Polyphenolic compounds of Euphorbia umbellata (Pax) Bruyns (Euphorbiaceae) improved endothelial dysfunction through arginase inhibition.

Euphorbia umbellata is used for its anti-inflammatory properties; however, there are limited data available regarding its effects on vascular function. Its bark is rich in polyphenolic compounds, which potentially improve endothelial dysfunction (ED). This study proposes to investigate the effects of E. umbellata bark extracts and its polyphenolic compounds on arginase (ARG) activity and nitric oxide (NO)-related targets. Chromatographic procedures were used for the chemical characterisation of the extracts. Furthermore, in silico (molecular docking), in vitro (ARG inhibition), in vivo (streptozotocin-induced hyperglycemia model), and ex vivo (l-arginine metabolism, vascular reactivity, western blot, and biochemical) techniques were carried out. Quercetin, gallic acid, and ellagic acid were identified in the extracts. In silico screening predicted that gallic acid and quercetin would have the most promising interactions with ARG -identified cavities. This was confirmed in vitro as both compounds had a direct inhibitory effect on ARG, as was the case regarding the extracts. Oral treatment preserved endothelium-dependent vasodilation through ARG inhibition together with an increase in l-arginine bioavailability and endothelial NO synthase expression. Biochemical parameters determined the lack of toxicity for sub-chronic treatment. E. umbellata bark extracts and its compounds can contribute to ED treatment, at least partly, through the inhibition of vascular ARG.

Reduced Remodeling Biomarkers Tissue Expression in Nanotextured Compared With Polyurethane Implants Capsules: A Study in Rats.

BACKGROUND: In the biological response to biomaterials, the implant shell plays a key role in immune and inflammatory reactions. We hypothesized that the capsules formed around nanotextured implants exhibit an immunohistochemical behavior different to those formed around polyurethane implants. OBJECTIVES: The aim of this study was to evaluate through immunohistochemistry markers the capsules formed around nanotextured and polyurethane implants. METHODS: Sixty albino female Wistar rats were divided into 2 groups (nanotextured and polyurethane), with 30 animals in each group. A mini silicone implant was inserted on the back of the animals. After a predetermined period, the animals were killed, and the capsules formed around the implants were studied. The capsules in the 30-, 60-, and 90-day subgroups were analyzed via immunohistochemistry to detect markers for fibroblast α smooth muscle actin (α-SMA), transforming growth factor ß (TGF-ß), cluster of differentiation 34 (CD34), and CD68, via picrosirius staining to determine the density of type I and III collagen fibers and via hematoxylin and eosin staining to assess capsule thickness. A Wilcoxon-Mann-Whitney test was used to compare the groups, and a Kruskal-Wallis test was used to compare the subgroups. RESULTS: Lower α-SMA, TGF-ß, CD34 and CD68 immunoexpression was observed in the nanotextured 30- and 60-day subgroups than in the corresponding polyurethane subgroups. In the 90-day subgroup, more pronounced α-SMA and CD34 immunoexpression was observed in the nanotextured group; however, TGF-ß and CD68 immunoexpression remained lower. The nanotextured implants showed reduced capsular thickness and greater formation of type I collagen in all the analyzed subgroups. CONCLUSIONS: Nanotextured implants led to reduced immune and inflammatory reactions compared with polyurethane implants according to all analyzed variables.

Experimental, comparative, duplex mapping study of arterial flow distribution in ischemia and reperfusion by retrograde circulation.

Treatment options for critical lower limb ischemia in the absence of the distal bed are limited. Diverting blood flow in a retrograde direction through the venous circulation is one alternative option that is supported by evidence from several published articles. Duplex scanning was used to compare the distribution of arterial flow in hind limbs of pigs maintained in physiological circulation to contralateral limbs subjected to ischemia and reperfusion by retrograde circulation. Flow in limbs with physiological and retrograde circulation was evaluated by duplex scanning with analysis of Peak Systolic Velocity (PSV), End Diastolic Velocity (EDV), and the Resistivity Index (RI) for selected arteries. This comparative analysis of extremities maintained in physiological circulation in relation to those subjected to ischemia and reperfusion by retrograde circulation showed, via duplex scanning, that changes in spectral wave patterns and hemodynamic variables are satisfactory indicators and suggest good distribution of distal blood flow.

