Analytical Quality by Design-Compliant Development of a Cyclodextrin-Modified Micellar ElectroKinetic Chromatography Method for the Determination of Trimecaine and Its Impurities.

In 2022, the International Council for Harmonisation released draft guidelines Q2(R2) and Q14, intending to specify the development and validation activities that should be carried out during the lifespan of an analytical technique addressed to assess the quality of medicinal products. In the present study, these recommendations were implemented in Capillary Electrophoresis method development for the quality control of a drug product containing trimecaine, by applying Analytical Quality by Design. According to the Analytical Target Profile, the procedure should be able to simultaneously quantify trimecaine and its four impurities, with specified analytical performances. The selected operative mode was Micellar ElectroKinetic Chromatography employing sodium dodecyl sulfate micelles supplemented with dimethyl-ß-cyclodextrin, in a phosphate-borate buffer. The Knowledge Space was investigated through a screening matrix encompassing the composition of the background electrolyte and the instrumental settings. The Critical Method Attributes were identified as analysis time, efficiency, and critical resolution values. Response Surface Methodology and Monte Carlo Simulations allowed the definition of the Method Operable Design Region: 21-26 mM phosphate-borate buffer pH 9.50-9.77; 65.0 mM sodium dodecyl sulfate; 0.25-1.29% v/v n-butanol; 21-26 mM dimethyl-ß-cyclodextrin; temperature, 22 °C; voltage, 23-29 kV. The method was validated and applied to ampoules drug products.

Stimulation of B-Lymphopoiesis by Administration of a Trimecaine-Based Ionic Compound in Cyclophosphamide-Induced Hematopoietic-Depressive Model.

According to the WHO, the secondary form of hematopoietic-depressive status increases the risk of death in people with oncological, infectious, and hormonal diseases. The choice of drugs that stimulate the hematopoietic activity of B-lymphopoiesis is limited. The current leucopoiesis drugs have a number of side effects: thymic preparations stimulate the production of PGE2, which causes chronic inflammation and various autoimmune diseases through the differentiation of T helper 1 (Th1) cells, the proliferation of Th17 cells, and the production of IL-22 from Th22 cells through EP2 and EP4 receptors; cytokine preparations can cause uncontrolled immune reactions and impaired contractility of smooth and cardiac muscles; drugs based on nucleic acids can stimulate the division of all cells, including bacterial and cancerous ones. The use of oligonucleotides such as ribozymes and antisense oligodeoxynucleotides (AS-ODNs) shows promise as therapeutic moieties, but faces a number of challenges such as nuclease sensitivity, off-target effects, and efficient delivery. The search for substances that stimulate B-lymphopoiesis among ionic compounds was motivated by the discovery of the unique properties of lidocaine docusate, one of the first ionic liquid forms of the known drugs. The lidocaine docusate (protonated form of lidocaine (2-(diethylamino)-N-(2,6-dimethylphenyl) acetamide + docusate-anion (dioctylsulfosuccinate))) suppresses the division of pheochromocytoma cells and activates immunity in rats. The trimecaine-based ionic compound (TIC) demonstrates high B-lymphopoiesis-stimulating activity. The TIC compound stimulates an increase in the volume of transitional B cells, which play an important role for further differentiation and formation of a sufficient number of mature B1 cells and mature B2 cells, where mature B2 cells make up the bulk of the functional population of B lymphocytes. The TIC compound most strongly stimulated the restoration of the number of marginal zone B cells, follicular B cells, and activated germinal center B cells after the cytotoxic emptying of the follicular centers of the spleen induced cyclophosphamide. It significantly exceeds the activity of the comparison drug methyluracil. The TIC compound does not affect the level of pro-B, pre-B-I, or pre-B-II bone marrow cells, which prevents the risk of the formation of immature functionally defective cells.

Ultrasonographic approach for a foot ganglion after sewing masks in the COVID-19 pandemic: Blessing in disguise.

BACKGROUND: During the coronavirus disease (COVID-19) pandemic, people volunteered for sewing hand-made face masks. However, sewing-machine operating might be associated with high ergonomic risk and a negative impact on musculoskeletal health. OBJECTIVE AND METHODS: This paper describes an ultrasonographic diagnosis of a foot ganglion - after sewing 300 face masks within two months using a foot-operated sewing machine. RESULTS: The patient significantly improved after an ultrasound-guided aspiration and corticosteroid injection. CONCLUSION: In short, we highlight the importance of ultrasound examination in the management of work (overuse)-related disorders in occupational medicine practice.

