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1.
Pan Afr Med J ; 38: 114, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33912284

RESUMO

Sepsis results in intense disturbances in homoeostasis and is responsible for considerable morbidity and mortality in early infancy. Owing to insufficiency on part of infant to develop adequate inflammatory response to localize the infection, they usually progress to disseminated systemic infection, pneumonia and/or meningitis. We present the case of a 26 weeks preterm boy with acute digital ischemia in right index finger progressing to impending gangrene as a manifestation of septicemia. Use of topical nitroglycerin patch with meticulous monitoring successfully alleviated the impending peripheral gangrene without any adverse effects.


Assuntos
Isquemia/tratamento farmacológico , Sepse Neonatal/complicações , Nitroglicerina/administração & dosagem , Administração Cutânea , Dedos/irrigação sanguínea , Gangrena/etiologia , Gangrena/prevenção & controle , Humanos , Recém-Nascido , Isquemia/etiologia , Masculino , Nitroglicerina/efeitos adversos , Adesivo Transdérmico , Resultado do Tratamento , Vasodilatadores/administração & dosagem , Vasodilatadores/efeitos adversos
2.
Life Sci ; 273: 119235, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33607152

RESUMO

Although the central role of Nurr-1/GDNF has been reviewed amply, scarce data are available on their peripheral impact. Carvedilol and morin hydrate have previously conferred their hepatic anti-fibrotic action. AIM: Thus, our aim was to unveil the potential hepatoprotective role of carvedilol (CR) and/or morin hydrate (MH) using a hepatic 70% partial warm ischemia/reperfusion (I/R) rat model. MAIN METHOD: Rats were allocated into sham-operated, hepatic I/R, and I/R preceded by oral administration of CR (10 and 30 mg/kg; CR10/CR30), MH (30 mg/kg), or CR10 + MH for one week. KEY FINDINGS: On the molecular level, pretreatment with CR and/or MH increased the hepatic contents of Nurr-1, GDNF, and the protein expression of active/p-AKT. On the other hand, they inactivated GSK3ß and NF-κB to increase the antioxidant enzymes (GPx, SOD, CAT). All regimens also enhanced the autophagy/lysosomal function and boosted the protein expression of beclin-1, LC3II, and TFEB. Moreover, their antiapoptotic effect was signified by increasing the anti-apoptotic molecule Bcl2 and inhibiting Bax, Bax/Bcl2 ratio, and caspase-3, effects that were confirmed by the TUNEL assay. These improvements were reflected on liver function, as they decreased serum aminotransferases and liver structural alterations induced by I/R. Despite its mild impact, CR10 showed marked improvements when combined with MH; this synergistic interaction overrides the effect of either regimen alone. SIGNIFICANCE: In conclusion, CR, MH, and especially the combination regimen, conferred hepatoprotection against I/R via activating the Nurr-1/GDNF/AKT trajectory to induce autophagy/lysosomal biogenesis, inhibit GSK3ß/NF-кB hub and apoptosis, and amend redox balance.


Assuntos
Carvedilol/farmacologia , Flavonoides/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Isquemia/tratamento farmacológico , Hepatopatias/tratamento farmacológico , Substâncias Protetoras/farmacologia , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Antioxidantes/farmacologia , Apoptose , Autofagia , Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Isquemia/metabolismo , Isquemia/patologia , Hepatopatias/metabolismo , Hepatopatias/patologia , Masculino , Membro 2 do Grupo A da Subfamília 4 de Receptores Nucleares/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Wistar , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia
3.
Life Sci ; 269: 119080, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33465387

RESUMO

S-Allylcysteine (SAC) is an extensively studied natural product which has been proven to confer cardioprotection. This potentiates SAC into many clinical relevance possibilities, hence, the use of it ought to be optimally elucidated. To further confirm this, an ischemia/reperfusion model has been used to determine SAC at 10 mM and 50 mM on cardiac function, cardiac marker, and mitochondrial permeability. Using Langendorff setup, 24 adult male Wistar rats' hearts were isolated to be perfused with Kreb-Henseleit buffer throughout the ischemia/reperfusion method. After 20 min of stabilization, global ischemia was induced by turning off the perfusion for 35 min followed by 60 min of reperfusion with either Kreb-Henseleit buffer or SAC with the dose of 10 mM or 50 mM. The cardiac function was assessed and coronary effluent was collected at different timepoints throughout the experiment for lactate dehydrogenase (LDH) measurement. The harvested hearts were then used to measure glutathione while isolated mitochondria for mPTP analysis. SAC-reperfused hearts were shown to prevent the aggravation of cardiac function after I/R induction. It also dose-dependently upregulated glutathione reductase and glutathione level and these were also accompanied by significant reduction of LDH leakage and preserved mitochondrial permeability. Altogether, SAC dose-dependently was able to recover the post-ischemic cardiac function deterioration alongside with improvement of glutathione metabolism and mitochondrial preservation. These findings highly suggest that SAC when sufficiently supplied to the heart would be able to prevent the deleterious complications after the ischemic insult.


