Oxigenoterapia hiperbárica. Sus aplicaciones en Cirugía Plástica / Hyperbaric oxygen therapy. Its applications in Plastic Surgery

La oxigenoterapia hiperbárica (OHB) puede mejorar la cicatrización de las heridas. La hipoxia, la alteración de la angiogénesis y la inflamación prolongada son condiciones constantes que la OHB favorece su reversibilidad; hace ya muchos años que, en el listado de indicaciones reconocidas por Sociedades Científicas que rigen esta práctica, se encuentra como indicación aceptada para el tratamiento coadyuvante en injertos o colgajos en riesgo isquémico, como también en heridas refractarias; en la última década, paulatinamente, con la difusión y el aumento de las facilidades para acceder a equipos hiperbáricos, las indicaciones se extendieron al área de la cirugía plástica, para tratamiento de complicaciones posoperatorias en tejidos isquémicos o necrosados y también para preacodicionamiento preoperatorio y sostén posoperatorio de cierto grupo de pacientes con mayor riesgo de sufrir una complicación, en las lipotransferencias como coadyuvante para aumento de la preservación de una mayor cantidad de tejido graso. Las publicaciones al respecto son cada día más frecuentes, algunas presentan un pequeño número de casos, otras son estudios de cohorte retrospectivos, con un nivel de evidencia elevado. El objetivo de este artículo es presentar el concepto básico de los efectos de la OHB, referencia al estado actual de las distintas indicaciones en uso en cirugía plástica y medicina cosmética y la experiencia personal al respecto.

Hyperbaric oxygen therapy (HOT) can improve wound healing, hypoxia, alteration of angiogenesis and prolonged infl ammation are constant conditions that HOT favors its reversibility for many years now, in the list of indications recognized by Scientifi c Societies. that govern this practice, is a recognized indication for adjuvant treatment in grafts or fl aps at ischemic risk, as well as in refractory wounds; In the last decade, gradually, with the dissemination and increase in the facilities to access hyperbaric equipment, the indications were extended to the area of plastic surgery, for the treatment of post-operative complications in ischemic or necrotic tissues as well as for preconditioning. operative and post-operative support of a certain group of patients with a higher risk of suff ering a complication, in lipotransferences as an adjuvant to increase the preservation of a greater amount of fatty tissue. Publications in this regard are becoming more frequent every day, some present a small number of cases, others are retrospective cohort studies, with a high level of evidence. The objective of this article is to present the basic concept of the eff ects of HOT, reference to the current state of the diff erent indications in use in plastic surgery, and cosmetic medicine and personal experience in this regard

Breviscapine alleviates myocardial ischemia-reperfusion injury in diabetes rats

Purpose: To investigate the protective effect of breviscapine on myocardial ischemia-reperfusion injury (MIRI) in diabetes rats. Methods: Forty rats were divided into control, diabetes, MIRI of diabetes, and treatment groups. The MIRI of diabetes model was established in the latter two groups. Then, the treatment group was treated with 100 mg/kg breviscapine by intraperitoneal injection for 14 consecutive days. Results: After treatment, compared with MIRI of diabetes group, in treatment group the serum fasting blood glucose, fasting insulin, homeostasis model assessment of insulin resistance, and glycosylated hemoglobin levels decreased, the serum total cholesterol, triacylglycerol, and low-density lipoprotein cholesterol levels decreased, the serum high-density lipoprotein cholesterol level increased, the heart rate decreased, the mean arterial pressure, left ventricular ejection fraction, and fractional shortening increased, the serum cardiac troponin I, and creatine kinase-MB levels decreased, the myocardial tumor necrosis factor α and interleukin-6 levels decreased, the myocardial superoxide dismutase level increased, and the myocardial malondialdehyde level decreased (all P < 0.05). Conclusions: For treating MIRI of diabetes in rats, the breviscapine can reduce the blood glucose and lipid levels, improve the cardiac function, reduce the myocardial injury, and decrease the inflammatory response and oxidative stress, thus exerting the alleviating effect.

E-cadherin and NF-κB expression in the vagina after ovarian ischemia and reperfusion

Purpose: To investigate inflammation and cell adhesion molecules in the vagina after ovarian ischemia-reperfusion (IR) injury. Methods: 20 Wistar albino female rats were divided into two groups: control, and IR groups. In IR group, blood flow was restricted for 2 hours for ovarian ischemia. Then, tissues were re-blood 2 hours for reperfusion. Vagina tissues were excised and processed for histopathological analysis. Histopathological and biochemical follow-ups were performed. Results: Both malondialdehyde and myeloperoxidase values were increased in IR group compared to control group. Glutathione content was decreased in IR group compared to control group. Epithelial degeneration, inflammation, dilatation, and nuclear factor-κB (NF-κB) expression were increased in IR group compared to control group. E-cadherin expression was significantly decreased in IR group. In the IR group, E-cadherin showed a positive reaction in adenomas, gland-like cryptic structures, cellular junctions with clustered inflammatory cells. In the IR group, NF-κB expression was increased in basement membrane, inflammatory cells, in blood vessels. Conclusions: Ovarian ischemia caused degeneration of epithelial cells in the vaginal region and disruptions in the cell junction complex, which leads to activation of E-cadherin and NF-κB signaling pathway and alterations in reproductive and embryonal development in the vaginal region.

