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1.
Aesthetic Plast Surg ; 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38191862

RESUMO

Authors comment on the paper "The effect of drains and compressive garments versus progressive tensioning sutures on seroma formation in abdominoplasty" written by Brown et al in Aesthetic Plastic Surgery.Although the authors present interesting results on the effectiveness of progressive tensioning sutures proposed originally by Pollok and Pollok, we express some considerations about the analyzed data and patients, hoping in a new research extending these findings to include both aesthetic and post-bariatric abdominoplasty patients, evaluating the effectiveness of these sutures in varied contexts.Level of Evidence V 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 Table of Contents or online Instructions to Authors www.springer.com/00266 .

2.
Int Wound J ; 21(3): e13946, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38477426

RESUMO

Keloids seem to overexpress cyclo-oxygenase-2 (COX-2), suggesting a role in its deregulated pathway in inducing an altered epithelial-mesenchymal interaction, which may be responsible for the overgrowth of dermal components resulting in scars or keloid lesions. This study aimed to evaluate the effect of Parecoxib, a COX-2 inhibitor, on cell growth in fibroblast primary cultures obtained from human keloid tissues. Tissue explants were obtained from patients who underwent intralesional excision of untreated keloids; central fractions were isolated from keloid tissues and used for establishing distinct primary cultures. Appropriate aliquots of Parecoxib, a COX-2 inhibitor were diluted to obtain the concentration used in the experimental protocols in vitro (1, 10 or 100 µM). Treatment with Parecoxib (at all concentrations) caused a significant decrease in cellular growth from 24 hours onwards, and with a maximum at 72 hours (P < .02). Moreover, at 72 hours Parecoxib significantly reduced cellular vitality. Parecoxib treatment also induced an increase in fragmented nuclei with a maximum effect at 100 µM and a significant decrease in Bcl-2 and an increase in activated caspase-3 protein levels at 72 hours compared with control untreated cultures. Our findings suggest a potential use of the COX-2 inhibitor, Parecoxib, as the therapy for keloids.


Assuntos
Cicatriz Hipertrófica , Queloide , Humanos , Queloide/patologia , Inibidores de Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase 2/farmacologia , Isoxazóis/metabolismo , Isoxazóis/farmacologia , Fibroblastos , Cicatriz Hipertrófica/metabolismo
3.
Aesthetic Plast Surg ; 2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-37932508

RESUMO

Authors comment on the paper "Meta-analysis of the oncological safety of autologous fat grafting after breast cancer on basic science and clinical studies" written by Kai Wang et al in Aesthetic Plastic Surgery. Although the authors present interesting results on the safety of autologous fat graft after breast cancer and breast reconstruction, we express some considerations about the analyzed manuscript and about the safety of this procedure in specific cohort of patients having particular cancer characteristics.Level of Evidence V 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 https://www.springer.com/00266 .

4.
Aesthetic Plast Surg ; 2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-37891328

RESUMO

Authors comment on the paper "Platelet-Rich Plasma for Treatment of Hair Loss Improves Patient-Reported Quality of Life" written by Abigail Meyers et al in Aesthetic Plastic Surgery. Although the authors present interesting results on the quality of life of patients after platelet-rich plasma, we express some considerations about the proposed composition of PRP and hoping in larger sample study.Level of Evidence V 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.

5.
Aesthetic Plast Surg ; 47(5): 2197-2198, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37169891

RESUMO

Authors comment on the paper "An Original Approach to Massive Weight Loss Deformities in the Lower Thigh: A Retrospective Assessment of Results and Patients" written by Dr. Pierfranco Simone et al. Although the authors present excellent results on medial tight lift, we express some considerations about the proposed follow-up and hope in new research on this topic by Dr. Simone et al. using his interesting technique.Level of Evidence V 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 .


