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Indian Journal of Medical Ethics 2023I have been practising medicine in an under-served rural setting since 1976, and have published around 109 papers in PubMed-indexed journals - including The Lancet, BMJ,...
I have been practising medicine in an under-served rural setting since 1976, and have published around 109 papers in PubMed-indexed journals - including The Lancet, BMJ, NEJM and several tropical medicine journals - on scorpion and snakebite cases causing acute life-threatening conditions. I have researched in detail, with restricted resources, the acute clinical effects of envenomation and management of scorpion and snakebite cases [1, 2]. In Mahad, the fatality rate due to refractory heart failure arising from autonomic storm evoked by scorpion venom was previously 30% [3]. Since the advent of prazosin and scorpion antivenom, it has dropped to less than 1% [4]. Similarly, fatalities due to snakebite poisoning have been reduced from 18% to 5.
Topics: Animals; Humans; Snake Bites; Scorpion Stings; Prazosin; Antivenins; Scorpion Venoms; Scorpions
PubMed: 36420604
DOI: 10.20529/IJME.2022.068 -
Antibiotics (Basel, Switzerland) Nov 2022is a Gram-negative orofecal transmitted pathogen that causes a wide diversity of local and systemic illnesses. utilizes several interplayed systems to regulate its...
is a Gram-negative orofecal transmitted pathogen that causes a wide diversity of local and systemic illnesses. utilizes several interplayed systems to regulate its invasion and pathogenesis: namely, quorum sensing (QS) and type three secretion system (T3SS). In addition, could sense the adrenergic hormones in the surroundings that enhance its virulence. The current study aimed to evaluate the ability of α-adrenoreceptor antagonist prazosin to mitigate the virulence of serovar Typhimurium. The prazosin effect on biofilm formation and the expression of , , , and T3SS-type II encoding genes was evaluated. Furthermore, the prazosin intracellular replication inside macrophage and anti-virulence activity was evaluated in vivo against . . The current finding showed a marked prazosin ability to compete on SdiA and QseC and downregulate their encoding genes. Prazosin significantly downregulated the virulence factors encoding genes and diminished the biofilm formation, intracellular replication inside macrophages, and in vivo protected mice. To sum up, prazosin showed significant inhibitory activities against QS, T3SS, and bacterial espionage, which documents its considered anti-virulence activities.
PubMed: 36358239
DOI: 10.3390/antibiotics11111585 -
Journal of Applied Physiology... Dec 2022We assessed hypercapnic cerebrovascular reactivity (CVR) and endothelium-dependent function [cerebral shear-mediated dilation (cSMD)] in the internal carotid artery... (Randomized Controlled Trial)
Randomized Controlled Trial
We assessed hypercapnic cerebrovascular reactivity (CVR) and endothelium-dependent function [cerebral shear-mediated dilation (cSMD)] in the internal carotid artery (ICA) with and without systemic α-adrenoreceptor blockade via Prazosin. We hypothesized that CVR would be reduced, whereas cSMD would remain unchanged, after Prazosin administration when compared with placebo. In 15 healthy adults (3 female, 26 ± 4 years), we conducted ICA duplex ultrasound during CVR [target +10 mmHg partial pressure of end-tidal carbon dioxide ([Formula: see text]) above baseline, 5 min] and cSMD (+9 mmHg [Formula: see text] above baseline, 30 s) using dynamic end-tidal forcing with and without α-adrenergic blockade (Prazosin; 0.05 mg/kg) in a placebo-controlled, double-blind, and randomized design. The CVR in the ICA was not different between placebo and Prazosin ( = 0.578). During CVR, the reactivities of mean arterial pressure and cerebrovascular conductance to hypercapnia were also not different between conditions ( = 0.921 and = 0.664, respectively). During Prazosin, cSMD was lower (1.1 ± 2.0% vs 3.8 ± 3.0%; = 0.032); however, these data should be interpreted with caution due to the elevated baseline diameter (+1.3 ± 3.6%; condition: = 0.0498) and lower shear rate (-14.5 ± 23.0%; condition: < 0.001). Therefore, lower cSMD post α-adrenoreceptor blockade might not indicate a reduction in cerebral endothelial function per se, but rather, that α-adrenoreceptors contribute to resting cerebral vascular restraint at the level of the ICA. We assessed steady-state hypercapnic cerebrovascular reactivity and cerebral endothelium-dependent function, with and without α-adrenergic blockade (Prazosin), in a placebo-controlled, double-blind, and randomized study, to assess the contribution of α-adrenergic receptors to cerebrovascular CO regulation. After administration of Prazosin, cerebrovascular reactivity to CO was not different compared with placebo despite lower blood flow, whereas cerebral endothelium-dependent function was reduced, likely due to elevated baseline internal carotid arterial diameter. These findings suggest that α-adrenoreceptor activity does not influence cerebral blood flow regulation to CO and cerebral endothelial function.