Protective effects of hesperidin in gastric damage caused by experimental ischemia-reperfusion injury model in rats

Purpose: This study evaluated the protective effect of hesperidin on injury induced by gastric ischemia-reperfusion. Methods: Fifty male Sprague Dawley rats (250­300 g) were divided into five groups: control (C), sham (S), ischemia (I), ischemia-reperfusion (I/R) and hesperidin + ischemia-reperfusion (Hes + I/R). Hesperidin was injected intraperitoneally at the dose of 100 mg/kg one hour before the experimental stomach ischemia-reperfusion. Celiac artery was ligated. After 45 minutes ischemia and 60 minutes reperfusion period, blood samples were obtained under anesthesia. Then, animals were sacrificed, stomach tissues were excised for biochemical, and histopathological analyses were performed. Malondialdehyde levels and superoxide dismutase, glutathione peroxidase activities and total antioxidant status (TAS), total oxidant status (TOS), protein, total thiol parameters were measured in plasma, and tissue homogenate samples. H + E, periodic acid­Schiff, hypoxia inducible factor, terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end-labeling (TUNEL), and proliferating cell nuclear antigen (PCNA) for cell proliferation as immunohistochemical parameters were determined. Results: Upon biochemical and histopathological assessment, hesperidin decreased stomach tissue changes in comparison with IR group. Ischemia-reperfusion injury led to a considerably increase in malondialdehyde, protein, and TOS levels (p < 0.001) in stomach tissue. Hesperidin treatment significantly decreased malondialdehyde, protein, and TOS levels (p < 0.001). Hesperidin increased superoxide dismutase, TAS, total thiol and glutathione peroxidase activities in comparison with IR group. Hesperidin reduced damage and also increased TUNEL and PCNA immunoreactivity in stomach tissue. Conclusions: Hesperidin was able to decrease I/R injury of the stomach tissue due to inhibition of lipid peroxidation and protein oxidation, duration of antioxidant, and free radical scavenger properties. Consequently, hesperidin can provide a beneficial therapeutic choice for preventing stomach tissue ischemia-reperfusion injury in clinical application.

Prediction of Preterm Delivery Using Serum Ischemia Modified Albumin, Biglycan, and Decorin Levels in Women with Threatened Preterm Labor / Previsão de parto prematuro usando albumina modificada por isquemia sérica, biglicano e níveis de decorina em mulheres com ameaça de trabalho de parto prematuro

Abstract Objective The serum ischemia modified albumin (IMA), biglycan, and decorin levels of pregnant women who were hospitalized for threatened preterm labor were measured. Methods Fifty-one consecutive pregnant women with a single pregnancy between the 24th and 36th weeks with a diagnosis of threatened preterm labor were included in the present prospective cohort study. Results As a result of multivariate logistic regression analysis for predicting preterm delivery within 24 hours, 48 hours, 7 days, 14 days, ≤ 35 gestational weeks, and ≤ 37 gestational weeks after admission, area under the curve (AUC) (95% confidence interval [CI[) values were 0.95 (0.89-1.00), 0.93 (0.86-0.99), 0.91 (0.83-0.98), 0.92 (0.85-0.99), 0.82 (0.69-0.96), and 0.89 (0.80-0.98), respectively. In the present study, IMA and biglycan levels were found to be higher and decorin levels lower in women admitted to the hospital with threatened preterm labor and who gave preterm birth within 48 hours compared with those who gave birth after 48 hours. Conclusion In pregnant women admitted to the hospital with threatened preterm labor, the prediction preterm delivery of the combined model created by adding IMA, decorin, and biglycan in addition to the TVS CL measurement was higher than the TVS CL measurement alone. Clinical trial registration The present trial was registered at ClinicalTrials.gov, number NCT04451928.

Resumo Objetivo Medir os níveis séricos de albumina modificada por isquemia (IMA), biglicano e decorina de gestantes hospitalizadas por ameaça de parto prematuro. Métodos Cinquenta e uma mulheres grávidas consecutivas com uma única gravidez entre a 24ᵃ e a 36ᵃ semanas com diagnóstico de ameaça de trabalho de parto prematuro foram incluídas no presente estudo de corte prospectivo. Resultados Como resultado da análise de regressão logística multivariada para prever parto prematuro dentro de 24 horas, 48 horas, 7 dias, 14 dias, ≤ 35 semanas gestacionais e ≤ 37 semanas gestacionais após a admissão, área sob a curva (AUC) (95% de confiança os valores de intervalo [CI[) foram 0,95 (0,89-1,00), 0,93 (0,86-0,99), 0,91 (0,83-0,98), 0,92 (0,85-0,99), 0,82 (0,69-0,96) e 0,89 (0,80-0,98), respectivamente. No presente estudo, os níveis de IMA e biglican foram maiores e os níveis de decorin menores em mulheres admitidas no hospital com ameaça de trabalho de parto prematuro e que tiveram parto prematuro em 48 horas em comparação com aquelas que deram à luz após 48 horas. Conclusão Em gestantes admitidas no hospital com ameaça de trabalho de parto prematuro, a predição de parto prematuro do modelo combinado criado pela adição de IMA, decorin e biglican, além da medição do TVS CL, foi maior do que a medição do TVS CL isoladamente. Registro do ensaio clínico O presente ensaio foi registrado em ClinicalTrials.gov, número NCT04451928.

