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PURPOSE: Cutaneous adverse effects from cyclin-dependent 4 and 6 kinase inhibitors (CDK4/6i) used in metastatic breast cancer are prevalent and well described. Vitiligo-like lesions have been reported and are rare. They can negatively impact patients' quality of life and may be associated with survival benefits. We describe the clinical characteristics of vitiligo-like lesions in an international cohort of patients treated with CDK4/6i to help improve recognition and management. METHODS: Retrospective review of patients diagnosed with vitiligo-like lesions from CDK4/6i from five academic institutions in the USA and Europe was performed. Ten patients were included in the study. RESULTS: Median age of our patients was 55 (range 37-86). Median progression-free survival was 24 months in 5 patients. The median time to rash was 10 months. Sun-exposed areas such as the arms and face were the most affected areas. Multiple skin-directed therapies such as topicals, laser, and phototherapy were trialed with minor success. Mild repigmentation was seen in one patient treated with ruxolitinib cream. CDK4/6 treatment was discontinued due to the vitiligo-like lesions in one patient. CONCLUSION: Clinical characteristics are similar to previously reported findings in case reports and series. We add topical ruxolitinib as a potential treatment option for these patients and include data regarding progression-free survival that should continue to be collected. No definitive conclusions can be made regarding survival benefits from our cohort. Clinicians should refer these patients to dermatologists to aid with management.
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Neoplasias da Mama , Nitrilas , Pirazóis , Pirimidinas , Vitiligo , Humanos , Feminino , Neoplasias da Mama/complicações , Neoplasias da Mama/tratamento farmacológico , Aminopiridinas , Piridinas/efeitos adversos , Vitiligo/tratamento farmacológico , Vitiligo/induzido quimicamente , Estudos Retrospectivos , Quinase 4 Dependente de Ciclina , Qualidade de Vida , Inibidores de Proteínas Quinases/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
Seborrheic keratosis (SK) is a common, benign tumor that can occur on everybody site and can be conservatively managed. Cosmetic concerns, especially when a lesion involves the facial area, are the most common reason for excision. SK shows male gender preponderance and increasing age is an independent association with the condition. Even though more prevalent in the elderly, it has also been reported in younger age groups like adolescents and young adults. Precise pathogenesis is still obscure, but ultra-violet exposure represents a predisposing factor to SK by altering the biochemical concentration and expression of factors like Glutamine deaminases, endothelin, and stem cell factor. Moreover, the accumulation of amyloid-associated protein has also been postulated. Involvement of genitalia has been associated with human papillomavirus infection. Recently, Merkel cell polyomavirus nucleic acid was also detected in SK. Several oncogenic mutations involving FGFR-3 and FOXN1 have been identified. SKs are usually classified clinically and histologically. Dermatoscopy is a noninvasive alternative diagnostic technique widely used in differentiating SK from other benign and malignant tumors. In terms of treatment, topical agents, shave dissection, cryosurgery, electrodesiccation, laser application and curettage under local anesthesia are safe methods for eradication of SKs, mostly for cosmetic purposes. Though generally safe, the latter techniques may occasionally cause post-procedure depigmentation, scarring, and recurrence. Nanosecond-pulsed electric field technology is a promising new technique with fewer side-effects.
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Criocirurgia , Ceratose Seborreica , Adulto Jovem , Masculino , Humanos , Adolescente , Idoso , Ceratose Seborreica/diagnóstico , Ceratose Seborreica/terapia , Ceratose Seborreica/patologia , Eletrocoagulação , FaceRESUMO
INTRODUCTION: The accumulation of tissue-advanced glycation end products in skin results from complex and consecutive reactions and can be measured by skin autofluorescence (SAF) reader devices. This overview discusses studies evaluating the utilization of SAF in screening renal and cardiac disease. MATERIALS AND METHODS: Literature search was performed using Google Scholar, PubMed, Springer, Ovid, and ScienceDirect. RESULTS: SAF was an independent predictor of progression of chronic kidney disease (CKD) and was elevated in subjects on hemodialysis and peritoneal dialysis. Furthermore, SAF was significantly associated with cardiovascular events, cardiovascular mortality, and all-cause mortality in CKD patients. Other studies revealed a correlation between SAF and arterial stiffness, vascular damage, and subclinical atherosclerosis. A vegetarian diet was associated with lower SAF levels, whereas malnutrition was correlated with higher levels and increased mortality. CONCLUSIONS: SAF measurement may be useful in managing renal and cardiac disease. Future studies are needed to clarify the specific role of SAF in the management of CKD and its noninvasive office utilization to identify comorbidities in inflammatory diseases, such as psoriasis.
