Tracking Radiolabeled Endothelial Microvesicles Predicts Their Therapeutic Efficacy: A Proof-of-Concept Study in Peripheral Ischemia Mouse Model Using SPECT/CT Imaging

Microvesicles, so-called endothelial large extracellular vesicles (LEVs), are of great interest as biological markers and cell-free biotherapies in cardiovascular and oncologic diseases. However, their therapeutic perspectives remain limited due to the lack of reliable data regarding their systemic biodistribution after intravenous administration. Methods: Applied to a mouse model of peripheral ischemia, radiolabeled endothelial LEVs were tracked and their in vivo whole-body distribution was quantified by microSPECT/CT imaging. Hindlimb perfusion was followed by LASER Doppler and motility impairment function was evaluated up to day 28 post-ischemia. Results: Early and specific homing of LEVs to ischemic hind limbs was quantified on the day of ischemia and positively correlated with reperfusion intensity at a later stage on day 28 after ischemia, associated with an improved motility function. Conclusions: This concept is a major asset for investigating the biodistribution of LEVs issued from other cell types, including cancer, thus partly contributing to better knowledge and understanding of their fate after injection.

Lifesaving Medications Use By Athletic Trainers

The athletic trainer's (AT) emergency management skill set requires competency in the delivery of basic lifesaving medications. Some lifesaving medications have been a part of athletic training practice for decades, but that list has grown as ATs' practice setting has expanded - increasing the types of em ergent conditions that the AT may have to treat. The 2020 CAATE curricular standards require athletic training students be trained to administer the following: supplemental oxygen, nitroglycerine, low dose aspirin, bronchodilators, epinephrine using automated injection device, glucagon, and naloxone. Clinically, the conditions treated by these medications can be categorized as follows: cardiac, respiratory, hypoglycemia, or anaphylaxis. All ATs should know the indications, contraindications, administration methods, and the details of patient monitoring for each medication. Generally, these medications are safe, have clear indications for use, and few contraindications. While ATs are trained to administer these medications, they must consider state laws and local policies.

SARS-CoV-2 Post Vaccinated Adverse Effects and Efficacy in the Egyptian Population

Vaccines are the solution to overcome SARS-CoV-2. This study aimed to determine the post-Sinopharm vaccine safety-profile and immunity through antibody titers. Data were collected using a structured questionnaire from Egyptian participants who received two doses of Sinopharm vaccine. Data were divided into three parts, the first and second parts were to detect participants’ post-first and second dose symptoms and practices, and the third for the results of IgG anti spike protein antibodies test and laboratory tests. Pain, redness, swelling at the injection site, headache, fatigue, and lethargy were the most common post-vaccine symptoms for both first and second doses. Most of the participants felt mild or no symptoms after vaccination. The symptoms started mostly during the first day post-vaccination and lasted for no more than two days. Forty-nine percent of the participants resulted in positive antibodies tests on day 18 post-vaccination. The average antibody level for vaccinated participants with past SARS-CoV-2 infection was much higher than that for non-past infected participants. These vaccines’ administration methods need to be reevaluated by changing the dose, dose interval, adding a third dose, or mixing it with other vaccines with different techniques to improve their protection rates. Further studies are required to validate this finding.

Correction of ultrastructural paclitaxel-induced spinal cord motoneurons lesions

Background. Paclitaxel-induced peripheral neuropathy (PIPN) is a major side effect of paclitaxel in patients with cancer with no fully known mechanisms. The aim of the study was to investigate the fine sub-microscopic structure of the spinal cord anterior horn neurons in PIPN combined with 2-ethyl-6-methyl-3-hydroxypyridine succinate administration. Methods. The experiment was performed on 80 white rats, which were administered intraperitoneally with Paclitaxel (Actavis, Romania), pre-dissolved in an isotonic saline at a dose of 2 mg / kg body weight four times a day to achieve a dose of 8 mg / kg. Then 48 of these animals were injected intraperitoneally 2-ethyl-6-methyl-3-hydroxypyridine succinate at a dose of 10 mg / kg (32 rats received intraperitoneally water for injection). Observation periods were 1, 7, 14, 21, 28 days. Results. We found that 2-ethyl-6-methyl-3-hydroxypyridine corrects the morpho-functional state of the motor neurons of the spinal cord and revealed a positive metabolic effect on them. Conclusion. This was manifested by the improvement of the electron microscopic picture of the neuronal structures responsible for their protein-synthetic (granular endoplasmic reticulum, ribosomes and polysomes), respiratory (mitochondria), and protective (lysosomes) functions.

Molecular Hydrogen as Medicine: An Assessment of Administration Methods

Since the late 18th century, molecular hydrogen (H2) has been shown to be well tolerated, firstly in animals, and then in humans. However, although research into the beneficial effects of molecular hydrogen in both plant and mammalian physiology is gaining momentum, the idea of utilising this electrochemically neutral and non-polar diatomic compound for the benefit of health has yet to be widely accepted by regulatory bodies worldwide. Due to the precise mechanisms of H2 activity being as yet undefined, the lack of primary target identification, coupled with difficulties regarding administration methods (e.g., dosage and dosage frequencies, long-term effects of treatment, and the patient’s innate antioxidant profile), there is a requirement for H2 research to evidence how it can reasonably and most effectively be incorporated into medical practice. This review collates and assesses the current information regarding the many routes of molecular hydrogen administration in animals and humans, whilst evaluating how targeted delivery methods could be integrated into a modern healthcare system.