Animal Model Standardization for Studying Avascular Necrosis of the Femoral Head in Legg-Calvé-Perthes Disease / Padronização de modelo animal para o estudo da necrose isquêmica da cabeça femoral na doença de Legg-Calvé-Perthes

Abstract Objective Testing an experimental model for ischemic necrosis of the femoral head in Legg-Calvé-Perthes disease by evaluating gait, imaging and morphohistology. Methods The operation was done in 11 piglets. Necrosis by cerclage in the right femoral neck was induced. Piglets were divided into group A, with 8 animals, euthanizing two in the 2nd, 4th, 6th, and 8th weeks, respectively; and group B, with 2 animals (sham), submitted to the surgical procedure without cerclage of the right femoral neck. The gait classification used was that of Etterlin. The frozen femurs were submitted to digital radiography and computed tomography. The height and width of the epiphysis and epiphysary coefficient were measured at study times. Light microscopy and immunohistochemistry with TGF-β1 were performed. Results One animal died of sepsis in Group A. In this group, claudication was observed in all animals. On digital radiography and computed tomography, bone sclerosis, enlargement of the right femoral neck, flattening, collapse, and fragmentation of the right femoral head were observed. All epiphysis height and epiphysary coefficient values of the right femoral head were lower than the contralateral ones, in which were observed chondrocytes disordered and separated by gaps. A reduction in TGF-β1 expression was observed at 2 and 6 weeks in the right femoral head and at eight in the left. In group B, there were no signs of necrosis and gait was normal. Conclusions The model presented reproduced macroscopic necrosis on digital radiography, computed tomography, and microscopy. Gait evaluation showed a good correlation with other ischemia findings. Level of EvidenceV. Diagnostic studies.

Resumo Objetivo Testar um modelo experimental para necrose isquêmica da cabeça femoral na doença de Legg-Calvé-Perthes avaliando a marcha, exames de imagens e morfohistologia. Métodos Operaram-se 11 leitões. Induziu-se a necrose por cerclagem no colo femoral direito. Dividiram-se os leitões em grupo A com 8 animais, sacrificando-se dois na 2ª, 4ª, 6ª e 8ª semanas, respectivamente; e grupo B, com 2 animais (sham), submetidos ao procedimento cirúrgico sem a cerclagem do colo femoral direito. A classificação da marcha utilizada foi a de Etterlin. Os fêmures congelados foram submetidos à radiografia digital e tomografia computadorizada. Mediram-se a altura e largura da epífise e o coeficiente epifisário nos tempos de estudo. Realizou-se, microscopia de luz e imunohistoquímica com TGF-β1. Resultados Um animal morreu por sepse no grupo A. Neste grupo, observou-se claudicação em todos os animais. Na radiografia digital e tomografia computadorizada observaram-se: esclerose óssea, alargamento do colo femoral direito, achatamento, colapso e fragmentação da cabeça femoral direita. Todos os valores da altura da epífise e coeficiente epifisário da cabeça femoral direita foram menores que os contralaterais, nos quais observaram-se condrócitos desordenados e separados por lacunas. Observou-se redução da expressão do TGF-β1 com 2 e 6 semanas nas cabeças femorais direitas e nas esquerdas com oito. No grupo B, não ocorreram sinais de necrose e a marcha foi normal. Conclusões O modelo apresentado reproduziu a necrose macroscopicamente, na radiografia digital, tomografia computadorizada e microscopia. A avaliação da marcha demonstrou boa correlação com os demais achados de isquemia. Nível de EvidênciaV. Estudos diagnósticos.

Parto vaginal operatório / Operative vaginal delivery

PONTOS-CHAVE Quando utilizados na técnica correta, fórcipes e vácuo-extratores apresentam baixos índices de complicações. Para o feto com sinais de hipóxia no período expulsivo, o parto vaginal operatório tem potencial para reduzir a exposição aos fatores intraparto que promovem a encefalopatia hipóxico-isquêmica. Fórcipes médios e/ou rotacionais são opções apropriadas em circunstâncias selecionadas e exigem habilidade e experiência. Os fórcipes são mais resolutivos do que os vácuo-extratores para o parto vaginal operatório, porém são mais associados a lacerações perineais graves. Céfalo-hematoma é mais provável de ocorrer com o aumento na duração da vácuo-extração. Os vácuo-extratores de campânulas flexíveis apresentam taxas maiores de falha, porém apresentam menores incidências de trauma no couro cabeludo do neonato. (AU)

Cyanidin-3-O-glucoside plays a protective role against renal ischemia/ reperfusion injury via the JAK/STAT pathway

Purpose: To investigate the role of cyanidin-3-O-glucoside (C3G) in renal ischemia/reperfusion (I/R) injury and the potential mechanisms. Methods: Mouse models were established by clamping the left renal vessels, and in vitro cellular models were established by hypoxic reoxygenation. Results: Renal dysfunction and tissue structural damage were significantly higher in the I/R group. After treatment with different concentrations of C3G, the levels of renal dysfunction and tissue structural damage decreased at different levels. And its protective effect was most pronounced at 200 mg/kg. The use of C3G reduced apoptosis as well as the expression of endoplasmic reticulum stress (ERS)-related proteins. Hypoxia/reoxygenation (H/R)-induced apoptosis and ERS are dependent on oxidative stress in vitro. In addition, both AG490 and C3G inhibited the activation of JAK/STAT pathway and attenuated oxidative stress, ischemia-induced apoptosis and ERS. Conclusions: The results demonstrated that C3G blocked renal apoptosis and ERS protein expression by preventing reactive oxygen species (ROS) production after I/R via the JAK/STAT pathway, suggesting that C3G may be a potential therapeutic agent for renal I/R injury.

