Influence of Normo- and Hypogonadal Condition, Hyperuricemia, and High-Fructose Diet on Renal Changes in Male Rats

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International Journal of Endocrinology Volume 2017 (2017), Article ID 1623597

Jimena Soutelo,1,2 Yanina Alejandra Samaniego,1 Elsa Zotta,1 María Cecilia Fornari,3 Carlos Reyes Toso,1 and Osvaldo Juan Ponzo1

1Department of Physiology, Medicine School, University of Buenos Aires (UBA), Buenos Aires, Argentina
2Endocrinology Service Medical Complex, Argentine Federal Police (PFA), Churruca-Visca Hospital, Buenos Aires, Argentina
3Laboratory Fornari-Bioalpha, Buenos Aires, Argentina

Abstract

Background. There is a gender disparity in the incidence, prevalence, and progression of renal disease. The object of this paper is to evaluate the presence and type of renal lesion in normogonadic and hypogonadic male rats in a mild hyperuricemia induced condition and exposed to a high-fructose diet. Methods. 56 adult male Wistar rats were used. Animals were divided into two groups, one normogonadic (NGN) and one hypogonadic (HGN), and each group was divided into four subgroups in accordance with the treatment: control with only water (C), fructose (F), oxonic acid (OA), and fructose + oxonic acid (FOA). Renal changes were evaluated by measuring glomerulosclerosis, fibrosis, and arteriolar media/lumen (M/L) ratio. Results. The OA and FOA groups presented significantly hypertension (). The OA group significantly increased () the percentage of glomerulosclerosis as well as the FOA group (). When comparing NGN versus HGN, we observed a trend to a lower glomerulosclerosis in the latter. A higher arteriolar M/L ratio was observed in the OA () and FOA (). Conclusion. Hyperuricemia conditions and a high-fructose diet favor blood pressure increase together with changes in the arteriolar media/lumen ratio and renal glomerular damage. These changes were more apparent in normogonadic animals.



A prenylated flavanone from Dalea elegans inhibits rhodamine 6 G efflux and reverses fluconazole-resistance in Candida albicans.
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Planta Med. 2012 Jun;78(10):981-7. Epub 2012 Jun 6
























Peralta MA1, Calise M, Fornari MC, Ortega MG, Diez RA, Cabrera JL, Pérez C.




    

  • 1Farmacognosia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Instituto Multidisciplinario de Biología Vegetal-IMBIV-CONICET, Córdoba, Argentina.
    • 









Abstract




In previous studies, 2′,4′-dihydroxy-5′-(1»’,1»’-dimethylallyl)-6-prenylpinocembrin, a prenylated flavonoid isolated from Dalea elegans roots, showed activity against multiresistant Staphylococcus aureus and Candida albicans, as well as an uncoupling effect on mitochondria and antioxidant activity. The aim of this study was to evaluate the inhibitory effects of 2′,4′-dihydroxy-5′-(1»’,1»’-dimethylallyl)-6-prenylpinocembrin and fluconazole on the efflux of rhodamine 6 G in azole-resistant C. albicans 12-99 that expresses multidrug transporters Cdr1p, Cdr2p, and Mdr1p. The effect of fluconazole and 2′,4′-dihydroxy-5′-(1»’,1»’-dimethylallyl)-6-prenylpinocembrin on rhodamine 6 G efflux was assessed in both azole-sensitive and azole-resistant C. albicans. Between 1 and 1000 µM, 2′,4′-dihydroxy-5′-(1»’,1»’-dimethylallyl)-6-prenylpinocembrin inhibited rhodamine 6 G efflux only in azole-resistant C. albicans 12-99 in a concentration-dependent manner (IC50 = 119 µM); a competitive effect was observed. It also showed selectivity of action in comparison with other flavanones (6-prenylpinocembrin, isolated from aerial parts of D. elegans, pinocembrin, naringenin, and hesperetin, all at 250 µM). To check the possible implications of the inhibition of azole efflux on cell growth, antifungal assays were conducted. Minimal inhibitory concentration values were 150 µM for 2′,4′-dihydroxy-5′-(1»’,1»’-dimethylallyl)-6-prenylpinocembrin and higher than 400 µM for fluconazole. The combination of both compounds at either inhibitory or subinhibitory concentrations was significantly more effective than each compound separately. Minimal inhibitory concentration for fluconazole decreased by more than 400 times in the presence of 100 µM 2′,4′-dihydroxy-5′-(1»’,1»’-dimethylallyl)-6-prenylpinocembrin, reversing azole resistance and giving values similar to those of azole-sensitive C. albicans. These data are consistent with a dual action of 2′,4′-dihydroxy-5′-(1»’,1»’-dimethylallyl)-6-prenylpinocembrin: direct antifungal effect on azole-resistant C. albicans 12-99 and inhibition of azole transporters, which results in reversion of fluconazole resistance.