Assuntos
Coxa da Perna , Redução de Peso , Humanos , Estudos Retrospectivos
6.
Aesthetic Plast Surg ; 2023 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-37710054

RESUMO

Authors comment on the paper "Aesthetic, Quality of Life, and Clinical Outcomes after Inferior Pedicle Oncoplastic Reduction Mammoplasty" written by Thomas Y Xia et al. Although the authors present excellent results on Inferior Pedicle Oncoplastic Reduction Mammoplasty, we express some considerations about the proposed follow-up and hope in new research on this topic by Xia et al using his interesting data.Level of Evidence III 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 .

7.
Medicina (Kaunas) ; 59(11)2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-38004053

RESUMO

Background and Objectives: Signs and symptoms of vulvovaginitis, especially when recurrent, have a significant impact on a woman's quality of life. The aim of this study was to survey gynecologists about their habits regarding the treatments of the pathology and to evaluate the efficacy of a novel vaginal hydrogel composed of wheat extracts and polyhexanide aimed at reducing vulvovaginitis symptomatology. Materials and Methods: A cross-sectional analysis of a national survey using 155 Italian gynecologists and a prospective, open-label, observational study were carried out in 75 outpatient clinics across Italy. Pre- and postmenopausal women with suspicion of vulvovaginitis due to at least four of the following symptoms (leucoxanthorrhea, bad odor from genitalia, vulvovaginal dryness, petechiae, burning, and pruritus) while waiting for microbiological swab analysis were included and treated with one hydrogel application every 3 days for 1 week. Primary endpoint was the complete resolution of symptomatology. Results: The pre-study survey reported that, for most clinicians, local or oral treatment (65.7% and 82.8%, respectively) with antibiotics or antifungals is used very often. Therefore, we proceeded to carry out an observational study. Overall, 615 (362 of fertile age and 253 in postmenopause) women were included in this study. At the 28th follow-up examination, complete resolution of symptomatology was achieved in 578/615 (94.1%; p < 0.001) within 12.72 ± 6.55 and 13.22 ± 6.33 days for those of fertile age and in postmenopause, respectively (p = 0.342). All of the evaluated symptoms were significantly reduced after treatment (p = 0.001) without differences according to the patient's menopausal status. A slightly significant reduction in Gardnerella Vaginalis (p = 0.040) and Candida Albicans (p = 0.049) was found after treatment. No patient reported side effects, adverse reactions, or discontinued therapy. Conclusions: This pilot study showed that a hydrogel based on Rigenase® (wheat extract) and polyhexanide could be a promising treatment for the relief of vulvovaginitis symptoms. However, these results are limited by the absence of a control group. Additional comparative and randomized controlled trials between the hydrogel and other non-antibiotic devices as well as local antibiotic therapy should be performed to increase the validity of the findings.


Assuntos
Hidrogéis , Vulvovaginite , Feminino , Humanos , Estudos Transversais , Hidrogéis/uso terapêutico , Estudos Prospectivos , Projetos Piloto , Qualidade de Vida , Vulvovaginite/tratamento farmacológico , Vulvovaginite/microbiologia , Antibacterianos/uso terapêutico
8.
Neurobiol Dis ; 164: 105611, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34995755

RESUMO

Central post-stroke pain (CPSP) and associated depression remain poorly understood and pharmacological treatments are unsatisfactory. Recently, microglia activation was suggested to be involved in CPSP pathophysiology. The goal of this study was to investigate the effectiveness of a co-ultramicronized combination of N-palmitoylethanolamide and luteolin (PEALut) in a mouse model of thalamic hemorrhage (TH)-induced CPSP. TH was established through the collagenase-IV injection in thalamic ventral-posterolateral-nucleus. PEALut effects in CPSP-associated behaviors were evaluated during a 28-days observation period. We found that repeated administrations of co-ultra PEALut significantly reduced mechanical hypersensitivity after TH, as compared to vehicle, by reducing the early microglial activation in the perilesional site. Moreover, PEALut prevented the development of depressive-like behavior (21 days post-TH). These effects were associated with the restoration of synaptic plasticity in LEC-DG pathway and monoamines levels found impaired in TH mice. Hippocampal MED1 and TrkB expressions were significantly increased in TH compared to sham mice 21 days post-TH, whereas BDNF levels were decreased. PEALut restored MED1/TrkB/BDNF expression in mice. Remarkably, we found significant overexpression of MED1 in the human autoptic brain specimens after stroke, indicating a translational potential of our findings. These results pave the way for better-investigating depression in TH- induced CPSP, together with the involvement of MED1/TrkB/BDNF pathway, proposing PEALut as an adjuvant treatment.