Nephroprotective effects of Lippia sidoides ethanolic extract against ischemia/reperfusion-induced acute kidney injury

Abstract Ischemia/reperfusion injury (I/R) is commonly related to acute kidney injury (AKI) and oxidative stress. Antioxidant agents are used to treat this condition. Lippia sidoides is a brazillian shrub with anti-inflammatory and anti-oxidative properties. Thus, the aim of this study is to evaluate the effect of Lippia sidoides ethanolic extract (LSEE) on in vivo and in vitro models of AKI induced by I/R. Male Wistar rats were submitted to unilateral nephrectomy and ischemia on contralateral kidney for 60 min via clamping followed by reperfusion for 48 h. They were divided into four groups: Sham, LSEE (sham-operated rats pre-treated with LSEE), I/R (rats submitted to ischemia) and I/R-LSEE (rats treated with LSEE before ischemia). Kidney tissues homogenates were used to determine stress parameters and nephrin expression. Plasma and urine samples were collected for biochemical analysis. I/R in vitro assays were evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) and flow cytometry assays in Rhesus Monkey Kidney Epithelial Cells (LLC-MK2). The LSEE treatment prevented biochemical and nephrin expression alterations, as well as oxidative stress parameters. In the in vitro assay, LSEE protected against cell death, reduced the reactive oxygen species and increased mitochondrial transmembrane potential. LSEE showed biotechnological potential for a new phytomedicine as a nephroprotective agent.

Compound Danshen Dripping Pills pretreatment protects the heart from ischemia/reperfusion injury by enhancing autophagic flux

Abstract Compound Danshen Dripping Pills (CDDPs) have been used in clinical treatment to protect the heart from ischemia/reperfusion (IR) injury for many years. However, the underlying mechanism implicated in the protective effects remains to be explored. Here, we determined the effects of CDDPs in Sprague-Dawley rats with the IR model. Cardiac function in vivo was assessed by echocardiography. Transmission electron microscopy, histological and immunohistochemical techniques, Western blotting and recombinant adeno-associated virus 9 transfection were used to illustrate the effects of CDDPs on IR and autophagy. Our results showed that pretreatment with CDDPs decreased the level of serum myocardial enzymes and infarct size in rats after IR. Apoptosis evaluation showed that CDDPs significantly ameliorated the cardiac apoptosis level after IR. Meanwhile, CDDPs pretreatment increased myocardial autophagic flux, with upregulation of LC3B, downregulation of p62, and increased autophagosomes and autolysosomes. Moreover, the autophagic flux inhibitor chloroquine could increase IR injury, while CDDPs could partially reverse the effects. Furthermore, our results showed that the activation of AMPK/mTOR was involved in the cardioprotective effect exerted by CDDPs. Herein, we suggest that CDDPs partially protect the heart from IR injury by enhancing autophagic flux through the activation of AMPK/mTOR.

Enrichment of miR-17-5p enhances the protective effects of EPC-EXs on vascular and skeletal muscle injury in a diabetic hind limb ischemia model

BACKGROUND/AIMS: Diabetes mellitus (DM) is highly susceptible to diabetic hind limb ischemia (DHI). MicroRNA (MiR)-17-5p is downregulated in DM and plays a key role in vascular protection. Endothelial progenitor cell (EPC)-released exosomes (EPC-EXs) contribute to vascular protection and ischemic tissue repair by transferring their contained miRs to target cells. Here, we investigated whether miR-17-5p-enriched EPC-EXs (EPC-EXsmiR-17-5p) had conspicuous effects on protecting vascular and skeletal muscle in DHI in vitro and in vivo. METHODS: EPCs transfected with scrambled control or miR-17-5p mimics were used to generate EPC-EXs and EPC-EXsmiR-17-5p. Db/db mice were subjected to hind limb ischemia. After the surgery, EPC-EXs and EPC-EXsmiR-17-5p were injected into the gastrocnemius muscle of the hind limb once every 7 days for 3 weeks. Blood flow, microvessel density, capillary angiogenesis, gastrocnemius muscle weight, structure integrity, and apoptosis in the hind limb were assessed. Vascular endothelial cells (ECs) and myoblast cells (C2C12 cells) were subjected to hypoxia plus high glucose (HG) and cocultured with EPC-EXs and EPC-EXsmiR-17-5p. A bioinformatics assay was used to analyze the potential target gene of miR-17-5p, the levels of SPRED1, PI3K, phosphorylated Akt, cleaved caspase-9 and cleaved caspase-3 were measured, and a PI3K inhibitor (LY294002) was used for pathway analysis. RESULTS: In the DHI mouse model, miR-17-5p was markedly decreased in hind limb vessels and muscle tissues, and infusion of EPC-EXsmiR-17-5p was more effective than EPC-EXs in increasing miR-17-5p levels, blood flow, microvessel density, and capillary angiogenesis, as well as in promoting muscle weight, force production and structural integrity while reducing apoptosis in gastrocnemius muscle. In Hypoxia plus HG-injured ECs and C2C12 cells, we found that EPC-EXsmiR-17-5p could deliver their carried miR-17-5p into target ECs and C2C12 cells and subsequently downregulate the target protein SPRED1 while increasing the levels of PI3K and phosphorylated Akt. EPC-EXsmiR-17-5p were more effective than EPC-EXs in decreasing apoptosis and necrosis while increasing viability, migration, and tube formation in Hypoxia plus HG-injured ECs and in decreasing apoptosis while increasing viability and myotube formation in C2C12 cells. These effects of EPC-EXsmiR-17-5p could be abolished by a PI3K inhibitor (LY294002). CONCLUSION: Our results suggest that miR-17-5p promotes the beneficial effects of EPC-EXs on DHI by protecting vascular ECs and muscle cell functions.