Georg Thieme Verlag KG Stuttgart · New York.




Impaired anti-platelet effect of aspirin, inflammation and platelet turnover in cardiac surgery.
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Interact Cardiovasc Thorac Surg. 2010 Jun;10(6):863-7. Epub 2010 Mar
























Arazi HC1, Doiny DG, Torcivia RS, Grancelli H, Waldman SV, Nojek C, Fornari MC, Badimon JJ.


 




    

  • 1Department of Cardiology, FLENI, Montañeses 2325 (1430), Buenos Aires, Argentina. carazi@fleni.org.ar
    • 







Abstract




A reduced platelet inhibitory response to acetyl salicylic acid (ASA) has been associated with an increased risk of graft thrombotic occlusion after coronary artery bypass grafting (CABG). We performed a prospective, observational study of 18 patients on 100 mg/day ASA before and after CABG. We assessed antiplatelet response to ASA and its relationship with platelet turnover, inflammatory markers, and soluble thrombomodulin (sTM) levels. All patients showed optimal response to ASA preoperatively but had higher values during follow-up. Platelet aggregation and platelet count in the perioperative period were significantly associated (P=0.05). Platelet turnover was defined as the average daily turnover (ADTO). The lowest inhibitory value (28% of patients > or =6 Omega) was recorded at the same time of the highest platelet turnover (>10% daily in 77.77% of patients), one week after CABG. ADTO >10% was associated with an increased risk of platelet aggregation > or =6 Omega. Levels of sTM were significantly higher one week after CABG (median 13 vs. 3 ng/ml preoperatively, P=0.0011). There is a transient impairment in ASA antiplatelet effect after CABG related to an increased platelet turnover caused by the inflammatory process. This could be responsible for the high risk of occlusive thrombosis.




Alterations in biomarkers of cardiovascular disease (CVD) in active acromegaly
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Clin Endocrinol (Oxf). 2009 Jan;70(1):88-95
















































Boero L, Manavela M, Rosso LG, Insua C, Berardi V, Fornari MC, Brites F.




Department of Clinical Biochemistry, Faculty of Pharmacy and Biochemistry, CONICET, University of Buenos Aires, Buenos Aires, Argentina. lauraboero@fibertel.com.ar








OBJECTIVES: In acromegalic patients, cardiovascular and metabolic comorbidities contribute to enhance mortality. Available data on the lipoprotein profile of these patients are controversial. Our aim was to characterize the lipoprotein profile and emergent biomarkers of cardiovascular disease in active acromegalic patients in comparison with sex- and age-matched healthy controls. PATIENTS: Eighteen patients with active acromegaly and 18 controls were studied. MEASUREMENTS: Glucose levels, hormonal status, lipoprotein profile and C reactive protein (CRP) were evaluated by standardized methods. Cholesteryl ester transfer protein (CETP) and lipoprotein-associated phospholipase A(2 )(Lp-PLA(2)) were measured by radiometric techniques, endothelin-1 and vascular cell adhesion molecule (VCAM)-1 by enzyme-linked immunosorbent assay, and leucocytes CD18, CD49d and CD54 by flow cytometry. RESULTS: After adjusting for body mass index (BMI), acromegalic patients presented a more atherogenic lipoprotein profile, consisting of higher levels of triglycerides and apolipoprotein B and alterations in the ratios which estimate insulin resistance and atherogenic risk. CETP activity was significantly increased in acromegalic patients as compared to controls (168 +/- 17 vs. 141 +/- 30% per ml h, respectively; P < 0.05). Endothelin-1 levels evidenced an increase in the patients’ group (0.9 +/- 0.2 vs. 0.7 +/- 0.2 ng/l, respectively; P < 0.01) and showed positive and significant correlations with GH, IGF-1 and IGFBP-3 (r = 0.45, 0.42 and 0.44, respectively; P < 0.01 for all of them; with BMI as a fixed variable). Lymphocytes from acromegalic patients showed increased CD49d content (282 +/- 59 vs. 246 +/- 48 arbitrary units, respectively; P < 0.05). CONCLUSIONS: Taken together, the alterations described seem to contribute to constituting a state of higher propensity for the development of atherosclerotic cardiovascular disease, which adds to the presence of specific cardiomyopathy.
