Assuntos
Depressão/metabolismo , Hemorragias Intracranianas/metabolismo , Microglia/metabolismo , Dor/metabolismo , Transdução de Sinais/fisiologia , Tálamo/metabolismo , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Depressão/etiologia , Hemorragias Intracranianas/complicações , Subunidade 1 do Complexo Mediador/metabolismo , Camundongos , Atividade Motora/fisiologia , Dor/etiologia , Ratos Sprague-Dawley , Receptor trkB/metabolismo
9.
Int J Mol Sci ; 23(15)2022 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-35897786

RESUMO

Pulmonary fibrosis is a consequence of the pathological accumulation of extracellular matrix (ECM), which finally leads to lung scarring. Although the pulmonary fibrogenesis is almost known, the last two years of the COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its post effects added new particularities which need to be explored. Many questions remain about how pulmonary fibrotic changes occur within the lungs of COVID-19 patients, and whether the changes will persist long term or are capable of resolving. This review brings together existing knowledge on both COVID-19 and pulmonary fibrosis, starting with the main key players in promoting pulmonary fibrosis, such as alveolar and endothelial cells, fibroblasts, lipofibroblasts, and macrophages. Further, we provide an overview of the main molecular mechanisms driving the fibrotic process in connection with Galactin-1, -3, -8, and -9, together with the currently approved and newly proposed clinical therapeutic solutions given for the treatment of fibrosis, based on their inhibition. The work underlines the particular pathways and processes that may be implicated in pulmonary fibrosis pathogenesis post-SARS-CoV-2 viral infection. The recent data suggest that galectin-1, -3, -8, and -9 could become valuable biomarkers for the diagnosis and prognosis of lung fibrosis post-COVID-19 and promising molecular targets for the development of new and original therapeutic tools to treat the disease.


Assuntos
COVID-19 , Fibrose Pulmonar , COVID-19/complicações , Células Endoteliais/metabolismo , Galectina 1 , Humanos , Pandemias , Fibrose Pulmonar/metabolismo , SARS-CoV-2
10.
Int J Mol Sci ; 23(17)2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36077579

RESUMO

Background: Diabetic retinopathy (DR) is a neurovascular disease, characterized by a deficiency of brain-derived neurotrophic factor (BDNF), a regulator of autophagy. Beta-hydroxybutyrate (BHB), previously reported as a protective agent in DR, has been associated with BDNF promotion. Here, we investigated whether systemic BHB affects the retinal levels of BDNF and local autophagy in diabetic mice with retinopathy; Methods: C57BL/6J mice were administered with intraperitoneal (i.p.) streptozotocin (STZ) (75 mg/kg) injection to develop diabetes. After 2 weeks, they received i.p. injections of BHB (25−50−100 mg/kg) twice a week for 10 weeks. Retinal samples were collected in order to perform immunofluorescence, Western blotting, and ELISA analysis; Results: BHB 50 mg/kg and 100 mg/kg significantly improved retinal BDNF levels (p < 0.01) in diabetic mice. This improvement was negatively associated with autophagosome−lysosome formations (marked by LC3B and ATG14) and to higher levels of connexin 43 (p < 0.01), a marker of cell integrity. Moreover, BHB administration significantly reduced M1 microglial activation and autophagy (p < 0.01); Conclusions: The systemic administration of BHB in mice with DR improves the retinal levels of BDNF, with the consequent reduction of the abnormal microglial autophagy. This leads to retinal cell safety through connexin 43 restoration.