Does fasting protect liver from ischemia and reperfusion injury?

Purpose: To evaluate local and systemic effects of 24-hour fasting in liver ischemia and reperfusion injury. Methods: Twenty-one adult male Wistar rats (330-390 g) were submitted to 60 minutes of hepatic ischemia followed by 24 hours of reperfusion. Before the day of the experiment, the animals fasted, but free access to water was allowed. Two groups were constituted: Control: non-fasted, that is, feeding ad libitum before surgical procedure; Fasting: rats underwent previous fasting of 24 hours. Hepatic ischemia was performed using vascular clamp in hepatic pedicle. At 24 hours after liver reperfusion, blood and tissue samples were collected. To analysis, liver lobes submitted to ischemia was identified as ischemic liver and paracaval non-ischemic lobes as non-ischemic liver. We evaluated: malondialdehyde levels, hepatocellular function (alanine aminotransferase, aspartate aminotransferase activities, and both ratio), cytokines (interleukins-6, -10, and tumor necrosis factor-alpha), hepatic ischemia and reperfusion injury (histology). Results: Malondialdehyde measured in non-ischemic and ischemic liver samples, hepatocellular function and cytokines were comparable between groups. Histological findings were distinct in three regions evaluated. Microvesicular steatosis was comparable between 24-hour fasting and non-fasted control groups in periportal region of hepatic lobe. In contrast, steatosis was more pronounced in zones 2 and 3 of ischemic liver samples of fasting compared to control groups. Conclusions: These data indicates that fasting does not protect, but it can be also detrimental to liver submitted to ischemia/reperfusion damage. At that time, using long fasting before liver surgery in the real world may be contraindicated.

A rat model of dual-flow liver machine perfusion system

Purpose: As clinical liver perfusion systems use portal vein and artery flow, dual perfusion techniques are required even in small animal models in order to reproduce clinical setting. The aim of this study was to construct a new dual-flow perfusion system in rat model and optimized the oxygen supply to ensure the aerobic metabolization. Methods: The dual-flow circuit was fabricated using rat liver and whole blood samples as perfusates. The oxygen supply was controlled according to the amount of dissolved oxygen in the perfusate. Perfusate parameters and adenosine triphosphate (ATP) levels were analyzed to evaluate organ function and metabolic energy state. Stored whole blood also tested the suitability as perfusate. Results: Stored blood showed decrease oxygen delivery and liver function compared to fresh blood. Using fresh blood as perfusate with air only, the dissolved oxygen levels remained low and anaerobic metabolism increased. In contrast, with oxygen control at living body level, anaerobic metabolism was well suppressed, and tissue ATP content was increased. Conclusions: We developed a new dual-flow system that enable to reproduce the clinical settings. The perfusion system showed the possibility to improve the energy metabolic state of the perfused organ under appropriate partial pressure of oxygen.

Effects of daidzein on rat ovary against ischemia-reperfusion

Purpose: Our aim was to investigate protective effects of daidzein treatment on ischemia-reperfusion (I/R) injury-induced ovarian tissue by immunohistochemical techniques. Methods: Thirty Sprague Dawley female rats were categorized into three groups as sham, I/R group, and I/R+daidzein groups. Bloods were analyzed for malondialdehyde (MDA), glutathione peroxidase (GSH), and myeloperoxidase (MPO), and ovaries were processed for histological tissue protocol. Results: Both MDA and MPO values were increased in I/R group compared to sham and I/R+daidzein groups. GSH content was increased in I/R+daidzein group compared to I/R groups. In I/R group, theca and follicular cells were degenerated with apoptosis and dilatation and congestion, edema. In I/R+daidzein group, daidzein improved pathologies. In the I/R group, Bax expression was positive with follicular cells, granulosa cells and inflammatory cells. In the I/R+daidzein group, positive Bax reaction was observed in the epithelial, antral, and inflammatory cells. In I/R group, Bcl-2 reaction was in germinative epithelial cells, cells of antral follicle. In the I/R+daidzein group, Bcl-2 expression level was reduced after daidzein treatment. Conclusions: After the I/R procedure, ovarian cells and follicles were degenerated with apoptosis and inflammation. After daidzein treatment, Bax and Bcl-2 signal were decreased. It was observed that daidzein stopped the apoptotic process.

Spinal cord ischemia as intraoperatory complication in shoulder surgery positioned in beach chair: case report

Abstract Spinal cord infarction is an uncommon phenomenon, which can be caused by different etiologies, constituting a real diagnostic challenge which can lead to devastating consequences. General anesthesia in beach chair positioning with intraoperative hypotension in order to avoid surgical bleeding are associated with hypoperfusion and potential neurological ischemia-related complications. We present a case of spinal cord ischemia in the context of shoulder surgery in a beach chair position.

