Helena Vala | Polytechnic Institute of Viseu (original) (raw)

de Lemos by Helena Vala

This study was performed to assess the effect of chronic low-dose sitagliptin, a dipeptidyl pepti... more This study was performed to assess the effect of chronic low-dose sitagliptin, a dipeptidyl peptidase 4 inhibitor, on metabolic profile and on renal lesions aggravation in a rat model of type-2 diabetic nephropathy, the Zucker diabetic fatty (ZDF) rat. Diabetic and obese ZDF (fa/fa) rats and their controls ZDF (+/+) were treated for 6 weeks with vehicle (control) or sitagliptin (10 mg/kg/bw).Blood/serum glucose, HbA1c, insulin, Total-c, TGs, urea, and creatinine were assessed, as well as kidney glomerular and tubulointerstitial lesions (interstitial fibrosis/tubular atrophy), using a semiquantitative rating from 0 (absent/normal) to 3 (severe and extensive damage). Vascular lesions were scored from 0–2. Sitagliptin in the diabetic rats promoted an amelioration of glycemia, HbA1c, Total-c, and TGs, accompanied by a partial prevention of insulinopenia. Furthermore, together with urea increment prevention,renal lesions were ameliorated in the diabetic rats, including glomerular, tubulointerstitial, and vascular lesions, accompanied by reduced lipid peroxidation. In conclusion, chronic low-dose sitagliptin treatment was able to ameliorate diabetic nephropathy,which might represent a key step forward in the management of T2DM and this serious complication.

Papers by Helena Vala

A Bird's-Eye View of Veterinary Medicine, 2012

Emphasis will be given to the difficulties faced by the veterinary pathologist every day, in orde... more Emphasis will be given to the difficulties faced by the veterinary pathologist every day, in order to justify the development of new solutions to support the issuance of more accurate diagnoses. The authors describe a framework and a software system that can be useful for diagnosing diseases. The developed framework is based on analysis of the bibliography in this field. Both proposals can be useful to yield better diagnoses. Pathological diagnosis is a supplementary diagnostic test usually ordered by the veterinarian clinician, in order to direct treatment to administer to the sick animal, or living members of a group of animals (e.g. cattle), in which a death occurred. Thus, although the methods used are similar to those used in human medicine, the ends are quite different.

No presente trabalho são enumeradas as principais situações em que é fundamental recorrer ao labo... more No presente trabalho são enumeradas as principais situações em que é fundamental recorrer ao laboratório, os principais métodos de colheita de amostras a partir do animal vivo e sua execução.

Journal of Proteomics, 2016

Although the applications of Proteomics in Human Biomedicine have been explored for some time now... more Although the applications of Proteomics in Human Biomedicine have been explored for some time now, in animal and veterinary research, the potential of this resource has just started to be explored, especially when companion animal health is considered. In the last years, knowledge on the Canis lupus familiaris proteome has been accumulating in the literature and a resource compiling all this information and critically reviewing it was lacking. This article presents such a resource for the first time. CanisOme is a database of all proteins identified in Canis lupus familiaris tissues, either in health or in disease, annotated with information on the proteins present on the sample and on the donors. This database reunites information on 549 proteins, associated with 63 dog diseases and 33 dog breeds. Examples of how this information may be used to produce new hypothesis on disease mechanisms is presented both through the functional analysis of the proteins quantified in canine cutaneous mast cell tumors and through the study of the interactome of C. lupus familiaris and Leishmania infantum. Therefore, the usefulness of CanisOme for researchers looking for protein biomarkers in dogs and interested in a comprehensive analysis of disease mechanisms is demonstrated. This paper presents CanisOme, a database of proteomic studies with relevant protein annotation, allowing the enlightenment of disease mechanisms and the discovery of novel disease biomarkers for C. lupus familiaris. This knowledge is important not only for the improvement of animal health but also for the use of dogs as models for human health studies.

Introduction: Tools to store and catalog proteins identified in proteome surveys of tissues from ... more Introduction: Tools to store and catalog proteins identified in proteome surveys of tissues from subjects representing different physiological and pathological states are powerful instruments to integrate published information. Much of the information on molecular mechanisms can be generated using bioinformatics strategies powered by this tools. Within the scope of previous projects a database named OralOme was built, dedicated to the storage of all the information on the proteins of the human oral cavity. This database is available through the web interface OralCard. Objective: The present study aims the development of a database transferring the methodology used in humans to the storage and cataloguing of the proteins present in the oral cavity and other tissues of Ovis aries. This database will be essential to develop diagnosis methods to be applied to living animals targeting the most prevalent diseases affecting the flocks in Serra da Estrela region. Methods: The development of...

