Publications by authors named "Lorena Gonzalez"

103 Publications

Growth Hormone Modulation of Hepatic Epidermal Growth Factor Receptor Signaling.

Trends Endocrinol Metab 2021 Jun 7;32(6):403-414. Epub 2021 Apr 7.

Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Instituto de Química y Fisicoquímica Biológicas (IQUIFIB), Facultad de Farmacia y Bioquímica, Buenos Aires, Argentina.

Epidermal growth factor receptor (EGFR) signaling has a central role in the regenerative response of the liver upon injury and is involved in cellular transformation linked to chronic damage. Hepatic EGFR expression, trafficking, and signaling are regulated by growth hormone (GH). Chronically elevated GH levels are associated with liver cancer development and progression in mice. Studies in different in vivo experimental models indicate that EGF and GH mutually crossregulate in a complex manner. Several factors, such as the extent of exposure to supraphysiological GH levels and the pattern of GH administration, are important variables to be considered in exploring the interplay between the two hormones in connection with the progression of hepatic tumors.
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http://dx.doi.org/10.1016/j.tem.2021.03.004DOI Listing
June 2021

White adipose tissue-infiltrated CD11b+ myeloid cells are a source of S100A4, a new potential marker of hepatic damage.

Eur J Endocrinol 2021 Apr;184(4):533-541

Department of Endocrinology and Nutrition, Germans Trias i Pujol Research Institute.

Context: The endocrine and immunological properties of subcutaneous vs visceral adipose tissue (sWAT and vWAT, respectively) have turned a milestone in the study of metabolic diseases. The cytokine S100A4 is increased in obesity and has a role in adipose tissue dysfunction. However, the cellular source and its potential role in hepatic damage in obesity has not been elucidated.

Objective: We aim to study the regulation of S100A4 in immune cells present in sWAT and vWAT, as well as its potential role as a circulating marker of hepatic inflammation and steatosis.

Design: A cohort of 60 patients with obesity and distinct metabolic status was analyzed. CD11b+ myeloid cells and T cells were isolated from sWAT and vWAT by magnetic-activating cell sorting, and RNA was obtained. S100A4 gene expression was measured, and correlation analysis with clinical data was performed. Liver biopsies were obtained from 20 patients, and S100A4 circulating levels were measured to check the link with hepatic inflammation and steatosis.

Results: S100A4 gene expression was strongly upregulated in sWAT- vs vWAT-infiltrated CD11b+ cells, but this modulation was not observed in T cells. S100A4 mRNA levels from sWAT (and not from vWAT) CD11b+ cells positively correlated with glycemia, triglycerides, TNF-α gene expression and proliferation markers. Finally, circulating S100A4 directly correlated with liver steatosis and hepatic inflammatory markers.

Conclusion: Our data suggest that sWAT-infiltrated CD11b+ cells could be a major source of S100A4 in obesity. Moreover, our correlations identify circulating S100A4 as a potential novel biomarker of hepatic damage and steatosis.
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http://dx.doi.org/10.1530/EJE-20-1130DOI Listing
April 2021

Macrophage apoptosis using alendronate in targeted nanoarchaeosomes.

Eur J Pharm Biopharm 2021 Mar 10;160:42-54. Epub 2021 Jan 10.

Centro de Investigación y Desarrollo en Nanomedicinas (CIDeN), Universidad Nacional de Quilmes, Bernal, Buenos Aires, Argentina. Electronic address:

Nanoarchaeosomes are non-hydrolysable nanovesicles made of archaeolipids, naturally functionalised with ligand for scavenger receptor class 1. We hypothesized that nitrogenate bisphosphonate alendronate (ALN) loaded nanoarchaeosomes (nanoarchaeosomes(ALN)) may constitute more efficient macrophage targeted apoptotic inducers than ALN loaded nanoliposomes (nanoliposomes (ALN)). To that aim, ALN was loaded in cholesterol containing (nanoARC-chol(ALN)) or not (nanoARC(ALN)) nanoarchaeosomes. Nanoarchaeosomes(ALN) (220-320 nm sized, ~ -40 mV ξ potential, 38-50 μg ALN/mg lipid ratio) displayed higher structural stability than nanoliposomes(ALN) of matching size and ξ potential, retaining most of ALN against a 1/200 folds dilution. The cytotoxicity of nanoARC(ALN) on J774A.1 cells, resulted > 30 folds higher than free ALN and nanoliposomes(ALN) and was reduced by cholesterol in nanoARC-chol(ALN). Devoid of ALN, nanoARC-chol was non-cytotoxic, exhibited pronounced anti-inflammatory activity on J774.1 cells, strongly reducing reactive oxygen species (ROS) and IL-6 induced by LPS. Nanoarchaeosomes bilayer extensively interacted with serum proteins but resulted refractory to phospholipases. Upon J774A.1 cells uptake, nanoarchaeosomes induced cytoplasmic acid vesicles, reduced the mitochondrial membrane potential by 20-40 % without consuming ATP neither damaging lysosomes and increasing pERK. Refractory to chemoenzymatic attacks, either void or drug loaded, nanoarchaeosomes induced either anti-inflammation or macrophages apoptosis, constituting promising targeted nanovesicles for multiple therapeutic purposes.
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http://dx.doi.org/10.1016/j.ejpb.2021.01.001DOI Listing
March 2021

Unconscious Bias in Speaker Introductions at a Surgical Oncology Meeting: Hierarchy Reigns Over Gender.