Study of laser fluorescence spectroscopy in livers of rats with hypothermic ischemia

Purpose: After partial hepatectomy (PH), the remaining liver (RL) undergoes regenerative response proportional to the host. Limited literature exists on hepatic viability after tissue injury during hypothermic preservation. Spectroscopy measures cellular fluorescence and is explored for tissue characterization and parameter investigation. This study aimed to assess fluorescence analysis (spectroscopy) in evaluating liver viability and its relationship with hepatic tissue regeneration 24 hours after PH. Additionally, we analyzed liver regeneration in RL after 70% partial hepatectomy under hypothermic conditions with laser irradiation. Methods: Fifty-six Wistar rats were divided into four groups: total non-perfused liver (control), total perfused liver, partial hepatectomy "in situ", and partial hepatectomy "ex situ". Tissue analysis was performed at 0 and 24 hours using spectroscopy with laser devices emitting at 532 (green) and 405 nm (violet). Results: Spectroscopy identified tissue viability based on consistent results with Ki67 staining. The fluorescence spectra and Ki67 analysis displayed similar patterns, linking proliferative activity and absorption intensity. Conclusions: Fluorescence spectroscopy proves to be promising for real-time analysis of cellular activity and viability. Metabolic activity was observed in groups of live animals and hypothermically preserved samples, indicating cellular function even under blood deprivation and hypothermic conditions.

CD38: rol en la electrofisiología cardíaca normal y en arritmias por isquemia y reperfusión / CD38: role in normal cardiac electrophysiology and in arrhythmias due to ischemia and reperfusion

Introducción: CD38 es una glicoproteína transmembrana de 300 aminoácidos y 45 kDa expresada de forma ubicua en el organismo que cumple importantes funciones en el metabolismo del cofactor NAD+ y en la regulación del movimiento del calcio celular. Uno de los productos enzimáticos de CD38 es el adenosín difosfato ribosa cíclico o ADP-ribosil cíclico (ADPRc), que actúa como segundo mensajero sensibilizando la liberación de calcio inducida por calcio (CICR por su sigla en inglés). En las últimas 3 décadas se han hecho esfuerzos en la investigación del papel de esta enzima en el sistema cardiovascular, sin embargo aún resta mucho por saber. Antecedentes: Los primeros estudios sobre el papel de CD38/ADPRc a nivel miocárdico mostraron un efecto potenciador del transitorio del calcio por parte del ADPRc. Además se ha descrito un papel arritmogénico utilizando distintas técnicas tanto en modelos reduccionistas como en organismos de mamíferos in vivo. Entre ellos se encuentran modelos de ratones Knock Out para CD38 (CD38KO). La enzima forma parte de la vía de señalización adrenérgica a través de la producción de ADPRc, y se la ha vinculado también a procesos patológicos relacionados con hipertrofia ventricular e isquemia miocárdica. Por ejemplo, la inhibición de la actividad de CD38 protegería al corazón contra la injuria por isquemia y reperfusión (I-R) in vivo e in vitro, disminuyendo el área de infarto. Nuestro grupo ha estado estudiando el rol de CD38 en la actividad cardíaca. Hemos reportado alteraciones en el manejo del Ca++ en miocitos ventriculares aislados de ratones CD38KO, y, en ratones CD38KO in vivo, menor frecuencia cardíaca (FC), marcada variabilidad de la FC, así como menor incidencia de arritmias ventriculares ante un estímulo suprafisiológico de cafeína/adrenalina. No obstante, no se ha investigado su papel en las arritmias por isquemia y reperfusión (I-R) teniendo en cuenta la conocida sobrecarga celular de calcio en este contexto y sabiendo que es la principal causa de muerte súbita en la población general. Tampoco sabemos cómo contribuye a la electrofisiología miocárdica en condiciones fisiológicas, específicamente a la morfología del potencial de acción miocárdico (PA) o a la morfología del trazado electrocardiográfico (ECG). Objetivo: Analizar el papel de CD38 en la actividad eléctrica miocárdica estudiando desde el PA celular hasta el ECG de superficie y su posible impacto en arritmias ventriculares producidas por isquemia y reperfusión. Estrategia: Para el desarrollo de la tesis trabajé con modelos de ratones salvajes (wild type, WT) y CD38KO tanto in vivo como in vitro. Estudié el corazón aislado y perfundido mediante el sistema Langendorff realizando registro extracelular (EMG) e intracelular (potencial de acción, PA). Realicé una caracterización de la morfología del PA midiendo la duración al 30% (APD30) y al 90% (APD90) de la repolarización. Comparé entre las cepas WT y CD38KO con y sin estimulo adrenérgico y en la cepa WT entre estado control y ante la inhibición de CD38 con 78c, un fármaco inhibidor de la actividad enzimática de CD38. Para comparar el potencial arritmogénico de los corazones de ambas cepas a la injuria provocada por I-R registré la actividad eléctrica espontánea mediante EMG, en condiciones basales, durante isquemia global y reperfusión. En el modelo in vivo analicé el ECG de ratones WT y CD38KO anestesiados y comparé la actividad basal y la respuesta arrítmica ante un modelo de infarto de miocardio por sobrecarga adrenérgica con isoproterenol. Resultados y discusión: Describí por primera vez la morfología del PA en la cepa CD38KO y no fue distinta a la de los ratones salvajes en condiciones basales. Esta falta de diferencias podría deberse a compensaciones fisiológicas que ocurren ante la carencia de la enzima como el aumento en la expresión de la bomba SERCA2a. Por lo contrario, cuando sometí el preparado a un desequilibrio homeostático estimulando con un agonista beta adrenérgico, la APD90 de los corazones CD38KO no disminuyó como la de los WT. En concordancia, la inhibición aguda de CD38 en el PA miocárdico de corazones WT perfundidos con 78c aumentó la APD90 significativamente sin cambios en el APD30. Cuando sometí a los corazones CD38KO aislados a un medio arritmogénico con alto contenido de calcio y bajo en potasio, la FC en estos no aumentó a diferencia de lo que ocurrió marcadamente en los WT. La respuesta arrítmica ante la isquemia global en el corazón aislado no fue menor en la cepa CD38KO a diferencia de lo esperado, mostrando una incidencia de 57 % en los WT y 75 % en los CD38KO (valor p = 0.61). En el modelo in vivo describí por primera vez el trazado electrocardiográfico (DII) de animales carentes de CD38. No hubo diferencias en la FC, intervalo PR, intervalo QT, amplitud de onda S, ni amplitud de onda T. Sin embargo la duración del QRS fue menor, mientras que la amplitud de la onda R fue mayor en los ratones CD38KO, probablemente secundario a una mayor velocidad de conducción. Estas diferencias se perdieron en la etapa aguda de la isquemia por sobrecarga adrenérgica. En la cepa CD38KO como era esperado vi mayor proporción de pausas sinusales, que se hicieron más evidentes ante la injuria por isoproterenol, lo que podría estar evidenciando una mayor refractariedad del CICR por disminución del contenido de calcio reticular. No se demostró la protección ante arritmias generadas por isquemia en la cepa CD38KO ya que el incremento de la carga arrítmica fue similar en ambas cepas. No hubo diferencias significativas en la proporción de ratones afectados ni en la suma total de extrasístoles ventriculares registradas pero la mortalidad que generó la sobrecarga adrenérgica en el grupo WT fue de 1/3 mientras que la totalidad de los ratones CD38KO sobrevivieron. Conclusiones: En esta tesis presento una caracterización electrofisiológica de CD38 desde el PA en corazón entero hasta la manifestación electrocardiográfica de superficie, con una evaluación especial de su papel en arritmias por I-R y desarrollando técnicas innovadoras a nivel nacional. Las principales conclusiones son: CD38: rol en la electrofisiología cardíaca normal y en arritmias por isquemia y reperfusión 12 - CD38 contribuye a la repolarización tardía disminuyendo el APD90. - La ausencia de la enzima evita el aumento de la FC en un medio arritmogénico con sobrecarga de Ca++ . - CD38 contribuye con un enlentecimiento en la velocidad de conducción miocárdica manifiesta en un descenso de la duración y aumento del voltaje del QRS en los corazones de ratones que no expresan CD38La deleción de CD38 genera un aumento marcado de pausas sinusales ante la isquemia. - No hay evidencia de una protección ante arritmias malignas por I-R in vitro mediante la deleción de CD38. - No se vio una contribución de CD38 a arritmias malignas por isquemia in vivo aunque la ausencia de la enzima parece mejorar el perfil de supervivencia.

