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Article ; Online: Remnant cholesterol levels are associated with severity and death in COVID-19 patients.

Fabre, Bibiana / Fernandez Machulsky, Nahuel / Olano, Carolina / Jacobsen, Darío / Gómez, María Eugenia / Perazzi, Beatriz / Zago, Valeria / Zopatti, Damián / Ferrero, Andrés / Schreier, Laura / Berg, Gabriela

Scientific reports

2022 Volume 12, Issue 1, Page(s) 17584

Abstract: Coronavirus disease-19 (COVID-19) patients with severe complications present comorbidities like cardiovascular-disease, hypertension and type-2 diabetes mellitus (DM), sharing metabolic alterations like insulin resistance (IR) and dyslipidemia. Our ... ...

Abstract	Coronavirus disease-19 (COVID-19) patients with severe complications present comorbidities like cardiovascular-disease, hypertension and type-2 diabetes mellitus (DM), sharing metabolic alterations like insulin resistance (IR) and dyslipidemia. Our objective was to evaluate the association among different components of the lipid-lipoprotein profile, such as remnant lipoprotein (RLP)-cholesterol, in patients with COVID-19, and to analyze their associations with the severity of the disease and death. We studied 193 patients (68 (29-96) years; 49.7% male) hospitalized for COVID-19 and 200 controls (46 (18-79) years; 52.5% male). Lipoprotein profile, glucose and procalcitonin were assessed. Patients presented higher glucose, TG, TG/HDL-cholesterol and RLP-cholesterol levels, but lower total, LDL, HDL and no-HDL-cholesterol levels (p < 0.001). When a binary logistic regression was performed, age, non-HDL-cholesterol, and RLP-cholesterol were associated with death (p = 0.005). As the COVID-19 condition worsened, according to procalcitonin tertiles, a decrease in all the cholesterol fractions (p < 0.03) was observed with no differences in TG, while levels of RLP-cholesterol and TG/HDL-cholesterol increased (p < 0.001). Lower levels of all the cholesterol fractions were related with the presence and severity of COVID-19, except for RLP-cholesterol levels and TG/HDL-cholesterol index. These alterations indicate a lipid metabolic disorder, characteristic of IR states in COVID-19 patients. RLP-cholesterol levels predicted severity and death in these patients.
MeSH term(s)	Female ; Humans ; Male ; Cholesterol/blood ; Cholesterol, HDL/blood ; COVID-19/mortality ; COVID-19/physiopathology ; Glucose ; Lipoproteins/blood ; Procalcitonin/blood ; Triglycerides/blood ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Aged, 80 and over
Chemical Substances	Cholesterol (97C5T2UQ7J) ; Cholesterol, HDL ; Glucose (IY9XDZ35W2) ; Lipoproteins ; Procalcitonin ; Triglycerides
Language	English
Publishing date	2022-10-20
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-022-21177-5
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Article ; Online: Hair Cortisol Measurement by an Automated Method.

Gonzalez, Diego / Jacobsen, Dario / Ibar, Carolina / Pavan, Carlos / Monti, José / Fernandez Machulsky, Nahuel / Balbi, Ayelen / Fritzler, Analy / Jamardo, Juan / Repetto, Esteban M / Berg, Gabriela / Fabre, Bibiana

Scientific reports

2019 Volume 9, Issue 1, Page(s) 8213

Abstract: We present the development of the first procedure for hair cortisol measurement through an automated method. Hair samples were obtained from 286 individuals. After cortisol extraction, samples were measured in a Siemens Immulite 2000 (Gwynedd, UK) ... ...

Abstract	We present the development of the first procedure for hair cortisol measurement through an automated method. Hair samples were obtained from 286 individuals. After cortisol extraction, samples were measured in a Siemens Immulite 2000 (Gwynedd, UK) automated chemoluminiscent immunoassay analyzer. Normal reference values were obtained from hair cortisol levels measured in 213 healthy individuals with low levels of stress. Hair cortisol concentration median was 55 pg/mg hair (2.5-97.5 percentile (40-128)) in healthy individuals with low levels of stress and 250 pg/mg hair (range 182-520) in stressed individuals. No significant differences were observed in hair cortisol levels between subjects with and without dye (40 (40-107) and 40 (40-155) pg/mg hair, respectively; p = 0.128). The novel procedure presented here shows an adequate analytical performance.
MeSH term(s)	Adult ; Automation ; Female ; Hair/chemistry ; Humans ; Hydrocortisone/analysis ; Luminescent Measurements/methods ; Male ; Middle Aged ; Reference Standards ; Stress, Psychological/metabolism ; Tandem Mass Spectrometry
Chemical Substances	Hydrocortisone (WI4X0X7BPJ)
Language	English
Publishing date	2019-06-03
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-019-44693-3
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Article ; Online: Adiponectin predicts MMP-2 activity independently of obesity.