Ann Surg Oncol 2020 Oct 25;27(10):3754-3761. Epub 2020 Jul 25.

Division of Surgical Oncology, Department of Surgery, City of Hope National Medical Center, Duarte, CA, USA.

Background: Recent reviews of medical conferences have shown that women were less likely to receive a formal introduction compared with men. We examined speaker introductions at the Society of Surgical Oncology (SSO) annual meeting to determine whether similar biases exist within our organization.

Methods: An observational study of video-archived speaker introductions at the 2018 and 2019 SSO annual meetings was conducted. Professional address was defined as professional title followed by full name or last name. Multivariable logistic regression was used to identify factors associated with form of address.

Results: There were 499 speaker introductions reviewed. Speakers included 290 (58%) men and 238 (49%) post-graduate trainees (residents and fellows). A non-professional form of address was used to introduce 148 (30%) speakers and was most often used for post-graduate trainees (33%). Full professors were more likely than junior faculty to introduce speakers with a non-professional form of address (37% of full professors vs 18% of assistant professors, p < 0.001). In multivariable regression analysis these findings persisted. Trainees were 2.8 times more likely to receive a non-professional form of address (p = 0.003). Use of a non-professional introduction did not significantly vary by the speaker's nor the introducer's gender.

Conclusions: Residents and fellows were more likely to receive a non-professional form of address, and the likelihood of this increased with rising seniority of the introducer. The manner of speaker introduction did not vary by gender in our organization. More research is needed to explore the influence of these disparities on academic advancement for the next generation of surgical oncologists.
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http://dx.doi.org/10.1245/s10434-020-08906-8DOI Listing
October 2020

Hydroxymethylfurfural determination in cereal and insect bars by high-performance liquid chromatography-mass spectrometry employing a functionalized mesostructured silica as sorbent in solid-phase extraction.

J Chromatogr A 2020 Jul 15;1622:461124. Epub 2020 Apr 15.

Departamento de Tecnología Química y Ambiental, E.S.C.E.T, Universidad Rey Juan Carlos, C/Tulipán s/n, 28933 Móstoles, Madrid, Spain. Electronic address:

In this work a new method for the determination of 5-hydroxymethylfurfural (HMF) in cereal and insect bars has been developed and validated. The method consisted of a solid-liquid extraction (SLE) followed by a solid phase extraction (SPE), employing functionalized mesostructured silica as sorbent, and prior to high-performance liquid chromatography coupled to mass spectrometry analysis (HPLC-MS/MS). Mesostructured silica with a large pore (SBA-15-LP) functionalized with aminopropyl- groups (SBA-15-LP-NH), octyl- groups (SBA-15-LP-C8) and bifunctionalized with both organic ligands (SBA-15-LP-C8-NH) were prepared, characterized and tested for this purpose. The optimal conditions showed that the best extraction solvent was water acidified with HCl (pH 1.0) and the best material for SPE was SBA-15-LP-NH (recoveries near 100%). Results were compared with other analogous commercial sorbent (Discovery® DSC-NH), evaluated under similar conditions, and SBA-15-LP-NH sorbent showed better recoveries than the commercial one (62 ± 1%). The developed method was validated and good detection and quantification limits (MDL: 11 µg kgand MQL: 38 µg kg), good precision in terms of repeatability and within-laboratory reproducibility (RSD < 8%) and good accuracy (recoveries between 99-102%) were obtained. The method was successfully applied to the determination of HMF in different samples of cereals and insect bars. In all the samples analysed, high concentrations of HMF (ranging from 336 to 962 mg kg) have been found.
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http://dx.doi.org/10.1016/j.chroma.2020.461124DOI Listing
July 2020

Concentration-dependent effects of sodium cholate and deoxycholate bile salts on breast cancer cells proliferation and survival.

Mol Biol Rep 2020 May 15;47(5):3521-3539. Epub 2020 Apr 15.

Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Instituto de Química y Fisicoquímica Biológicas (IQUIFIB), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.

Bile acids (BAs) are bioactive molecules that have potential therapeutic interest and their derived salts are used in several pharmaceutical systems. BAs have been associated with tumorigenesis of several tissues including the mammary tissue. Therefore, it is crucial to characterize their effects on cancer cells. The objective of this work was to analyse the molecular and cellular effects of the bile salts sodium cholate and sodium deoxycholate on epithelial breast cancer cell lines. Bile salts (BSs) effects over breast cancer cells viability and proliferation were assessed by MTS and BrdU assays, respectively. Activation of cell signaling mediators was determined by immunobloting. Microscopy was used to analyze cell migration, and cellular and nuclear morphology. Interference of membrane fluidity was studied by generalized polarization and fluorescence anisotropy. BSs preparations were characterized by transmission electron microscopy and dynamic light scattering. Sodium cholate and sodium deoxycholate had dual effects on cell viability, increasing it at the lower concentrations assessed and decreasing it at the highest ones. The increase of cell viability was associated with the promotion of AKT phosphorylation and cyclin D1 expression. High concentrations of bile salts induced apoptosis as well as sustained activation of p38 and AKT. In addition, they affected cell membrane fluidity but not significant effects on cell migration were observed. In conclusion, bile salts have concentration-dependent effects on breast cancer cells, promoting cell proliferation at physiological levels and being cytotoxic at supraphysiological ones. Their effects were associated with the activation of kinases involved in cell signalling.
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http://dx.doi.org/10.1007/s11033-020-05442-2DOI Listing
May 2020