Assuntos
Antioxidantes/farmacologia , Permeabilidade da Membrana Celular/efeitos dos fármacos , Cisteína/análogos & derivados , Coração/efeitos dos fármacos , Isquemia/tratamento farmacológico , Mitocôndrias/efeitos dos fármacos , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Animais , Antineoplásicos/farmacologia , Cisteína/farmacologia , Coração/fisiopatologia , Isquemia/metabolismo , Isquemia/patologia , Masculino , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Ratos , Ratos Wistar
4.
Am J Physiol Heart Circ Physiol ; 320(3): H1124-H1135, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33481698

RESUMO

Critical limb ischemia (CLI) is a severe state of peripheral artery disease with high unmet clinical needs. Further, there are no effective treatment options for patients with CLI. Based on preclinical study results, predicting the clinical efficacy of CLI treatments is typically difficult because conventional hindlimb ischemia (HLI) rodent models display spontaneous recovery from ischemia, which is not observed in patients with CLI. Therefore, we aimed to develop a novel chronic and severe HLI model to properly evaluate the therapeutic effects of drug candidates for CLI. Severe HLI mice (Type-N) were generated by increasing the excised area of blood vessels in a hindlimb of NOG mice. Immunohistochemistry and gene expression analysis at 9 wk after the Type-N operation revealed that the ischemic limb was in a steady state with impaired angiogenesis, like that observed in patients with CLI. We did selection of chronic Type-N mice based on the number of necrotic nails and blood flow rate at 2 wk after surgery because some Type-N mice showed mild symptoms. Therapeutic treatment with cilostazol, which is used for intermittent claudication, did not restore blood flow in chronic Type-N mice. In contrast, therapeutic transplantation of pericytes and vascular endothelial cells, which can form new blood vessels in vivo, significantly improved blood flow in a subset of Type-N mice. These findings suggest that this novel chronic and severe HLI model may be a valuable standard animal model for therapeutic evaluation of the angiogenic effects of CLI drug candidates.NEW & NOTEWORTHY We developed a chronic and severe hindlimb ischemia (HLI) mouse model for preclinical research on critical limb ischemia (CLI). This model partially reflects human CLI pathology in that it does not show spontaneous restoration of blood flow or expression of angiogenic genes in the ischemic limb. This novel model may be valuable for therapeutic evaluation of the angiogenic effects of CLI drug candidates.


Assuntos
Indutores da Angiogênese/farmacologia , Cilostazol/farmacologia , Avaliação Pré-Clínica de Medicamentos , Isquemia/tratamento farmacológico , Músculo Esquelético/irrigação sanguínea , Neovascularização Fisiológica/efeitos dos fármacos , Animais , Velocidade do Fluxo Sanguíneo , Células Cultivadas , Doença Crônica , Modelos Animais de Doenças , Membro Posterior , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais da Veia Umbilical Humana/transplante , Humanos , Isquemia/metabolismo , Isquemia/fisiopatologia , Masculino , Camundongos Endogâmicos NOD , Camundongos SCID , Pericitos/metabolismo , Pericitos/transplante , Fluxo Sanguíneo Regional , Índice de Gravidade de Doença
5.
ACS Appl Mater Interfaces ; 13(5): 5907-5918, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33506676

RESUMO

Critical limb ischemia (CLI) is a severe form of peripheral artery disease (PAD). It is featured by degenerated skeletal muscle and poor vascularization. During the development of CLI, the upregulated matrix metalloproteinase-2 (MMP-2) degrades muscle extracellular matrix to initiate the degeneration. Meanwhile, MMP-2 is necessary for blood vessel formation. It is thus hypothesized that appropriate MMP-2 bioactivity in ischemic limbs will not only attenuate muscle degeneration but also promote blood vessel formation. Herein, we developed ischemia-targeting poly(N-isopropylacrylamide)-based nanogels to specifically deliver an MMP-2 inhibitor CTTHWGFTLC (CTT) into ischemic limbs to tailor MMP-2 bioactivity. Besides acting as an MMP-2 inhibitor, CTT promoted endothelial cell migration under conditions mimicking the ischemic limbs. The nanogels were sensitive to the pH of ischemic tissues, allowing them to largely aggregate in the injured area. To help reduce nanogel uptake by macrophages and increase circulation time, the nanogels were cloaked with a platelet membrane. An ischemia-targeting peptide CSTSMLKA (CST) was further conjugated on the platelet membrane for targeted delivery of nanogels into the ischemic area. CTT gradually released from the nanogels for 4 weeks. The nanogels mostly accumulated in the ischemic area for 28 days. The released CTT preserved collagen in the muscle and promoted its regeneration. In addition, CTT stimulated angiogenesis. Four weeks after CLI, the blood flow and vessel density of the ischemic limbs treated with the nanogels were remarkably higher than the control groups without CTT release. These results demonstrate that the developed nanogel-based CTT release system has the potential to stimulate ischemic limb regeneration.