Miksztowicz, Verónica / Fernandez Machulsky, Nahuel / Lucero, Diego / Fassio, Eduardo / Schreier, Laura / Berg, Gabriela

European journal of clinical investigation

2014 Volume 44, Issue 10, Page(s) 951–957

Abstract: Background: Matrix metalloproteinases (MMPs), especially MMP-2 and MMP-9, have been identified in atherosclerotic plaques and have been directly associated with plaque remodelling and vulnerability. Cardiovascular disease (CVD) is related to insulin ... ...

Abstract	Background: Matrix metalloproteinases (MMPs), especially MMP-2 and MMP-9, have been identified in atherosclerotic plaques and have been directly associated with plaque remodelling and vulnerability. Cardiovascular disease (CVD) is related to insulin resistance (IR) and obesity, characterized by changes in plasma levels of inflammatory markers, such as adiponectin and C-reactive protein (CRP). Our aim was to evaluate the impact of both proteins on MMP-2 and MMP-9 behaviour in individuals with IR. Materials and methods: Plasma MMP-2 and MMP-9 activity, adiponectin and hs-CRP concentration and lipoprotein profile were determined in 52 patients with metabolic syndrome (MS) and 27 controls. Results: Patients with MS presented significantly higher MMP-2 activity than controls: 0·95 ± 0·12 vs. 0·77 ± 0·15 relative units (RU) (P < 0·001), while MMP-9 activity was not detectable. MMP-2 activity decreased across quartiles of adiponectin, being significantly reduced in individuals with the highest levels of adiponectin in compared with the lowest levels (0·75 ± 0·17 vs. 0·93 ± 0·09 RU, P < 0·005). This difference persisted significant after adjusting by obesity markers. MMP-2 activity was significantly increased in individuals with the highest levels (G3) compared with those with the lowest levels (G1) of hs-CRP (0·94 ± 0·12 vs. 0·86 ± 0·12, P = 0·041) CONCLUSION: In this study, we observed that adiponectin levels predicted MMP-2 plasma activity independently of obesity. This finding suggests that the inflammatory process, associated with the highest CVD risk, would be involved in MMPs vascular production.
MeSH term(s)	Adiponectin/physiology ; Adult ; Aged ; Biomarkers/metabolism ; C-Reactive Protein/physiology ; Case-Control Studies ; Female ; Humans ; Insulin Resistance/physiology ; Lipid Metabolism/physiology ; Lipoproteins/metabolism ; Male ; Matrix Metalloproteinase 2/metabolism ; Metabolic Syndrome/enzymology ; Middle Aged ; Obesity/enzymology ; Young Adult
Chemical Substances	Adiponectin ; Biomarkers ; Lipoproteins ; C-Reactive Protein (9007-41-4) ; Matrix Metalloproteinase 2 (EC 3.4.24.24)
Language	English
Publishing date	2014-10
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	186196-7
ISSN	1365-2362 ; 0014-2972 ; 0960-135X
ISSN (online)	1365-2362
ISSN	0014-2972 ; 0960-135X
DOI	10.1111/eci.12328
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Zs.A 677: Show issues

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Article ; Online: Nebivolol is more effective than atenolol for blood pressure variability attenuation and target organ damage prevention in L-NAME hypertensive rats.

Del Mauro, Julieta S / Prince, Paula D / Santander Plantamura, Yanina / Allo, Miguel A / Parola, Luciano / Fernandez Machulsky, Nahuel / Morettón, Marcela A / Bin, Eliana P / González, Germán E / Bertera, Facundo M / Carranza, Andrea / Berg, Gabriela / Taira, Carlos A / Donato, Martín / Chiappetta, Diego A / Polizio, Ariel H / Höcht, Christian

Hypertension research : official journal of the Japanese Society of Hypertension

2021 Volume 44, Issue 7, Page(s) 791–802

Abstract: β-Adrenergic blockers are no longer recommended as first-line therapy due to the reduced cardioprotection of traditional β-blockers compared with other antihypertensive drugs. It is unknown whether third-generation β-blockers share the limitations of ... ...