Activation of Leukopoiesis in Rat Blood with Trimecaine-Based Ionic Compounds.

A study of myelostimulating activity of ionic compounds-trimecaine alkyl iodide derivatives under the cipher BIV (BIV-117, BIV-118, and BIV-119) was conducted on a model of doxorubicin pancytopenia in white laboratory rats. It was established that the compounds BIV-117 and BIV-119 had a pronounced leukopoiesis-stimulating activity, exceeding the activity of the methyluracil as a comparison drug. Compounds BIV-117 and BIV-119 had erythropoiesis- and thrombocytopoiesis-stimulating activity at the level of methyluracil.

Efficacy and tolerability of injectable collagen-containing products in comparison to trimecaine in patients with acute lumbar spine pain (Study FUTURE-MD-Back Pain).

Low back pain (LBP) represents an important subgroup of vertebrogenic pain with estimated prevalence around 80 %. Locally acting injectable collagen for topical application has recently extended the limited range of treatment options. The aim of the study was to evaluate the efficacy and safety of injectable collagen in patients with LBP. Patients suffering from LBP (< three months) were enrolled. They were administered either collagen 4 ml or trimecaine 1 % 4 ml in the form of subcutaneous paravertebral injections into eight pre-specified points (0.5 ml per each point) in the following schedule: two administrations in the first and second week, one in the third week. The pain intensity, Thomayer distance, Oswestry disability index, Lasseque test, quality of life, consumption of rescue medication and safety were evaluated. Exertional and rest pain, evaluated by a visual analogue scale, gradually decreased in both groups. Both treatments showed a statistically significant improvement in mobility and quality of life. The consumption of paracetamol as a rescue medication was significantly lower in patients treated with collagen than in the group treated with trimecaine (p=0.048). The analgesic efficacy of locally acting injectable collagen, as well as an analgesic sparing effect when compared to local anesthetics were demonstrated.

[Injection of anaesthetic-corticosteroid to relieve sacroiliac joint pain after lumbar stabilisation]. / Injekce anestetika s kortikoidem pri resení bolestí sakroilických kloubu po lumbálních stabilizacích.

PURPOSE OF THE STUDY: Both the range of motion and load transfer of the sacroiliac (SI) joint improve considerably after lumbar spine surgery. When, following surgery, SI joint pain develops in spite of appropriate physical therapy, injection of an anaesthetic with added corticosteroid into the SI joint is a first choice treatment. The aim of this presentation is to provide information on our experience with this therapy. MATERIAL AND METHODS: Thirty-four patients after lumbar spine fusion reported lumbalgia different form pain before surgery. In 14 (41%) of them, pain in one of the SI joints was diagnosed as the cause. This group included 12 women and two men at an average age of 56 (range, 47 to 68) years. Ten patients underwent lumbosacral fixation and four had segmental ("floating") lumbar spine fusion. All patients experienced lumbalgia at more than 3 months following surgery, at 8 months on the average (range, 4 to 12 months). None of them had SI joint pain before surgery. The diagnosis was based on specific manoeuvres on physical examination of the joint. Each patient was given an injection of 20 mg (0.5 ml) Methylprednisolone (Depo-Medrol®, Pfizer, Puurs, Belgium) and 4.5 ml 1% Mesocain (Zentiva, Praha, CR).They were inquired as to pain relief 24 h later and then at 1, 3 and 6 months after injection. Subjective feelings were assessed by a visual analogue scale (VAS). The results were analysed using descriptive statistics. RESULTS: All patients reported pain relief within 24 h of injection, but not its complete resolution. The average VAS score before and after the blockage of the SI joint was 9.1 points (8-10) and 4.8 points (2-7), respectively; this implies improvement by an average of 4.3 points (1-6), i.e., approximately by 47.3% (12.5-62.5). The duration of effects varied greatly from patient to patient. The average interval between injection and pain recurrence lasted for 5 weeks (1-28). Most frequently, relief was experienced for 2 weeks, or for 6.8 weeks with the standard deviation included. DISCUSSION Sacroiliac joint dysfunction is a very frequent cause of lumbalgia, particularly after lumbar spine surgery. Physical therapy may not always be effective. SI joint arthrodesis is indicated only in rare cases. One of the few possibilities of pain relief involves intra-articular injection of an anaesthetic with corticosteroid for booster effect. The treatment of SI joint blockage after spinal fusion has recently been dealt with in three reports in the international literature; their conclusions are in accordance with the results of this study. CONCLUSIONS: Lumbar spine stabilisation surgery may result in overloading the SI joints as the "adjacent segments". An intra-articular injection of anaesthetic can be considered a reliable method for ascertaining the SI joint as the source of a patient's problems. However, even with corticosteroid added, pain relief is not usually long-lasting.