Assuntos
Isquemia/tratamento farmacológico , Metaloproteinase 2 da Matriz/metabolismo , Inibidores de Metaloproteinases de Matriz/farmacologia , Músculo Esquelético/efeitos dos fármacos , Nanogéis/química , Neovascularização Patológica/tratamento farmacológico , Animais , Sistemas de Liberação de Medicamentos , Feminino , Humanos , Isquemia/patologia , Inibidores de Metaloproteinases de Matriz/síntese química , Inibidores de Metaloproteinases de Matriz/química , Camundongos , Camundongos Endogâmicos C57BL , Estrutura Molecular , Músculo Esquelético/patologia , Neovascularização Patológica/patologia , Tamanho da Partícula , Propriedades de Superfície
6.
Angiol Sosud Khir ; 26(3): 37-43, 2020.
Artigo em Russo | MEDLINE | ID: mdl-33063750

RESUMO

Critical ischaemia of lower limbs is a cause of death and invalidity in the whole world. Stem cells and products of their secretion find wide application in treatment of vascular diseases, including critical ischaemia of the lower limbs. Erythropoietin promotes an increase in the angiogenic potential of stem cells. The authors examined the therapeutic potential of a biomedical cellular product (mesenchymal stem cells and products of their secretion) and mesenchymal stem cells with erythropoietin on the processes of restoration of vessels in the hind legs of Wistar male rats following induction of lower limb critical ischaemia. Mesenchymal stem cells were derived from the bone marrow of male Wistar rats. Critical ischaemia of hind legs was modulated by transaction of the femoral artery. The parameters of microcirculation in the foot were assessed with the help of laser Doppler flowmetry. In the blood serum and crural muscles by means of solid-phase enzyme immunoassay we examined the levels of cytokines, growth factors, and persistent metabolites of nitrogen oxide - nitrites. Muscles morphology and the number of blood vessels were assessed by the findings of histological examination. It was shown that the biomedical cellular product alone and in combination with erythropoietin stimulated angiogenesis. The results of Doppler flowmetry revealed restoration of the parameters of microcirculation in the lower limb by 35-75% of the baseline values. Besides, we observed a decrease of muscle necrosis, connective tissue proliferation, and an increase in the number of the vessels supplying the muscles in the experimental groups. It was also determined that the biomedical cellular product influenced the levels of cytokines in blood serum and crural muscles. Hence, the obtained findings proved the therapeutic potential of the biomedical cellular product in critical ischaemia of lower limbs.


Assuntos
Isquemia , Doenças Vasculares Periféricas , Animais , Modelos Animais de Doenças , Humanos , Isquemia/tratamento farmacológico , Extremidade Inferior , Masculino , Ratos , Ratos Wistar
7.
Khirurgiia (Mosk) ; (10): 79-87, 2020.
Artigo em Russo | MEDLINE | ID: mdl-33047590

RESUMO

Active collagen type I successfully used in regenerative medicine. However, despite the large amount of material of cellular and molecular mechanisms underlying skin repair, the molecular mechanisms of wound healing with use collagen type I, not studied enough. PURPOSE OF THE STUDY: To study the mechanism of the native collagen type I wound-healing action of native type I collagen on the example of the medical device Collost (7% gel) in a model of the rats difficult-to-heal skin wounds. MATERIAL AND METHODS: Male rats in population SD (72 individuals) surgically formed an ischemic dorsal skin flap (3×10 cm) with two full-thickness skin wounds 6 mm in diameter.The trained animals divided into 2 groups: in the experimental group, medical device Collost (gel) applied once after the operation, in the control group - a standard medical device for comparison. The dynamics of wound healing assessed, the number of M2 macrophages, myofibroblasts, vascularization and expression of the main markers of the repair process in the wound tissues and time points for assessment were: after 3, 7 and 14 days after operation using macroscopic, immunohistochemical, and molecular methods. RESULTS: It has been established that the mechanism of action of native collagen type I is associated with the acceleration of the appearance of «progenitorous¼ M2-macrophages in the wound tissues, decrease in the severity of inflammation or reduction in the duration of the inflammatory stage of the repair process, change in the expression spectrum of number of growth factors, an acceleration of neovasculogenesis. CONCLUSION: In this work, on the modern experimental model shown regenerative efficiency of a medical device based on collagen type I and described the molecular and cellular processes of wound healing when using it It has been shown that the acceleration of wound healing processes occurs when using a medical device based on native collagen type 1, it is also accompanied by a better aesthetic closure of the damaged skin area.