Assuntos
Diabetes Mellitus Experimental , Retinopatia Diabética , Ácido 3-Hidroxibutírico/farmacologia , Animais , Autofagia , Fator Neurotrófico Derivado do Encéfalo , Conexina 43 , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Retinopatia Diabética/complicações , Retinopatia Diabética/etiologia , Camundongos , Camundongos Endogâmicos C57BL , Retina
11.
Dermatology ; 237(3): 473-478, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33053549

RESUMO

BACKGROUND: Congenital melanocytic nevi (CMN) are benign proliferations of melanocytes usually present at birth. The magnitude of the melanoma risk for CMN is controversial, generating an ongoing debate on the best approach to manage these lesions. OBJECTIVE: To perform a retrospective, observational study with the aim to evaluate the prevalence of CMN-associated melanomas in tertiary referral centers, as well as the eventual correlation between clinical, dermoscopic, and histological features of CMN-associated melanomas. METHODS: A single-center retrospective observational study was performed on all clinical and dermoscopic images of histologically confirmed melanomas arising on CMN over a 14-year period (January 2005 to March 2019). RESULTS: Our database included 2,159 melanomas in the considered period. Of those, 27 (1.3%) were CMN-associated melanomas. The mean age of patients with CMN-associated melanoma was 33 years (range, 11-70 years). The mean diameter of CMN-associated melanoma was 18 mm (range, 6 mm to 20 cm), and 56% were located on the back. Twenty-one (77.8%) of CMN-associated melanomas arose on small CMN (<1.5 cm), 5 (18.5%) on medium-sized CMN (1.5-19.9 cm), and 1 (3.7%) on a large/giant type (≥20 cm). The majority of CMN-associated melanomas (63%) exhibited a globular dermoscopic pattern in their benign part, while a blue-white veil and irregular blotches were the most frequent dermoscopic features in the malignant part. About three quarters of melanomas occupied 10-50% of the nevus surface. Breslow thickness was higher in melanomas involving less than 10% of nevus surface (mean thickness, 1 mm) than in those affecting 10-50 and >50% of the nevus surface (0.8 and 0.7 mm, respectively). CONCLUSIONS: In our series, small CMN was the most frequent type of CMN-associated melanoma. Although the risk of melanoma is increasing by the increasing size of CMN, our finding is definitely related to the much higher prevalence of small CMN in the general population as compared to the prevalence of intermediate-sized and large CMN. LIMITATIONS: Small sample size, single-center experience, retrospective design.


Assuntos
Melanoma/patologia , Nevo Pigmentado/congênito , Nevo Pigmentado/patologia , Neoplasias Cutâneas/patologia , Adolescente , Adulto , Idoso , Criança , Dermoscopia , Feminino , Humanos , Itália , Masculino , Melanoma/epidemiologia , Melanoma/cirurgia , Pessoa de Meia-Idade , Nevo Pigmentado/cirurgia , Prevalência , Estudos Retrospectivos , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/cirurgia , Adulto Jovem
12.
Int J Mol Sci ; 22(7)2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33808491