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Dermatologia , Cardiopatias , Insuficiência Renal Crônica , Humanos , Pacientes Ambulatoriais , Produtos Finais de Glicação Avançada , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/terapia , Insuficiência Renal Crônica/complicações , Pele , Cardiopatias/complicações , BiomarcadoresRESUMO
Atrioventricular nodal reentrant tachycardia (AVNRT) is the most common sustained supraventricular arrhythmias. An understanding of gender-related differences in AVNRT epidemiology, diagnosis, treatment, outcome, and complications can help guide a more effective diagnosis and treatment of the condition. The study aimed to perform a review of the available literature regarding all aspects of gender-related differences of AVNRT. We focused on all aspects of gender-related differences regarding AVNRT between men and women. A literature search was performed using Google Scholar, PubMed, Springer, Ovid, and Science Direct. Many investigations have demonstrated that the prevalence of AVNRT exhibited a twofold women-to-men predominance. The potential mechanism behind this difference due to sex hormones and autonomic tone. Despite being more common in women, there is a delay in offering and performing the first-line therapy (catheter ablation) compared to men. There were no significant gender-related discrepancies in patients who underwent ablation therapy for AVNRT, regarding the acute success rate of the procedure, long-term success rate, and recurrence of AVNRT. AVNRT is more common in women due to physiological factors such as sex hormones and autonomic tone. Catheter ablation is equally safe and efficacious in men and women; however, the time between the onset of symptoms and ablation is significantly prolonged in women. It is important for the medical community to be aware of this discrepancy and to strive to eliminate such disparities that are not related to patients' choices.
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Ablação por Cateter , Taquicardia por Reentrada no Nó Atrioventricular , Taquicardia Ventricular , Arritmias Cardíacas , Feminino , Humanos , Masculino , Recidiva , Taquicardia por Reentrada no Nó Atrioventricular/diagnóstico , Taquicardia por Reentrada no Nó Atrioventricular/epidemiologia , Taquicardia por Reentrada no Nó Atrioventricular/cirurgia , Resultado do TratamentoRESUMO
The optimal fluence for treating hirsutism with the diode laser has not been elucidated. The aim of this study is to evaluate and compare the satisfaction and side effects of patients who have been treated with two diode laser therapy techniques: high-fluence and low-fluence. In this cross-sectional study, the medical records of 182 patients referred to Yazd Laser center were collected. Various side effects of laser therapy were assessed, and the satisfaction rate of the patients was evaluated at three points: after the first session, at the end of the treatment course, and six months after the end of the treatment. The satisfaction level after the first session of the laser treatment was higher with the low-fluence technique (P-value<0.001). The satisfaction level at the end of treatment was the same in the two groups (P-value = 0.394). However, six months after the treatment, satisfaction level was significantly higher with the low-fluence technique (P-value = 0.005). The rate of complications, such as burn and pain, was higher in the high-fluence group, while the number of treatment sessions was lower with the high-fluence technique. The low-fluence method of laser therapy has fewer complications associated with greater patient satisfaction.