Assuntos
Colágeno Tipo I/administração & dosagem , Fármacos Dermatológicos/administração & dosagem , Pele/efeitos dos fármacos , Lesões dos Tecidos Moles/tratamento farmacológico , Cicatrização/fisiologia , Animais , Materiais Biocompatíveis/administração & dosagem , Modelos Animais de Doenças , Géis , Isquemia/tratamento farmacológico , Masculino , Ratos , Pele/lesões , Lesões dos Tecidos Moles/terapia , Retalhos Cirúrgicos/irrigação sanguínea
9.
Acta Cir Bras ; 35(9): e202000901, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32996998

RESUMO

PURPOSE: To evaluate the effects of treatment with Indigo Carmine (IC) on rat livers subjected to ischemia-reperfusion injury. METHODS: The animals were subdivided into 4 groups: 1.SHAM group(SH) - saline; 2.SHAM group with IC-2mg/Kg(SHIC); 3.IR group - rats submitted to ischemia and reperfusion with saline(IR); 4.IR group with IC-2mg/Kg(IRIC). The IR protocol consists of liver exposure and administration of drug or saline intravenously, followed by 60 minutes of ischemia and 15 of reperfusion. Liver samples were collected for biochemical analysis. RESULTS: State 3 of mitochondrial respiration showed a significant worsening of the IRIC group in relation to all others. State 4 showed a difference between IRIC and SHIC. The Respiratory Control Ratio showed statistical decrease in IR and IRIC versus Sham. The osmotic swelling showed significant difference between SHxIR; SHICxIRIC and SHxIRIC. There was a significant increase in ALT in the IRIC group in relation to all the others. Concerning the nitrate dosage, there was a decrease in the group treated with IC(IRxIRIC). There was no difference regarding the dosage of Malondialdehyde. CONCLUSION: IC was not able to protect mitochondria from IR injury and proved to be a potentiating agent, acting in synergy with the IR injury promoting damage to the hepatocyte membranes.


Assuntos
Índigo Carmim , Isquemia , Traumatismo por Reperfusão , Animais , Aspartato Aminotransferases , Índigo Carmim/uso terapêutico , Isquemia/tratamento farmacológico , Isquemia/prevenção & controle , Masculino , Ratos , Ratos Wistar , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/prevenção & controle
10.
Vnitr Lek ; 66(5): 76-79, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32942875

RESUMO

We present a case report of a patient with acute upper and lower limb ischemia due to paradoxical embolism. A 67-year old woman without history of venous thromboembolism suffered dislocated patellar fracture requiring surgery in November 2017. Two months after surgery she presented to the emergency room with bilateral pulmonary embolism, occlusion of the left subclavian artery, left common femoral artery and superior mesenteric artery. Transesophageal echocardiography detected patent foramen ovale. Vascular surgeon decided against embolectomy, interventional radiologist against pharmacomechanical thrombolysis due to the extent of the occlusions. Systemic thrombolysis (alteplase) was administered successfully with resolution of the emboli in the left subclavian artery, left common femoral artery and superior mesenteric artery.


Assuntos
Embolia Paradoxal , Forame Oval Patente , Embolia Pulmonar , Idoso , Embolectomia , Embolia Paradoxal/tratamento farmacológico , Embolia Paradoxal/cirurgia , Feminino , Forame Oval Patente/complicações , Forame Oval Patente/diagnóstico por imagem , Forame Oval Patente/tratamento farmacológico , Humanos , Isquemia/tratamento farmacológico , Embolia Pulmonar/cirurgia , Terapia Trombolítica
11.
Rev Soc Bras Med Trop ; 53: e20200472, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32965455