Pre-treatment of the beta3-adrenergic receptor agonist BRL37344 reduces in vivo myocardial ischemia/reperfusion injury by improving AMPK and SIRT1 activity and by suppressing mTOR and p70S6K signaling pathways

Abstract This study aimed to investigate the role and signaling pathways of β3-AR in myocardial ischemia/reperfusion (I/R) injury, which is one of the leading causes of death worldwide. 47 male rats were randomly divided into two main groups to evaluate infarct size and molecular parameters. Rats in both groups were randomly divided into 4 groups. Control (sham), I/R (30 min ischemia/120 min reperfusion), BRL37344 (BRL) (A) (5 µg/kg single-dose pre-treatment (preT) before I/R) and BRL (B) (5 µg/kg/day preT for 10 days before I/R). Infarct size was determined with triphenyltetrazolium chloride staining and analyzed with ImageJ program. The levels of AMPK, SIRT1, mTOR, and p70SK6 responsible for cellular energy and autophagy were evaluated by western blot. Infarct size increased in the I/R group (44.84 ± 1.47%) and reduced in the single-dose and 10-day BRL-treated groups (32.22 ± 1.57%, 29.65 ± 0.55%; respectively). AMPK and SIRT1 levels were decreased by I/R but improved in the treatment groups. While mTOR and p70S6K levels increased in the I/R group, they decreased with BRL preT. BRL preT protects the heart against I/R injury. These beneficial effects are mediated in part by activation of AMPK and SIRT1, inhibition of mTOR and p70S6K, and consequently protected autophagy.