Smooth Muscle Alpha Actin Immunoexpression (α-Sma) and CD-117 Antibody (C-Kit) in Capsules Formed by Polyurethane Foam-Coated Silicone Implants and with Textured Surface: A Study on Rats.

BACKGROUND: One of the undesirable complications that might occur after breast augmentation with silicone implants is capsular contracture. In its etiology, the relations between mast cells and myofibroblasts play an important role in collagen synthesis. Mast cells are able to activate fibroblasts into myofibroblasts, through paracrine secretions, inducing collagen production. The objectives of this study were to analyze the myofibroblast concentration through the α-SMA immunomarker and evaluate the intensity of mast cell expression against the C-Kit immunomarker. MATERIAL AND METHOD: Sixty-four Wistar rats were used, divided into two groups (polyurethane foam and textured surface) with 32 animals in each. The animals received silicone implants on the back, below the panniculus carnosus, and after the determined period, they were killed and the capsules formed around the implants were studied. The capsules were analyzed employing the immunohistochemical technique, with the α-SMA and C-Kit immunomarkers in subgroups of 30, 50, 70 and 90 days. RESULTS: The myofibroblast concentration was higher in the polyurethane group when compared to the textured group (30 days p = 0.105; 50 days p = 0.247; 70 days p = 0.014 and 90 days p = 0.536). The intensity of mast cell expression was more pronounced in the polyurethane group when compared to the textured group (30 days p = 0.798; 50 days p = 0.537; 70 days p = 0.094 and 90 days p = 0.536). CONCLUSIONS: Polyurethane-coated implants induced higher concentrations of myofibroblasts and higher expression of mast cells, when compared to the textured surface implants. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Effects of curcumin supplementation on abdominal surgical wound healing.

PURPOSE: To evaluate the effects of curcumin supplementation on abdominal surgical wound healing in rats using clinical, histological, and hematological parameters. METHODS: Forty Wistar rats were randomly divided into two groups: the curcumin group, and the control group. The curcumin group received, in addition to water and standard feed, curcumin via gavage at the dose of 200 mg/kg for seven days preceding and seven days following surgery. The control group received only water and standard feed. Both groups underwent median laparotomy and left colotomy. On the eighth postoperative day, the groups were euthanized, and the left colon was resected for histological analysis. RESULTS: In the preoperative evaluation, there was a significant decrease in the mean C-reactive protein levels in the curcumin group (0.06) compared to the control group (0.112) (p = 0.0001). In the postoperative wound healing assessment, a significant decrease was observed in inflammatory infiltrate (p = 0.0006) and blood vessel count (p = 0.0002) in the curcumin group compared to the control group. CONCLUSIONS: Curcumin supplementation was able to significantly reduce inflammatory parameters in both pre-and post-operative phases of abdominal surgical wounds in rats.

Dental implants in large animal models with experimental systemic diseases: A systematic review.