RESUMO

INTRODUCTION: In the genesis of coronavirus disease (COVID-19), there is a process of endotheliitis associated with thrombotic changes, no studies have reported the use of acetylsalicylic acid (ASA) as a possible therapeutic approach. Statins could potentiate the ASA therapy. METHODS: This is a series of 14 cases with a laboratory-confirmed diagnosis of COVID-19. All patients underwent the ASA therapy. Those who had risk factors for vascular disease also underwent the high-potency statin therapy. When symptoms were totally or practically resolved, patients were discharged and advised to continue medications for a complementary time, according to the clinical evolution of each patient. RESULTS: The mean age of monitored patients was 48.6 years. A total of 78.6% patients presented with at least one comorbidity, which could have contributed as a risk factor for a poor prognosis in the evolution of COVID-19. Four patients had secondary bacterial infections; three patients needed hospitalization. None of the cases progress to stage III, and all patients had remission of symptoms, with 100% survival. CONCLUSIONS: the process of endothelial dysfunction in COVID-19 involves disseminated thrombosis, initially microvascular and later expansion into larger vessels. ASA could act as a secondary prophylaxis and prevent thrombosis from developing and reaching stage III of the disease. As this was a case series, we cannot provide definitive conclusions; however, this study allows us to formulate hypotheses and support clinical trials to evaluate benefits of the ASA therapy in the treatment of COVID-19.


Assuntos
Aspirina/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Inflamação/tratamento farmacológico , Isquemia/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Trombose/tratamento farmacológico , Betacoronavirus , Comorbidade , Endotélio/efeitos dos fármacos , Endotélio/patologia , Humanos , Pessoa de Meia-Idade , Pandemias
12.
Khirurgiia (Mosk) ; (8): 55-60, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32869616

RESUMO

OBJECTIVE: To study the immediate results of therapy and indirect revascularization in patients with critical ischemia of the lower limbs. MATERIAL AND METHODS: The results of medication and surgical treatment were analyzed in 210 patients with critical ischemia of the lower limbs. Atherosclerosis obliterans was diagnosed in 142 patients, thromboangiitis obliterans - in 68 patients. Lesion of femoropopliteal segment was observed in 32 (15.2%) cases, popliteal-tibial segment - 68 (32.8%) patients, tibial and foot segment - 62 (29.5%) cases, foot - 31 (14.8%) cases, multiple-level lesion - 17 (8.1%) cases. Survey consisted of Doppler ultrasound, CT angiography, rheovasography with analysis of rheographic index (RI) and pulse oximetry. Circulatory parameters were compared with identical values in 48 almost healthy persons ("reference group"). The results of medication and surgical treatment were evaluated by using of the scale of Rutherford R.B. et al. (1997). RESULTS: Conservative treatment was performed in 48 patients (control group). The following types of indirect revascularization operations were performed to stimulate regional circulation: bone trepanation in 42 patients, lumbar sympathectomy in 51 patients, bone trepanation + lumbar sympathectomy in 38 patients, bone trepanation with intraosseous irradiation in 31 cases. CONCLUSION: Indirect revascularization improves early postoperative outcomes, ensures maintaining support function of the limb and active lifestyle in patients with critical ischemia of the lower limbs. Technical simplicity of these procedures facilitates widespread introduction of indirect revascularization in multi-field hospitals.


Assuntos
Arteriopatias Oclusivas/cirurgia , Isquemia/cirurgia , Extremidade Inferior/irrigação sanguínea , Extremidade Inferior/cirurgia , Arteriopatias Oclusivas/diagnóstico por imagem , Arteriopatias Oclusivas/tratamento farmacológico , Arteriosclerose Obliterante/diagnóstico por imagem , Arteriosclerose Obliterante/tratamento farmacológico , Arteriosclerose Obliterante/cirurgia , Osso e Ossos/cirurgia , Tratamento Conservador , Humanos , Isquemia/diagnóstico por imagem , Isquemia/tratamento farmacológico , Salvamento de Membro/métodos , Extremidade Inferior/diagnóstico por imagem , Estudos Retrospectivos , Simpatectomia , Tromboangiite Obliterante/diagnóstico por imagem , Tromboangiite Obliterante/tratamento farmacológico , Tromboangiite Obliterante/cirurgia , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares/métodos
13.
Medicine (Baltimore) ; 99(32): e21594, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32769914

RESUMO

BACKGROUND: To evaluate the effect of dl-3-N-butylphthalide (NBP) on new cerebral microbleeds (CMBs) in patients with acute ischemic stroke (AIS). METHODS: We will prospectively enroll patients with AIS admitted to the stroke center of Jingjiang People's Hospital. Qualified participants will be randomly assigned to either the NBP group (NBP injection) or the control group (NBP injection placebo) in a ratio of 1:1. Patients will complete the brain magnetic resonance imaging within 48 hours and 14 days after stroke onset to observe the CMBs through susceptibility weighted imaging, and evaluate whether the use of NBP will affect the new CMBs in AIS patients. SPSS 20.0 will be used for statistical analyses. RESULT: We will provide practical and targeted results assessing the safety of NBP for AIS patients, to provide reference for clinical use of NBP. CONCLUSION: The stronger evidence about the effect of NBP on new CMBs in AIS patients will be provided for clinicians.