Exposure to growth hormone is associated with hepatic up-regulation of cPLA2α and COX.

Mol Cell Endocrinol 2020 06 4;509:110802. Epub 2020 Apr 4.

Universidad de Buenos Aires, Consejo Nacional de lnvestigaciones Científicas y Técnicas, Instituto de Química y Fisicoquímica Biológicas (IQUIFIB), Departamento de Química Biológica, Facultad de Farmacia y Bioquímica, Buenos Aires, Argentina. Electronic address:

Continuously elevated levels of growth hormone (GH) during life in mice are associated with hepatomegaly due to hepatocytes hypertrophy and hyperplasia, chronic liver inflammation, elevated levels of arachidonic acid (AA) at young ages and liver tumors development at old ages. In this work, the hepatic expression of enzymes involved in AA metabolism, cPLA2α, COX1 and COX2 enzymes, was evaluated in young and old GH-transgenic mice. Mice overexpressing GH exhibited higher hepatic expression of cPLA2α, COX1 and COX2 in comparison to controls at young and old ages and in both sexes. In old mice, when tumoral and non-tumoral tissue were compared, elevated expression of COX2 was observed in tumors. In contrast, exposure to continuous lower levels of hormone for a short period affected COX1 expression only in males. Considering the role of inflammation during liver tumorigenesis, these findings support a role of alterations in AA metabolism in GH-driven liver tumorigenesis.
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http://dx.doi.org/10.1016/j.mce.2020.110802DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7211091PMC
June 2020

A Role for Oncostatin M in the Impairment of Glucose Homeostasis in Obesity.

J Clin Endocrinol Metab 2020 Mar;105(3)

Department of Endocrinology and Nutrition, Germans Trias i Pujol Research Institute, Barcelona, Spain.

Context: Oncostatin M (OSM) plays a key role in inflammation, but its regulation and function during obesity is not fully understood.

Objective: The aim of this study was to evaluate the relationship of OSM with the inflammatory state that leads to impaired glucose homeostasis in obesity. We also assessed whether OSM immunoneutralization could revert metabolic disturbances caused by a high-fat diet (HFD) in mice.

Design: 28 patients with severe obesity were included and stratified into two groups: (1) glucose levels <100 mg/dL and (2) glucose levels >100 mg/dL. White adipose tissue was obtained to examine OSM gene expression. Human adipocytes were used to evaluate the effect of OSM in the inflammatory response, and HFD-fed C57BL/6J mice were injected with anti-OSM antibody to evaluate its effects.

Results: OSM expression was elevated in subcutaneous and visceral fat from patients with obesity and hyperglycemia, and correlated with Glut4 mRNA levels, serum insulin, homeostatic model assessment of insulin resistance, and inflammatory markers. OSM inhibited adipogenesis and induced inflammation in human adipocytes. Finally, OSM receptor knockout mice had increased Glut4 mRNA levels in adipose tissue, and OSM immunoneutralization resulted in a reduction of glucose levels and Ccl2 expression in adipose tissue from HFD-fed mice.

Conclusions: OSM contributes to the inflammatory state during obesity and may be involved in the development of insulin resistance.
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http://dx.doi.org/10.1210/clinem/dgz090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7112982PMC
March 2020

Mice lacking angiotensin type 2 receptor exhibit a sex-specific attenuation of insulin sensitivity.

Mol Cell Endocrinol 2019 12 17;498:110587. Epub 2019 Sep 17.

Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Química Biológica, IQUIFIB (UBA-CONICET), Buenos Aires, Argentina. Electronic address:

The renin-angiotensin system modulates insulin action. Pharmacological stimulation of angiotensin type 2 receptor (AT2R) was shown to have beneficial metabolic effects in various animal models of insulin resistance and type 2 diabetes and also to increase insulin sensitivity in wild type mice. In this study we further explored the role of the AT2R on insulin action and glucose homeostasis by investigating the glycemic profile and in vivo insulin signaling status in insulin-target tissues from both male and female AT2R knockout (KO) mice. When compared to the respective wild-type (WT) group, glycemia and insulinemia was unaltered in AT2RKO mice regardless of sex. However, female AT2RKO mice displayed decreased insulin sensitivity compared to their WT littermates. This was accompanied by a compensatory increase in adiponectinemia and with a specific attenuation of the activity of main insulin signaling components (insulin receptor, Akt and ERK1/2) in adipose tissue with no apparent alterations in insulin signaling in either liver or skeletal muscle. These parameters remained unaltered in male AT2RKO mice as compared to male WT mice. Present data show that the AT2R has a physiological role in the conservation of insulin action in female but not in male mice. Our results suggest a sexual dimorphism in the control of insulin action and glucose homeostasis by the AT2R and reinforce the notion that pharmacological modulation of the balance between the AT1R and AT2R receptor could be important for treatment of metabolic syndrome and type 2 diabetes.
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http://dx.doi.org/10.1016/j.mce.2019.110587DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6903409PMC
December 2019

Frailty and Biomarkers of Frailty Predict Outcome in Veterans After Open and Endovascular Revascularization.

