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Brain Sciences May 2023Erectile dysfunction (ED) is the inability to get and maintain an adequate penile erection for satisfactory sexual intercourse. Due to its negative impacts on men's life... (Review)
Review
Erectile dysfunction (ED) is the inability to get and maintain an adequate penile erection for satisfactory sexual intercourse. Due to its negative impacts on men's life quality and increase during aging (40% of men between 40 and 70 years), ED has always attracted researchers of different disciplines, from urology, andrology and neuropharmacology to regenerative medicine, and vascular and prosthesis implant surgery. Locally and/or centrally acting drugs are used to treat ED, e.g., phosphodiesterase 5 inhibitors (first in the list) given orally, and phentolamine, prostaglandin E1 and papaverine injected intracavernously. Preclinical data also show that dopamine D receptor agonists, oxytocin and α-MSH analogues may have a role in ED treatment. However, since pro-erectile drugs are given on demand and are not always efficacious, new strategies are being tested for long lasting cures of ED. These include regenerative therapies, e.g., stem cells, plasma-enriched platelets and extracorporeal shock wave treatments to cure damaged erectile tissues. Although fascinating, these therapies are laborious, expensive and not easily reproducible. This leaves old vacuum erection devices and penile prostheses as the only way to get an artificial erection and sexual intercourse with intractable ED, with penile prosthesis used only by accurately selected patients.
PubMed: 37239274
DOI: 10.3390/brainsci13050802 -
European Journal of Translational... Jan 2022This article was not intended to be a complete review of the electromyography of pathological muscle states, but it was written to illustrate how the "Coletti Method of...
This article was not intended to be a complete review of the electromyography of pathological muscle states, but it was written to illustrate how the "Coletti Method of EMG ChemoDenervation" (CMECD®) protocol for the treatment of chronic pain resulting from chronic muscle spasm was developed and established. That process led to an unexpected understanding of the underlying pathophysiology of chronic muscle spasm, which represents a paradigm shift in our understanding and ultimately in our treatment of muscle spasm-induced chronic pain. Other investigators had brought to light the presence of spontaneous electrical activity (SEA) in states of muscle spasm. Those findings were all but ignored by standard EMG/Nerve conduction studies in clinical practice. Starting with a simple EMG device I experimented with various medications to treat patients with chronic pain associated with chronic muscle spasm. Suppression of SEA with long-acting medications resolved both the chronic spasm and chronic pain. A successful protocol using phenoxybenzamine was established and clinical outcomes were followed. More than 200 patients were successfully treated during last 12 years. Correlating known exercise muscle physiology with the development of the pathological state of chronic muscle spasm as seen by electromyography led to the postulation of the ischemic model of chronic muscle spasm. Light microscopy pathophysiologic supportive findings are presented and discussed. Predictions from this model to various aspects of treatment were supportive. Implications regarding treatment by the CMECD procedure, as well as other standard therapies, are discussed. Application of the ischemic model to other pain conditions was explored with implications of therapeutic modification. Recommendations for changes in rehabilitation therapy are discussed.
PubMed: 35044134
DOI: 10.4081/ejtm.2022.10323 -
Frontiers in Endocrinology 2020
Topics: Humans; Angiotensin-Converting Enzyme 2; Arthritis, Rheumatoid; Autoimmune Diseases; Drug Combinations; Gastrointestinal Neoplasms; Inflammation; Inflammatory Bowel Diseases; Neurodegenerative Diseases; Phentolamine; Receptors, G-Protein-Coupled; Vasoactive Intestinal Peptide
PubMed: 33101216
DOI: 10.3389/fendo.2020.588157 -
Anesthesia Progress Apr 2022Reversal agents are defined as any drug used to counteract the pharmacologic effects of another drug. Several pharmacologic antagonists serve as essential drugs in the... (Review)
Review
Reversal agents are defined as any drug used to counteract the pharmacologic effects of another drug. Several pharmacologic antagonists serve as essential drugs in the contemporary practices of sedation providers and anesthesiologists. Reversal or "antidote" drugs, such as flumazenil and naloxone, are often used in unintentional overdose situations involving significant benzodiazepine- and/or opioid-induced respiratory depression. Within the context of skeletal muscle relaxation, neostigmine and sugammadex are routinely used to reverse the effects of nondepolarizing neuromuscular blocking agents. In addition, the alpha-adrenergic antagonist phentolamine is used in dentistry as a local anesthetic reversal agent, decreasing its duration of action by inducing vasodilation. This review article discusses the pharmacology, uses, practical implications, adverse effects, and precautions needed for flumazenil, naloxone, neostigmine, sugammadex, and phentolamine within the context of sedation and anesthesia practice for dentistry.