Topics: Adult; Female; Humans; Adrenergic Agents; Blood Flow Velocity; Carbon Dioxide; Carotid Artery, Internal; Cerebrovascular Circulation; Hypercapnia; Prazosin; Receptors, Adrenergic, alpha-1; Male; Young Adult
PubMed: 36326471
DOI: 10.1152/japplphysiol.00400.2022 -
Cureus Sep 2022Introduction Scorpion sting in children is still a serious health problem today. Children are at greater risk of developing severe cardiac, respiratory, and neurological...
Introduction Scorpion sting in children is still a serious health problem today. Children are at greater risk of developing severe cardiac, respiratory, and neurological complications because of their low body weight. In this study, we retrospectively evaluated the demographical changes, complaints, clinical findings, and laboratory results of scorpion sting cases admitted to the pediatric emergency department. Materials and Methods The records of 72 patients who were followed up with the diagnosis of scorpion sting in the Dicle University Pediatric Emergency Department between 2013 and 2017 were retrospectively analyzed. Results The patients included in the study were between one and 15 years (7.64±4.04 years) and 43.1% were male, and 56.9% were female. While 65.3% of the cases lived in rural areas, 34.7% lived in the city center. The most common stung areas in the cases were the lower extremity (51.4%) and the upper extremity (34.7%). The most common complaints in the patients were 70.8% pain, 58.3% edema, 41.7% cold extremities, 23.6% sweating, 22.2% vomiting, and 12.5% excessive salivation. Of the cases, 71.4% had mild, 25.7% had moderate, and 2.9% had severe stages. Of the patients, 91.6% were given antivenom, 75.7% were given antihistamines, 74.3% were given steroids, 65.7% were given antibiotics, 64.3% were given analgesics, 44.3% were given tetanus vaccine, 2.8% were given erythrocyte suspension and 1.4% were given platelet suspension. In addition, 11.4% of the cases were given prazosin treatment. While 32.9% of the cases required intensive care, two patients died. A statistically significant difference was found between the glucose, urea, creatine, total protein, sodium, potassium, alanine aminotransferase, white blood cell count, red blood cell count, hemoglobin, hematocrit, neutrophil count values of the patients at admission and discharge. Conclusion Scorpion sting cases are still a significant health problem. The severe clinical course is more common in children. The management of patients with severe clinical forms is based on early recognition of the sting, antivenom serum administration, and cardiorespiratory and systemic support.
PubMed: 36320957
DOI: 10.7759/cureus.29606 -
Brain Research Dec 2022Here we studied spinal neurotransmitter mechanisms involved in the reduction of mechanical hypersensitivity by inhibition of the amygdaloid central nucleus (CeA) in male...
Here we studied spinal neurotransmitter mechanisms involved in the reduction of mechanical hypersensitivity by inhibition of the amygdaloid central nucleus (CeA) in male and female rats with spared nerve injury (SNI) model of neuropathy. SNI induced mechanical hypersensitivity that was stronger in females. Reversible blocking of the CeA with muscimol (GABA receptor agonist) induced a reduction of mechanical hypersensitivity that did not differ between males and females. Following spinal co-administration of atipamezole (α-adrenoceptor antagonist), the reduction of mechanical hypersensitivity by CeA muscimol was attenuated more in males than females. In contrast, following spinal co-administration of raclopride (dopamine D2 receptor antagonist) the reduction of hypersensitivity by CeA muscimol was attenuated more in females than males. The reduction of mechanical hypersensitivity by CeA muscimol was equally attenuated in males and females by spinal co-administration of WAY-100635 (5-HT receptor antagonist) or bicuculline (GABA receptor antagonist). The CeA muscimol induced attenuation of ongoing pain-like behavior (conditioned place preference test) that was reversed by spinal co-administration of atipamezole in both sexes. The results support the hypothesis that CeA contributes to mechanical hypersensitivity and ongoing pain-like behavior in SNI males and females. Disinhibition of descending controls acting on spinal α-adrenoceptors, 5-HT, dopamine D2 and GABA receptors provides a plausible explanation for the reduction of mechanical hypersensitivity by CeA block in SNI. The involvement of spinal dopamine D2 receptors and α-adrenoceptors in the CeA muscimol-induced reduction of mechanical hypersensitivity is sexually dimorphic, unlike that of spinal α-adrenoceptors in the reduction of ongoing neuropathic pain.