BioMed Research International, 2014

Protocols of conversion from cyclosporin A (CsA) to sirolimus (SRL) have been widely used in immu... more Protocols of conversion from cyclosporin A (CsA) to sirolimus (SRL) have been widely used in immunotherapy after transplantation to prevent CsA-induced nephropathy, but the molecular mechanisms underlying these protocols remain nuclear. This study aimed to identify the molecular pathways and putative biomarkers of CsA-to-SRL conversion in a rat model. Four animal groups ( = 6) were tested during 9 weeks: control, CsA, SRL, and conversion (CsA for 3 weeks followed by SRL for 6 weeks). Classical and emergent serum, urinary, and kidney tissue (gene and protein expression) markers were assessed. Renal lesions were analyzed in hematoxylin and eosin, periodic acid-Schiff, and Masson's trichrome stains. SRL-treated rats presented proteinuria and NGAL (serum and urinary) as the best markers of renal impairment. Short CsA treatment presented slight or even absent kidney lesions and TGF-, NF-, mTOR, PCNA, TP53, KIM-1, and CTGF as relevant gene and protein changes. Prolonged CsA exposure aggravated renal damage, without clear changes on the traditional markers, but with changes in serums TGF-and IL-7, TBARs clearance, and kidney TGF-and mTOR. Conversion to SRL prevented CsA-induced renal damage evolution (absent/mild grade lesions), while NGAL (serum versus urine) seems to be a feasible biomarker of CsA replacement to SRL.

Diabetology & Metabolic Syndrome, 2014

Background: The purpose of this study was to investigate some of the possible mechanisms underlyi... more Background: The purpose of this study was to investigate some of the possible mechanisms underlying the protective effects of a dipeptidyl peptidase IV (DPP-IV) inhibitor, sitagliptin, on pancreatic tissue in an animal model of type 2 diabetes mellitus (T2DM), the Zucker Diabetic Fatty (ZDF) rat, focusing on glycaemic, insulinic and lipidic profiles, as well as, on apoptosis, inflammation, angiogenesis and proliferation mediators. Methods: Male obese diabetic ZDF (fa/fa) rats, aged 20 weeks, were treated with sitagliptin (10 mg/kg bw/day) during 6 weeks and compared to untreated diabetic and lean control littermates. Metabolic data was evaluated at the beginning and at the end of the treatment, including glycaemia, HbA1c, insulinaemia, HOMA-beta and TGs. Endocrine and exocrine pancreas lesions were assessed semiquantitatively by histopathological methods. Pancreas gene (mRNA) and protein expression of mediators of apoptotic machinery, inflammation and angiogenesis/ proliferation (Bax, Bcl2, IL-1β, VEGF, PCNA and TRIB3) were analyzed by RT-qPCR and/or by immunohistochemistry. Results: Sitagliptin treatment for 6 weeks (between 20 and 26 week-old) was able to significantly (p < 0.001) ameliorate all the metabolic parameters, by preventing the increase in blood glucose and in serum TGs contents (16.54% and 37.63%, respectively, vs untreated), as well as, by preventing the decrease in serum insulin levels and in the functional beta cells capacity accessed via HOMA-beta index (156.28% and 191.74%, respectively, vs untreated). Sitagliptin-treated diabetic rats presented a reduced pancreas Bax/Bcl2 ratio, suggestive of an antiapoptotic effect; in addition, sitagliptin was able to completely reduce (p < 0.001) the pancreas overexpression of IL-1β and TRIB3 found in the untreated diabetic animals; and promoted a significant (p < 0.001) overexpression of VEGF and PCNA.

Journal of veterinary emergency and critical care (San Antonio, Tex. : 2001), Jan 16, 2016

To determine the effect of fluid resuscitation with 2 different physiological solutions, Ringer&#... more To determine the effect of fluid resuscitation with 2 different physiological solutions, Ringer's lactate (RL) and hydroxyethyl starch (HES) 130/0.4, on histological lesions of the small intestinal mucosa in anesthetized pigs subjected to severe acute bleeding. Prospective experimental study. University teaching hospital. Twenty-eight healthy Large White pigs, 3 months of age. Pigs were subjected to severe acute bleeding (30 mL/kg) under total intravenous anesthesia with propofol and remifentanil. Pigs were randomly allocated to 3 groups: Group 1 (n = 11) received RL solution (25 mL/kg) after bleeding; Group 2 (n = 11) received HES 130/0.4 solution (20 mL/kg) after bleeding; and Group 3 (n = 6) volume replacement nor induced bleeding. Pigs were euthanized and the small intestine was harvested for histopathological analysis. The small intestine was histologically evaluated and the presence of the following lesions were characterized: edema, congestion, hyperemia, hemorrhage, infl...