RESUMO

The bioactive form of vitamin D, 1,25-dihydroxyvitamin D (1,25D3), exerts immunomodulatory actions resulting in neuroprotective effects potentially useful against neurodegenerative and autoimmune diseases. In fact, vitamin D deficiency status has been correlated with painful manifestations associated with different pathological conditions. In this study, we have investigated the effects of vitamin D deficiency on microglia cells, as they represent the main immune cells responsible for early defense at central nervous system (CNS), including chronic pain states. For this purpose, we have employed a model of low vitamin D intake during gestation to evaluate possible changes in primary microglia cells obtained from postnatal day(P)2-3 pups. Afterwards, pain measurement and microglia morphological analysis in the spinal cord level and in brain regions involved in the integration of pain perception were performed in the parents subjected to vitamin D restriction. In cultured microglia, we detected a reactive-activated and proliferative-phenotype associated with intracellular reactive oxygen species (ROS) generation. Oxidative stress was closely correlated with the extent of DNA damage and increased ß-galactosidase (B-gal) activity. Interestingly, the incubation with 25D3 or 1,25D3 or palmitoylethanolamide, an endogenous ligand of peroxisome proliferator-activated-receptor-alpha (PPAR-α), reduced most of these effects. Morphological analysis of ex-vivo microglia obtained from vitamin-D-deficient adult mice revealed an increased number of activated microglia in the spinal cord, while in the brain microglia appeared in a dystrophic phenotype. Remarkably, activated (spinal) or dystrophic (brain) microglia were detected in a prominent manner in females. Our data indicate that vitamin D deficiency produces profound modifications in microglia, suggesting a possible role of these cells in the sensorial dysfunctions associated with hypovitaminosis D.


Assuntos
Dor Crônica/etiologia , Microglia/efeitos dos fármacos , Deficiência de Vitamina D/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Células Cultivadas , Dor Crônica/metabolismo , Modelos Animais de Doenças , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microglia/metabolismo , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Fenótipo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Medula Espinal/efeitos dos fármacos , Vitamina D/metabolismo , Vitamina D/farmacologia , Deficiência de Vitamina D/fisiopatologia
13.
J Cell Mol Med ; 24(21): 12298-12307, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33058526

RESUMO

The aim of this study was to investigate the effects of the lipid mediator Resolvin D1 in experimental keratitis. C57BL/6J mice were injected with lipopolysaccharide (2 µg/eye), and after 24 hours, the corneal damage was assessed. Clinical score was quantified, and corneal inflammatory biomarkers were detected by immunohistochemistry. A robust accumulation of sub-epithelial macrophages and polymorphonuclear leucocytes, chemokine (C-X-C motif) ligand 1 (also known as keratinocyte-derived chemokine), interleukin-10 and promoters of apoptosis was also observed in lipopolysaccharide-treated mice. Formyl peptide receptor 2 corneal expression was also assessed. The corneal stroma treated with lipopolysaccharide was characterized by presence of macrophages of M1-like subtype and immature fibroblastic cells, marked with Ki67, not fully differentiated in fibroblasts. Indeed, the staining of the cornea with anti-vimentin antibodies, a marker of differentiated myofibroblasts, was very faint. Resolvin D1 attenuated all the inflammatory parameters assessed in the present study, except for IL-10. In conclusion, the data presented here seem to be consistent with the hypothesis that Resolvin D1 protected the cornea from the lipopolysaccharide-induced keratitis by acting on several inflammatory components of this damage, pivoted by Formyl peptide receptor 2 (FPR2) activation and macrophages-leucocytes activity.


Assuntos
Substância Própria/metabolismo , Ácidos Docosa-Hexaenoicos/metabolismo , Inflamação/metabolismo , Ceratite/tratamento farmacológico , Animais , Apoptose , Conexina 43/metabolismo , Córnea/efeitos dos fármacos , Modelos Animais de Doenças , Fibroblastos/metabolismo , Imuno-Histoquímica , Interleucina-10/metabolismo , Ceratite/induzido quimicamente , Ceratite/metabolismo , Antígeno Ki-67/metabolismo , Leucócitos/metabolismo , Lipopolissacarídeos , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fenótipo , Vimentina/metabolismo
14.
J Cell Physiol ; 235(5): 4256-4267, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31612492

