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1.
J Clin Med ; 9(11)2020 Nov 20.
Article in English | MEDLINE | ID: mdl-33233686

ABSTRACT

For critically ill patients with coronavirus disease 2019 (COVID-19) who require intensive care unit (ICU) admission, extremely high mortality rates (even 97%) have been reported. We hypothesized that overburdened hospital resources by the extent of the pandemic rather than the disease per se might play an important role on unfavorable prognosis. We sought to determine the outcome of such patients admitted to the general ICUs of a hospital with sufficient resources. We performed a prospective observational study of adult patients with COVID-19 consecutively admitted to COVID-designated ICUs at Evangelismos Hospital, Athens, Greece. Among 50 patients, ICU and hospital mortality was 32% (16/50). Median PaO2/FiO2 was 121 mmHg (interquartile range (IQR), 86-171 mmHg) and most patients had moderate or severe acute respiratory distress syndrome (ARDS). Hospital resources may be an important aspect of mortality rates, since severely ill COVID-19 patients with moderate and severe ARDS may have understandable mortality, provided that they are admitted to general ICUs without limitations on hospital resources.

2.
Clin Exp Pharmacol Physiol ; 45(12): 1245-1256, 2018 12.
Article in English | MEDLINE | ID: mdl-30019784

ABSTRACT

Choline deprivation is a recognized experimental approach to nonalcoholic steatohepatitis, while thioacetamide (TAA)-induced liver fibrosis resembles alcoholic liver fibrogenesis. In order to elucidate the effect of TAA on liver extracellular matrix composition under choline deprivation due to choline-deficient diet (CDD) administration, we evaluated the transcriptional and immunohistochemical (IHC) pattern of major hepatic matrix metalloproteinases (namely, MMP-2, -9) and their tissue inhibitors (TIMP-1, -2) in adult male albino Wistar rats at 30, 60 and 90 days. In the CDD+TAA group, IHC showed an early progressive increase in MMP-2 expression, while MMP-9 initially exhibited a significant increase followed by a gradual decrease; TIMP-1 and TIMP-2 IHC expressions showed gradual increase throughout the experiment. The MMPs-TIMPs regulation at the transcriptional level was found to be increased in all groups throughout the experiment. The increased MMP-2/TIMP-2 and suppressed MMP-9/TIMP-1 ratios in IHC and in real-time polymerase chain reaction (RT-PCR) seemed to correlate with the degree of liver fibrosis. These results support the important role of MMPs and TIMPs in controlling the hepatic pathogenesis and shed more light on the recently described experimental approach to liver disease (steatohepatitis) under the impact of two insults (TAA and CDD).


Subject(s)
Choline/analysis , Diet , Extracellular Matrix/drug effects , Extracellular Matrix/metabolism , Liver/cytology , Thioacetamide/pharmacology , Animals , Gene Expression Regulation, Enzymologic/drug effects , Liver/drug effects , Male , Matrix Metalloproteinases/genetics , Rats , Rats, Wistar , Thioacetamide/administration & dosage , Tissue Inhibitor of Metalloproteinases/genetics
3.
Fundam Clin Pharmacol ; 30(1): 47-57, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26501493

ABSTRACT

Choline has been identified as an essential nutrient with crucial role in many vital biological functions. Recent studies have demonstrated that heart dysfunction can develop in the setting of choline deprivation even in the absence of underlying heart disease. Matrix metalloproteinases (MMPs) are responsible for extracellular matrix degradation, and the dysregulation of MMP-2 and MMP-9 has been involved in the pathogenesis of various cardiovascular disorders. The aim of the study was to investigate the role of MMPs and their inhibitors (TIMPs), in the pathogenesis of choline deficiency-induced cardiomyopathy, and the way they are affected by carnitine supplementation. Male Wistar Albino adult rats were divided into four groups and received standard or choline-deficient diet with or without L-carnitine in drinking water (0.15% w/v) for 1 month. Heart tissue immunohistochemistry for MMP-2, MMP-9, TIMP-1, and TIMP-2 was performed. Choline deficiency was associated with suppressed immunohistochemical expression of MMP-2 and an increased expression of TIMP-2 compared to control, while it had no impact on TIMP-1. MMP-9 expression was decreased without, however, reaching statistical significance. Carnitine did not affect MMP-2, MMP-9, TIMP-1 or TIMP-2 expression. The pattern of TIMP and MMP modulation observed in a choline deficiency setting appears to promote fibrosis. Carnitine, although shown to suppress fibrosis, does not seem to affect MMP-2, MMP-9, TIMP-1 or TIMP-2 expression. Further studies will be required to identify the mechanism underlying the beneficial effects of carnitine.