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Remoção de Cabelo , Lasers Semicondutores , Estudos Transversais , Feminino , Remoção de Cabelo/efeitos adversos , Remoção de Cabelo/métodos , Hirsutismo/etiologia , Hirsutismo/radioterapia , Humanos , Lasers Semicondutores/efeitos adversos , Satisfação do Paciente , Resultado do TratamentoRESUMO
Anxiety and stress are considered as universal psychiatric exhibitions of the present societies and lifestyles. Several experiments have been conducted to examine natural anxiolytic agents to find out an alternative to synthetic anxiolytic drugs. The present study investigated the anxiolytic effects of cinnamaldehyde (Cin) on mice behavior in the elevated plus maze (EPM) and open field (OF) tests. Sixty male Swiss mice, weighing 20-30 g, were divided into six groups including: acute stress + mazola oil; chronic stress + oil; acute stress + Cin (20 mg/kg); chronic stress + Cin; non-stress + oil; and non-stress + Cin groups. The groups were administered for seven days (once a day). The acute stress + Cin group showed a meaningful rise in the percentage of entries into the open arms compared to the acute stress + oil group (p <.05). The percentage of time spent in the open arms in the chronic stress + Cin group was significantly higher compared to the chronic stress + oil group (p < .01). The percentage of entries into the open arms increased significantly (p < .01) in the chronic stress + Cin group in comparison with the chronic stress + oil group. The Cin treated groups showed significant increases in the time spent in the center area and in the number of entries into the center area compared with the oil treated groups in OF test. The number of entries into the arms (total activity), as well as locomotor activity was not significant among groups. The results of the present study indicated that Cin, as a natural product, might have anxiolytic effects in mice behavior in the EPM and OF tests. Lay summary The results demonstrated that the administration of cinnamaldehyde (Cin) produced anxiolytic effects in mice. Natural antioxidant products have been reported effective for anxiety. Synthetic medications have notable adverse effects. Therefore, these natural substances with broad therapeutic applicability are able to reduce anxiety-related behavior with rare side effects. According to the results, Cin could decrease anxiety-related behavior in mice.
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Acroleína/análogos & derivados , Ansiedade/tratamento farmacológico , Atividade Motora/efeitos dos fármacos , Estresse Psicológico/tratamento farmacológico , Acroleína/farmacologia , Animais , Ansiolíticos/farmacologia , Ansiedade/psicologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , CamundongosRESUMO
BACKGROUND: Atrioventricular nodal reentrant tachycardia (AVNRT) is the most common type of supraventricular tachycardia (SVT). Similar to other cardiac tests and interventions, gender bias may influence clinical decision making in providing appropriate care for AVNRT patients. We assessed for gender differences in the diagnosis and management of AVNRT patients who underwent catheter ablation. METHODS: Patients who underwent catheter ablation for AVNRT were included. We explored the gender difference on various clinical parameters such as the time from SVT symptoms, SVT diagnosis, and first electrophysiology consult to time of catheter ablation. RESULTS: Among 140 patients screened, 116 patients met the inclusion criteria, including 67.2% women. Median time from symptoms onset to SVT diagnosis was 18.5 months (interquartile range [IQR] 4.0-58.5) in women versus 4.0 months (0.75-34.7) in men, P = .005. Once SVT was diagnosed, women took a median of 12.5 months (IQR 3.0-57.0) to proceed with ablation versus 3.0 months (1.0-7.0) for men, P ≤ .001. It took a longer time from the first electrophysiology consultation to ablation: 54.5 days (20.75-144.75) for women versus 20.5 days (6.0-46.25) for men, P = .008. Overall, it took 60.0 months (IQR 12.8-132.0) for women to have an ablation from initial symptoms onset versus 15 months (IQR 4.6-48.0) for men, P = .001. Prior to ablation, women had 3.78 ± 3.79 (mean ± SD) emergency department visits for SVT versus men 1.52 ± 1.72 and women tried 1.28 ± 0.82 medications versus men 0.76 ± 0.68, P < .001 and .001, respectively. CONCLUSIONS: This study demonstrates significant and multifactorial gender-related disparities in AVNRT diagnosis and treatment. Larger studies are needed to confirm these results.