Abstract	β-Adrenergic blockers are no longer recommended as first-line therapy due to the reduced cardioprotection of traditional β-blockers compared with other antihypertensive drugs. It is unknown whether third-generation β-blockers share the limitations of traditional β-blockers. The aim of the present study was to compare the effects of nebivolol or atenolol on central and peripheral systolic blood pressure (SBP) and its variability and target organ damage (TOD) in N-nitro-L-arginine methyl ester (L-NAME) hypertensive rats. Male Wistar rats were treated with L-NAME for 8 weeks together with oral administration of nebivolol 30 mg/kg (n = 8), atenolol 90 mg/kg (n = 8), or vehicle (n = 8). The control group was composed of vehicle-treated Wistar rats. SBP and its variability, as well as echocardiographic parameters, were assessed during the last 2 weeks of treatment. Tissue levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and transforming growth factor β (TGF-β), and histopathological parameters were evaluated in the left ventricle and aorta. Nebivolol had a greater ability than atenolol to decrease central SBP and mid-term and short-term blood pressure variability (BPV) in L-NAME rats. Echocardiographic analysis showed that nebivolol was more effective than atenolol on E/A wave ratio normalization. Compared with atenolol treatment, nebivolol had a greater protective effect on different TOD markers, inducing a decrease in collagen deposition and a reduction in the proinflammatory cytokines IL-6 and TNF-α in the left ventricle and aorta. Our findings suggest that the adverse hemodynamic profile and the reduced cardiovascular protection reported with traditional β-blockers must not be carried forward to third-generation β-blockers.
MeSH term(s)	Animals ; Antihypertensive Agents/pharmacology ; Atenolol/pharmacology ; Blood Pressure/drug effects ; Blood Pressure/physiology ; Hypertension/drug therapy ; Male ; Nebivolol/pharmacology ; Rats ; Rats, Wistar ; Treatment Outcome
Chemical Substances	Antihypertensive Agents ; Nebivolol (030Y90569U) ; Atenolol (50VV3VW0TI)
Language	English
Publishing date	2021-02-22
Publishing country	England
Document type	Journal Article
ZDB-ID	1175297-x
ISSN	1348-4214 ; 0916-9636
ISSN (online)	1348-4214
ISSN	0916-9636
DOI	10.1038/s41440-021-00630-4
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Zs.A 3898: Show issues

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Article ; Online: Matrix metalloproteinases and psychosocial factors in acute coronary syndrome patients.

Fernandez Machulsky, Nahuel / Gagliardi, Juan / Fabre, Bibiana / Miksztowicz, Verónica / Lombardo, Micaela / García Escudero, Alejandro / Gigena, Gerardo / Blanco, Federico / Gelpi, Ricardo J / Schreier, Laura / Gidron, Yori / Berg, Gabriela

Psychoneuroendocrinology

2016 Volume 63, Page(s) 102–108

Abstract: Unlabelled: Psychosocial factors have been linked to cardiovascular diseases independently of traditional risk factors. The impact of psychosocial factors on plaque destabilizing factors, such as matrix metalloproteinases (MMPs) has been proposed ... ...

Abstract	Unlabelled: Psychosocial factors have been linked to cardiovascular diseases independently of traditional risk factors. The impact of psychosocial factors on plaque destabilizing factors, such as matrix metalloproteinases (MMPs) has been proposed although scarcely studied. Objective: To evaluate the relationships between hostility, perceived stress and social support with MMPs activity in patients after an Acute Myocardial Infarction (AMI). Methods: Blood samples were obtained from 76 patients on admission, post-angioplasty, 24h, 7 days and 3 months after AMI. Hostility, perceived stress and social support were evaluated by validated questionnaires. Results: Social support was positively correlated with patientś ejection fraction (r=0.453, p=0.009). Patients with higher infarct size presented increased MMP-2 activity at admission (p=0.04). Patients with one diseased vessel had more social support than those with three diseased vessels (p=0.05). The highest values of MMP-2 and MMP-9 activity were observed at the acute event, decreasing, with the lowest activity at 3 months post-AMI (p<0.001). Only in patients with low social support, hostility correlated with MMP-2 activity, from AMI onset (r=0.645, p=0.013), to 7 days post AMI (r=0.557, p=0.038). Hostility explained up to 28% of the variance in MMP-2 activity (R(2)=0.28, p=0.005). Finally, in patients with high hostility, MMP-9 was positively correlated with IL-1β (r=0.468, p=0.02). Conclusions: This study adds weight to the idea that two psychosocial factors, namely hostility and social support, acting jointly, may affect MMP-2 activity. Moreover, in hostile patients, there is a link between IL-1β and MMP-9. These findings support the role of psychosocial factors in plaque destabilization and in the inflammatory process in AMI.
MeSH term(s)	Acute Coronary Syndrome/metabolism ; Acute Coronary Syndrome/psychology ; Acute Coronary Syndrome/therapy ; Aged ; Angioplasty, Balloon, Coronary ; C-Reactive Protein/metabolism ; Cohort Studies ; Creatine Kinase/metabolism ; Creatine Kinase, MB Form/metabolism ; Female ; Hostility ; Humans ; Hydrocortisone/metabolism ; Interleukin-1beta/metabolism ; Male ; Matrix Metalloproteinase 2/metabolism ; Matrix Metalloproteinase 9/metabolism ; Matrix Metalloproteinases/metabolism ; Middle Aged ; Myocardial Infarction/metabolism ; Myocardial Infarction/psychology ; Myocardial Infarction/therapy ; Prospective Studies ; Social Support ; Stress, Psychological/metabolism ; Stress, Psychological/psychology
Chemical Substances	IL1B protein, human ; Interleukin-1beta ; C-Reactive Protein (9007-41-4) ; Creatine Kinase (EC 2.7.3.2) ; Creatine Kinase, MB Form (EC 2.7.3.2) ; Matrix Metalloproteinases (EC 3.4.24.-) ; MMP2 protein, human (EC 3.4.24.24) ; Matrix Metalloproteinase 2 (EC 3.4.24.24) ; MMP9 protein, human (EC 3.4.24.35) ; Matrix Metalloproteinase 9 (EC 3.4.24.35) ; Hydrocortisone (WI4X0X7BPJ)
Language	English
Publishing date	2016-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	197636-9
ISSN	1873-3360 ; 0306-4530
ISSN (online)	1873-3360
ISSN	0306-4530
DOI	10.1016/j.psyneuen.2015.09.015
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Article ; Online: Effects of carvedilol or amlodipine on target organ damage in L-NAME hypertensive rats: their relationship with blood pressure variability.

