Treatment and diagnosis of chemotherapy-induced peripheral neuropathy: An update.

When peripheral neuropathy occurs due to chemotherapy treatment, it is referred to as chemotherapy-induced peripheral neuropathy (CIPN). Typically, symptoms are sensory rather than motor and include reduced feeling and heightened sensitivity to pressure, pain, temperature, and touch. The pathophysiology of CIPN is very complex, and it involves multiple mechanisms leading to its development which will be described specifically for each chemotherapeutic class. There are currently no approved or effective agents for CIPN prevention, and Duloxetine is the only medication that is an effective treatment against CIPN. There is an unavoidable necessity to develop preventative and treatment approaches for CIPN due to its detrimental impact on patients' lives. The purpose of this review is to examine CIPN, innovative pharmacological and nonpharmacological therapy and preventive strategies for this illness, and future perspectives for this condition and its therapies.

Impact of COVID-19 infection on the cardiovascular system: An evidence-based analysis of risk factors and outcomes.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as COVID-19, emerged in late 2019 in Wuhan, China. The World Health Organization declared the virus a pandemic on March 11, 2020. Disease progression from COVID-19 infection has shown significant symptom manifestations within organ systems beyond the respiratory system. The literature has shown increasing evidence of cardiovascular involvement during disease course and an associated increase in mortality among infected patients. Although the understanding of this novel virus is continually evolving, it is currently proposed that the mechanism by which the SARS-CoV-2 virus contributes to cardiovascular manifestations involves the ACE2 transmembrane protein. The protein ACE2 is highly expressed in blood vessel pericytes, and infection can result in microvascular dysfunction and subsequent acute coronary syndromes. Complications involving the cardiovascular system include myocardial infarction, arrhythmias, shock, and heart failure. In this evidence-based review, we discuss risk factors of cardiovascular involvement in COVID-19 infection, pathophysiology of COVID-19-related cardiovascular infection, and injury, COVID-19 effects on the cardiovascular system and corresponding treatments, and hematologic effects of COVID-19 and COVID-19 in heart transplant patients. Clinicians managing COVID-19 patients should appreciate the potential cardiovascular effects related to the disease process.

Effects of a methamphetamine vaccine, IXT-v100, on methamphetamine-related behaviors.

RATIONALE: Vaccines have been developed as a potential treatment for methamphetamine (meth) use disorder (MUD). Immunization with the meth vaccine IXT-v100 has previously been shown to elicit antibodies with high affinity for meth and thus may be an effective treatment for MUD. OBJECTIVES: These studies were designed to determine the efficacy of IXT-v100 on meth-taking and meth-seeking behaviors in rats. METHODS: In the acquisition and maintenance study, male and female rats were trained to self-administer meth (0.06 mg/kg/infusion) over an 8-week period following vaccination. In the last 4 weeks, the dose of meth was increased or decreased each week. To assess meth-seeking behavior, the meth-primed reactivity model was used. Rats were trained to self-administer meth for 5 weeks, followed by a 5-week or 11-week forced abstinence period during which the animals were vaccinated. Rats were then placed back into the self-administration chamber immediately after being injected with meth (1 mg/kg, i.p.) but did not receive meth during the session. Responses were recorded and used as a measure of meth seeking. RESULTS: Results from the acquisition and maintenance study in Wistar rats show that vaccination with IXT-v100 adjuvanted with glucopyranosyl lipid A stable emulsion decreases the percentage of animals that will self-administer a moderate level of meth. In the meth-primed reactivity studies, results from males showed that vaccination significantly attenuates meth-seeking behavior. CONCLUSION: Together, these results suggest vaccination with IXT-v100 may be effective at decreasing meth-taking and meth-seeking behaviors in humans suffering with MUD.

The role of regional anesthesia in the propagation of cancer: A comprehensive review.