J Surg Res 2019 11 1;243:539-552. Epub 2019 Aug 1.

Division of Vascular and Endovascular Services, Upstate Medical University, Syracuse, New York; Department of Surgery, Syracuse VA Medical Center, Syracuse, New York.

Background: Frailty predicts poor outcome after vascular surgery. We determined the predictive utility of the modified frailty index (mFI) after first-time revascularization and identified biomarkers of frailty predictive of outcome in veterans with peripheral arterial disease.

Methods: A retrospective study was performed of first-time revascularizations (open surgery [OS] and endovascular surgery [ES]) in male veterans (2003-2016). Preoperative mFI scores were calculated, and serum and nonserum biomarkers of frailty were recorded. The primary endpoint was 2-y incidence of reintervention, amputation, and mortality. Secondary endpoints included 30-day morbidity and readmissions.

Results: Four hundred and thirty one patients (OS, n = 188; ES, n = 243), mean age of 66 ± 9 y, and 16 mo of median follow-up were studied. Mean mFI was 0.39 ± 0.16 for OS and 0.38 ± 0.15 for ES (P = 0.43). 30-day complications (adjusted odds ratio, 4.89; 95% confidence interval [CI]: 1.67-14.33) and readmissions (adjusted hazard ratio [aHR] 3.32; 95% CI: 1.16-9.55) were increased in the OS versus ES group when stratified by mFI. Survival analysis showed a correlation between risk of amputation, death, and composite outcome with increasing mFI (P < 0.005) in both groups. Frailty independently predicted major amputation (aHR 2.16; 1.06-4.39), mortality (aHR 2.62; 95% CI: 1.17-5.88), and composite outcome (aHR 1.97; 95% CI: 1.06-3.68) when the groups are combined. Except for absolute neutrophil count, all preoperative lab values correlated with mFI (P < 0.5). Higher albumin was independently associated with lower risk of amputation (aHR: 0.58 [0.36-0.94]) and mortality (aHR: 0.45 [0.25-0.83]); higher hemoglobin predicted limb salvage (aHR 0.7 [0.62-0.84]).

Conclusions: Frailty predicts short- and long-term outcomes after first-time revascularization in veterans. Hypoalbuminemia and anemia are associated with higher mFI and independently predict poor outcome, suggesting albumin and hemoglobin are viable biomarkers of frailty in veterans.
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http://dx.doi.org/10.1016/j.jss.2019.06.040DOI Listing
November 2019

Regulation of tumor angiogenesis and mesenchymal-endothelial transition by p38α through TGF-β and JNK signaling.

Nat Commun 2019 07 11;10(1):3071. Epub 2019 Jul 11.

Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, 08028, Barcelona, Spain.

The formation of new blood vessels is essential for normal development, tissue repair and tumor growth. Here we show that inhibition of the kinase p38α enhances angiogenesis in human and mouse colon tumors. Mesenchymal cells can contribute to tumor angiogenesis by regulating proliferation and migration of endothelial cells. We show that p38α negatively regulates an angiogenic program in mesenchymal stem/stromal cells (MSCs), multipotent progenitors found in perivascular locations. This program includes the acquisition of an endothelial phenotype by MSCs mediated by both TGF-β and JNK, and negatively regulated by p38α. Abrogation of p38α in mesenchymal cells increases tumorigenesis, which correlates with enhanced angiogenesis. Using genetic models, we show that p38α regulates the acquisition of an endothelial-like phenotype by mesenchymal cells in colon tumors and damage tissue. Taken together, our results indicate that p38α in mesenchymal cells restrains a TGF-β-induced angiogenesis program including their ability to transdifferentiate into endothelial cells.
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http://dx.doi.org/10.1038/s41467-019-10946-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6624205PMC
July 2019

Hybrid endovascular exclusion of a bleeding innominate artery pseudoaneurysm in a patient with no open surgical options.

J Vasc Surg Cases Innov Tech 2019 Jun 28;5(2):132-135. Epub 2019 Apr 28.

Division of Vascular Surgery and Endovascular Services, SUNY Upstate University, Syracuse, NY.