ΔFosB: A Molecular Mechanism of MDMA Dependence

<p>Rationale. 3,4-methylenedioxymethamphetamine (MDMA) is a widely used illicit substance and some users show signs of abuse and dependence. It has been suggested that addiction reflects persistent neuroplasticity and one proposed mechanism has been a change in the expression of the transcription factor, ΔFosB. Objectives. This study determined whether ΔFosB expression in reward-relevant brain areas was altered as a function of MDMA self-administration. Methods. Rats were separated into triads. One rat self-administered MDMA (master rat) and the other 2 rats received either MDMA (yoked MDMA) or saline (yoked saline) infusions contingent on the behaviour of the master rat. Testing continued until a total intake of 350 mg/kg of MDMA was delivered. Two days following the final self-administration session, rats were sacrificed and perfused transcardially. Brains were removed, and ΔFosB immunohistochemistry was conducted. ΔFosB expression in striatum and medial prefrontal cortex was compared across groups. Results. Unfortunately the tissue from many of the yoked MDMA rats was compromised and therefore data from this group were not included in any analyses. MDMA self-administration produced a significantly greater expression of ΔFosB in the ventromedial and ventrolateral portions of the caudate putamen when compared to expression produced following yoked saline exposure. Within the infralimbic cortex, accumbens shell and dorsolateral caudate putamen differences approached significance. A significant correlation between ΔFosB expression in the ventromedial caudate putamen and cumulative active lever presses across the final 5 days of self-administration was also found. Conclusions. These findings provide the first evidence of MDMA-induced expression of ΔFosB. Increased expression of ΔFosB was observed in regions associated with the development and maintenance of drug addiction. These data support the idea that induction of ΔFosB may present a mechanism by which MDMA can induce alterations in genetic transcription, which may underlie the development of MDMA dependence. Future studies should utilise antagonism of ΔFosB via region-selective administration of Δc-jun in order to further elucidate the role of these transcriptional changes in the development and maintenance of self-administration.</p>

ΔFosB: A Molecular Mechanism of MDMA Dependence

<p>Rationale. 3,4-methylenedioxymethamphetamine (MDMA) is a widely used illicit substance and some users show signs of abuse and dependence. It has been suggested that addiction reflects persistent neuroplasticity and one proposed mechanism has been a change in the expression of the transcription factor, ΔFosB. Objectives. This study determined whether ΔFosB expression in reward-relevant brain areas was altered as a function of MDMA self-administration. Methods. Rats were separated into triads. One rat self-administered MDMA (master rat) and the other 2 rats received either MDMA (yoked MDMA) or saline (yoked saline) infusions contingent on the behaviour of the master rat. Testing continued until a total intake of 350 mg/kg of MDMA was delivered. Two days following the final self-administration session, rats were sacrificed and perfused transcardially. Brains were removed, and ΔFosB immunohistochemistry was conducted. ΔFosB expression in striatum and medial prefrontal cortex was compared across groups. Results. Unfortunately the tissue from many of the yoked MDMA rats was compromised and therefore data from this group were not included in any analyses. MDMA self-administration produced a significantly greater expression of ΔFosB in the ventromedial and ventrolateral portions of the caudate putamen when compared to expression produced following yoked saline exposure. Within the infralimbic cortex, accumbens shell and dorsolateral caudate putamen differences approached significance. A significant correlation between ΔFosB expression in the ventromedial caudate putamen and cumulative active lever presses across the final 5 days of self-administration was also found. Conclusions. These findings provide the first evidence of MDMA-induced expression of ΔFosB. Increased expression of ΔFosB was observed in regions associated with the development and maintenance of drug addiction. These data support the idea that induction of ΔFosB may present a mechanism by which MDMA can induce alterations in genetic transcription, which may underlie the development of MDMA dependence. Future studies should utilise antagonism of ΔFosB via region-selective administration of Δc-jun in order to further elucidate the role of these transcriptional changes in the development and maintenance of self-administration.</p>

Effects of Cannabis on Cardiovascular System: The Good, the Bad, and the Many Unknowns

Cannabis is currently the most consumed illicit substance in the world, and gradual legalization in the USA makes it important to understand the health consequences of the use of this substance. With growing body of evidence that some cannabis ingredients may be beneficial in various aspects of hemostasis, additional research is clearly needed in various clinical areas. In addition to understanding the efficacy, research efforts should also include studies that address any harmful effects of the compounds or administration methods that may result in adverse effects. This review is focused on the cardiometabolic effects of cannabis use. Cardiometabolic diseases are among the leading causes of death in the USA and around the world. The purpose of this review was to provide an overview of the known medicinal benefits of selected cannabis cannabinoids and the known side effects or contraindications. More importantly, we have proposed new questions and signposts in cannabis research to uncover additional medicinal benefits and identify the health hazards with focus on cardiovascular disease.