New cancer incidences worldwide will eclipse 18 million in 2019, with nearly 10 million cancer-related deaths. It is estimated that in the United States, almost 40% of individuals will be diagnosed with cancer in their lifetime. Surgical resection of primary tumors remains a cornerstone of cancer treatment; however, the surgical process can trigger an immune-suppressing sympathetic response, which promotes tumor growth of any residual cancerous cells post surgery. Regional and local anesthesia have become staples of anesthesia and analgesia during and after surgery. Recently, much evidence in the form of retrospective and prospective studies has come to light regarding the protective, antitumor properties of anesthetic and analgesic agents across a wide variety of cancers and patient demographics. It is believed that by blocking afferent pain signals, the body does not mount the sympathetic response that contributes to the perpetuation of disease after surgical treatment. This review, therefore, investigates these studies as they pertain to the treatment and outcomes of cancers treated surgically to elucidate the role of regional anesthesia in the propagation of cancer.

The differential effects of alprazolam and oxazepam on methamphetamine self-administration in rats.

BACKGROUND: Methamphetamine is the second most commonly used illicit drug in the world, and despite recent attempts by the Drug Enforcement Administration to combat this epidemic, methamphetamine use is still on the rise. As methamphetamine use increases so does polydrug use, particularly that involving methamphetamine and benzodiazepines. The present study was designed to examine the effects of two benzodiazepines on methamphetamine self-administration. METHODS: Five doses of methamphetamine (0.0075, 0.015, 0.03, 0.09, and 0.12mg/kg/infusion) were tested, producing an inverted U-shaped dose-response curve. Rats were then pretreated with oxazepam, alprazolam, or vehicle prior to methamphetamine self-administration. To determine if the effects of these drugs were due to the GABAA receptor and/or translocator protein (TSPO), we also pretreated rats with an antagonist for the benzodiazepine-binding site on the GABAA receptor (i.e., flumazenil) and a TSPO antagonist (i.e., PK11195) prior to alprazolam or oxazepam administration. RESULTS: Oxazepam significantly reduced methamphetamine self-administration as demonstrated by a downward shift of the dose-response curve. In contrast, alprazolam significantly enhanced methamphetamine self-administration as evidenced by a leftward shift of the dose-response curve. Flumazenil completely blocked the effects of alprazolam on methamphetamine self-administration. When administered individually, both flumazenil and PK11195 partially reversed the effects of oxazepam on methamphetamine self-administration. However, when these two antagonists were combined, the effects of oxazepam were completely reversed. CONCLUSIONS: The GABAA receptor is responsible for the alprazolam-induced enhancement of methamphetamine self-administration, while the activation of both the GABAA receptor and TSPO are responsible for the oxazepam-induced reduction of methamphetamine self-administration.

Resveratrol promotes endothelial cell wound healing under laminar shear stress through an estrogen receptor-α-dependent pathway.

Restenosis is an adverse outcome of angioplasty, characterized by vascular smooth muscle cell (VSMC) hyperplasia. However, therapies targeting VSMC proliferation delay re-endothelialization, increasing the risk of thrombosis. Resveratrol (RESV) inhibits restenosis and promotes re-endothelialization after arterial injury, but in vitro studies assessing RESV-mediated effects on endothelial cell growth contradict these findings. We thus hypothesized that fluid shear stress, mimicking physiological blood flow, would recapitulate RESV-dependent endothelial cell wound healing. Since RESV is an estrogen receptor (ER) agonist, we tested whether RESV promotes re-endothelialization through an ER-α-dependent mechanism. Mice fed a high-fat diet or a diet supplemented with RESV were subjected to carotid artery injury. At 7 days after injury, RESV significantly accelerated re-endothelialization compared with vehicle. In vitro wound healing assays demonstrated that RESV exhibits cell-type selectivity, inhibiting VSMC, but not endothelial cell growth. Under laminar shear stress (LSS), RESV dramatically enhanced endothelial cell wound healing and increased both the activation of extracellular signal-regulated kinase (ERK) and endothelial cell proliferation. Under LSS, small interfering RNA against ER-α, but not endothelial nitric oxide synthase, abolished RESV-induced ERK activation, endothelial cell proliferation, and wound healing. Thus these studies suggest that the EC phenotype induced by LSS better models the prohealing effects of RESV and that RESV and LSS interact to promote an ER-α-dependent mitogenic effect in endothelial cells.