Mycotic pseudoaneurysms (MPs) rarely affect the aortic arch vessels and usually require surgical resection for definitive treatment. In this case, a 58-year-old woman developed a bleeding innominate artery MP after primary lung cancer resection complicated by an infected chest wound. Because of her previous surgery, irradiation, and chest wall reconstruction, she was not a candidate for open resection. A hybrid endovascular approach successfully excluded her innominate artery MP through placement of an aortic arch stent graft. Cerebral circulation was maintained through a periscoped left common carotid artery stent graft to the descending thoracic aorta graft, which supplied a left-to-right carotid-carotid bypass.
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http://dx.doi.org/10.1016/j.jvscit.2018.12.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6529683PMC
June 2019

Neutrinoless Double-β Decay with Nonstandard Majoron Emission.

Phys Rev Lett 2019 May;122(18):181801

AHEP Group, Instituto de Física Corpuscular-CSIC/Universitat de València Edificio de Institutos de Paterna, Apartado 22085, E-46071 València, Spain.

We present a novel mode of neutrinoless double-β decay with emission of a light Majoron-like scalar particle ϕ. We assume it couples via an effective seven-dimensional operator with a (V+A) lepton current and (V±A) quark currents leading to a long-range contribution that is unsuppressed by the light neutrino mass. We calculate the total double-β decay rate and determine the fully differential shape for this mode. We find that future double-β decay searches are sensitive to scales of the order Λ_{NP}≈1  TeV for the effective operator and a light scalar m_{ϕ}<0.2  MeV, based on ordinary double-β decay Majoron searches. The angular and energy distributions can deviate considerably from that of two-neutrino double-β decay, which is the main background. We point out possible ultraviolet completions where such an effective operator can emerge.
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http://dx.doi.org/10.1103/PhysRevLett.122.181801DOI Listing
May 2019

Drug treatment of type 2 diabetes: Its cost is significantly associated with HbA1c levels.

Int J Clin Pract 2019 Apr 21;73(4):e13336. Epub 2019 Mar 21.

CENEXA. Center of Experimental and Applied Endocrinology (UNLP-CONICET), School of Medicine, National University of La Plata, La Plata, Argentina.

Aims: To examine the relationship between costs of hyperglycaemia drug treatment and glycemic control amongst people with type 2 diabetes (T2D).

Methods: This observational study utilised data from the QUALIDIAB database on 3,452 T2D patients seen in Diabetes Centers in Argentina. Patients were classified according to their HbA1c value into two groups: on target (OT; HbA1c ≤ 7%), and not on target (NOT; HbA1c > 7%); within each category we considered clinical and metabolic indicators, as well as type of hyperglycaemia treatment. Monthly expenditure on drugs was estimated by micro-costing. Multivariable regression analysis was used to evaluate the association between cost of hyperglycaemia treatment and HbA1c values.

Results: In total, 48.9% of the participants have HbA1c OT values. Overall monthly per capita costs of this treatment increased significantly (134%) in the NOT group. Multivariable regression analysis showed that expenditure for hyperglycaemia drugs treatment was significant associated with glycemic control (OR: 0.705), diabetes duration (OR: 1.017), systolic blood pressure (OR: 1.006) and treatment of T2D (OR: 2.622).

Conclusions: HbA1c NOT significantly increases drugs monthly cost of hyperglycaemia treatment in people with T2D in a country with an emerging market economy.
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http://dx.doi.org/10.1111/ijcp.13336DOI Listing
April 2019

A laboratory work to introduce biochemistry undergraduate students to basic enzyme kinetics-alkaline phosphatase as a model.

Biochem Mol Biol Educ 2019 01 21;47(1):93-99. Epub 2018 Dec 21.

Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas, IQUIFIB, Facultad de Farmacia y Bioquímica, Departamento de Química Biológica, Buenos Aires, Argentina.

Enzyme kinetics is an essential topic in undergraduate Biochemistry courses. A laboratory work that covers the principal basic concepts of enzyme kinetics in steady state is presented. The alkaline phosphatase catalyzed reaction of phenyl-phosphate hydrolysis was studied as a model. The laboratory experience was designed to reinforce the concepts of initial velocity dependence on substrate and enzyme concentration, and to highlight the importance of the accurate determination of initial reaction rate. The laboratory work consists in two parts, in which students first determine the enzyme concentration and the time to be used in the following session to obtain the kinetic parameters (K and V ) by non-lineal fitting of the Michaelis-Menten equation to the initial velocity dependence with substrate concentration results. The experimental methodology is robust, the cost per student is low and the equipment and reagents used are of easy access. © 2018 International Union of Biochemistry and Molecular Biology, 47(1):93-99, 2018.
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http://dx.doi.org/10.1002/bmb.21195DOI Listing
January 2019

[A front-of-pack labelling system for food and beverages for Mexico: a strategy of healthy decision-making.]

Salud Publica Mex 2018 Jul-Ago;60(4):479-486

Instituto Nacional de Salud Pública. Morelos, México.