Errors associated with the concentration of epinephrine in endonasal surgery.

This paper presents two cases of using erroneous concentrations of epinephrine during endonasal surgery. The two patients discussed were part of a larger study aimed at monitoring the absorption of epinephrine upon injection into the nasal mucosa. During this study, we observed major cardiovascular reactions in two consecutive patients--ventricular tachycardia with ventricular extrasystole and a significant rise in systolic and diastolic blood pressure and pulse rate. This state required pharmacological intervention. In hindsight, it was found that an erroneous application of ten times higher (1:10,000) concentration of epinephrine than the usual was injected. The applied solution was prepared in our institutional pharmacy and was labelled incorrectly (1:100,000 instead of 1:10,000). The authors have analysed the steps leading to the erroneous applications and recommend safety precautions for the prevention of errors in the concentration levels of epinephrine. Epinephrine injections in concentrations of 1:10,000, followed by analyses of epinephrine levels in venous blood, have not yet been described in available literature.

Convergence of nasal and tracheal neural pathways in modulating the cough response in guinea pigs.

In the present study we investigated the possibility of central convergence of neural pathways coming from distant anatomical regions in modulating the cough response. We addressed this issue by inducing cough from the tracheo-bronchial region on the background of capsaicin-stimulated and mesocain-blocked nasal mucosa in 14 anesthetized guinea pigs. The control group consisted of 6 guinea pigs in which the active agents, capsaicin and mesocain, were substituted for by inert physiological saline. All animals were tracheostomized, and the larynx was disconnected from the proximal part of the trachea with preserved innervations, and all were subjected to the same protocol. Cough, induced by mechanical irritation of the tracheo-bronchial mucosa, was elicited three times: in the control condition, after intranasal capsaicin challenge, and after another capsaicin challenge preceded by intranasal instillation of a local anesthetic, mesocain. The main finding of the study was that the number of cough efforts per bout, assessed from positive deflections on the intrapleural pressure recordings, was significantly enhanced by intranasal capsaicin challenge and this effect was reversed by intranasal pretreatment with the anesthetic mesocain [2.1 +/-0.2 (control) vs. 3.5 +/-0.4 (capsaicin) vs. 2.2 +/-0.2 (capsaicin after mesocain) (P<0.01)], with no appreciable changes in the magnitude of cough efforts. The cough response in the control group remained unchanged. We conclude that tracheo-bronchial cough may be modified by neural sensory input to the brain coming from nasal mucosa. Therefore, cough reflex is subject to central convergence of peripheral neural pathways originating at distant anatomical locations.

Prenatal diagnosis and management of fetal Long QT syndrome.

This report describes a fetus presenting with second-degree atrioventricular block, sinus bradycardia, and transient ventricular tachycardia with ventriculoatrial dissociation. Long QT syndrome (LQTS) was suspected due to the association of heart rhythm disturbances and very short transmitral early deceleration time. This impaired relaxation of the left ventricle was explained by the extreme prolongation of the refractory period caused by the prolonged relaxation time. The infant was treated successfully with beta-blockers and implantation of a pacemaker. The prognosis is poor when LQTS presents utero or during the first week of life. To date, only a few case reports of a fetus with LQTS have been published.

The epidural postoperative analgesia after a major urological procedures--a comparison of trimecaine and morphine to bupivacaine and fentanyl.

OBJECTIVES: To compare the analgesic potency and side effects of epidural combination trimecaine with morphine and bupivacaine with fentanyl in postoperative analgesia after a major urological surgery. METHODS: We randomised 150 consecutive patients. In the trimecain/morphine group (n = 75) trimecaine 50 mg with 4 mg morphine was given epidurally in 8 hour intervals. In the bupivacain/fentanyl group (n = 75) the infusion of 0.25 % bupivacaine and fentanyl 2 microg/ml was administered at an infusion rate of 8 ml/h. RESULTS: The postoperative pain scores were lower in the trimecain/morphine group, the difference was significant during the first 6 hours after surgery, there was also a trend toward higher postoperative SpO2 values in this group, the difference was significant 36 hours after surgery. The total sum of postoperative complications and side effects was significantly higher in the bupivacian/fentanyl group (p = 0.002). CONCLUSION: The combination of epidural trimecaine with morphine after a major urological surgery provides a superior analgesia with fewer side effects when compared to epidurally delivered bupivacaine with fentanyl (Tab. 2, Fig. 5, Ref. 17). Full Text (Free, PDF) www.bmj.sk.