Topics: Anesthesia, Dental; Anesthetics; Humans; Neostigmine; Sugammadex
PubMed: 35377935
DOI: 10.2344/anpr-69-01-09 -
Environmental Science and Pollution... Feb 2022Vasoactive intestinal peptide (VIP) is a neuropeptide that is produced by the lymphoid cells and plays a major role in immunological functions for controlling the... (Review)
Review
Vasoactive intestinal peptide (VIP) is a neuropeptide that is produced by the lymphoid cells and plays a major role in immunological functions for controlling the homeostasis of the immune system. VIP has been identified as a potent anti-inflammatory factor, in boosting both innate and adaptive immunity. Since December 2019, SARS-Cov-2 was found responsible for the disease COVID-19 which has spread worldwide. No specific therapies or 100% effective vaccines are yet available for the treatment of COVID-19. Drug repositioning may offer a strategy and several drugs have been repurposed, including lopinavir/ritonavir, remdesivir, favipiravir, and tocilizumab. This paper describes the main pharmacological properties of synthetic VIP drug (Aviptadil) which is now under clinical trials. A patented formulation of vasoactive intestinal polypeptide (VIP), named RLF-100 (Aviptadil), was developed and finally got approved for human trials by FDA in 2001 and in European medicines agency in 2005. It was awarded Orphan Drug Designation in 2001 by the US FDA for the treatment of acute respiratory distress syndrome and for the treatment of pulmonary arterial hypertension in 2005. Investigational new drug (IND) licenses for human trials of Aviptadil was guaranteed by both the US FDA and EMEA. Preliminary clinical trials seem to support Aviptadil's benefit. However, such drugs like Aviptadil in COVID-19 patients have peculiar safety profiles. Thus, adequate clinical trials are necessary for these compounds.
Topics: COVID-19; Drug Combinations; Humans; Phentolamine; SARS-CoV-2; Vasoactive Intestinal Peptide
PubMed: 34846667
DOI: 10.1007/s11356-021-17824-5 -
Journal of Plastic, Reconstructive &... Oct 2021The use of Wide Awake Local Anaesthetic No Tourniquet (WALANT) amongst Plastic and Orthopaedic Hand Surgeons has been accelerated by the impact of the COVID-19 pandemic...
The use of Wide Awake Local Anaesthetic No Tourniquet (WALANT) amongst Plastic and Orthopaedic Hand Surgeons has been accelerated by the impact of the COVID-19 pandemic and associated risks of general anaesthesia. Benefits of WALANT include a bloodless field, improved recovery, on-table testing, as well as cost and time savings. Whilst more clinical trials are underway to fully elucidate safety-profile and outcomes, there is a lack of consensus and clarity over contraindications to WALANT. A survey of trainees identified that only one-in-five were aware of the appropriate reversal agent in the event of inadequate perfusion. We feel that a WALANT checklist should be developed and implemented for use immediately prior to administration of local anaesthetic with adrenaline to an extremity, building on the successes of the World Health Organisation (WHO) and the Royal College of Anaesthetists checklists. Such a checklist should include contraindications to WALANT and make the operator aware of the availability, dose and location of Phentolamine as a reversal agent. Introducing this checklist will help to facilitate safer and more effective use of WALANT within Hand Surgery.
Topics: Anesthesia, Local; COVID-19; Comorbidity; Humans; Orthopedic Procedures; Pandemics; Tourniquets
PubMed: 34193391
DOI: 10.1016/j.bjps.2021.05.025 -
BMC Nephrology Dec 2022Chronic kidney disease (CKD) is a major risk factor for contrast induced acute kidney injury (CI-AKI) in chronic coronary syndrome (CCS) patients undergoing coronary... (Randomized Controlled Trial)
Randomized Controlled Trial
Association of periprocedural phentolamine infusion with favorable outcome in patients with chronic kidney disease and chronic coronary syndrome undergoing coronary catheterization: a prospective randomized controlled pilot study.