The Mexican Ministry of Health requested the National Institute of Public Health to constitute a group of independent, free of conflict-of-interest academic experts on front-of-pack labelling (FOP). This group was instructed to created a positioning paper to contribute to the development of a FOP system for industrialized products that offers useful information for purchase decision making. This position paper uses the best available scientific evidence, and recommendations from experts of international organizations. The FOP proposal focuses on the contents of energy, nutrients, ingredients and components that if consumed in excess on the diet, can be harmful to people's health, such as added sugars, sodium, total fat, saturated fat and energy. The academic expert group recommends the implementation of a FOP that provides an easy way to quickly assess the quality of a product. It is essential that this FOP provides direct, simple, visible and easily understandable information.
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http://dx.doi.org/10.21149/9615DOI Listing
February 2019

Outcomes following operative management of thoracic outlet syndrome in the pediatric patients.

Vascular 2018 Aug 4;26(4):410-417. Epub 2018 Jan 4.

1 Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houstan, TX, USA.

Objectives Thoracic outlet syndrome, a condition commonly reported in adults, occurs infrequently in the pediatric population. The objective of this study was to assess the outcome of surgical interventions of thoracic outlet syndrome in pediatric patients. Methods Clinical records of all pediatric patients with thoracic outlet syndrome who underwent operative repair from 2002 to 2015 in a tertiary pediatric hospital were reviewed. Pertinent clinical variables and treatment outcomes were analyzed. Results Sixty-eight patients underwent a total of 72 thoracic outlet syndrome operations (mean age 15.7 years). Venous, neurogenic, and arterial thoracic outlet syndromes occurred in 39 (57%), 21 (31%), and 8 (12%) patients, respectively. Common risk factors for children with venous thoracic outlet syndrome included sports-related injuries (40%) and hypercoagulable disorders (33%). Thirty-five patients (90%) with venous thoracic outlet syndrome underwent catheter-based interventions followed by surgical decompression. All patients underwent first rib resection with scalenectomy via either a supraclavicular approach (n = 60, 88%) or combined supraclavicular and infraclavicular incisions (n = 8, 12%). Concomitant temporary arteriovenous fistula creation was performed in 14 patients (36%). Three patients with arterial thoracic outlet syndrome underwent first rib resection with concomitant subclavian artery aneurysm repair. The mean follow-up duration was 38.4 ± 11.6 months. Long-term symptomatic relief was achieved in 94% of patients. Conclusions Venous thoracic outlet syndrome is the most common form of thoracic outlet syndrome in children, followed by neurogenic and arterial thoracic outlet syndromes. Competitive sports-related injuries remain the most common risk factor for venous and neurogenic thoracic outlet syndromes. Temporary arteriovenous fistula creation was useful in venous thoracic outlet syndrome patients in selective children. Surgical decompression provides durable treatment success in children with all subtypes of thoracic outlet syndrome.
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http://dx.doi.org/10.1177/1708538117747628DOI Listing
August 2018

Relation between cost of drug treatment and body mass index in people with type 2 diabetes in Latin America.

PLoS One 2017 20;12(12):e0189755. Epub 2017 Dec 20.

CENEXA. Center of Experimental and Applied Endocrinology (UNLP-CONICET La Plata), School of Medicine, National University of La Plata, La Plata, Argentina.

Aims: Despite the frequent association of obesity with type 2 diabetes (T2D), the effect of the former on the cost of drug treatment of the latest has not been specifically addressed. We studied the association of overweight/obesity on the cost of drug treatment of hyperglycemia, hypertension and dyslipidemia in a population with T2D.

Methods: This observational study utilized data from the QUALIDIAB database on 3,099 T2D patients seen in Diabetes Centers in Argentina, Chile, Colombia, Peru, and Venezuela. Data were grouped according to body mass index (BMI) as Normal (18.5≤BMI<25), Overweight (25≤BMI<30), and Obese (BMI≥30). Thereafter, we assessed clinical and metabolic data and cost of drug treatment in each category. Statistical analyses included group comparisons for continuous variables (parametric or non-parametric tests), Chi-square tests for differences between proportions, and multivariable regression analysis to assess the association between BMI and monthly cost of drug treatment.

Results: Although all groups showed comparable degree of glycometabolic control (FBG, HbA1c), we found significant differences in other metabolic control indicators. Total cost of drug treatment of hyperglycemia and associated cardiovascular risk factors (CVRF) increased significantly (p<0.001) with increment of BMI. Hyperglycemia treatment cost showed a significant increase concordant with BMI whereas hypertension and dyslipidemia did not. Despite different values and percentages of increase, this growing cost profile was reproduced in every participating country. BMI significantly and independently affected hyperglycemia treatment cost.

Conclusions: Our study shows for the first time that BMI significantly increases total expenditure on drugs for T2D and its associated CVRF treatment in Latin America.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0189755PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5738071PMC
January 2018

Echocardiographic assessment with right ventricular function improvement following ultrasound-accelerated catheter-directed thrombolytic therapy in submassive pulmonary embolism.

Vascular 2018 Jun 24;26(3):271-277. Epub 2017 Sep 24.

1 Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, USA.