Epidemiology of Communicable and Non-Communicable Diseases - Attributes of Lifestyle and Nature on Humankind, 2016

Mycoses, Jan 13, 2016

We report an outbreak of dermatophytoses in rabbits, which was the origin of a dermatophytose epi... more We report an outbreak of dermatophytoses in rabbits, which was the origin of a dermatophytose epidemic in an agricultural school in central Portugal, affecting 15 people. Both the phenotypic characteristics and internal transcribed spacer (ITS) sequence of the dermatophytes isolated from the rabbits and patients were identical, suggesting that a single strain was responsible for both the epizootic and epidemic dermatophytoses and confirming that these two outbreaks were linked. The ITS sequences were also 100% identical to the ITS sequence of five strains isolated from rabbits in Greece and Italy, but different from that of Trichophyton mentagrophytes commonly isolated from dogs and cats. These results suggest that a particular T. mentagrophytes genotype could be prevalent in rabbits in southern Europe.

Medical Science Monitor International Medical Journal of Experimental and Clinical Research, Aug 1, 2007

BACKGROUND: Chronic low-grade systemic inflammation is a feature of such chronic diseases as card... more BACKGROUND: Chronic low-grade systemic inflammation is a feature of such chronic diseases as cardiovascular disease and type 2 diabetes (T2D). There is evidence that regular exercise is effective as a treatment in these situations. This study intended to assess the levels of two inflammatory mediators, C-reactive protein (CRP) and adiponectin, in Zucker Diabetic Fatty (ZDF, fa/fa) rats, an experimental model of T2D, and to determine whether exercise-induced changes in insulin resistance could be explained by modifications in these inflammation markers.MATERIAL/METHODS: Male ZDF (Gmi fa/fa) rats and their littermates (Gmi +/+), aged 8 weeks, were randomly assigned in two groups: an exercise trained and a sedentary one. Swimming was conducted 1 h/day 3 days/week for 12 weeks. The rats were sacrificed 48 h after the last round of exercise. Rats had their body weight, insulin, adiponectin, CRP, as well as glucose, total cholesterol, triglycerides, MDA, and SOD measured and HOMA-IR calculated before and after the 12-week swimming training.RESULTS: In the ZDF (fa/fa) rats underwent swimming exercise, all the metabolic abnormalities were totally or partially prevented (p<0.001), namely the hyperglycemic, hyperinsulinemic, and dyslipidemic pattern observed in their sedentary counterparts. Furthermore, even without body weight change, a plasma adiponectin increase (28.0%) and a CRP decrease (12.7%) were also observed.CONCLUSIONS: A 12-week thrice-weekly swimming training was associated with improved measures of chronic inflammation markers as measured by adiponectin and CRP. Moreover, improvements in insulin sensitivity resulting from swimming exercise appeared to be related to changes in these inflammatory mediators.

Biochimie, 2016

Anemia of chronic kidney disease (CKD) can be corrected by treatment with recombinant human eryth... more Anemia of chronic kidney disease (CKD) can be corrected by treatment with recombinant human erythropoietin (rHuEPO); however, some patients become hyporesponsive. The molecular mechanisms underlying this resistance remain to be elucidated. Our aim was to study hyporesponsiveness to rHuEPO therapy using the remnant kidney rat model of anemia associated with CKD induced by 5/6 nephrectomy. At starting, male Wistar rats were divided in 3 groups, for a 3-week protocol: Sham, CRF (vehicle) and two rHuEPO (200IU/kg body weight [BW]/week) treated groups; at the end of protocol, the rHuEPO treated rats were subdivided in responders (CRF200) and non-responders (CRF200NR), according to their hematologic response; blood, cellular and tissue studies were performed. The CRF200 group achieved correction of anemia, while the CRF200NR group developed anemia, after an initial response (1(st) week) to rHuEPO therapy. CRF and CRF200NR groups presented a trend to higher serum CRP levels; CRF200NR showed also high levels of renal inflammatory markers, such as interleukin (IL)-6, IL-1β, nuclear factor kappa B, connective tissue growth factor (CTGF) and transforming growth factor beta 1 (TGF-β1); no changes were found in iron metabolism. Our data suggest that the development of anemia/rHuEPO hyporesponsiveness is associated with a higher systemic and renal inflammatory condition, favoring hypoxia and triggering an increase in renal expression of HIF-1α, TGF-β1 and CTGF that will further aggravate renal fibrosis, which will enhance the inflammatory response, creating a cycle that promotes disease progression. New therapeutic strategies to reduce inflammation in CKD patients could improve the response to rHuEPO therapy and reduce hyporesponsiveness.