This systematic review aims to identify and discuss the most used methodologies in pre-clinical studies for the evaluation of the implementation of dental implants in systemically compromised pigs and sheep. This study provides support and guidance for future research, as well as for the prevention of unnecessary animal wastage and sacrifice. Preferred Reporting for Systematic Reviews and Meta-Analyses (PRISMA) was used as a guideline; electronic searches were performed in PubMed, Scopus, Scielo, Web of Science, Embase, Science Direct, Brazilian Bibliography of Dentistry, Latin American and Caribbean Literature in Health Sciences, Directory of Open Access Journals, Database of Abstracts of Reviews of Effects, and gray literature until January 2022 (PROSPERO/CRD42021270119). Sixty-eight articles were chosen from the 2439 results. Most studies were conducted in pigs, mainly the Göttinger and Domesticus breeds. Healthy animals with implants installed in the jaws were predominant among the pig studies. Of the studies evaluating the effect of systemic diseases on osseointegration, 42% were performed in osteoporotic sheep, 32% in diabetic sheep, and 26% in diabetic pigs. Osteoporosis was primarily induced by bilateral ovariectomy and mainly assessed by X-ray densitometry. Diabetes was induced predominantly by intravenous streptozotocin and was confirmed by blood glucose analysis. Histological and histomorphometric analyses were the most frequently employed in the evaluation of osseointegration. The animal models presented unique methodologies for each species in the studies that evaluated dental implants in the context of systemic diseases. Understanding the most commonly used techniques will help methodological choices and the performance of future studies in implantology.

Preclinical Trial of Ocotea puberula (Rich.) Nees ("Canela-Guaicá") in Wound Healing: Validation of a Traditional Medicine Practice Used by Indigenous Groups in Southern Brazil.

Background: "Canela-guaicá," "guaicá," or "canela-sebo" [Ocotea puberula (Rich.) Nees] is a native species that is traditionally used by Kaingang indigenous groups for wound healing in southern Brazil. The aim of this study was to extract the mucilage from O. puberula barks, perform its phytochemical and physicochemical characterization, and investigate its healing potential. Methods: A murine wound model was used as a preclinical trial for authentication of the traditional knowledge from Kaingang indigenous communities. Results: Alkaloids and polysaccharides were identified by usual qualitative reactions and Fourier-transform infrared spectroscopy. This natural product showed thermal stability and pseudoplastic properties that were considered suitable for the intended use. A higher initial exacerbation of inflammatory response after 7 days, an improved angiogenesis after 14 days, and an increased wound shrinkage after 21 days were statistically significant for the "canela-guaicá" bark extract in the preclinical trial when compared to the silver calcium alginate dressing (positive control). Conclusion: The healing potential of the "canela-guaicá" bark extract, traditionally used by the Kaingang indigenous community from southern Brazil, was preclinically validated. This study paves the way for designing novel wound dressings containing this natural product in order to treat acute and chronic wounds.

Effect of pentoxifylline and α-tocopherol on medication-related osteonecrosis of the jaw in rats: Before and after dental extraction.

OBJECTIVE: Evaluate the effect of pentoxifylline and α-tocopherol administration in the prevention or treatment of medication-related jaw osteonecrosis (MRONJ). METHODOLOGY: Sixty Wistar rats were divided into three prevention (C-prev, BP-prev and BP/PT-prev) and three treatment groups (C-treat, BP-treat and BP/PT-treat), n = 10. The animals in the BP-prev, BP/PT-prev, BP-treat and BP/PT-treat groups received zoledronic acid (0.1 mg/kg) for 12 weeks, while the animals in the C-prev and C-treat groups received saline solution. At week 6, all animals underwent tooth extraction. Between week 5 and week 12, the BP/PT-prev group was treated with pentoxifylline (50 mg/kg/day) and α-tocopherol (80 mg/kg/day), with euthanasia at the end of week 12. The BP/PT-treat group received the same drug protocol, but it was performed between week 12 and week 16, with euthanasia at the end of week 16. Afterwards, the presence of osteonecrosis was evaluated by clinical analysis, radiographic and histological. RESULTS: BP/PT-treat group showed a reduction in the histological incidence of osteonecrosis by 50%, decrease the percentage of empty osteocyte gaps and the necrotic area, decrease the presence of bone sequestration and increase the number of osteocytes and alveolar blood flow (p < 0.05). However, BP/PT-prev group showed only a reduction in the necrotic area percentage when compared to BP-prev (p < 0.05). CONCLUSIONS: Pentoxifylline and α-tocopherol administration before tooth extraction was not effective in preventing MRONJ. However, this drug protocol was able to reduce MRONJ manifestation when administrate after discontinuation of bisphosphonate, thus it can be considered as a viable strategy for the treatment of this pathological condition.