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Ablação por Cateter/métodos , Taquicardia por Reentrada no Nó Atrioventricular/diagnóstico , Taquicardia por Reentrada no Nó Atrioventricular/cirurgia , Adulto , Técnicas Eletrofisiológicas Cardíacas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Padrões de Prática Médica/estatística & dados numéricos , Fatores SexuaisRESUMO
Despite previous findings on the effects of cannabinoid and vanilloid systems on learning and memory, the effects of the combined stimulation of these 2 systems on learning and memory have not been studied. Therefore, in this study, we tested the interactive effects of cannabinoid and vanilloid systems on learning and memory in rats by using passive avoidance learning (PAL) tests. Forty male Wistar rats were divided into the following 4 groups: (1) control (DMSO+saline), (2) WIN55,212-2, (3) capsaicin, and (4) WIN55,212-2 + capsaicin. On test day, capsaicin, a vanilloid receptor type 1 (TRPV1) agonist, or WIN55,212-2, a cannabinoid receptor (CB1/CB2) agonist, or both substances were injected intraperitoneally. Compared to the control group, the group treated with capsaicin (TRPV1 agonist) had better scores in the PAL acquisition and retention test, whereas treatment with WIN55,212-2 (CB1/CB2 agonist) decreased the test scores. Capsaicin partly reduced the effects of WIN55,212-2 on PAL and memory. We conclude that the acute administration of a TRPV1 agonist improves the rats' cognitive performance in PAL tasks and that a vanilloid-related mechanism may underlie the agonistic effect of WIN55,212-2 on learning and memory.
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Aprendizagem da Esquiva/efeitos dos fármacos , Benzoxazinas/farmacologia , Agonistas de Receptores de Canabinoides/farmacologia , Capsaicina/farmacologia , Cognição/efeitos dos fármacos , Memória/efeitos dos fármacos , Morfolinas/farmacologia , Naftalenos/farmacologia , Canais de Cátion TRPV/agonistas , Animais , Benzoxazinas/administração & dosagem , Bloqueadores dos Canais de Cálcio/farmacologia , Canabinoides , Capsaicina/administração & dosagem , Injeções Intraperitoneais , Masculino , Morfolinas/administração & dosagem , Naftalenos/administração & dosagem , Ratos , Ratos Wistar , Fármacos do Sistema Sensorial/farmacologiaRESUMO
Stenotrophomonas maltophilia is a Gram-negative bacillus that causes skin and soft tissue infections (SSTI), as well as bacteremia, pneumonia, and urinary tract infections. S. maltophilia infections are typically nosocomial and are often transmitted through water sources. Although historically described in immunocompromised hosts, S. maltophilia prevalence is increasing in both immunocompromised and immunocompetent populations. In light of high morbidity and mortality, it is critical that dermatologists are aware of this organism because of the limited options for therapy. Here, we describe a case of a S. maltophilia abscess with bacteremia in a patient with chronic lymphocytic leukemia and aplastic anemia that was successfully treated with trimethoprim-sulfamethoxazole. We also review the current standard of care and propose an algorithm for the treatment of S. maltophilia infection.
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BACKGROUND/PURPOSE: Mortality associated with prescription opioids has significantly increased over the past few decades and is considered a global pandemic. Prescribed opioids can cause cardiac arrhythmias, leading to fatal outcomes and unexpected death, even in the absence of structural cardiac disease. Despite the extent of cardiac toxicity and death associated with these medications, there is limited data to suggest their influences on cardiac electrophysiology and arrhythmias, with the exception of methadone. The goal of our review is to describe the possible mechanisms and to review the different ECG changes and arrhythmias that have been reported. METHODS: A literature search was performed using Google Scholar, PubMed, Springer, Ovid, and Science Direct to identify studies that demonstrated the use of prescription opioids leading to electrocardiogram (ECG) changes and cardiac arrhythmias. RESULTS: Many of the commonly prescribed opioid medications can uniquely effect the ECG, and can lead to the development of various cardiac arrhythmias. One of the most significant side effects of these drugs is QTc interval prolongation, especially when administered to patients with a baseline risk for QTc prolongation. A prolonged QTc interval can cause lethal torsades de pointes and ventricular fibrillation. Obtaining an ECG at baseline, following a dosage increase, or after switching an opioid medication, is appropriate in patients taking certain prescribed opioids. Opioids are often used first line for the treatment of acute and chronic pain, procedural sedation, medication opioid use disorders, and maintenance therapy. CONCLUSIONS: To reduce the risk of cardiac arrhythmias and to improve patient outcomes, consideration of accurate patient selection, concomitant medications, electrolyte monitoring, and vigilant ECG monitoring should be considered.
