Objectification of the evaluation of a pharmacological test with alpha-adrenergic blocking agents during uroflowmetry

The tactics of treating dysuric disorders are largely determined by the pathophysiological and morpho-clinical basis: infravesical obstruction, impaired bladder contractility, complex neurogenic urination disorders, etc. Among the diseases that most often cause infravesical obstruction in men, the most common pathologies are benign prostatic hyperplasia, prostate cancer, prostate sclerosis, obstructive processes of the bladder neck (contractures, fibrosis), urethral strictures of various etiologies. The use of a comprehensive urodynamic study makes it possible to differentiate the causes of urinary disorders. One of the most common and non-invasive methods used in the urologist’s clinical practice is uroflowmetry. The use of the fuzzy logic algorithm described in the article for making a decision on the presence of obstructive urination allows one to assess the urodynamic situation using the home uroflow monitoring technique. Analytical urodynamics in conjunction with the fuzzy logic block increases the accuracy of describing the examination results, and the introduction of the proposed model into the software simplifies the work with diagnostic urological equipment and increases the efficiency of the examination.

Comment on Katsarelias, D., et al. “The Effect of Beta-Adrenergic Blocking Agents in Cutaneous Melanoma—A Nation-Wide Swedish Population-Based Retrospective Register Study” Cancers 2020, 12, 3228

We read the paper by Katsarelias et al. with great interest, regarding the effect of beta-adrenergic blocking agents on cutaneous melanoma [1]. However, the study presents some methodology biases that do not allow us to support the authors’ conclusions. The paper suffers from the unification and evaluation of multiple registries, which do not provide essential data for any of the targets for research. Unlike studies in the literature [...]

Reply to Comment on Katsarelias, D., et al. “The Effect of Beta-Adrenergic Blocking Agents in Cutaneous Melanoma—A Nation-Wide Swedish Population-Based Retrospective Register Study.” Cancers 2020, 12, 3228

We thank De Giorgi et al for their interest in our study, and for raising important and relevant questions [...]

Enantioselective lipase-catalyzed O-acylation of (RS)-propranolol: analysis of the hydrogen bonds essential for catalysis

We investigated the effect of the acyl group size in the enantioselectivity of the acylation of propranolol, an amino alcohol used as β-adrenergic blocking agent. We applied a methodology frequently used to model enantioselectivity that is based on the hydrogen bonds present in the tetrahedral intermediate, which occurs in lipase-catalyzed reactions. We sampled the conformations of the tetrahedral intermediate corresponding to the esterification of both enantiomers of propranolol with ethanoyl and butanoyl, employing molecular dynamics simulation together with a quantum mechanics/molecular mechanics approach. We found that the population of these hydrogen bonds provides insight into the mechanism of the reaction. However, they are not conclusive about the role of the acyl group in the enantioselectivity. For both acyl groups, we found that the reaction from the Michaelis complex to the tetrahedral intermediate is more favorable for (R)-propranolol and the reaction from the tetrahedral intermediate to the enzyme/product complex is more favorable for (S)-propranolol.

The Effect of Beta-Adrenergic Blocking Agents in Cutaneous Melanoma—A Nation-Wide Swedish Population-Based Retrospective Register Study

Previous studies have demonstrated an anti-tumoral effect of beta-adrenergic blocking agents on cutaneous melanoma (CM). The aim of this study was to investigate if beta-adrenergic blocking agents have an impact on survival in Swedish patients with melanoma. A population-based retrospective registry study including all patients diagnosed with a primary invasive melanoma between 2009 and 2013 was performed. Data from the Swedish Melanoma Register were linked to the Swedish Prescribed Drug Registry and the Swedish Cause of Death Register. Cox regression analyses including competing risk assessments were performed. There were 12,738 patients included, out of which 3702 were exposed to beta-blockers vs. 9036 non-exposed patients. Age, male sex, Breslow thickness, ulceration, and nodal status were independent negative prognostic factors for melanoma-specific survival (MSS). Adding beta-blockers to the analysis did not add any prognostic value to the model (HR 1.00, p = 0.98), neither when adjusting for competing risks (HR 0.97, p = 0.61). When specifically analyzing the use of non-selective beta-blockers, the results were still without statistical significance (HR 0.76, p = 0.21). In conclusion, this population-based registry study could not verify that the use of beta-adrenergic blocking agents improve survival in patients with melanoma.

A hitherto unreported impurity in Terazosin – elucidation of the structure, synthesis and cytotoxicity

<p>Analysis of several batches of the a₁–adrenergic blocking agent terazosin being used as a medication for treating benign prostatic hyperplasia and hypertension revealed the presence of a hitherto not reported impurity. The latter was isolated, and its structure was elucidated from NMR and Mass Spectrometry (MS) data and unambiguously confirmed by independent synthesis. This contamination, represented in 1-[4-(amino-6,7-dimethoxyquinazolin-2-yl)-piperazin-1-yl]-pentane-1,2-dione <strong>2 </strong>is likely to occur as the product of a side-reaction in the catalytic hydrogenation step during the synthesis of the drug. Biological screening showed this compound as not cytotoxic for several human tumor cell lines and non-malignant fibroblasts.<strong></strong></p>

Effect of silodosin in post operative retention of urine

Background: Post-operative urinary retention (POUR) is a common yet potentially serious morbidity with a reported incidence of 3 to 25%. This study aims to evaluate the effect of Silodosin, a super-selective alpha- 1a adrenergic blocking agent, as prophylaxis for post operative urinary retention in patients undergoing various surgical procedures.Methods: 100 patients were divided into two groups of 50 each. In group 1, patients were given prophylactic silodosin to evaluate its effect in post operative retention of urine and in group 2, patients were not given any medication.Results: In this study, POUR was diagnosed. POUR was higher in the older age group i.e. more in the age group of 41-60 yrs but in group 1, it was less as compared to group 2. POUR rate in general anaesthesia (GA) patients are less (11.1%) in group 1 as compared to (23.6%) in group 2. POUR rate in spinal anaesthesia (SA) patients are more (21.4%) in group 1 as compared (16.6%) in group 2. The total POUR rate in group 1 was lower (14%) as compared to (22%) in group 2.Conclusions: In our opinion patients operated under GA, irrespective of gender and type of surgery will benefit from prophylactic silodosin given in pre-operative period for the prevention of POUR and we highly recommend this. Patients who were operated under SA were not benefitted by giving prophylactic silodosin. Probably this is due to use of long acting spinal anesthetic agent in the form of bupivacaine in our patients.

Prevention of Hypertension at Intubation: A Controlled Study of Sublingual Nifedipine

Background: Hypertension and tachycardia-induced after laryngoscopy and intubation can be prevented by various methods like deep inhalation anesthesia, intravenous opioids, topical intravenous lidocaine, intravenous adrenergic blocking drugs, and pretreatment with antihypertensive.Methods: It is a randomized controlled double-blind prospective study of two groups consisting of 30 patients in each group. Group A was the control group and group B were Nifedipine group who were pretreated with Nifedipine. This study aimed to assess the effectiveness of pretreatment with nifedipine in the prevention of the hypertensive response to laryngoscopy and endotracheal intubation in normotensive patients undergoing elective surgery.Result: Sublingual nifedipine was significantly effective in decreasing systolic and diastolic blood pressure produced by laryngoscopy and tracheal intubation, but its role in decreasing pulse rate was not significant. Conclusion: Nifedipine is useful to prevent laryngoscopy and intubation induced hemodynamic response.