Ursolic acid-loaded lipid-core nanocapsules reduce damage caused by estrogen deficiency in wound healing.

The skin aging process in women is accelerated due to decreases in serum estrogen levels triggered by the menopause process. Hence, poly(L-lactic acid) lipid-core nanocapsules containing ursolic acid (NPLA-UA) were developed using the interfacial deposition of the preformed polymer methodology as a strategy to reduce damages to the healing process caused by hormonal deficiency in ovariectomized rats. The colloidal suspensions of nanocapsules presented adequate size and morphology (254 and 375 nm), negative zeta potential (-31 and -37 mV), high encapsulation efficiency (99.89 %), and amorphous character. The analyses performed in an in vivo healing trial showed that the treatment with NPLA-UA resulted in faster wound retraction with less inflammatory response. In addition, the angiogenic process was stimulated increased synthesis of dermal collagen occurred. Ursolic acid-loaded, lipid-core nanocapsules are suitable for treating skin changes triggered by decreased estrogen in menopause.

Risk factors associated with ticks and Rickettsia spp. exposure in wild boars (Sus scrofa), hunting dogs, and hunters of Brazil.

BACKGROUND AND AIM: Wild boars have recently been implicated as the maintainers and carriers of Amblyomma spp. ticks, which are essential for Rickettsia spp. transmission. Consequently, wild boar hunting may increase the risk of tick exposure and subsequent human tick-borne infection and disease. Therefore, this study was conducted to evaluate the risk factors for ticks and Rickettsia spp. exposure in wild boars, hunting dogs, and hunters in Brazilian biomes. MATERIALS AND METHODS: The statistical relationship of Rickettsia spp. antibodies were evaluated using the Chi-square test in 80 wild boars, 170 hunting dogs, and 49 hunters. RESULTS: The only statistically significant difference in seropositivity found in this study was between male and female wild boars (p=0.034), probably associated with in-park exposure to Amblyomma brasiliense infected with Rickettsia spp. CONCLUSION: The absence of statistical differences in the associated risk factors for hunting dogs and hunters may indicate a random exposure to Rickettsia spp.

Serosurvey of anti-Leishmania (Leishmania) infantum antibodies in hunting dogs and hunters in Brazil.

BACKGROUND AND AIM: Although wild boar hunting activities and the hunting dog trade in the Atlantic Forest and Cerrado biomes of Brazil overlap both with endemic and with non-endemic areas for visceral leishmaniasis, no study to date has focused on Leishmania spp. exposure among hunting dogs and hunters. The aim of the present study was to assess the presence of Leishmania spp. antibodies in hunting dogs and hunters in different anthropized areas of two Brazilian biomes. MATERIALS AND METHODS: Blood samples were collected from 170 hunting dogs and 46 hunters between October 2016 and May 2018. The presence of antibodies against Leishmania spp. in hunting dogs was screened through a dual-path platform immunochromatographic test (DPP rapid test; Bio-Manguinhos/Fundação Oswaldo Cruz, Rio de Janeiro, Brazil) and in hunters through an rK39-based rapid immunochromatographic test. Both tests were used in accordance with Brazilian Ministry of Health recommendations. RESULTS: Overall, although antibodies were detected through the immunochromatographic test in 3/170 (0.02%) of these female asymptomatic hunting dogs, all living in anthropized areas of the Atlantic Forest biome in South Brazil, no sample was confirmed through the enzyme-linked immunosorbent assay. All the hunters were non-reactive in the rapid immunochromatographic test. CONCLUSION: Our study on three suspicious hunting dogs has suggested that Leishmania (Leishmania) infantum may circulate both in endemic and non-endemic areas in Brazil. In addition, a high rate of hunting dog replacement due to death and trade may have led to less chance of infection and transmission between animals and between animals and humans, which would corroborate the outcomes reported here. Further studies should be conducted to fully establish whether hunting dogs and hunters may be used as sentinels in other areas endemic for Leishmania spp.