Topics: Female; Rats; Male; Animals; Muscimol; Receptors, GABA-A; Neuralgia; Amygdala; Receptors, Neurotransmitter; GABA-A Receptor Antagonists; Receptors, Adrenergic
PubMed: 36265669
DOI: 10.1016/j.brainres.2022.148128 -
Molecules (Basel, Switzerland) Sep 2022Cardiovascular diseases are one of the major causes of mortalities worldwide. In the present research, new synthetic derivatives of thiazole were studied using isolated...
Cardiovascular diseases are one of the major causes of mortalities worldwide. In the present research, new synthetic derivatives of thiazole were studied using isolated hearts and blood vessels of rats. The heart and thoracic aorta were tested with six new synthesized thiazole acetic acid derivatives (SMVA-10, SMVA-35, SMVA-40, SMVA-41, SMVA-42 and SMVA-60), and the data obtained were statistically analyzed and compared. Isolated rat hearts were used to record the changes in developed tension and heart rate, while thoracic aortas were used to measure the contractile response, before and after treatments. Analysis of the results indicated a significant (p < 0.01) increase in developed tension with the addition of SMVA-35, SMVA-40, SMVA-41 and SMVA-42, which was augmented in the presence of adrenaline without affecting the heart rate. On the other hand, acetylcholine significantly decreased the developed tension, which was significantly reversed (p < 0.01) in the presence of compounds (SMVA-35 and SMVA-60). However, in the presence of SMVA-35 and SMVA-40, acetylcholine-induced bradycardia was significantly (p < 0.01) reduced. Furthermore, only SMVA-42 induced a dose-dependent contractile response in the isolated blood vessel, which was abolished in the presence of prazosin. Therefore, it can be concluded that some of the new synthesized thiazole derivatives exhibited promising results by raising the developed tension without changing the heart rate or blood vessel function, which could be helpful in failing heart conditions. However, more research is required to fully comprehend the function, mechanism and effectiveness of the compounds.
Topics: Acetic Acid; Acetylcholine; Animals; Epinephrine; Prazosin; Rats; Thiazoles
PubMed: 36234675
DOI: 10.3390/molecules27196138 -
Journal of Clinical Hypertension... Sep 2022There is emerging evidence that α1-blockers can be safely used in the treatment of hypertension. These drugs can be used in almost all hypertensive patients for blood... (Review)
Review
There is emerging evidence that α1-blockers can be safely used in the treatment of hypertension. These drugs can be used in almost all hypertensive patients for blood pressure control. However, there are several special indications. Benign prostatic hyperplasia is a compelling indication of α1-blockers, because of the dual treatment effect on both high blood pressure and lower urinary tract symptoms. Many patients with resistant hypertension would require α1-blockers as add-on therapy. Primary aldosteronism screen is a rapidly increasing clinical demand in the management of hypertension, where α1-blockers are useful for blood pressure control in the preparation for the measurement of plasma aldosterone and renin. Nonetheless, α1-blockers have to be used under several considerations. Among the currently available agents, only long-acting α1-blockers, such as doxazosin gastrointestinal therapeutic system 4-8 mg daily and terazosin 2-4 mg daily, should be chosen. Orthostatic hypotension is a concern with the use of α1-blockers especially in the elderly, and requires careful initial bedtime dosing and avoiding overdosing. Fluid retention is potentially also a concern, which may be overcome by combining an α1-blocker with a diuretic.
Topics: Adrenergic alpha-Antagonists; Aged; Aldosterone; Antihypertensive Agents; Diuretics; Doxazosin; Humans; Hypertension; Renin
PubMed: 36196467
DOI: 10.1111/jch.14556 -
Current Research in Physiology 2022The autonomic profile of mice submitted to sustained hypoxia (SH) was not yet fully evaluated. Herein, we characterized the cardiovascular and autonomic profile of...
The autonomic profile of mice submitted to sustained hypoxia (SH) was not yet fully evaluated. Herein, we characterized the cardiovascular and autonomic profile of conscious freely moving mice submitted to SH using two sequential experimental protocols to evaluate the parasympathetic and sympathetic tone to the heart and the sympathetic tone to the vascular resistance. In the first protocol the sequence of antagonists was methyl-atropine followed by propranolol and then by prazosin, while in the second protocol the sequence was propranolol followed by methyl-atropine and then by prazosin. In SH the baseline heart rate was significantly lower than in control mice and the antagonism of the parasympathetic and sympathetic tone to the heart in both experimental protocols indicated an increased parasympathetic tone in SH mice and no changes in the sympathetic tone. Antagonism of the sympathetic tone to the vascular resistance with prazosin produced similar changes in arterial pressure in control and SH mice. Altogether these findings support the concept that mice submitted to SH present a significant increase in the parasympathetic but not in the sympathetic tone, which may explain why the baseline arterial pressure was not increased in SH mice.