RESUMO

No study has investigated the interaction of Resolvin D1 (RvD1) with mitochondrial damage of retinal cells caused by diabetes. This study aims to investigate the effects of RvD1 (50 nM) on morphological and biochemical indicators of mitochondrial damage in primary retinal cells exposed to 30 mM d-glucose high glucose (HG). HG-cells exhibited photoreceptor damage characterized by short and small mitochondria with prevalent mitochondrial disruption, fragmentation, and aggregation. The cells had low mitochondrial transporters TIMM44 and TOMM40, Connexin 43, NAD/NADH ratio, and ATP levels, whereas increased cytosolic cytochrome c. Moreover, they expressed high cytosolic metalloproteinase matrix metallopeptidase 9 (MMP-9) and MMP-2 activity. HG-cells treated with RvD1 (50 nM) showed reduced reactive oxygen species levels, improved mitochondrial morphology and function, promoted mitochondrial DNA repair by OGG1, and reduced cell apoptosis and metalloproteinase activity. Therefore, RvD1 induces protection from high glucose-load to the retinal cell and promotes their survival by decreasing cytosolic MMP and mitochondrial damage.


Assuntos
Ácidos Docosa-Hexaenoicos/farmacologia , Glucose/toxicidade , Mitocôndrias/efeitos dos fármacos , Células Fotorreceptoras/efeitos dos fármacos , Trifosfato de Adenosina/metabolismo , Animais , Caspase 3/genética , Caspase 3/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Citocromos c/metabolismo , DNA Glicosilases/genética , DNA Glicosilases/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Metaloproteinases da Matriz/genética , Metaloproteinases da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Proteínas de Transporte da Membrana Mitocondrial , Proteínas do Complexo de Importação de Proteína Precursora Mitocondrial , NAD/metabolismo , Espécies Reativas de Oxigênio/metabolismo
15.
Wound Repair Regen ; 28(6): 780-788, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32706138

RESUMO

BACKGROUND: Chronic wounds are one of the most important challenge for regenerative surgery. Plastic surgeon can use fat graft to increase wound healing because its growth factors can enhance tissue regeneration. In a recent study, the authors evaluated a reduction of pain in a cohort of patients submitted to breast reconstruction with breast implant and lipofilling, putting into evidence that growth factors in fat graft can reduce post-surgical pain. The aim of this work is to evaluate ultra-filtered fat graft potential in reducing pain in chronic wounds. PATIENTS AND METHODS: Fifty new patients with chronic wounds of different etiology were recruited for this study and divided into two groups: A, treatment and B, control. Twenty-five patients per group. Negative pressure therapy dressing was applied after surgical debridement. Three days later patients in group A received ultrafiltered fat graft. Pain was evaluated with preoperative Visual Analogic Scale, repeated twice a day for 14 days and finally 21 days from procedures. RESULTS: In group A (treated patients), pain was lower. These data were confirmed even after 7 days. The overall statistical analysis of the average of all values (SD 1.72) confirmed that the differences were significant at the 95% with the Chi-square test and analysis of variance (P value < .05). CONCLUSIONS: The ultra-filtered fat graft placed on the wound bed and edges was effective in reducing pain in chronic wounds. The reduction of pain was statistically significant.


Assuntos
Tecido Adiposo/transplante , Dor/cirurgia , Ferimentos e Lesões/complicações , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Feminino , Seguimentos , Humanos , Masculino , Dor/diagnóstico , Dor/etiologia , Medição da Dor/métodos , Resultado do Tratamento , Cicatrização , Ferimentos e Lesões/cirurgia
16.
J Cell Mol Med ; 23(10): 6635-6645, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31369209