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Síndrome do QT Longo , Torsades de Pointes , Analgésicos Opioides/efeitos adversos , Arritmias Cardíacas/induzido quimicamente , Arritmias Cardíacas/tratamento farmacológico , Eletrocardiografia , Humanos , Síndrome do QT Longo/induzido quimicamente , Síndrome do QT Longo/diagnóstico , Síndrome do QT Longo/tratamento farmacológico , Metadona/efeitos adversos , Receptores Opioides , Torsades de Pointes/induzido quimicamenteRESUMO
Dyschromatosis universalis hereditaria (DUH) is a rare pigmentary genodermatosis mostly reported from Japan. It is usually characterized by widespread hyper/hypopigmented macules all over the body. Here, we report the case of a patient from Iran who presented with disseminated hyper and hypopigmented lesions over the trunk, neck, and extremities since the age of eight. To the best of our knowledge, to date, there has been only one reported case of DUH from Iran.
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Becker's nevus (BN) is one of the cutaneous hamartomatous lesions that often presents as an acquired, single unilateral pigmented hairy patch on the upper trunk, scapular region, or upper arm. Hereby we introduce a 13-year-old girl with the unusual manifestation of BN with multiple acquired, pigmented hairy patches for six months without any musculoskeletal or developmental involvements. After carefully reviewing the literature, to the best of our knowledge, this is the first case in this regard in Iran.
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BACKGROUND: Although risk factors for atrial fibrillation (AF) and atrial flutter (AFL) are known, identifying patients who will develop AF/AFL within the near future remains challenging. We sought to evaluate if the CHA2DS2-VASc risk score (CVRS) can identify hospital readmissions with AF, AFL, or acute cerebrovascular accident (CVA) among hospitalized patients without prior history of AF/AFL. METHODS: Using the Nationwide Readmission Database, a study cohort included patients without prior AF/AFL or new diagnosis of AF/AFL at the index hospitalization from 2012 to 2014. Patients were stratified based on the CVRS into three groups: Low (CVRS ≤1), Intermediate (CVRS 2-5), and High (CVRS ≥6).The primary outcome of interest was 180-day readmission rate with a primary or secondary diagnosis of AF/AFL. Secondary outcomes of interest were acute CVA and 6-month mortality rate. RESULTS: A total of 17,820,640 patients were included in our study. Over a 6-month follow up duration from the index hospitalization, the overall re-admission rate for new onset atrial arrhythmias (AF/AFL) was 3.48% (n = 620,986), acute CVA 0.13% (n = 22,522), and all-cause mortality 0.31% (n = 55,632). When compared to other groups, patients with a higher CVRS were readmitted more frequently for AF/AFL [odds ratio (OR) 2.43; 95% confidence interval (CI) 2.41-2.45, P < .0001), acute CVA (OR 3.96; 95%CI 3.85-4.08, P < .0001), and all-cause mortality (OR 2.19; 95%CI 2.14-2.24, P < .0001). CONCLUSION: In this large contemporary cohort, a CHADS2VA2SC score ≥ 6 identified patients without known prior atrial arrhythmias at an elevated risk of developing AF/AFL or acute CVA within 6 months of hospitalization.
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Fibrilação Atrial , Flutter Atrial , Acidente Vascular Cerebral , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Flutter Atrial/diagnóstico , Flutter Atrial/epidemiologia , Humanos , Readmissão do Paciente , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologiaRESUMO
Little is known about the effects of methamphetamine (Meth) and buprenorphine (Bup) on memory and learning in rats. The aim of this investigation was to examine the impact of Meth and Bup on memory and learning. Fourteen male Wistar rats weighing 250-300 g were assigned to four groups: Sham, Meth, Bup, and Meth + Bup and were treated for 1 week. Spatial learning and memory, avoidance learning, and locomotion were assessed using the Morris water maze, passive avoidance learning, and open field tests, respectively. Meth and Bup impaired spatial learning and memory in rats. Co-administration of Meth + Bup did not increase the time spent in the target quadrant compared to Meth alone in the MWM. The Bup and Meh + Bup groups were found with an increase in step-through latency (STLr) and a decrease in the time spent in the dark compartment (TDC). Meth and Bup had no effects on locomotor activity in the open field test. Bup showed a beneficial effect on aversive memory. Since Bup demonstrates fewer side effects than other opioid drugs, it may be preferable for the treatment of avoidance memory deficits in patients with Meth addiction.