Local administration of 2% trimecaine affects the content of fucosylated glycoconjugates in goblet cells in rabbit tracheal epithelium.

The proportion of fucosylated glycoconjugate-containing rabbit tracheal goblet cells after intratracheal application of trimecaine was studied to evaluate its possible unfavourable effects. This lapine model is comparable with diagnostic findings in humans because airway epithelia in humans and rabbits are similar; tracheal epithelium is also practically identical to bronchial epithelium in both species. Local trimecaine anaesthesia caused a proportional decrease in percentage of the tracheal goblet cells containing both alpha(1-2)- and alpha(1-6)-, alpha(1-3)- and alpha(1-4)-fucosylated glycoconjugates as revealed 10 min postexposure using lectin histochemistry. In previous studies, only mild ultrastructural damage to the airway's epithelium was revealed, but a conspicuous decrease in sialylated glycoconjugate-containing tracheal goblet cells and the dominance of acidic sulphated glycoconjugates were observed as after-effects of the same treatment. Glycoconjugate changes can influence the inner environment of airways (e.g. viscoelastic properties of the airways' mucus and mucosal barrier functions) and thus the patient's defence barriers in airways may be weakened. Concurrently, the histochemical properties of goblet cells can be altered in bronchoscopic specimens. Since trimecaine is widely used as local anaesthesia in airways in bronchoscopy, it is necessary to heed these aforementioned effects.

Membrane mechanisms of antiarrhythmic effect of quaternidine.

Complex electrophysiological study of the effects of quaternidine carried out on intact hearts from cats, myocardial fragments from rats, and single ionic channels of large edible snail showed that quaternidine demonstrates properties of class 1B antiarrhythmic drug according to Vaughan-Williams nomenclature. This agent did not suppress nomotopic pacemaker automaticity, did not change conduction in ventricles, atria, and atrioventricular junction in hearts with preserved sinus rhythm, did not prolong refractoriness of the atria and atrioventricular junction, but prolonged efficient refractory period of heart ventricles. Quaternidine decelerated rapid depolarization of the action potential, but had no effect on its duration. It did not affect potassium conductance.

[Effect of polymer concentration on rheological properties of Carbopol 980 hydrogels containing trimecainium chloride]. / Vplyv koncentrácie polyméru na reologické vlastnosti hydrogélov Carbopolu 980 s obsahom trimekaíniumchloridu.

Rheological properties exert influence on the manufacturing processes, stability and usability of a dosage form as well as the biological availability of an active ingredient. The present paper examines the effect of Carbopol 980 concentration on rheological properties of hydrogels with and without trimecainium chloride for a period of 2, 7, and 14 days after their preparation. On the basis of an evaluation of the changes in structural viscosity in dependence on the period of measurement, it has been concluded that for formulation of trimecainium chloride to a dermal dosage form, Carbopol 980 concentrations of 0.5 and 1.2 % are suitable.

[Effect of trimecaine derivatives and lidocaine on hemodynamics]. / Vliianie proizvodnykh trimekaina i lidokaina na gemodinamiku.

The results of experiments on cats showed that quaternidine, a quaternary ammonium derivative of trimecaine, does not induce significant variations in the hemodynamic parameters, being advantageous in this respect to some well-known antiarrhythmic drugs. LKhT-3-00 (dialkylaminophenylacetamide glutaminate)--a tertiary derivative of lidocaine--leads to a slight decrease in the heart rate, an insignificant decrease in the arterial pressure for 10 min, and a pronounced enhancement of the pumping ability of the left ventricle over a time period of 30 min.

[Study of antiarrhythmic activity and duration of action of quaternidine]. / Issledovanie protivoaritmicheskoi activnosti i prodolzhitel'nosti deistviia kvaternidina.

The results of experiments on dogs showed that quaternidine, a quaternary ammonium derivative of trimecaine, produces a significant antiarrhythmogenic effect in cases of rhythm disorders in the late stage of a model myocardial infarction. For drugs administered in a single isotoxic dose, the therapeutic effect of quaternidine in animals with acute myocardial ischemia considerably exceeds the duration of action of lidocaine and trimecaine.

[The antiarrhythmic activity of the trimecain ammonium derivative in myocardial ischemia]. / Protivoaritmicheskaia aktivnost' ammonievogo proizvodnogo trimekaina na fone ishemicheskogo povrezhdeniia serdtsa.

