Evaluation of the Therapeutic Potential of Amantadine in a Vincristine-Induced Peripheral Neuropathy Model in Rats.

This study aimed to evaluate the therapeutic potential of amantadine in a vincristine-induced peripheral neuropathy model in rats. Forty-eight male Wistar rats were used. The treated groups received oral amantadine at doses of 2, 5, 12, 25 and 50 mg/kg, with daily applications for 14 days. The mechanical paw withdrawal threshold was measured using a digital analgesimeter. Immunohistochemical analysis of IL-6, TNFα, MIP1α, IL-10, CX3CR1, CXCR4, SOD, CAT and GPx, and enzymatic activity analysis of CAT, SOD and GPx were performed, in addition to quantitative PCR of Grp78, Chop, Ho1, Perk, Bax, Bcl-xL, Casp 3, Casp 9, IL-6, IL-10, IL-18 and IL-1ß. The results showed an increase in nociceptive thresholds in animals that received 25 mg/kg and 50 mg/kg amantadine. Immunohistochemistry showed a decrease in the immunostaining of IL-6, TNFα, MIP1α and CX3CR1, and an increase in IL-10. CAT and SOD showed an increase in both immunochemistry and enzymatic analysis. qPCR revealed a reduced expression of genes related to endoplasmic reticulum stress and regulation in the expression of immunological and apoptotic markers. Amantadine demonstrated antinociceptive, anti-inflammatory and antioxidant effects in the vincristine-induced peripheral neuropathy model in rats, suggesting that amantadine may be considered an alternative approach for the treatment of vincristine-induced peripheral neuropathic pain.

Post-treatment with maropitant reduces oxidative stress, endoplasmic reticulum stress and neuroinflammation on peripheral nerve injury in rats.

OBJECTIVE: To determine the effective dose and therapeutic potential of maropitant using through expression of mediators of oxidative stress, inflammatory and of the unfolded protein response (UPR) (bio) markers on spinal cord using a model of neuropathic pain induced through chronic constriction injury (CCI) in rats. STUDY DESIGN: Randomized, blinded, prospective experimental study. ANIMALS: 98 male Wistar rats. METHODS: Rats were anesthetized with sevoflurane and after CCI, they were randomly assigned to the following groups that received: vehicle, 3, 6, 15, 30 e 50 mg/kg/24q of maropitant. The effect on inflammatory mediators (IL10, TNFα), oxidative stress (GPx, CAT, SOD), microglial (IBA-1) and neuronal (NeuN, TACR1) markers was evaluated though immunohistochemistry and expression levels of markers of hypoxia (HIF1α, Nrf2), antioxidant enzymes (Catalse, Sod1 and GPx1), and endoplasmic reticulum stress mediators (GRP78, CHOP and PERK) through qRT-PCR. RESULTS: Intraperitoneal injection (IP) of maropitant inhibited nociception with ID50 values of 4,1 mg/kg (5,85-19,36) in a neuropathic pain model through CCI. A dose of 30 mg/kg/24q was significantly effective in reducing mechanical allodynia 1 to 4h after treatment with nociception inhibition (145,83%). A reduction in the expression of hypoxia factors (HIF1α, Nrf2) was observed, along with an increase in antioxidant activity (CAT, SOD and GPX). Additionally, there was a reduction in inflammatory markes (IL10, TNFα), microglial (IBA-1), and neuronal markers (NeuN, TACR1). CONCLUSION AND CLINICAL RELEVANCE: These findings demonstrate that the determined dose, administered daily for seven days, had an antinociceptive effect, as well as anti-inflammatory and antioxidant activity.

Factors Associated With Long Survival in Patients With Cancer Admitted to Palliative Care: An Exploratory Study.

Objective: Some patients with cancer admitted to palliative care have relatively long survivals of 1 year or more. The objective of this study was to find out factors associated with prolonged survival. Methods: Retrospective case-control study comparing the available data of patients with cancer who survived more than 1 year after admission in a palliative care service with patients with cancer who survived 6 months or less. The intended proportion was 4 controls for each case. Patients were identified through electronic records from 2012 until 2018. Results: And 1721 patients were identified. Of those patients, 111 (6.4%) survived for at least 1 year, and 363 (21.1%) were included as controls according to the established criteria. The intended proportion could not be reached; the proportion was only 3.3:1. The median survival of cases was 581 days (range: 371-2763), and the median survival of controls was 57 days (range: 1-182). In the multivariable analysis, patients with a hemoglobin ≥ 10.6 g/dL and a creatinine level >95 µmol/L had a higher probability of living more than 1 year. In contrast, patients with abnormal cognition, pain, anorexia, liver metastases, an Eastern Cooperative Oncology Group performance status >1, and a neutrophil/lymphocyte ratio ≥ 3.43 had a low probability of living more than 1 year. Conclusion: Several factors were statistically associated positively or negatively with prolonged survival. However, the data of this study should be confirmed in other studies.

Comparative Analysis of the Collapsibility Index and Distensibility Index of the Inferior Vena Cava Through Echocardiography with Pulse Pressure Variation That Predicts Fluid Responsiveness in Surgical Patients: An Observational Controlled Trial.

OBJECTIVE: The objective for the present study was to compare the collapsibility (IcIVC) and distensibility (IdIVC) indices of the inferior vena cava with pulse pressure variation (PPV) and determine the accuracy and cutoff points of IcIVC and IdIVC that best predict response to intravenous fluid therapy in surgical patients. DESIGN: Observational, prospective, nonblinded, single center. SETTING: Hospital do Servidor Público Estadual de São Paulo, in São Paulo, Brazil. PARTICIPANTS: Volunteer surgical patients. INTERVENTIONS: This prospective study evaluated adult surgical patients before and after they underwent mechanical ventilation. IcIVC and IdIVC measurements were obtained with echocardiography and PPV through arterial catheterization. MEASUREMENTS AND MAIN RESULTS: Twenty-two patients with a mean age of 55.7 ± 10.9 years were included; 31.8% of the study participants had PPV values >13% and were shown to be responsive to fluid. A good correlation was detected between PPV and icIVC (R2 = 0.71; p < 0.001) and between PPV and idIVC (R2 = 0.79; p < 0.001). The area under the receiver operating characteristic curve was 0.98 for icIVC (95% confidence interval 0.81-0.99; p < 0.001) and 0.88 for idIVC (95% confidence interval 0.67-0.98; p < 0.001). CONCLUSIONS: PPV was found to have good correlation with the inferior vena cava diameter variation using echocardiography in surgical patients undergoing spontaneous and artificial ventilation. The cutoff values that best predicted PPV >13% were >40% for icIVC and >17.6% for idIVC.

Thoracoscopic pericardiectomy associated with fully implantable catheter via thoracoscopy in the management of mesothelioma in a bitch.

Mesothelioma is a very aggressive malignant tumor with low survival rates that is often diagnosed belatedly. Pericardial effusion is a common consequence in cases of mesothelioma, with pericardiocentesis and pericardiectomy indicated; therefor thoracocentesis is necessary to drain the contents no longer retained in the pericardium. The present report describes a mesothelioma-carrying dog with a history of cardiac tamponade that underwent thoracoscopic pericardiectomy and, later, thoracoscopic implantation of a fully implantable catheter to function as a thoracic drain. In the consulted literature, there is no use of a fully implantable catheter for this purpose. The authors consider that there was an improvement in the quality of life.