PubMed: 36185816
DOI: 10.1016/j.crphys.2022.09.006 -
BMC Geriatrics Sep 2022Adrenergic alpha-1 receptor antagonists (alpha-1 antagonists) are frequently used medications in the management of lower urinary tract symptoms (LUTS) suggestive of... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of adrenergic alpha-1 receptor antagonists in older adults: a systematic review and meta-analysis supporting the development of recommendations to reduce potentially inappropriate prescribing.
BACKGROUND
Adrenergic alpha-1 receptor antagonists (alpha-1 antagonists) are frequently used medications in the management of lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) and in the management of therapy-resistant arterial hypertension, two conditions frequently found in older adults. This systematic review aims at presenting a complete overview of evidence over the benefits and risks of alpha-1 antagonist treatment in people ≥ 65 years, and at deriving recommendations for a safe application of alpha-1 antagonists in older adults from the evidence found.
METHODS
A comprehensive literature search was performed (last update March 25 2022) including multiple databases (Medline/Pubmed, Embase, the Cochrane Library) and using the PICOS framework to define search terms. The selection of the studies was done by two independent reviewers in a two-step approach, followed by a systematic data extraction. Quality appraisal was performed for each study included using standardised appraisal tools. The studies retrieved and additional literature were used for the development of recommendations, which were rated for strength and quality according to the GRADE methodology.
RESULTS
Eighteen studies were included: 3 meta-analyses, 6 randomised controlled trials and 9 observational trials. Doxazosin in the management of arterial hypertension was associated with a higher risk of cardiovascular disease, particularly heart failure, than chlorthalidone. Regarding treatment of LUTS suggestive of BPH, alpha-1 antagonists appeared to be effective in the relief of urinary symptoms and improvement of quality of life. They seemed to be less effective in preventing disease progression. Analyses of the risk profile indicated an increase in vasodilation related adverse events and sexual adverse events for some agents. The risk of falls and fractures as well as the effects of long-term treatment remained unclear. All meta-analyses and 5 out of 6 interventional studies were downgraded in the quality appraisal. 7 out of 9 observational studies were of good quality.
CONCLUSIONS
It cannot be recommended to use doxazosin as first-line antihypertensive agent neither in older adults nor in younger patients. In the management of BPH alpha-1 antagonists promise to effectively relieve urinary symptoms with uncertainty regarding their efficacy in preventing long-term progression events.
Topics: Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Aged; Antihypertensive Agents; Chlorthalidone; Doxazosin; Humans; Hypertension; Inappropriate Prescribing; Lower Urinary Tract Symptoms; Male; Prostatic Hyperplasia; Quality of Life
PubMed: 36171560
DOI: 10.1186/s12877-022-03415-7 -
Biology Sep 2022Quorum sensing (QS) controls the production of several bacterial virulence factors. There is accumulative evidence to support that targeting QS can ensure a significant...
Quorum sensing (QS) controls the production of several bacterial virulence factors. There is accumulative evidence to support that targeting QS can ensure a significant diminishing of bacterial virulence. Lessening bacterial virulence has been approved as an efficient strategy to overcome the development of antimicrobial resistance. The current study aimed to assess the anti-QS and anti-virulence activities of α-adrenoreceptor prazosin against three virulent Gram-negative bacteria , , and . The evaluation of anti-QS was carried out on a series of in vitro experiments, while the anti-virulence activities of prazosin were tested in an in vivo animal model. The prazosin anti-QS activity was assessed on the production of QS-controlled pigment violacein and the expression of QS-encoding genes in . In vitro tests were performed to evaluate the prazosin effects on biofilm formation and production of extracellular enzymes by , , and . A protective assay was conducted to evaluate the in vivo anti-virulence activity of prazosin against , , and . Moreover, precise in silico molecular docking was performed to test the prazosin affinity to different QS receptors. The results revealed that prazosin significantly decreased the production of violacein and the virulent enzymes, protease and hemolysins, in the tested strains. Prazosin significantly diminished biofilm formation in vitro and bacterial virulence in vivo. The prazosin anti-QS activity was proven by its downregulation of QS-encoding genes and its obvious binding affinity to QS receptors. In conclusion, prazosin could be considered an efficient anti-virulence agent to be used as an adjuvant to antibiotics, however, it requires further pharmacological evaluations prior to clinical application.
PubMed: 36138828
DOI: 10.3390/biology11091349