Characterization and In Vitro and In Vivo Evaluation of Tacrolimus-Loaded Poly(ε-Caprolactone) Nanocapsules for the Management of Atopic Dermatitis.

BACKGROUND: Tacrolimus (TAC) is a drug of natural origin used in conventional topical dosage forms to control atopic dermatitis. However, direct application of the drug often causes adverse side effects in some patients. Hence, drug nanoencapsulation could be used as an improved novel therapy to mitigate the adverse effects and enhance bioavailability of the drug. METHODS: Physicochemical properties, in vitro drug release experiments, and in vivo anti-inflammatory activity studies were performed. RESULTS: TAC-loaded nanocapsules were successfully prepared by the interfacial deposition of preformed polymer using poly(ε-caprolactone) (PCL). The nanoparticulate systems presented a spherical shape with a smooth and regular surface, adequate diameter (226 to 250 nm), polydispersity index below 0.3, and suitable electrical stability (-38 to -42 mV). X-ray diffraction confirmed that the encapsulation method provided mainly the drug molecular dispersion in the nanocapsule oily core. Fourier-transform infrared spectra suggested that nanoencapsulation did not result in chemical bonds between drug and polymer. In vitro drug dissolution experiments showed a controlled release with a slight initial burst. The release kinetics showed zero-order kinetics. As per the Korsmeyer-Peppas model, anomalous transport features were observed. TAC-loaded PCL nanocapsules exhibited excellent anti-inflammatory activity when compared to the free drug. CONCLUSIONS: TAC-loaded PCL nanocapsules can be suitably used as a novel nano-based dosage form to control atopic dermatitis.

Seroprevalence of Anti-Brucella spp. Antibodies in Wild Boars (Sus scrofa), Hunting Dogs, and Hunters of Brazil.

All 86 wild boars (Sus scrofa), 170 hunting dogs, and 49 hunters sampled from three Brazilian regions were seronegative to Brucella spp. by the standard tube agglutination and 2-mercaptoethanol tests, suggesting a low circulation of Brucella spp. in wild boars, hunting dogs, and hunters in such areas.

Serosurvey of anti-Neospora caninum antibodies in wild boars (Sus scrofa), hunting dogs and hunters of Brazil.

The protozoan Neospora caninum is an important cause of abortion in cattle worldwide, with domestic dogs serving as the definitive hosts. Although hunting activities have been indicated as a potential risk factor for N. caninum infection in dogs, no serological evidence has so far been reported in hunting dogs, wild boars (Sus scrofa), and hunters. A total of 98 wild boars, 168 hunting dogs, and 15 hunters from three Brazilian regions were sampled and tested for anti-N. caninum antibodies by indirect immunofluorescence antibody test, resulting in 15/168 (9%) seropositive hunting dogs, and 0/98 wild boars, and 0/15 hunters seropositive. The absence of N. caninum antibodies in wild boars may suggest low exposure to oocysts shed by hunting dogs and wild canids in three different Brazilian regions. Finally, the absence of hunter seropositivity supports the current lack of evidence that N. caninum is a zoonotic parasite.

Evaluation of wound healing effect of alginate film containing Aloe vera gel and cross-linked with zinc chloride.