Assuntos
Benzofuranos/uso terapêutico , Hemorragia Cerebral/tratamento farmacológico , Protocolos Clínicos , Acidente Vascular Cerebral/tratamento farmacológico , Benzofuranos/normas , Hemorragia Cerebral/complicações , Humanos , Isquemia/complicações , Isquemia/tratamento farmacológico , Imagem por Ressonância Magnética/métodos , Inibidores da Agregação de Plaquetas/normas , Inibidores da Agregação de Plaquetas/uso terapêutico , Estudos Prospectivos
14.
Medicine (Baltimore) ; 99(29): e21340, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32702932

RESUMO

RATIONALE: Circumcision like any other surgical procedure is not devoid of complications. Serious complications are rare and include iatrogenic hypospadias, glans ischemia/necrosis, and glans amputation, all of which require an emergent treatment. PATIENT CONCERNS: We report here a case of 6 months-old-boy with a superficial glans ischemia following circumcision. DIAGNOSIS: Physical examination revealed a severely cyanotic glans with the moderate edema of the dorsal penile skin. Plasma levels of D-dimer were 8.57 mg/L. Urine passage was unremarkable while color Doppler ultrasonography revealed a normal blood flow. INTERVENTIONS: The patient was successfully treated with subcutaneous injection of enoxaparin (low-molecular-weight heparin) and topical 2.5% dihydrotestosterone. OUTCOMES: The appearance of the glans penis on the 5th day was close to normal while the control levels of D-dimer dropped to the reference range. The patient was discharged from the hospital on the 6th day. At 6-month follow-up, the appearance of the glans penis was normal. LESSONS: Acute glans penis ischemia following circumcision is a rare complication. Its successful treatment with enoxaparin and topical dihydrotestosterone has not been previously reported in the literature.


Assuntos
Circuncisão Masculina/efeitos adversos , Di-Hidrotestosterona/uso terapêutico , Heparina de Baixo Peso Molecular/uso terapêutico , Isquemia/etiologia , Administração Tópica , Di-Hidrotestosterona/administração & dosagem , Humanos , Lactente , Isquemia/tratamento farmacológico , Masculino , Pênis/irrigação sanguínea
16.
Stroke ; 51(7): 1983-1990, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32568651

RESUMO

BACKGROUND AND PURPOSE: Delayed recanalization increases the risk of infarct growth and poor clinical outcome in acute ischemic stroke. The vasoactive agent theophylline has shown neuroprotective effects in animal stroke models but inconclusive results in case series and randomized clinical trials. The primary objective of this study was to evaluate whether theophylline, as an add-on to thrombolytic therapy, is safe and effective in acute ischemic stroke patients. METHODS: The TEA-Stroke trial (The Theophylline in Acute Ischemic Stroke) was an investigator-initiated 2-center, proof-of-concept, phase II clinical study with a randomized, double-blinded, placebo-controlled design. The main inclusion criteria were magnetic resonance imaging-verified acute ischemic stroke, moderate to severe neurological deficit (National Institutes of Health Stroke Scale score of ≥4), and treatment with thrombolysis within 4.5 hours of onset. Participants were randomly assigned in the ratio 1:1 to either 220 mg of intravenous theophylline or placebo. The co-primary outcomes were early clinical improvement on the National Institutes of Health Stroke Scale score and infarct growth on magnetic resonance imaging at 24-hour follow-up. RESULTS: Theophylline as an add-on to thrombolytic therapy improved the National Institutes of Health Stroke Scale score at 24 hours by mean 4.7 points (SD, 5.6) compared with an improvement of 1.3 points (SD, 7.5) in the control group (P=0.044). Mean infarct growth was 141.6% (SD, 126.5) and 104.1% (SD, 62.5) in the theophylline and control groups, respectively (P=0.146). Functional independence at 90 days was 61% in the theophylline group and 58% in the control group (P=0.802). CONCLUSIONS: This proof-of-concept trial investigated theophylline administration as an add-on to thrombolytic therapy in acute ischemic stroke. The co-primary end points early clinical improvement and infarct growth at 24-hour follow-up were not significantly different after post hoc correction for multiplicity (Bonferroni technique). The small study size precludes a conclusion as to whether theophylline has a neuroprotective effect but provides a promising clinical signal that may support a future clinical trial. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: EudraCT number 2013-001989-42.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Acidente Vascular Cerebral/tratamento farmacológico , Teofilina/uso terapêutico , Ativador de Plasminogênio Tecidual/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Feminino , Fibrinolíticos/uso terapêutico , Humanos , Isquemia/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Terapia Trombolítica/métodos
17.
Ann Vasc Surg ; 68: 88-92, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32589931