 


Alterations in cell adhesion molecules and other biomarkers of cardiovascular disease in patients with metabolic syndrome
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Atherosclerosis. 2008 Aug;199(2):415-23. Epub 2007 Dec 21














































Gómez Rosso L, Benítez MB, Fornari MC, Berardi V, Lynch S, Schreier L, Wikinski R, Cuniberti L, Brites F.


























Laboratory of Lipids and Lipoproteins, Department of Clinical Biochemistry, School of Pharmacy and Biochemistry, University of Buenos Aires, CONICET, Argentina.






































































Metabolic syndrome is considered a hyperinsulinemic and inflammatory state closely associated to endothelial dysfunction causing an increased incidence of ischemic cardiovascular events and high mortality. The main objective of the present study was to determine whether leukocitary and soluble cell adhesion molecules were altered in patients with metabolic syndrome in comparison with control subjects. Cell adhesion molecules, mainly of leukocitary location, have been not previously evaluated in specifically designed cross-sectional studies involving male patients with metabolic syndrome. Moreover, other circulating markers of different candidate atherogenic risk parameters were also studied and the potential existence of a progressive relation between the number of metabolic syndrome components and the above mentioned biomarkers was analyzed. Thirty one male patients with metabolic syndrome (ATPIII definition) and 56 male control subjects were studied. We evaluated different markers of insulin resistance, inflammation and atherosclerosis, as well as protective factors. Patients with metabolic syndrome showed (a) hypoadiponectinemia (4551 +/- 2302 ng/ml vs. 5865 +/- 2548 ng/ml, respectively; p<0.05), (b) an atherogenic lipid and lipoprotein profile, (c) altered HDL chemical composition accompanied by higher cholesteryl ester-triglyceride interchange carried out by CETP, (d) diminished Lp-PLA(2) activity (6.5 +/- 1.9 vs. 7.3 +/- 2.2, p<0.05, respectively), antioxidant enzyme related with LDL oxidation, which was positively associated with QUICKI and negatively with VCAM-1 and lymphocyte CD18, and (e) high soluble (VCAM-1: 17 +/-5 vs. 13 +/- 4 ng/ml, respectively; p<0.0005) and leukocyte adhesion molecule expression (monocyte CD54: 52 +/- 15 vs. 45 +/-12 arbitrary units, respectively; p<0.0005; and lymphocyte CD49d: 312 +/- 56 vs. 284 +/- 64 arbitrary units, respectively; p < 0.05). The increment in leukocyte and soluble cell adhesion molecules, crucial for leukocyte interaction with the endothelium and migration into the artery wall, in combination with the other disorders described above reinforce the presence of a clinical status with high propensity to type 2 diabetes and atherosclerotic cardiovascular disease.


PMID: 18096167 [PubMed – in process]






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Alterations in biomarkers of cardiovascular disease in active acromegaly.
/4.540 Comentarios/en  /por 




















Clin Endocrinol (Oxf). 2008 Jun 25.










































Boero L, Manavela M, Gómez Rosso L, Insua C, Berardi V, Fornari M, Brites F




Department of Clinical of Biochemistry, School of Pharmacy and Biochemistry, University of Buenos Aires, Argentina. CONICET.






.