Introduction The objective of this study was to evaluate the efficacy of ultrasound-accelerated catheter-directed thrombolytic therapy in patients with submassive pulmonary embolism. Methods Clinical records of 46 patients with submassive pulmonary embolism who underwent ultrasound-accelerated catheter-directed pulmonary thrombolysis using tissue plasminogen activator, from 2007 to 2017, were analyzed. All patients experienced clinical symptoms with computed tomography evidence of pulmonary thrombus burden. Right ventricular dysfunction was present in all patients by echocardiographic finding of right ventricle-to-left ventricle ratio > 0.9. Treatment outcome, procedural complications, right ventricular pressures, and thrombus clearance were evaluated. Follow-up evaluation included echocardiographic assessment of right ventricle-to-left ventricle ratio at one month, six months, and one year. Results Technical success was achieved in all patients ( n = 46, 100%). Our patients received an average of 18.4 ± 4.7 mg of tissue plasminogen activator using ultrasound-accelerated thrombolytic catheter with an average infusion time of 16.5± 5.4 h. Clinical success was achieved in all patients (100%). Significant reduction of mean pulmonary artery pressure occurred following the treatment, which decreased from 36 ± 8 to 21 ± 5 mmHg ( p < 0.001). There were no major bleeding complications. All-cause mortality at 30 days was 0%. No patient developed recurrent pulmonary embolism during follow-up. During the follow-up period, 43 patients (93%) showed improvement of right ventricular dysfunction based on echocardiographic assessment. The right ventricle-to-left ventricle ratio decreased from 1.32 ± 0.18 to 0.91 ± 0.13 at the time of hospital discharge ( p < 0.01). The right ventricular function remained improved at 6 months and 12 months of follow-up, as right ventricle-to-left ventricle ratio were 0.92 ± 0.14 ( p < 0.01) and 0.91 ± 0.15 ( p < 0.01), respectively. Conclusion Ultrasound-accelerated catheter-directed thrombolysis is a safe and efficacious treatment for submassive pulmonary embolism. It reduces pulmonary hypertension and improves right ventricular function in patients with submassive pulmonary embolism.
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http://dx.doi.org/10.1177/1708538117733645DOI Listing
June 2018

Mixed micelles for encapsulation of doxorubicin with enhanced in vitro cytotoxicity on breast and ovarian cancer cell lines versus Doxil.

Biomed Pharmacother 2017 Nov 10;95:894-903. Epub 2017 Sep 10.

Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Cátedra de Tecnología Farmacéutica I, Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina. Electronic address:

Doxorubicin (DOX) is used as a "first-line" antineoplastic drug in ovarian and metastatic breast cancer. However, serious side effects, such as cardiotoxicity have been reported after DOX intravenous administration. Hence, we investigated different micelle-former biomaterials, as Soluplus, Pluronic F127, Tetronic T1107 and d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) to develop a potential mixed micellar nanocarrier for DOX delivery. Since DOX hydrochloride is a poor candidate to be encapsulated inside the hydrophobic core of the mixed micelles, we assayed a hydrophobic complex between DOX and sodium deoxycholate (NaDC) as an excellent candidate to be encapsulated within polymeric micelles. The combination of T1107:TPGS (1:3, weight ratio) demonstrated the best physicochemical properties together with a high DL capacity (6.43% w/v). Particularly, DOX in vitro release was higher at acidic tumour microenvironment pH value (5.5) than at physiological counterpart (7.4). The hydrodynamic diameter of the DOX/NaDC-loaded mixed micellar system was 10.7nm (PDI=0.239). The in vitro cytotoxicity of the mixed micellar formulation resulted significantly (p<0.05) higher than Doxil against ovarian (SKOV-3) and triple-negative breast cancer cells (MDA-MB- 231). Further, the in vitro cellular uptake assays demonstrated a significant increment (p<0.05) of the DOX intracellular content for the mixed micelles versus Doxil for both, SKOV-3 (at 2, 4 and 6h of incubation) and MDA-MB-231 (at 4h of incubation) cells. These findings suggest that T1107:TPGS (1:3) mixed micelles could be employed as a potential nanotechnological platform for drug delivery of DOX.
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http://dx.doi.org/10.1016/j.biopha.2017.09.006DOI Listing
November 2017

Diabetes primary prevention program: New insights from data analysis of recruitment period.

Diabetes Metab Res Rev 2018 01 19;34(1). Epub 2017 Oct 19.

Faculty of Medical Sciences (UNLP), CENEXA Center for Experimental and Applied Endocrinology (UNLP-CONICET La Plata), La Plata, Argentina.

Background: Primary Prevention of Diabetes Program in Buenos Aires Province evaluates the effectiveness of adopting healthy lifestyle to prevent type 2 diabetes (T2D) in people at high risk of developing it. We aimed to present preliminary data analysis of FINDRISC and laboratory measurements taken during recruitment of people for the Primary Prevention of Diabetes Program in Buenos Aires Province in the cities of La Plata, Berisso, and Ensenada, Argentina.

Methods: People were recruited through population approach (house-to-house survey by FINDRISC in randomized areas) and opportunistic approach (FINDRISC completed by participants during consultations for nonrelated prediabetes/diabetes symptoms in public and private primary care centres of cities involved). In people with FINDRISC score ≥ 13 points, we evaluated blood concentrations of HbA , creatinine, lipids, and an oral glucose tolerance test (OGTT).