BACKGROUND
Chronic kidney disease (CKD) is a major risk factor for contrast induced acute kidney injury (CI-AKI) in chronic coronary syndrome (CCS) patients undergoing coronary catheterization. We aimed to evaluate the efficacy of phentolamine in prevention of CI-AKI in CKD and CCS patients undergoing percutaneous coronary catheterization for diagnostic angiography ± stenting.
METHODS
Participants with CKD and CCS planned for percutaneous coronary catheterization were included, while participants with normal kidney functions were excluded. A consecutive sample of 107 participants (mean age 58.62 ± 8.96 years, 64.5% males) was selected, underwent diagnostic coronary angiography or percutaneous coronary intervention, and received either conventional CI-AKI prevention strategy (group 1) or periprocedural phentolamine and conventional CI-AKI prevention strategy (group 2).
RESULTS
The percentages of study participants who had CI-AKI were 82.9% for group 1 and 17.1% for group 2, respectively. The incidence rate of CI-AKI was significantly lower in group 2 versus group 1 (p < 0.001). The urine output (ml/kg) and the urine output (ml/hour) within 72 hours post procedure was significantly higher in group 2 versus group 1 (t(105) = - 0.69, p < 0.001, t(105) = - 52.46, p < 0.001, respectively), the peak change in serum creatinine and the percentage of change relative to the baseline serum creatinine at 72 hours post procedure was significantly lower in group 2 versus group 1 (t(102) = 0.2, p 0.018, t(102) = 23.54, p < 0.001, respectively), and the incidence rate of major adverse cardiac and cerebrovascular events within 90 days post procedure was significantly lower in group 2 versus group 1 (t(102) = 1.168, P < 0.001), respectively. There was a statistically significant association of periprocedural phentolamine infusion with prevention of CI-AKI (OR = 0.041, 95% CI 0.0149-0.1128, P < 0.0001).
CONCLUSION
Our study highlights the potential role of phentolamine for protection of the kidney in CKD patients planned for coronary catheterization.
TRIAL REGISTRATION
Pan African Clinical Trial Registry Number: PACTR202209493847741. Date of Trial Registration: 22/09/2022.
Topics: Male; Humans; Middle Aged; Aged; Female; Phentolamine; Contrast Media; Prospective Studies; Pilot Projects; Creatinine; Coronary Angiography; Renal Insufficiency, Chronic; Risk Factors; Acute Kidney Injury; Cardiac Catheterization; Percutaneous Coronary Intervention
PubMed: 36585656
DOI: 10.1186/s12882-022-03050-9 -
Theranostics 2022Excessive sympathetic activity and norepinephrine (NE) release play crucial roles in the pathogeneses of hypertension. Sympathetic fibers innervate adventitia rather...
Excessive sympathetic activity and norepinephrine (NE) release play crucial roles in the pathogeneses of hypertension. Sympathetic fibers innervate adventitia rather than media of arteries. However, the roles of NE in adventitial fibroblasts (AFs) are unknown. This study investigated the roles of NE in regulating AFs-derived extracellular vesicles (EVs) release and vascular smooth muscle cells (VSMCs) proliferation in hypertension. AFs and VSMCs were prepared from aorta of Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). AFs were treated with NE (10 μM) for 24 h (every 6 h, 4 times), and cultured in exosomes-depleted medium for 48 h. EVs were isolated from AFs medium with ultracentrifugation for identification and transfer to VSMCs. NE promoted AFs phenotypic transformation and proliferation, which were prevented by α-receptor antagonist phentolamine rather than β-receptor antagonist propranolol. NE-treated AFs conditioned medium stimulated VSMCs proliferation, which was inhibited by either exosome inhibitor GW4869 or phentolamine. NE increased small EVs number, diameter and angiotensin converting enzyme (ACE) contents. The NE-induced EVs release was abolished by GW4869. The EVs from NE-treated AFs stimulated VSMCs proliferation, which was prevented by angiotensin II type 1 receptor antagonist losartan. The EVs from the ACE knockdown-treated AFs showed lower ACE contents, and lost their roles in stimulating VSMCs proliferation. NE promotes AFs-derived small EVs release and ACE transfer, and then causes VSMCs proliferation in hypertension. Intervention of AFs-derived EVs release may be potential therapeutics for excessive sympathetic activation-related vascular remodeling in hypertension.