Objectives: In acromegalic patients, cardiovascular and metabolic co-morbidities contribute to enhance mortality. Available data on the lipoprotein profile of these patients are controversial. Our aim was to characterize the lipoprotein profile and emergent biomarkers of cardiovascular disease in active acromegalic patients in comparison with sex- and age-matched healthy controls. Patients: Eighteen patients with active acromegaly and eighteen controls were studied. Measurements: Glucose levels, hormonal status, lipoprotein profile and C reactive protein (CRP) were evaluated by standardized methods. Cholesteryl ester transfer protein (CETP) and lipoprotein-associated phospholipase A(2 )(Lp-PLA(2)) were measured by radiometric techniques, endothelin-1 and vascular cell adhesion molecule (VCAM)-1 by enzyme-linked immunosorbent assay, and leukocytes CD18, CD49d and CD54 by flow cytometry. Results: After adjusting for body mass index (BMI), acromegalic patients presented a more atherogenic lipoprotein profile, consisting of higher levels of triglycerides and apolipoprotein B and alterations in the ratios which estimate insulin resistance and atherogenic risk. CETP activity was significantly increased in acromegalic patients as compared to controls (168+/-17 vs. 141+/-30 %/ml.h, respectively; p<0.05). Endothelin-1 levels evidenced an increase in the patients’ group (0.9+/-0.2 vs. 0.7+/-0.2 pg/ml; respectively; p<0.01) and showed positive and significant correlations with GH, IGF-1 and IGFBP-3 (r = 0.45, 0.42, and 0.44; respectively; p<0.01 for all of them; with BMI as a fixed variable). Lymphocytes from acromegalic patients showed increased CD49d content (282+/-59 vs. 246+/-48 arbitrary units; respectively; p<0.05). Conclusions: Taken together, the alterations described seem to contribute to constituting a state of higher propensity for the development of atherosclerotic cardiovascular disease, which adds to the presence of specific cardiomyopathy






















 


Endothelial and leukocyte adhesion molecules in primary hypertriglyceridemia.
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Atherosclerosis. 2008 Apr;197(2):679-87. Epub 2007 May 25
























Benítez MB1, Cuniberti L, Fornari MC, Gómez Rosso L, Berardi V, Elikir G, Stutzbach P, Schreier L, Wikinski R, Brites F.


 




    

  • 1Laboratory of Lipids and Lipoprotein, Department of Clinical Biochemistry, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Junin 956, Buenos Aires 1113, Argentina.
    • 







Abstract




Hypertriglyceridemia is known to be associated to functional impairment of the endothelium and, consequently, to higher risk of atherosclerosis. Nevertheless, some crucial steps in the development of the atherosclerotic plaque are still unknown in primary hypertriglyceridemia. The aim of the present study was to explore the expression of soluble and leukocyte-associated cell adhesion molecules in a group of patients with primary hypertriglyceridemia, both including (n=50) and excluding (n=24) subjects with metabolic syndrome, in comparison with control normotriglyceridemic individuals (n=30). Lipid profile, CETP activity, HDL and VLDL chemical composition were evaluated. Soluble (VCAM-1, ICAM-1 and E-selectin) and leukocyte cell adhesion molecules (CD18, CD49d and CD54) were measured by enzyme-linked immunosorbent assay and flow cytometry, respectively. Patients with primary hypertriglyceridemia as compared with control subjects showed significantly higher VCAM-1 (15.6+/-4.5 ng/ml versus 13.9+/-3.8 ng/ml, respectively; p<0.05) and ICAM-1 (16.9+/-3.1 ng/ml versus 15.2+/-3.2 ng/ml, respectively; p<0.05). Regarding leukocyte cell adhesion molecules, significant increases were also detected in monocyte CD18 (398+/-180 versus 332+/-136 arbitrary units, respectively; p<0.05) and CD54 (49+/-14 versus 42+/-12 arbitrary units, respectively; p<0.05), and lymphocyte CD18 (122+/-53 versus 101+/-33 arbitrary units, respectively; p<0.05). ICAM-1 plasma levels, as well as monocyte CD18 and CD54, and lymphocyte CD18 persisted elevated even if patients with metabolic syndrome were discarded among those with hypertriglyceridemia. The increase in circulating and leukocyte cell adhesion molecules in primary hypertriglyceridemic patients would highlight the inflammatory process which is a key event in atherogenesis.