The results of experiments on cats and dogs showed that quaternidine, a quaternary ammonium derivative of trimecaine, exceeds the structural precursors (trimecaine and lidocaine), as well as the reference drugs quinidine and propranolol, in intensity of the antiarrhythmic action upon single administration on the occlusive and reperfusive arrhythmia models. The therapeutic effect of quaternidine in animals with acute myocardial ischemia lasts for about 8 h, which more than 20 times longer as compared to the duration of action of both lidocaine and trimecaine.

[Laboratory and clinical study of therapeutic efficacy of medicinal films for surgical procedures]. / Laboratorno-klinicheskoe issledovanie terapevticheskoi éffektivnosti lekarstvennykh plenok khirurgicheskogo naznacheniia.

An analysis of the experimental data showed that anesthetic medicinal films (AMFs) offer an effective medicinal form for the treatment of suppurative inflammatory disorders(SIDs) of soft tissues. The results of preclinical experiments with AMFs showed evidence of anesthetic, antimicrobial, and hemostatic effects. The therapeutic effect was established in the course of clinical investigations and confirmed by the results of cytological, histological, morphological, and bacteriological testing. The experimental data indicate that AMF application offers a promising means of SID treatment. Further development of this medicinal form must lead to an increase in the therapeutic efficacy, decrease the drug dose, and reduce the probability of side effects during the treatment of SIDs in soft tissues of various localization.

[Magnetically-guided anesthetics based on highly dispersed iron powders coated by polyacrylamide]. / Magnitoupravliaemye anestetiki na osnove vysokodispersnykh poroshkov zheleza s poliakrilamidnym pokrytiem.

The effect of external magnetic field (direct and alternating) on the targeted delivery and distribution in body tissues of experimental animals of anesthetics (novocain, lidocaine, and trimecaine) immobilized on highly dispersed ferromagnetics with biocompatible coating was studied by the method of emission spectral analysis. The results are compared with the results obtained earlier on highly dispersed iron powders with dextran coating. The parameters for the powders with dextran coating are considerably lower than those for the magnetic carriers with the polyacrylamide coating.

[Infiltration of local anesthetics into the thyroid gland capsule for surgery and the postoperative period]. / Prínos infiltrace pouzdra stítné zlázy lokálním anestetikem pro operacní a bezprostrední pooperacní prubeh.

In a prospective randomized study the hypothesis was tested whether infiltration of the thyroid capsule by a local anaesthetic will reduce the haemodynamic response to surgical trauma, consumption of anaesthetics and opioids during surgery and will shorten the time of arousal. A total of 64 patients indicated for planned goitre surgery were divided at random into a control group (C, n = 32) and experimental group (LA, n = 32). The preoperative medication and anesthesia did not differ in the two groups. In group C into the thyroid capsule a maximum of 40 ml saline was administered, in LA the same volume of 0.5% trimecain. A highly significant difference was found (p < 0.001) in the incidence of hypertension during surgery (21 C vs. 5 LA) and the need of further pharmacological interventions (21 vs. 8). In the control group was a higher consumption (p < 0.95) of the opioid phentanyl (167.5 +/- 111 micrograms vs. 125 +/- 93.5 micrograms), a trend of longer arousal and the need to antagonize the effect of opioid (p < 0.1). The substitution of saline by a local anaesthetic for infiltration of the thyroid capsule is a safe and simple method leading to a reduction of cardiovascular complications during surgery.

[Some aspects of epidural anesthesia in patients with chronic renal insufficiency]. / Osobennosti epidural'noi anestezii u bol'nykh s khronicheskoi pochechnoi nedostatochnost'iu.

In 231 patient with chronic renal impairment (CRI) the quality was studied of epidural anesthesia with different doses and concentrations of lidocaine hydrochloride, prilocaine hydrochloride, trimecaine hydrochloride, and bupivacaine. In patients in the terminal stage of CRI placed on the program-hemodialysis, the use of standard concentrations and volumes of the local anesthetsic (LA) has been found out to be associated with lower levels of the sensory and motor blocks than in CRI-free patients or in other stages of CRI. Intensification of epidural anesthesia in the above patients is achieved through employing a higher concentration of LA or epidural administration of narcotic analgesics and/or cloffelin. Patients with other stages of CRI do not require the renal-insufficiency stage-dependent correction of LA dose, an optimum option being administration of 2% solution of lidocaine and prilocaine, 2.5% solution of trimecaine and 0.5% solution of bupivacaine, 1.5% ml, on the spinal segment in combination with adjuvant drugs.