RESUMO

The aim of this study was to investigate whether telmisartan protects the heart from the ischaemia/reperfusion damage through a local microRNA-1 modulation. Studies on the myocardial ischaemia/reperfusion injury in vivo and on the cardiomyocyte hypoxia/reoxygenation damage in vitro were done. In vivo, male Sprague-Dawley rats administered for 3 weeks with telmisartan 12 mg/kg/d by gastric gavage underwent ischaemia/reperfusion of the left descending coronary artery. In these rats, infarct size measurement, ELISA, immunohistochemistry (IHC) and reverse transcriptase real-time polymerase chain reaction showed that expressions of connexin 43, potassium voltage-gated channel subfamily Q member 1 and the protein Bcl-2 were significantly increased by telmisartan in the reperfused myocardium, paralleled by microRNA-1 down-regulation. In vitro, the transfection of cardiomyocytes with microRNA-1 reduced the expressions of connexin 43, potassium voltage-gated channel subfamily Q member 1 and Bcl-2 in the cells. Telmisartan (50 µmol/L) 60 minutes before hypoxia/reoxygenation, while not affecting the levels of miR-1 in transfected cells in normoxic condition, almost abolished the increment of miR-1 induced by the hypoxia/reoxygenation to transfected cells. All together, telmisartan cardioprotected against the myocardial damage through the microRNA-1 modulation, and consequent modifications of its downstream target connexin 43, potassium voltage-gated channel subfamily Q member 1 and Bcl-2.


Assuntos
MicroRNAs/metabolismo , Infarto do Miocárdio/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Telmisartan/uso terapêutico , Animais , Hipóxia Celular/efeitos dos fármacos , Hipóxia Celular/genética , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Conexina 43/metabolismo , Canal de Potássio KCNQ1/metabolismo , Masculino , MicroRNAs/genética , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/patologia , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/patologia , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Sprague-Dawley , Telmisartan/administração & dosagem
17.
Int J Vitam Nutr Res ; 89(1-2): 22-28, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30694119

RESUMO

Micronutrient deficiencies (MD) shortly after sleeve gastrectomy (SG) are frequent and patients with obesity often show MD preoperatively. Our aim was to assess whether the correction of MD before SG could play a role in preventing early postoperative MD. Eighty patients (58 females, 22 males) who underwent SG were evaluated retrospectively. Patients were divided according to whether they had received preoperative MD correction (Group A, n = 42; 30 females, 12 males) or not (Group B, n = 38; 28 females, 10 males). Micronutrient status was assessed preoperatively, at 3 and 12-months after SG in both groups. After SG, Group A and Group B patients received the same multivitamin supplement and followed the same diet. Nutrient intake of all patients was evaluated by food frequency questionnaires. Before SG, patients of Group A had no MD, whereas patients of Group B were mostly deficient in vitamin B12 (10.5%, 3 women, 1 man), folate (15.8%, 5 women, 1 man), 25-vitamin D (39.5%, 10 women, 5 men), iron (26.3%, 8 women, 2 men), and zinc (7.9%, 2 women, 1 men). At 3- and 12-month follow-up, no patient in group A had developed new MD, whereas all patients of Group B continued to be deficient in one or more micronutrient, despite systematic postoperative supplementation. No statistical differences (p<0.05) in estimated nutrient intake were observed in either group. Based on our findings, we are able to support the hypothesis that pre-SG correction of MD may be useful in preventing early post-SG MD.


Assuntos
Gastrectomia/métodos , Micronutrientes/metabolismo , Obesidade Mórbida , Vitamina D/metabolismo , Vitaminas/metabolismo , Feminino , Humanos , Masculino , Estudos Retrospectivos , Vitamina D/química , Vitaminas/química
19.
Int J Mol Sci ; 20(7)2019 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-30970677