RESUMO

Heparin resistance is an uncommon phenomenon defined as the need for high-dose unfractionated heparin (UFH) of more than 35,000 IU/day to achieve the target activated partial-thromboplastin time ratio or the failure to achieve the desired activated clotting time after a full UFH dose. This rare phenomenon is being more commonly observed in Covid-19 patients in a hypercoagulable state. We describe a Covid-19 patient confirmed by reverse-transcriptase polymerase chain reaction assay, with acute limb ischemia, who developed heparin resistance. The patient was managed by the departments of vascular surgery, anesthesia and intensive care, and the Coagulation Service and Thrombosis Research from San Raffaele Scientific Institute, Milan, Italy.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Resistência a Medicamentos , Heparina/farmacologia , Isquemia/tratamento farmacológico , Extremidade Inferior/irrigação sanguínea , Pneumonia Viral/complicações , Doença Aguda , Idoso , Anticoagulantes/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Humanos , Isquemia/sangue , Isquemia/etiologia , Masculino , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Tomografia Computadorizada por Raios X
18.
PLoS One ; 15(6): e0234271, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32525925

RESUMO

OBJECTIVES: Antiplatelet therapy following peripheral arterial endovascular intervention lacks high quality evidence to guide practice. The aim of this study was to assess the effect of three months of dual antiplatelet therapy on amputation-free survival following peripheral arterial endovascular intervention in patients with chronic limb threatening ischemia. METHODS: A retrospective review of symptomatic patients undergoing primary peripheral arterial endovascular intervention over a seven-year period was performed. The primary outcome measure was amputation-free survival. A sample size calculation based on previous cohort studies suggested that 629 limbs would be required to show a difference between single and dual therapy. Kaplan-Meier estimates and multivariate logistic regression analysis of recorded baseline characteristics was performed to determine predictors of amputation-free survival. Dual antiplatelet therapy was routinely given for 3 months. RESULTS: 754 limbs were treated with primary angioplasty and/or stenting over a 7-year period, 508 of these for chronic limb threatening ischemia. There was no difference in unadjusted amputation-free survival between patients with chronic limb threatening ischaemia taking single vs. dual antiplatelet therapy (69% vs. 74% respectively Log rank Chi2 = 0.1, p = .72). After adjusting for confounders, at 1 year there was also no significant difference in amputation-free survival between patients taking single vs. dual antiplatelet therapy [OR 0.8, 95% CI 0.5-1.2, p = .3]. There was no difference in rates of major bleeding between single and dual antiplatelet therapy. CONCLUSIONS: There was no clear evidence of reduced amputation-free survival in patients with chronic limb threatening ischemia undergoing peripheral arterial endovascular intervention being treated with dual antiplatelet therapy for 3 months. This is at odds with other retrospective case series and highlights the limitations in basing clinical practice on such data. There is a need for an adequately powered, independent randomised trial to definitively answer the question.


Assuntos
Procedimentos Endovasculares , Isquemia/tratamento farmacológico , Isquemia/cirurgia , Extremidade Inferior/irrigação sanguínea , Inibidores da Agregação de Plaquetas/farmacologia , Idoso , Estudos de Coortes , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Inibidores da Agregação de Plaquetas/uso terapêutico , Estudos Retrospectivos , Análise de Sobrevida
19.
J Vasc Res ; 57(4): 185-194, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32526735

RESUMO

Information on the function of transient receptor potential vanilloid 1 (TRPV1) in arteriogenesis is limited. We aimed to verify whether TRPV1 is involved in collateral vessel growth in rat hind limbs and elucidate the possible subcellular action mechanisms. Adult Sprague Dawley rats were chosen to establish the hind limb ischemic model and treatment with capsaicin. Angiographies were performed, and tissue was isolated for immunohistochemistry. In vitro, rat aortic endothelial cells (RAECs) were treated with capsaicin and antagonist capsazepine. The RAEC proliferation was determined, and the protein and mRNA levels of Ca2+-dependent transcription factors were assessed. In vivo, the collateral vessels exhibited positive outward remodeling characterized by enhanced inflammatory cell/macrophage accumulation in the adventitia and activated cell proliferation in all layers of the vascular wall and elevated endothelial NO synthetase expression in the rats with hind limb ligation. In RAECs, TRPV1 activation-induced Ca2+-dependent transcriptional factors, nuclear factor of activated T cells 1, calsenilin and myocyte enhancer factor 2C increase, and augmented RAEC proliferation could be a subcellular mechanism for TRPV1 in endothelial cells and ultimately contribute to collateral vessel growth. TRPV1, a novel candidate, positively regulates arteriogenesis, meriting further studies to unravel the potential therapeutic target leading to improved collateral vessel growth for treating ischemic diseases.