Topics: Adventitia; Animals; Cell Proliferation; Cells, Cultured; Extracellular Vesicles; Fibroblasts; Hypertension; Muscle, Smooth, Vascular; Norepinephrine; Phentolamine; Rats; Rats, Inbred WKY
PubMed: 35832088
DOI: 10.7150/thno.70974 -
Journal of Atherosclerosis and... Jun 2021The mechanism underlying the stiffness of the aorta and iliofemoral artery that is required to maintain blood pressure (BP) is unclear. A new stiffness index of the...
AIM
The mechanism underlying the stiffness of the aorta and iliofemoral artery that is required to maintain blood pressure (BP) is unclear. A new stiffness index of the aorta (aBeta) and iliac-femoral arteries (ifBeta) was defined by applying the cardio-ankle vascular index (CAVI). We compared changes in stiffness of the two arteries in response to reduced BP, due to the non-selective α adrenergic blocker phentolamine and the β adrenergic blocker atenolol, in rabbits.
METHODS
Pressure waves at the origin (oA) and distal ends of the aorta (dA) and the distal end of the left femoral artery (fA) were recorded simultaneously using three pressure sensors in 25 anesthetized rabbits. Phentolamine (50 µg/kg/min) and atenolol (10 mg/kg/min) were infused for 2 min. The pulse wave velocity (PWV) in each artery was determined; aBeta, ifBeta, and whole Beta (aifBeta) were calculated by the following formula; Beta=2ρ/PP×ln(SBP/DBP)×PWV (ρ: blood density; SBP, SBP, and PP: systolic, diastolic, and pulse pressures, respectively).
RESULTS
SBP and DBP at oA, dA, and fA decreased by the administration of phentolamine and atenolol, with and without decreased total peripheral vascular resistance. After phentramine infusion, cardiac output (CO), aBeta, and aifBeta increased, while ifBeta decreased. After infusion of atenolol, CO decreased, while aBeta, ifBeta, and aifBeta remained unchanged.
CONCLUSION
The contradictory reactions of aBeta and ifBeta to phentolamine suggest that the stiffness of the aorta and ilio-femoral artery is regulated separately during decreased BP induced by phentolamine, but not by atenolol.
Topics: Animals; Antihypertensive Agents; Aorta; Atenolol; Blood Flow Velocity; Blood Pressure Determination; Cardiac Output; Disease Models, Animal; Femoral Artery; Hypertension; Phentolamine; Pulse Wave Analysis; Rabbits; Vascular Stiffness
PubMed: 32921698
DOI: 10.5551/jat.57364 -
Revista Da Associacao Medica Brasileira... Sep 2020The vascular evaluation of the erectile function through Color Duplex-Doppler Ultrasound (CDDU) of the penis can benefit the therapeutic decision-making process.... (Review)
Review
INTRODUCTION
The vascular evaluation of the erectile function through Color Duplex-Doppler Ultrasound (CDDU) of the penis can benefit the therapeutic decision-making process. Unfortunately, there is no standard procedure for CDDU conduction, a fact that results in high result-interpretation variability.
OBJECTIVE
The aims of this review are to promote greater standardization during CDDU of the penis and discuss the fundamental principles for its accurate conduction.
METHODS
CDDU is initially conducted with the penis in the flaccid state; the whole penis must be assessed (images at B mode) with a high-frequency linear transducer (7.5-18 MHz). Intracavernous injection of vasodilating agents (prostaglandin E1, papaverine, phentolamine) is performed to induce a rigid erection. Serial measurements at different times should be taken during the CDDU session and penile rigidity must be assessed in each evaluation.
RESULTS
It is important to monitor the erection response after the vasoactive agent (hardness scale), and scanning during the best-quality erection should be contemplated. Manual self-stimulation, audiovisual sexual stimulation (AVSS), and vasoactive agent re-dosing protocols must be taken into account to reduce the influence of psychogenic factors and to help the patient to get the hardest erection possible. Such measurements contribute to the maximal relaxation of the erectile tissue, so the hemodynamic parameters are not underestimated.
CONCLUSIONS
CDDU is a relevant specialized tool to assess patients with erectile dysfunction; therefore, this guideline will help to standardize and establish uniformity in its conduction and interpretation, taking into consideration the complexity and heterogeneity of CDDU evaluations of the penis.
Topics: Erectile Dysfunction; Hemodynamics; Humans; Male; Penile Erection; Penis; Ultrasonography, Doppler, Color
PubMed: 33027442
DOI: 10.1590/1806-9282.66.9.1180