5303
ISSN (online)	2212-3873
ISSN	1871-5303
DOI	10.2174/1871530318666180423121833
Database	MEDical Literature Analysis and Retrieval System OnLINE

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