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BACKGROUND: There are limited data on differences in angiographic distribution of peripheral artery disease and endovascular revascularization strategies in patients presenting with intermittent claudication (IC) and critical limb ischemia (CLI). We aimed to compare anatomic features, treatment strategies, and clinical outcomes between patients with IC and CLI undergoing endovascular revascularization. METHODS: We examined 3326 patients enrolled in the Excellence in Peripheral Artery Disease registry from 2006 to 2019 who were referred for endovascular intervention for IC (n=1983) or CLI (n=1343). The primary outcome was 1-year major adverse limb events, which included death, repeat target limb revascularization, or target limb amputation. RESULTS: Patients with CLI were older and more likely to have diabetes and chronic kidney disease and less likely to receive optimal medical therapy compared with IC. Patients with IC had higher femoropopliteal artery interventions (IC 87% versus CLI 65%; P<0.001), while below the knee interventions were more frequent in CLI (CLI 47% versus IC 12%; P<0.001). Patients with CLI were more likely to have multilevel peripheral artery disease (CLI 32% versus IC 15%, P<0.001). Patients with IC were predominantly revascularized with stents (IC 48% versus CLI 37%; P<0.001) while balloon angioplasty was more frequent in CLI (CLI 37% versus IC 25%; P<0.001). All-cause mortality was higher in patients with CLI (CLI 4% versus IC 2%; P=0.014). Major adverse limb event rates for patients with IC and CLI were 16% and 26%, respectively (P<0.001) and remained higher in CLI after multivariable adjustment of baseline risk factors. CONCLUSIONS: Patients with IC and CLI have significant anatomic, lesion, and treatment differences with significantly higher mortality and adverse limb outcomes in CLI. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01904851. Graphic Abstract: A graphic abstract is available for this article.
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Procedimentos Endovasculares , Doença Arterial Periférica , Amputação Cirúrgica , Procedimentos Endovasculares/efeitos adversos , Humanos , Claudicação Intermitente/diagnóstico por imagem , Claudicação Intermitente/epidemiologia , Isquemia/diagnóstico por imagem , Isquemia/terapia , Salvamento de Membro , Doença Arterial Periférica/cirurgia , Doença Arterial Periférica/terapia , Sistema de Registros , Fatores de Risco , Resultado do TratamentoRESUMO
BACKGROUND: Recent publications have raised serious concerns regarding the safety of digoxin for atrial fibrillation (AF). However, the subgroup of patients with reduced ejection fraction and AF have been speculated to derive clinical benefit from digoxin. We aimed to assess the impact of digoxin on mortality and cardiovascular hospitalizations in the Atrial Fibrillation and Congestive Heart Failure (AF-CHF) trial since all AF-CHF patients had an ejection fraction ≤35% and AF. METHODS AND RESULTS: Using marginal structural modeling, a contemporary statistical method that overcomes limitations of traditional modeling techniques and reduces bias, we assessed the impact of digoxin on the pre-specified primary and secondary outcomes of the AF-CHF trial, i.e., all-cause, cardiac and arrhythmic death as well as cardiovascular hospitalization. Among 1376 patients, 869 (65%) were on digoxin at one-year follow-up. Over a mean (SD) follow-up of 37 (19) months (maximum 74â¯months), 445 (32%) patients died, 357 (26%) from cardiovascular causes and 159 (12%) from arrhythmic death. Digoxin was significantly associated with all-cause, cardiac, and arrhythmic death, with estimated hazard ratios (HR) of 1.39 (95% confidence interval [CI] 1.11-1.73, Pâ¯=â¯0.004), 1.44 (95% CI 1.13-1.82, Pâ¯=â¯0.003), and 2.03 (95% CI 1.63-2.54, Pâ¯<â¯0.0001), respectively. Digoxin was not associated with cardiovascular hospitalizations [HR 1.12 (95% CI 0.91-1.37), Pâ¯=â¯0.29]. CONCLUSION: Digoxin is associated with increased all-cause mortality among patients with combined heart failure with reduced ejection fraction and AF, which is predominantly driven by arrhythmic deaths. In contrast, cardiovascular hospitalizations were not impacted by digoxin.