Life sciences, Jan 25, 2016

Our aim was to study the effect of a broad range of recombinant human erythropoietin (rHuEPO) dos... more Our aim was to study the effect of a broad range of recombinant human erythropoietin (rHuEPO) doses on hematological and biochemical parameters, blood pressure (BP), renal function and damage in the rat, focusing on endothelial nitric oxide synthase (eNOS) and hypoxia-inducible factors (HIFs). Male Wistar rats were divided in 5 groups receiving different doses of rHuEPO (100, 200, 400 and 600IU/kg body weight (BW)/week) and saline solution (control), during 3weeks. Blood and 24h urine were collected to perform hematological and biochemical analysis. BP was measured by the tail-cuff method. Kidney tissue was collected to mRNA and protein expression assays and to characterize renal lesions. A dose-dependent increase in red blood cells count, hematocrit and hemoglobin levels was found with rHuEPO therapy, in rHuEPO200, rHuEPO400 and rHuEPO600 groups. Increased reticulocyte count was found in rHuEPO400 and rHuEPO600 groups. BP raised in all groups receiving rHuEPO. The rHuEPO200 and rHu...

Vector-Borne and Zoonotic Diseases, 2016

Between November and December of 2014, a serosurvey was set up to evaluate the presence of Schmal... more Between November and December of 2014, a serosurvey was set up to evaluate the presence of Schmallenberg virus (SBV) antibodies in sheep of Portugal. Sera (n = 1068) were tested using an indirect enzyme linked immunosorbent assay (ID Screen(®) Schmallenberg virus indirect, IDvet Innovative Diagnostics, Montpellier, France). The estimated occurrence of immunogobulin G (IgG) antibodies against SBV in sheep of Portugal was 12.8% (95% confidence interval 11.0-15.0%). This is the first study reporting the presence of SBV antibodies in sheep of Portugal.

A Bird's-Eye View of Veterinary Medicine, 2012

Journal of Proteomics, 2016

BioMed Research International, 2014

Diabetology & Metabolic Syndrome, 2014

Journal of veterinary emergency and critical care (San Antonio, Tex. : 2001), Jan 16, 2016

Epidemiology of Communicable and Non-Communicable Diseases - Attributes of Lifestyle and Nature on Humankind, 2016

Mycoses, Jan 13, 2016

Medical Science Monitor International Medical Journal of Experimental and Clinical Research, Aug 1, 2007

Biochimie, 2016

Life sciences, Jan 25, 2016

Vector-Borne and Zoonotic Diseases, 2016

Clinical and Experimental Pharmacology and Physiology, 2016

Clinical studies showed that high doses of recombinant human erythropoietin (rHuEPO) used to corr... more Clinical studies showed that high doses of recombinant human erythropoietin (rHuEPO) used to correct anaemia in chronic kidney disease (CKD) hyporesponsive patients may lead to deleterious effects. The aim of this study was to analyze the effects of rHuEPO in doses usually used to correct CKD-anaemia (100, 200 IU/kg body weight (BW) per week) and in higher doses used in the treatment of hyporesponsive patients (400, 600 IU/kg BW per week), focusing on renal damage, hypoxia, inflammation and fibrosis. Male Wistar rats with chronic renal failure (CRF) induced by 5/6 nephrectomy were treated with rHuEPO or with vehicle, over a 3-week period. Haematological, biochemical and renal function analyses were performed. Kidney and liver mRNA levels were evaluated by quantitative real-time polymerase chain reaction (qPCR) and protein expression by Western blot and immunohistochemistry. Kidney histopathological evaluations were also performed. The CRF group developed anaemia, hypertension and a high score of renal histopathologic lesions. Correction of anaemia was achieved with all rHuEPO doses, with improvement in hypertension, renal function and renal lesions. In addition, the higher rHuEPO doses also improved inflammation. Blood pressure was reduced in all rHuEPO-treated groups, compared to the CRF group, but increased in a dose-dependent manner. The current study showed that rHuEPO treatment corrected anaemia and improved urinary albumin excretion, particularly at lower doses. In addition, it is suggested that a short-term treatment with high doses, used to overcome an episode of hyporesponsiveness to rHuEPO therapy, can present benefits by reducing inflammation, without worsening of renal lesions; however, the pro-hypertensive effect should be considered, and carefully managed to avoid a negative cardiorenal impact.