Results: Approximately 3415 individuals completed the FINDRISC populational survey and 344 the opportunistic survey; 43% of the 2 groups scored over 13 points; 2.8 and 75.4% of them, respectively, took the prescribed OGTT. Approximately 53.7% of the OGTT showed normal values and 5.2% unknown T2D. The remaining cases showed 69.5% impaired fasting glucose, 13.6% impaired glucose tolerance, and 16.9% both impairments. HbA values showed significant differences compared with normal glucose tolerance (4.96 ± 0.43%), prediabetes (5.28 ± 0.51%), and T2D (5.60 ± 0.51%). Participants with prediabetes and T2D showed a predominant increase in low-density lipoprotein-cholesterol values. In prediabetes, >50% showed insulin resistance.

Conclusions: People with prediabetes/T2D had dyslipidemia associated with insulin resistance, which promotes the development of T2D and cardiovascular disease. Thus, it merits its appropriate treatment.
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http://dx.doi.org/10.1002/dmrr.2943DOI Listing
January 2018

Corrigendum to ''A glucose-targeted mixed micellar formulation outperforms Genexol in breast cancer cells'' [Euro. J. Pharmaceut. Biopharmaceut. 114 (2017) 305-316].

Eur J Pharm Biopharm 2017 10 26;119:454. Epub 2017 Jul 26.

Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Cátedra de Tecnología Farmacéutica I, Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina. Electronic address:

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http://dx.doi.org/10.1016/j.ejpb.2017.07.008DOI Listing
October 2017

The Handy Approach - Quick Integrated Person Centred Support Preparation.

BMJ Qual Improv Rep 2017 7;6(1). Epub 2017 Jun 7.

East London NHS Foundation Trust.

Cost effective care requires comprehensive person-centred formulation of solutions. The East London NHS Foundation Trust Community Health Services in Newham have piloted models of Integrated Care called 'Virtual Wards' which aim to keep people living with multiple long-term conditions, well at home by minimising system complexity. These Virtual Wards comprise Interdisciplinary Teams (IDTs) with a General Practitioner (GP) seconded to provide leadership. Historically assessments have been dominated by biomedical approaches with disability emphasised over personal aspirations and ability. New professional skills are needed to organise information from diverse approaches into a common framework, which can enable agreed goals of care to be delivered collaboratively. From June 2014 to January 2016 we aimed to improve the documentation of person-centred goals of care in 100% of our assessments. Change ideas were tested and team development addressed to improve documentation of aspirations for care for people being referred and if achieved, then to test ideas to improve coproduction of care. Change ideas included Enhanced Clinical Supervision (ECS) by a GP with additional expert skills; Flash Teaching (FT) defined as five-minute weekly discussion on topics generated from the case-mix to develop a shared understanding of Integrated Care; Structured Formulation using a novel, quick, integrated assessment framework called the Handy Approach (HA) with the hand as a memory prompt to bring the personal together with the mental, social and physical domains and finally we tested focusing on 'Team Primacy' (mutual regard within the team) to embed behaviour change. 181 cases were tracked and documentation of personal aspirations for care by case showed: ECS 0/21 (0%); FT 5/50 (10%); ECS/FT plus the HA 35/83 (42%); Team Primacy plus ECS/FT/HA 27/27 (100%). By January 2016 prompted by using the Handy Approach in a highly functional team, all members of the IDT consistently documented personal aspirations.
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http://dx.doi.org/10.1136/bmjquality.u214461.w5681DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5483530PMC
June 2017

Improving diabetes care at primary care level with a multistrategic approach: results of the DIAPREM programme.

Acta Diabetol 2017 Sep 17;54(9):853-861. Epub 2017 Jun 17.

CENEXA Centro de Endocrinología Experimental y Aplicada (UNLP-CONICET), Facultad de Ciencias Médicas (UNLP), 60 y 120, 1900, La Plata, Argentina.

Aim: To present results, 1 year postimplementation at primary care level, of an integrated diabetes care programme including systemic changes, education, registry (clinical, metabolic, and therapeutic indicators), and disease management (DIAPREM).

Methods: We randomly selected and trained 15 physicians and 15 nurses from primary care units of La Matanza County (intervention-IG) and another 15 physicians/nurses to participate as controls (control-CG). Each physician-nurse team controlled and followed up 10 patients with type 2 diabetes for 1 year; both groups used structured medical records. Patients in IG had quarterly clinical appointments, whereas those in CG received traditional care. Statistical data analysis included parametric/nonparametric tests according to data distribution profile and Chi-squared test for proportions.

Results: After 12 months, the dropout rate was significantly lower in IG than in CG. Whereas in IG HbA1c, blood pressure and lipid profile levels significantly decreased, no changes were recorded in CG. Drug prescriptions showed no significant changes in IG except a decrease in oral monotherapy.

Conclusions: DIAPREM is an expedient and simple multistrategic model to implement at the primary care level in order to decrease patient dropout and improve control and treatment adherence, and quality of care of people with diabetes.
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http://dx.doi.org/10.1007/s00592-017-1016-8DOI Listing
September 2017