Browsing by Author "Venâncio, Carlos"
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- Aloysia citrodora extract as a chemopreventive agent against HPV16-induced lesions: findings from K14-HPV16 micePublication . Medeiros-Fonseca, Beatriz; Faustino-Rocha, Ana I.; Silva, Jéssica; Silva, Mónica G.; Pires, Maria João; Neuparth, Maria João; Vala, Helena; C, Vasconcelos-Nóbrega; Dias, Maria I.; Barros, Lillian; Gonçalves, Lio; Gaivão, Isabel; Bastos, Margarida M. S. M.; Félix, Luís; Venâncio, Carlos; Medeiro, Rui; Costa, Rui M. Gil da; Oliveira, Paula A.Aim: Aloysia citrodora has a long history of traditional use in treating various ailments. This study evaluated the in vivo chemopreventive efficacy and systemic toxicity of an extract of A. citrodora in a transgenic mouse model of HPV16 (human papillomavirus type 16)-induced cancer. Methods: The experiment involved six groups (n = 5): group 1 (G1, wild-type (WT), water), group 2 (G2, HPV, water), group 3 (G3, WT, 0.013 g/mL), group 4 (G4, HPV, 0.006 g/mL), group 5 (G5, HPV, 0.008 g/mL), and group 6 (G6, HPV, 0.013 g/mL). Throughout the assay, humane endpoints, body weight, food, and water consumption were recorded weekly. The internal organs and skin of the mice were collected for analysis after they were sacrificed. Toxicological parameters that were studied included hematological and biochemical blood markers, splenic and hepatic histology, and hepatic oxidative stress. Results: A. citrodora extract seems to reduce the incidence of dysplastic and in situ carcinoma skin lesions induced by HPV16 in this model, suggesting that dietary supplementation with concentrations of 0.008 g/mL and 0.013 g/mL may have beneficial chemopreventive effects. Conclusions: The extract did not induce any concentration-dependent toxicological effects on any of the parameters included in the study, indicating a favorable toxicological profile under these experimental conditions.
- Evaluation of renal injury caused by acute volume replacement with hydroxyethyl starch 130/0.4 or Ringer's lactate solution in pigsPublication . Ferreira, David A.; Cruz, Rita; Venâncio, Carlos; Faustino-Rocha, Ana I.; Silva, Aura; Mesquita, João; Ortiz, Ana L.; Vala, HelenaThis work aimed to evaluate the effects on renal tissue integrity after hydroxyethyl starch (HES) 130/0.4 and Ringer’s lactate (RL) administration in pigs under general anesthesia after acute bleeding. A total of 30 mL/kg of blood were passively removed from the femoral artery in two groups of Large White pigs, under total intravenous anesthesia with propofol and remifentanil. After bleeding, Group 1 (n =11) received RL solution (25 mL/kg) and Group 2 (n = 11) received HES 130/0.4 solution (20 mL/kg). Additionally, Group 3 (n = 6) was not submitted to bleeding or volume replacement. Pigs were euthanized and kidneys were processed for histopathological and immunohistochemical analyses. Minimal to moderate glomerular, tubular, and interstitial changes, as well as papillary necrosis, were observed in all experimental groups. Pre-apoptosis and apoptosis indicators were higher in pigs that received HES 130/0.4, indicating a higher renal insult. Both HES 130/0.4 and RL administration may cause renal injury, although renal injury may be more significant in pigs receiving HES 13/0.4. Results also suggest that total intravenous anesthesia with propofol and remifentanil may cause renal injury, and this effect can be dose related.