RESUMO

This study investigated whether metabotropic glutamate receptor (mGluR) 5 and 8 are involved in the effect of ultramicronizedpalmitoylethanolamide (um-PEA) on the cognitive behavior and long term potentiation (LTP) at entorhinal cortex (LEC)-dentate gyrus (DG) pathway in mice rendered neuropathic by the spare nerve injury (SNI). SNI reduced discriminative memory and LTP. Um-PEA treatment started after the development of neuropathic pain had no effects in sham mice, whereas it restored cognitive behavior and LTP in SNI mice. 2-Methyl-6-(phenylethynyl) pyridine (MPEP), a selective mGluR5 antagonist, improved cognition in SNI mice and produced a chemical long term depression of the field excitatory postsynaptic potentials (fEPSPs) in sham and SNI mice. After theta burst stimulation (TBS) MPEP restored LTP in SNI mice. In combination with PEA, MPEP antagonized the PEA effect on discriminative memory and decreased LTP in SNI mice. The (RS)-4-(1-amino-1-carboxyethyl)phthalic acid (MDCPG), a selective mGluR8 antagonist, did not affect discriminative memory, but it induced a chemical LTP and prevented the enhancement of fEPSPs after TBS in SNI mice which were treated or not treated with PEA. The effect of PEA on LTP and cognitive behavior was modulated by mGluR5 and mGluR8. In particular in the SNI conditions, the mGluR5 blockade facilitated memory and LTP, but prevented the beneficial effects of PEA on discriminative memory while the mGluR8 blockade, which was ineffective in itself, prevented the favorable action of the PEA on LTP. Thus, although their opposite roles (excitatory/inhibitory of the two receptor subtypes on the glutamatergic system), they appeared to be required for the neuroprotective effect of PEA in conditions of neuropathic pain.


Assuntos
Etanolaminas/administração & dosagem , Neuralgia/tratamento farmacológico , Ácidos Palmíticos/administração & dosagem , Traumatismos dos Nervos Periféricos/tratamento farmacológico , Receptor de Glutamato Metabotrópico 5/metabolismo , Receptores de Glutamato Metabotrópico/metabolismo , Amidas , Animais , Giro Denteado/efeitos dos fármacos , Giro Denteado/metabolismo , Modelos Animais de Doenças , Etanolaminas/farmacologia , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Humanos , Potenciação de Longa Duração/efeitos dos fármacos , Masculino , Memória/efeitos dos fármacos , Camundongos , Neuralgia/etiologia , Neuralgia/metabolismo , Córtex Olfatório/efeitos dos fármacos , Córtex Olfatório/metabolismo , Ácidos Palmíticos/farmacologia , Traumatismos dos Nervos Periféricos/complicações , Traumatismos dos Nervos Periféricos/metabolismo , Piridinas/administração & dosagem , Piridinas/farmacologia
20.
Int J Mol Sci ; 20(5)2019 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-30845774

RESUMO

: The role of sirtuin 6 (SIRT6) in adipose abdominal tissue of pre-diabetic (pre-DM) patients is poorly known. Here, we evaluated SIRT6 expression in visceral abdominal fat of obese pre-diabetic patients and the potential effects of metformin therapy. Results indicated that obese pre-DM subjects showed low SIRT6 protein expression and high expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), peroxisome proliferator-activated receptor gamma (PPAR-γ), and sterol regulatory element-binding transcription factor 1 (SREBP-1). Obese pre-DM patients showed high values of glucose, insulin resistance (HOMA-IR), C reactive protein (CRP), nitrotyrosine, tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6), and low values of insulin (p < 0.05). Of note, abdominal fat tissue of obese pre-DM patients treated with metformin therapy presented higher SIRT6 expression and lower NF-κB, PPAR-γ, and SREBP-1 expression levels compared to pre-DM control group. Collectively, results show that SIRT6 is involved in the inflammatory pathway of subcutaneous abdominal fat of obese pre-DM patients and its expression responds to metformin therapy.


Assuntos
Gordura Abdominal/metabolismo , Metformina/administração & dosagem , Sobrepeso/metabolismo , Estado Pré-Diabético/metabolismo , Sirtuínas/metabolismo , Adulto , Regulação para Baixo/efeitos dos fármacos , Feminino , Humanos , Masculino , Metformina/farmacologia , Pessoa de Meia-Idade , NF-kappa B/metabolismo , Sobrepeso/tratamento farmacológico , PPAR gama/metabolismo , Estado Pré-Diabético/tratamento farmacológico , Estudos Prospectivos , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo
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