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Fibrilação Atrial , Insuficiência Cardíaca , Antiarrítmicos/uso terapêutico , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , Digoxina/efeitos adversos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Hospitalização , Humanos , Volume SistólicoRESUMO
High-fat diet (HFD) can induce deficits in neural function, oxidative stress, and decrease hippocampal neurogenesis. Hypericum (H.) scabrum extract (Ext) contains compounds that could treat neurological disorders. This study aimed to examine the neuroprotective impacts of the H. scabrum Ext on hippocampal synaptic plasticity in rats that were fed HFD. Fifty-four male Wistar rats (220 ± 10 g) were randomly arranged in six groups: (1) HFD group; (2) HFD + Ext300 group; (3) HFD + Ext100 group; (4) Control group; (5) Ext 300 mg/kg group; (6) Ext 100 mg/kg group. These protocols were administrated for 3 months. After this stage, a stimulating electrode was implanted in the perforant pathway (PP), and a bipolar recording electrode was embedded into the dentate gyrus (DG). Long-term potentiation (LTP) was provoked by high-frequency stimulation (HFS) of the PP. Field excitatory postsynaptic potentials (EPSP) and population spikes (PS) were recorded at 5, 30, and 60 min after HFS. The HFD group exhibited a large and significant decrease in their PS amplitude and EPSP slope as compared to the control and extract groups. In reverse, H. scabrum administration in the HFD + Ext rats reversed the effect of HFD on the PS amplitude and EPSP slope. The results of the study support that H. scabrum Ext can inhibit diminished synaptic plasticity caused by the HFD. These effects are probably due to the extreme antioxidant impacts of the Ext and its capability to scavenge free radicals.
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Encéfalo/efeitos dos fármacos , Giro Denteado/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Hypericum/química , Plasticidade Neuronal/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Antioxidantes/farmacologia , Encéfalo/fisiologia , Giro Denteado/fisiologia , Modelos Animais de Doenças , Hipocampo/efeitos dos fármacos , Hipocampo/fisiologia , Potenciação de Longa Duração , Masculino , Plasticidade Neuronal/fisiologia , Ratos , Ratos WistarRESUMO
PURPOSE: When patients with implantable cardioverter defibrillators (ICD) develop symptomatic atrial fibrillation (AF), external direct current cardioversion (EDCCV), as well as internal cardioversion using their ICD, are the options available. It is currently unknown which of these two methods are more effective. We compared the effectiveness of EDCCV versus internal cardioversion to terminate AF in patients with a single-coil ICD. METHODS: This randomized controlled trial (clinicaltrial.gov NCT03164395) enrolled consecutive patients with a single-coil ICD that presented with symptomatic AF of less than 1-year duration. They received either the maximum energy internal shock through the ICD or an EDCCV using transcutaneous pads of 200 J. The primary endpoint was a successful conversion to sinus rhythm after one shock. Crossover was permitted if the first shock was unsuccessful. RESULTS: Thirty-one patients were enrolled in the study, including 16 in the internal ICD cardioversion group. The study included patients with a mean age of 59.5 ± 16.0 years, 41.9% females, median AF duration 1 month (interquartile range 1-3), 45.2% non-ischemic cardiomyopathies, mean EF 28.6 ± 16.0%, and 45.2% biventricular ICD. There were no significant differences in baseline clinical characteristics between the two groups. In the internal cardioversion group, 5/16 patients (31.3%) met the primary endpoint versus 14/15 (93.3%) in the EDCCV group, p < 0.001. All patients that failed the first shock were subsequently cardioverted externally. CONCLUSION: Among patients with a single-coil ICD and symptomatic AF of less than 1 year, external direct current cardioversion is much more effective than internal shock through the ICD.