Diseño y validación de una herramienta para la predicción de desenlaces adversos en pacientes con obstrucción intestinal por bridas: La escala HALVIC / Design and validation of a predicting adverse outcomes toll for patients with adhesive small bowel obstruction: HALVIC score

Introducción. La obstrucción intestinal por bridas representa una causa común de consulta a los servicios de urgencias, pero hay poca claridad sobre qué pacientes tienen mayor riesgo de desarrollar complicaciones. El objetivo de este estudio fue diseñar y validar una escala de predicción de riesgo de desenlaces adversos en pacientes con obstrucción intestinal por bridas. Métodos. Estudio de cohorte retrospectivo realizado a partir de la base de datos MIMIC-IV. Se incluyeron pacientes adultos admitidos al servicio de urgencias entre 2008 y 2019, con diagnóstico de obstrucción intestinal por bridas. El desenlace principal fue el compuesto de resección intestinal, ingreso a unidad de cuidados intensivos y mortalidad por cualquier causa. Se diseñó una escala de predicción de riesgo asignando un puntaje a cada variable. Resultados. Se incluyeron 513 pacientes, 63,7 % hombres. El desenlace compuesto se presentó en el 25,7 % de los casos. La edad, historia de insuficiencia cardiaca y enfermedad arterial periférica, nivel de hemoglobina, recuento de leucocitos e INR constituyeron el mejor modelo de predicción de estos desenlaces (AUC 0,75). A partir de este modelo, se creó la escala simplificada HALVIC, clasificando el riesgo del desenlace compuesto en bajo (0-2 puntos), medio (3-4 puntos) y alto (5-7 puntos). Conclusión. La escala HALVIC es una herramienta de predicción simple y fácilmente aplicable. Puede identificar de manera precisa los pacientes con obstrucción intestinal por bridas con alto riesgo de complicaciones, permitiendo el ajuste individualizado de las estrategias de manejo para mejorar los desenlaces

Introduction. Adhesive Small Bowel Obstruction (ASBO) represents a common cause of consultation to the emergency department. Currently there is little clarity about which patients with ASBO are at increased risk of developing complications, potentially benefiting from early surgical management. The present study aims to design and validate a risk prediction scale for adverse outcomes in patients with ASBO. Methods. Retrospective cohort study performed from the MIMIC-IV database between 2008 and 2019. Adult patients admitted to the emergency department with a diagnosis of ASBO were included. The primary outcome was the composite of bowel resection, intensive care unit admission, and all-cause mortality. A risk prediction scale was designed by assigning a score to each variable according to the measure of association obtained in the logistic regression model. All analyses were performed in R statistical software (version 3.5.3). Results. Five-hundred-thirteen patients were included (men 63.7%, median age: 61 years). Composite outcome was present in 25.7% of cases. Age, history of heart failure and peripheral arterial disease, hemoglobin level, leukocyte count, and INR were the best predictors of these outcomes (AUC 0.75). Based on this model, the simplified HALVIC scale was created, classifying the risk of the composite outcome as low (0-2 points), medium (3-4 points) and high (5-7 points). Conclussion. The HALVIC scale is presented as a simple and easily applicable predictive tool in the clinical setting, which can accurately identify patients with ASBO at high risk of complications, allowing the surgeon to adjust management strategies individually and potentially improving the outcomes of these patients

Obstrucción intestinal por adherencias: un lienzo en blanco en el que el cirujano elige los colores / Intestinal obstruction due to adherences: a blank canvas on which the surgeon chooses the colors

Introducción. La obstrucción intestinal es una patología de alta prevalencia. Su abordaje diagnóstico y terapéutico ha evolucionado acorde con el avance del conocimiento e implementación de la tecnología. El impacto de sus complicaciones obliga a redoblar esfuerzos en pro de lograr una mayor efectividad. Se hizo una aproximación reflexiva al problema, mediante una identificación de los puntos controversiales de interés para el cirujano general. Métodos. Se realizó una búsqueda sistemática de la literatura en varias bases de datos, utilizando dos ecuaciones de búsqueda que emplearon términos seleccionados a partir de los tesauros "Medical Subject Heading" (MeSH) y "Descriptores en Ciencias de la Salud" (DeCS). Resultados. Se recolectaron 43 artículos y a partir de ellos se construyó el texto de revisión. La identificación pronta de los posibles candidatos a cirugía, mediante un esquema diagnóstico y terapéutico, se constituye en una prioridad en el manejo de estos pacientes. De igual manera, se efectúan consideraciones en la toma de decisiones con respecto a la vía quirúrgica, así como recomendaciones técnicas operatorias producto de la experiencia y lo reportado en la literatura. Existen factores propios del cirujano, del contexto y del paciente, que inciden en la resolución del problema. Conclusión. La obstrucción intestinal y sus implicaciones clínicas obligan a una reevaluación constante de su estado del arte y avances en el manejo, tendiente a una búsqueda de oportunidades para impactar favorablemente en su curso clínico. Hay estrategias por implementar, inclusive el manejo laparoscópico en casos seleccionados

Introduction. Intestinal obstruction is a pathology of high prevalence. Its diagnostic and therapeutic approach has evolved according to the progress in knowledge and implementation of technology. The impact of its complications makes it necessary to make the efforts to achieve higher effectiveness. A reflexive approach to the problem is made by identifying the controversial points of interest for the general surgeon. Methods. A systematic literature search was carried out in several databases, using two search equations from the review performed in the thesaurus "Medical Subject Heading" (MeSH) and "Descriptors in Health Sciences" (DeCS). Results. A total of 43 articles were collected using the selected methods and the review text was constructed from them. The early identification of possible candidates for surgery, by means of a diagnostic and therapeutic algorithm, is a priority in the management of these patients. Likewise, considerations are made in decision-making regarding the laparoscopic vs. traditional approach, as well as operative technical recommendations based on experience and what has been reported in the literature. There are factors specific to the surgeon, the context and the patient that influence the resolution of the problem. Conclusion. Intestinal obstruction and its clinical implications require a constant reevaluation of the state of the art and advances in management, tending to search for opportunities to favorably impact its clinical course. There are strategies to be implemented, including laparoscopic management in selected cases