Del Mauro, Julieta S / Prince, Paula D / Donato, Martín / Fernandez Machulsky, Nahuel / Morettón, Marcela A / González, Germán E / Bertera, Facundo M / Carranza, Andrea / Gorzalczany, Susana B / Chiappetta, Diego A / Berg, Gabriela / Morales, Celina / Gelpi, Ricardo J / Taira, Carlos A / Höcht, Christian

Journal of the American Society of Hypertension : JASH

2017 Volume 11, Issue 4, Page(s) 227–240

Abstract: The aim of the study was to compare the effects of chronic oral treatment with carvedilol or amlodipine on blood pressure, blood pressure variability and target organ damage in N-nitro-l-arginine methyl ester (L-NAME) hypertensive rats. Wistar rats were ... ...

Abstract	The aim of the study was to compare the effects of chronic oral treatment with carvedilol or amlodipine on blood pressure, blood pressure variability and target organ damage in N-nitro-l-arginine methyl ester (L-NAME) hypertensive rats. Wistar rats were treated with L-NAME administered in the drinking water for 8 weeks together with oral administration of carvedilol 30 mg/kg (n = 6), amlodipine 10 mg/kg (n = 6), or vehicle (n = 6). At the end of the treatment, echocardiographic evaluation, blood pressure, and short-term variability measurements were performed. Left ventricular and thoracic aortas were removed to assess activity of metalloproteinase 2 and 9 and expression levels of transforming growth factor β, tumor necrosis factor α, and interleukin 6. Histological samples were prepared from both tissues. Carvedilol and amlodipine induced a comparable reduction of systolic and mean arterial pressure and its short-term variability in L-NAME rats. The expression of transforming growth factor β, tumor necrosis factor α, and interleukin 6 decreased in both organs after carvedilol or amlodipine treatment and the activity of metalloproteinase was reduced in aortic tissue. Treatment with carvedilol or amlodipine completely prevented left ventricular collagen deposition and morphometric alterations in aorta. Oral chronic treatment with carvedilol or amlodipine significantly attenuates blood pressure variability and reduces target organ damage and biomarkers of tissue fibrosis and inflammation in L-NAME hypertensive rats.
Language	English
Publishing date	2017-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	2276144-5
ISSN	1878-7436 ; 1933-1711
ISSN (online)	1878-7436
ISSN	1933-1711
DOI	10.1016/j.jash.2017.02.007
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Article ; Online: Remnant cholesterol levels are associated with severity and death in COVID-19 patients.

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Article ; Online: Hair Cortisol Measurement by an Automated Method.

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Article ; Online: Adiponectin predicts MMP-2 activity independently of obesity.

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Article ; Online: Nebivolol is more effective than atenolol for blood pressure variability attenuation and target organ damage prevention in L-NAME hypertensive rats.

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Article ; Online: Matrix metalloproteinases and psychosocial factors in acute coronary syndrome patients.

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Article ; Online: Effects of carvedilol or amlodipine on target organ damage in L-NAME hypertensive rats: their relationship with blood pressure variability.

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