- Exploring the therapeutic potential of Quercus ilex acorn extract in papillomavirus-induced lesionsPublication . Medeiros-Fonseca, Beatriz; Faustino-Rocha, Ana I.; Pires, Maria João; Neuparth, Maria João; Vala, Helena; Nóbrega, Carmen; Gouvinhas, Irene; Barros, Ana Novo; Dias, Maria Inês; Barros, Lillian; Bastos, Margarida M. S. M.; Gonçalves, Lio; Félix, Luís; Venâncio, Carlos; Medeiros, Rui; Costa, Rui Miguel Gil da; Oliveira, Paula A.Background and Aim: Papillomaviruses (PVs) infections have been documented in numerous animal species across different regions worldwide. They often exert significant impacts on animal health and livestock production. Scientists have studied natural products for over half a century due to their diverse chemical composition, acknowledging their value in fighting cancer. Acorns (Quercus ilex) are believed to have several unexplored pharmacological properties. This study aimed to evaluate the in vivo safety and cancer chemopreventive activity of an infusion extract of Q. ilex in a transgenic mouse model of human PV (HPV)-16, which developed squamous cell carcinomas through a multistep process driven by HPV16 oncogenes. Materials and Methods: Q. ilex extract was prepared by heating in water at 90°C and then characterized by mass spectrometry. Phenolic compounds from this extract were administered in drinking water to female mice in three different concentrations (0.03, 0.06, and 0.09 g/mL) over a period of 28 consecutive days. Six groups (n = 6) were formed for this study: group 1 (G1, wildtype [WT], water), group 2 (G2, HPV, water), group 3 (G3, WT, 0.09 g/mL), group 4 (G4, HPV, 0.03 g/mL), group 5 (G5, HPV, 0.06 g/ mL), and group 6 (G6, HPV, 0.09 g/mL). Throughout the experiment, humane endpoints, body weight, food intake, and water consumption were recorded weekly. Following the experimental period, all mice were sacrificed, and blood, internal organs, and skin samples were collected. Blood was used to measure glucose and microhematocrit and later biochemical parameters, such as creatinine, urea, albumin, alanine aminotransferase, and total proteins. Histological analysis was performed on skin and organ samples. Results: The administration of Q. ilex extract resulted in a statistically significant increase in relative organ weight among HPV transgenic animals, indicating adaptive biological response to the tested concentrations. Moreover, a reduction in characteristic skin lesions was observed in animals treated with the 0.06 and 0.09 g/mL extract. Conclusion: These results provide a favorable chemopreventive profile for Q. ilex extract at concentrations of 0.06 and 0.09 g/mL. This study highlights the potential of Q. ilex extract as a safe and effective therapeutic strategy against HPV16- associated lesions in transgenic mouse models. The limitation of our study was the durability of transgenic animals. As a more sensitive species, we must always be careful with the durability of the test. We intend to study concentrations of 0.06 and 0.09 g/mL for longer to further investigate their possible effects.
- Immunofluorescence method to detect apoptotic events in the duodenum after a situation of hypoperfusion – preliminary resultsPublication . Ortiz, Ana; Vala, Helena; Garcia, Carla; Cruz, Rita; Venâncio, Carlos; Silva, Aura; Ferreira, DavidBackground: Apoptosis plays a key role in intestinal injury, as response to ischemia. In this study, apoptosis in the duodenum after haemorrhage and volume replacement was evaluated with M30, in a pig model. Material and methods: Apoptosis was evaluated in paraffin sections of duodenum from pigs that underwent total intravenous anaesthesia (TIVA) with propofol and remifentanil, and controlled bleeding and volume replacement using Ringer’s lactate (Group1, n=6). Apoptosis was also evaluated in a control group of animals that underwent TIVA, without bleeding (n=6). M30 Cytodeath immunofluorescence assay used a mouse monoclonal antibody (M30clone) (Roche) for detection of a caspase cleavage product of cytokeratin 18. Results: Group1: epithelial cells from the tips of the villi showed strong positive reaction, decreasing towards the body of the villi, negative in crypts and glands. Control group: epitelial cells from the tips of the villi showed a weak positive reaction, also decreasing towards the body and negative in crypts and glands. Discussion and Conclusions: Apoptosis occurred mainly in the epithelium of the villi, appearing to precede intestinal mucosa desquamation. Subsequent studies are being developed to determine the apoptotic index and correlation between immunohistochemical methods in small intestinal segments in the two groups of this study.
- Small Intestine mucosal injury and apoptosis following haemorrhage and volume replacement with different intravenous solutionsPublication . Ortiz, Ana Liza; Vala, Helena; Venâncio, Carlos; Garcia, Carla; Mesquita, João; Silva, Aura; Ferreira, DavidObjective: To characterize mucosal loss (ML) and apoptotic events in the small intestine after haemorrhage and volume replacement with a crystalloid, Lactated Ringers Solution (LR), and a colloid, HES130/0.4 solution, in a pig model. Methods: %ML and apoptotic events at the epithelium of the villi were evaluated in the small intestine from pigs that underwent total intravenous anaesthesia and passive controlled arterial bleeding, followed by volume replacement using LR (group1, n=9) and HES130/0.4 (group2, n=9). Apoptotic events were investigated by performing immunohistochemistry using Cytochrome c antibody and M30Cytodeath immunofluorescence assay. Results: %ML was significantly higher in group1 (P< 0.0001). Similar moderate to intense cytoplasmic immunoreactivity was seen in both groups for Cytochrome c antibody. The median percentage of apoptotic cells in the non-detached villi epithelium was 5.94% (1.46-31.47%) in group1 and 6.38% (0.36-47.48%) in group2. No significant differences were observed between groups. Conclusion: Results suggest that HES130/0.4 administration may more efficiently prevent the acute loss of intestinal mucosa, and, therefore, the integrity of the intestinal barrier. However, the indicators of intestinal apoptosis do not differ between HES 130/0.4 or RL administration.
- The influence of Ringer's lactate or HES 130/0.4 administration on the integrity of the small intestinal mucosa in a pig hemorrhagic shock model under general anesthesiaPublication . Ortiz, Ana Liza; Vala, Helena; Venâncio, Carlos; Mesquita, João; Silva, Aura; Gonzalo-Orden, Jose Manuel; Ferreira, DavidTo 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.