PURPOSE: To develop a new wound dressing composed of alginate and Aloe vera gel and cross-linked with zinc ions. METHODS: The aloe-alginate film was characterized using scanning electron microscopy (SEM), swelling profile, mechanical properties, polysaccharide content and X-ray diffraction (XRD). Thirty Wistar rats were divided in two groups a) treated with aloe-alginate film and b) control (treated with sterile gauze). Wound contraction measurements and hystological analysis were performed on 7th, 14th and 21st days after wound surgery. RESULTS: The aloe-alginate film presented adequated mechanical resistance and malleability for application as wound dressing. There was no statistical difference in wound contraction between two groups. Histological assay demonstrated that aloe-alginate film presented anti-inflammatory activity, stimulated angiogenesis on proliferative phase and a more significant increased in collagen type I fibers and decreased type III fibers which promoted a mature scar formation when compared to control. CONCLUSIONS: The aloe-alginate film showed adequate physicochemical characteristics for wound dressing applications. The in vivo assay demonstrated that aloe-alginate film enhanced the healing process of incisional skin wounds.

Serosurvey for Pseudorabies (Aujeszky's Disease) in Free-Range Wild Boars (Sus scrofa) of Brazil.

Free-ranging wild boars (Sus scrofa) from two different Brazilian biomes were sampled. Only one of 36 (2.8%) animals tested from central-western Brazil were positive for antibodies against pseudorabies virus (PRV) by enzyme-linked immunosorbent assay. Peccaries and other wildlife species can be exposed to PRV in these areas. In addition, wild boars could have impact on livestock and PRV eradication.

Effects of curcumin supplementation on abdominal surgical wound healing

ABSTRACT Purpose: To evaluate the effects of curcumin supplementation on abdominal surgical wound healing in rats using clinical, histological, and hematological parameters. Methods: Forty Wistar rats were randomly divided into two groups: the curcumin group, and the control group. The curcumin group received, in addition to water and standard feed, curcumin via gavage at the dose of 200 mg/kg for seven days preceding and seven days following surgery. The control group received only water and standard feed. Both groups underwent median laparotomy and left colotomy. On the eighth postoperative day, the groups were euthanized, and the left colon was resected for histological analysis. Results: In the preoperative evaluation, there was a significant decrease in the mean C-reactive protein levels in the curcumin group (0.06) compared to the control group (0.112) (p = 0.0001). In the postoperative wound healing assessment, a significant decrease was observed in inflammatory infiltrate (p = 0.0006) and blood vessel count (p = 0.0002) in the curcumin group compared to the control group. Conclusions: Curcumin supplementation was able to significantly reduce inflammatory parameters in both pre-and post-operative phases of abdominal surgical wounds in rats.

Analysis of temperature increase in swine gingiva after exposure to a Polywave® LED light curing unit.

OBJECTIVE: This study evaluated the temperature increase in swine gingival temperature after exposure to light emitted by a Polywave® LED light curing unit (LCU, Bluephase 20i, Ivoclar Vivadent). METHODS: After local Ethics Committee approval (protocol 711/2015), 40 pigs were subjected to general anesthesia and the LCU tip was placed 5mm from the buccal gingival tissue (GT) close to lower lateral incisors. A thermocouple probe (Thermes WFI, Physitemp) was inserted into the gingival sulcus before and immediately after exposure to light. Real-time temperature (°C) was measured after the following exposure modes were applied: High Power (20s-H, 40s-H, and 60s-H) or Turbo mode (5s-T), either with or without the presence of rubber dam (RD) interposed between the LCU tip and GT (n=10). The presence of gingival lesions after the exposures was also evaluated. Peak temperature (°C) and the temperature increase during exposure over that of the pre-exposure baseline value (ΔT) data were analyzed using 2-way ANOVA followed by Bonferroni's post-hoc test (α=5%). A binary logistic regression analysis determined the risk of gingival lesion development. RESULTS: Without RD, no significant difference in ΔT was observed among 20s-H, 40s-H, and 60s-H groups, which showed the highest temperature values, while the 5s-T exposure showed the lowest ΔT, regardless of RD. RD reduced ΔT only for the 20s-H group (p=0.004). Gingival lesions were predominantly observed using 40s-H, with RD, and 60s-H, with and without RD. SIGNIFICANCE: Exposure to a LCU light might be harmful to swine gingiva only when high radiant exposure values are delivered, regardless of the use of RD.