Detection of interleukin 10 in cerebrospinal fluid of patients with subacute sclerosing panencephalitis.
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J Neurovirol. 2005 Feb;11(1):66-9












































Mistchenko AS, Fornari MC, Viegas M, Barrero PR, Diez RA.




Laboratorio de Virología, Hospital de Niños R. Gutiérrez, Gallo 1330, 1425 Buenos Aires, Argentina. virologia@velocom.com.ar






Subacute sclerosing panencephalitis (SSPE) is a neurodegenerative disorder due to persistent measles virus infection, with high level of measles-specific antibodies in cerebrospinal fluid (CSF). To analyze whether such response arises from a TH2-biased response, the authors determined TH1 (interferon [IFN]-gamma) and TH2 (interleukin [IL]-4 and IL-10) cytokines in CSF, taken at diagnosis, of eight SSPE patients (median age, 57.5 month, range 42 to 76 months). All patients presented IL-10 (median 29.3 pg/ml, range 4.3 to 162 pg/ml), but not IL-4 (<10 pg/ml); only one case showed IFN-gamma (162 pg/ml). These results are consistent with a TH2 bias or with a local, anti-inflammatory or neuroprotective mechanism involving IL-10.


PMID: 15804961 [PubMed – indexed for MEDLINE]






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Effect of ovaric hyper-stimulation on blood lymphocyte subpopulations, cytokines, leptin and nitrite among patients with unexplained infertility.
/1.116 Comentarios/en  /por 




















Am J Reprod Immunol. 2002 Dec;48(6):394-403.






















Fornari MC1, Sarto A, Berardi VE, Martínez MA, Rocha MG, Pasqualini S, Diez RA.




    

  • 1Immunopharmacology Lab, Department of Pharmacology, School of Medicine, University of Buenos Aires, Argentina.
    • 







Abstract




PROBLEM:


To determine the effect of ovarian stimulation on TH1, TH2 and natural killer (NK) lymphocytes, plasma cytokines, leptin and nitrite levels.


METHODS:


Women with reproductive failure were studied during the implantation window, at baseline (n = 18) and under ovarian stimulation (gonadotropins + progesterone, n = 6).


CONTROLS:


eight fertile women. Lymphocyte subpopulations and NK function were determined by flow cytometry. Interleukin-2 (IL-2), IL-4, IL-10, IFN-gamma, TNF-alpha, TGF-beta1 and leptin were measured by enzyme immunoassay (EIA); nitrite by the Griess reaction.


RESULTS:


At baseline, patients had higher values of NK effectors, NK activity and plasma IFN-gamma and IL-2 than controls. Conversely, TGF-beta1 values were lower. Hormones induced leukocytosis. Under stimulation, THI CD4+ cells, NK effectors and function and plasma IFN-gamma and IL-2 decreased, while transforming growth factor (TGF)-beta1 increased. Other variables did not change.


CONCLUSION:


The abnormal distribution of leukocytes, high TH1 cytokines and a low TGF-beta1 associated with reproductive failure, respond to ovarian stimulation, achieving total or partial normalization.




High serum interleukin-10 and tumor necrosis factor alpha levels in chronic paracoccidioidomycosis
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Clin Diagn Lab Immunol. 2001 Sep;8(5):1036-8






































































Fornari MC, Bava AJ, Guereño MT, Berardi VE, Silaf MR, Negroni R, Diez RA
























Laboratorio de Inmunofarmacologia, Facultad de Medicina (UBA), Paraguay 2155, Piso 16, 1121 Buenos Aires, Argentina.






















































In patients with chronic paracoccidioidomycosis (n = 10), levels of tumor necrosis factor alpha, interleukin-10, and interleukin-2 in serum, measured by enzyme-linked immunosorbent assay (in picograms per milliliter, as mean +/- standard error of the mean), were higher than in normal controls (n = 8): 186 +/- 40 versus 40 +/- 7 (P < 0.05), 203 +/- 95 versus 20 +/- 8 (P = 0.001), and 96.3 +/- 78.57 versus 1.19 +/- 1.19 (P = 0.045), respectively. Gamma interferon and interleukin-4 levels were similar in patients and controls.


PMID: 11527826 [PubMed – indexed for MEDLINE]


PMCID: PMC96194






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