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Fibrilação Atrial , Desfibriladores Implantáveis , Fibrilação Atrial/terapia , Cardioversão Elétrica , Feminino , Humanos , Recém-Nascido , Masculino , Resultado do TratamentoRESUMO
Oxidative stress plays a key role in contributing to ß-amyloid (Aß) deposition in Alzheimer's disease (AD). Coenzyme Q10 (Q10) is a powerful antioxidant that buffers the potential adverse consequences of free radicals. In this study, we investigated the neuroprotective effects of Q10 on Aß-induced impairment in hippocampal long-term potentiation (LTP), a widely researched model of synaptic plasticity, which occurs during learning and memory, in a rat model of AD. In this study, 50 adult male Wistar rats were assigned to five groups: control group (saline); sham group; intraventricular PBS injection, Aß group; intraventricular Aß injection, Q10 group; and Q10 via oral gavage and Q10 + Aß group. Q10 was administered via oral gavage, once a day, for 3 weeks before and 3 weeks after the Aß injection. After the treatment period, in vivo electrophysiological recordings were performed to quantify the excitatory postsynaptic potential (EPSP) slope and population spike (PS) amplitude in the hippocampal dentate gyrus. LTP was created by a high-frequency stimulation of the perforant pathway. Following LTP induction, the EPSP slope and PS amplitude were significantly diminished in Aß-injected rats, compared with sham and control rats. Q10 treatment of Aß-injected rats significantly attenuated these decreases, suggesting that Q10 reduces the effects of Aß on LTP. Aß significantly increased serum malondialdehyde levels and total oxidant levels, whereas Q10 supplementation significantly reversed these parameters and increased total antioxidant capacity levels. The present findings suggested that Q10 treatment offers neuroprotection against the detrimental effects of Aß on hippocampal synaptic plasticity via its antioxidant activity.
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Doença de Alzheimer/metabolismo , Plasticidade Neuronal/efeitos dos fármacos , Ubiquinona/análogos & derivados , Doença de Alzheimer/fisiopatologia , Peptídeos beta-Amiloides/farmacologia , Animais , Antioxidantes/farmacologia , Giro Denteado/efeitos dos fármacos , Modelos Animais de Doenças , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Potenciação de Longa Duração/efeitos dos fármacos , Masculino , Memória/fisiologia , Transtornos da Memória/fisiopatologia , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/fisiologia , Fragmentos de Peptídeos/farmacologia , Ratos , Ratos Wistar , Transmissão Sináptica/efeitos dos fármacos , Lobo Temporal/efeitos dos fármacos , Ubiquinona/metabolismo , Ubiquinona/farmacologiaRESUMO
INTRODUCTION: Methamphetamine (Meth) and Buprenorphine (BUP) modulate pain perception. However, the antinociceptive effects of their interactions, which affect through different systems, are unclear in rats. This study aimed to compare the analgesic effects of Meth, BUP, and their coadministration, as well as the effect of withdrawal from these substances on nociception in male rats. METHODS: In this experiment, 40 male Wistar rats (weight: 250-300 g) were categorized into four groups: control, Meth, BUP, or BUP+Meth. After seven days of treatments, the antinociceptive effects were assessed using the hot plate and the tail flick tests. The differences among the groups were analyzed with ANOVA and Tukey's post hoc tests. P values less than 0.05 were considered significant. RESULTS: Meth and BUP increased the reaction times during the hot plate and tail flick tests. The combination of Meth and BUP increased reaction time more than Meth or BUP alone. CONCLUSION: The significantly high reaction times in rats treated with Meth and BUP indicate that these substances have antinociceptive effects. In addition, Meth enhanced the antinociceptive effects of BUP. These synergistic effects might occur through the dopaminergic, serotonergic, and or adrenergic systems.