Assuntos
Indutores da Angiogênese/farmacologia , Artérias/efeitos dos fármacos , Capsaicina/farmacologia , Circulação Colateral/efeitos dos fármacos , Isquemia/tratamento farmacológico , Músculo Esquelético/irrigação sanguínea , Neovascularização Fisiológica/efeitos dos fármacos , Canais de Cátion TRPV/agonistas , Animais , Artérias/metabolismo , Artérias/fisiopatologia , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Membro Posterior , Isquemia/metabolismo , Isquemia/fisiopatologia , Proteínas Interatuantes com Canais de Kv/metabolismo , Fatores de Transcrição MEF2/metabolismo , Fatores de Transcrição NFATC/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Ratos Sprague-Dawley , Fluxo Sanguíneo Regional , Transdução de Sinais , Canais de Cátion TRPV/metabolismo
20.
Ann Vasc Surg ; 69: 317-323, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32502677

RESUMO

BACKGROUND: Acute limb ischemia (ALI) is challenging to treat because of high morbidity and mortality. Endovascular-first options beginning with thrombolysis are technically feasible with similar results to open surgery. We examined our experience with thrombolysis to identify patients and target conduits that are predictive of improved outcomes. METHODS: We performed a retrospective review of our institutional database of thrombolysis cases for arterial lower extremity disease. Thrombolysis was the index procedure, and any subsequent treatment was a reintervention. Conversion to open surgery perioperatively such as thromboembolectomy or bypass was considered a technical failure. Primary outcomes included primary patency, secondary patency, amputation-free survival (AFS), and survival. Secondary outcomes included conversion to open, reintervention <30 days, and amputation <30 days. Descriptive statistics and analysis of variance were performed for preoperative and intraoperative risk factors. Kaplan-Meier estimation and Cox proportional hazard models were used for primary and secondary outcomes. RESULTS: Ninety-nine patients with ALI were treated with thrombolysis from 2007 to 2017. Thrombolysis was attempted on native artery (40%), vein bypass (7%), prosthetic bypass (33%), and stent (19%). Rutherford class distribution was 50% class 1, 41% class 2a, 5% class 2b, and 3% class 3. Technical success was 70%, characterized by an all-endovascular approach, patency at 30 days, and AFS for 30 days. Primary patency at 1- and 2-years was 31% and 22%, respectively. Secondary patency at 1- and 2-years was 39% and 27%, respectively. Overall, 30% required conversion to open surgery at the time of the index procedure, 7% reintervention <30 days, 5% mortality <30 days, and 5% major amputation <30 days. Prosthetic grafts and vein bypasses had the worst primary and secondary patency (P < 0.05). Five out of 7 vein bypasses required open conversion. Thrombolysis of native arteries was most successful maintaining primary patency (P < 0.05), secondary patency (P < 0.05), and AFS (P < 0.05). Patients who had adjunctive procedures at the time of thrombolysis had a significantly greater primary patency (P < 0.05) and secondary patency (P < 0.05) but not greater AFS. CONCLUSION: Outcomes in thrombolysis for ALI have not significantly improved 20 years after the STILE trial. Technical success and mid-term patency rates are modest at best. Thrombolysis of vein bypasses and prosthetic grafts have poor technical success and primary patency compared with native arteries. However, aggressive adjunctive interventions during thrombolysis appear to improve primary and secondary patency.


Assuntos
Oclusão de Enxerto Vascular/tratamento farmacológico , Isquemia/tratamento farmacológico , Extremidade Inferior/irrigação sanguínea , Doença Arterial Periférica/tratamento farmacológico , Terapia Trombolítica , Doença Aguda , Idoso , Amputação , Bases de Dados Factuais , Feminino , Oclusão de Enxerto Vascular/diagnóstico por imagem , Oclusão de Enxerto Vascular/mortalidade , Oclusão de Enxerto Vascular/fisiopatologia , Humanos , Isquemia/diagnóstico por imagem , Isquemia/mortalidade , Isquemia/fisiopatologia , Salvamento de Membro , Masculino , Pessoa de Meia-Idade , New York , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/mortalidade , Doença Arterial Periférica/fisiopatologia , Estudos Retrospectivos , Fatores de Risco , Centros de Atenção Terciária , Terapia Trombolítica/efeitos adversos , Terapia Trombolítica/mortalidade , Fatores de Tempo , Resultado do Tratamento , Grau de Desobstrução Vascular
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