Subject(s)
Cardiomyopathies/prevention & control , Carnitine/therapeutic use , Choline Deficiency/drug therapy , Extracellular Matrix/metabolism , Myocardium/metabolism , Administration, Oral , Animals , Cardiomyopathies/etiology , Cardiomyopathies/metabolism , Cardiomyopathies/pathology , Carnitine/administration & dosage , Choline Deficiency/complications , Choline Deficiency/metabolism , Choline Deficiency/pathology , Disease Models, Animal , Extracellular Matrix/pathology , Fibrosis , Immunohistochemistry , Male , Matrix Metalloproteinase 2/biosynthesis , Matrix Metalloproteinase 9/biosynthesis , Myocardium/pathology , Rats, Wistar , Tissue Inhibitor of Metalloproteinase-1/biosynthesis , Tissue Inhibitor of Metalloproteinase-2/biosynthesis
4.
Can J Physiol Pharmacol ; 92(1): 78-84, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24383876

ABSTRACT

Choline is an essential nutrient, and choline deficiency has been associated with cardiovascular morbidity. Choline is also the precursor of acetylcholine (cholinergic component of the heart's autonomic nervous system), whose levels are regulated by acetylcholinesterase (AChE). Cardiac contraction-relaxation cycles depend on ion gradients established by pumps like the adenosine triphosphatases (ATPases) Na(+)/K(+)-ATPase and Mg(2+)-ATPase. This study aimed to investigate the impact of dietary choline deprivation on the activity of rat myocardial AChE (cholinergic marker), Na(+)/K(+)-ATPase, and Mg(2+)-ATPase, and the possible effects of carnitine supplementation (carnitine, structurally relevant to choline, is used as an adjunct in treating cardiac diseases). Adult male albino Wistar rats were distributed among 4 groups, and were fed a standard or choline-deficient diet for one month with or without carnitine in their drinking water (0.15% w/v). The enzyme activities were determined spectrophotometrically in the myocardium homogenate. Choline deficiency seems to affect the activity of the aforementioned parameters, but only the combination of choline deprivation and carnitine supplementation increased myocardial Na(+)/K(+)-ATPase activity along with a concomitant decrease in the activities of Mg(2+)-ATPase and AChE. The results suggest that carnitine, in the setting of choline deficiency, modulates cholinergic myocardial neurotransmission and the ATPase activity in favour of cardiac work efficiency.


Subject(s)
Acetylcholinesterase/metabolism , Ca(2+) Mg(2+)-ATPase/metabolism , Cardiotonic Agents/pharmacology , Carnitine/pharmacology , Myocardium/enzymology , Sodium-Potassium-Exchanging ATPase/metabolism , Animals , Choline/blood , Choline Deficiency/enzymology , Male , Rats, Wistar
5.
Eur J Pharmacol ; 709(1-3): 20-7, 2013 Jun 05.
Article in English | MEDLINE | ID: mdl-23562624

ABSTRACT

Choline is a B vitamin co-factor and its deficiency seems to impair heart function. Carnitine, a chemical analog of choline, has been used as adjunct in the management of cardiac diseases. The study investigates the effects of choline deficiency on myocardial performance in adult rats and the possible modifications after carnitine administration. Wistar Albino rats (n=24), about 3 months old, were randomized into four groups fed with: (a) standard diet (control-CA), (b) choline deficient diet (CDD), (c) standard diet and carnitine in drinking water 0.15% w/v (CARN) and (d) choline deficient diet and carnitine (CDD+CARN). After four weeks of treatment, we assessed cardiac function under isometric conditions using the Langendorff preparations [Left Ventricular Developed Pressure (LVDP-mmHg), positive and negative first derivative of LVDP were evaluated], measured serum homocysteine and brain natriuretic peptide (BNP) levels and performed histopathology analyses. In the CDD group a compromised myocardium contractility compared to control (P=0.01), as assessed by LVDP, was noted along with a significantly impaired diastolic left ventricular function, as assessed by (-) dp/dt (P=0.02) that were prevented by carnitine. Systolic force, assessed by (+) dp/dt, showed no statistical difference between groups. A significant increase in serum BNP concentration was found in the CDD group (P<0.004) which was attenuated by carnitine (P<0.05), whereas homocysteine presented contradictory results (higher in the CDD+CARN group). Heart histopathology revealed a lymphocytic infiltration of myocardium and valves in the CDD group that was reduced by carnitine. In conclusion, choline deficiency in adult rats impairs heart performance; carnitine acts against these changes.


Subject(s)
Cardiotonic Agents/therapeutic use , Carnitine/therapeutic use , Choline Deficiency/diet therapy , Dietary Supplements , Heart Ventricles/physiopathology , Ventricular Dysfunction, Left/prevention & control , Animals , Cardiotonic Agents/adverse effects , Carnitine/adverse effects , Choline Deficiency/immunology , Choline Deficiency/pathology , Choline Deficiency/physiopathology , Dietary Supplements/adverse effects , Edema, Cardiac/etiology , Edema, Cardiac/prevention & control , Fibrosis , Heart Valves/immunology , Heart Valves/pathology , Heart Ventricles/immunology , Heart Ventricles/pathology , Homocysteine/blood , Hyperhomocysteinemia/etiology , Lymphocytes/immunology , Male , Myocardial Contraction , Natriuretic Peptide, Brain/blood , Random Allocation , Rats , Rats, Wistar , Ventricular Dysfunction, Left/etiology
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