Pharmacological Tests Research Articles

Pharmacological Provocation Test was Less Frequently Performed in Patients with Coronary Spastic Angina Onset during Coronavirus Disease Pandemic: A Multicenter Cross-sectional Study

Pharmacological Provocation Test was Less Frequently Performed in Patients with Coronary Spastic Angina Onset during Coronavirus Disease Pandemic: A Multicenter Cross-sectional Study

Targeting Immune Cells.

The respiratory tract with its vast surface area and very thin air-blood tissue barrier presents an extremely large interface for potential interaction with xenobiotics such as inhaled pathogens or medicaments. To protect its large and vulnerable surface, the lung is populated with several different types of immune cells. Pulmonary epithelial cells, macrophages and dendritic cells are key players in shaping the innate and adaptive immune response. Due to their localization, they represent a frontline of cell populations that are among the first to come in contact with inhaled xenobiotics. Furthermore, depending on the lung compartment they populate, these cells show a large variety in morphology, phenotype, and function. These unique characteristics make those cell populations ideal targets for specific immunomodulators that are designed for inhalation. Depending on cell population or lung compartment targeting, a specific immune response may be triggered or modulated. The purpose of a potent carrier for pulmonary immunomodulation is, first, to efficiently target a specific immunocompetent cell and, second, to affect its role in generating an immune response. Immunomodulation may occur at different levels of immune cell-antigen interaction, i.e. antigen uptake, trafficking, processing and presentation. Inhalation of nanosized carriers for drugs or vaccines shows great potential for both prophylactic and therapeutic approaches in order to modulate immune responses locally or systemically, due to the specific deposition and targeting properties of nanoparticles. Immune responses triggered by nanosized particles may be either immunostimulatory or immunosuppressive and depending on the specific purpose, stimulation or suppression may either be desired or unwanted. Meticulous analysis of immunomodulatory potential, pharmacologic and toxicologic testing of inhalable nanocarriers is required in order to find novel and optimal approaches for prophylaxis and therapy of pulmonary diseases. The design and characterization of such nanoparticles requires well-coordinated interdisciplinary research among engineers, biologists and clinicians.

On the choice of antiarrhythmic drug in patients with ventricular arrhythmia of mixed character

Background. The choice of an antiarrhythmic drug, proof of its effectiveness and safety in a short period of time in patients with non-coronary ventricular arrhythmia are the most pressing problems of practical arrhythmology. Objective. To resolve the issue of choosing an antiarrhythmic drug in patients with a mixed nature of ventricular arrhythmia, several ectopic foci, and to optimize further tactics for their management. Design and methods. Of 167 patients with ventricular arrhythmia distribution during periods of wakefulness who performed a stress test, 32 individuals with non-coronary arrhythmias of a mixed nature (by the participation of the autonomic nervous system) were selected. All patients underwent an acute pharmacological stress test with a beta-blocker. Antiarrhythmic therapy was selected under the control of multi-day ECG telemonitoring. Results. In the pretest of exercise tests, single ventricular parasystole was recorded in all 32 patients. In 3 patients, the arrhythmia persisted throughout the entire load, in 4 patients it progressed, in 25 patients the parasystole of the initial morphology disappeared, and at the peak of the load/early recovery period, arrhythmia of a different morphology appeared. Indications for drug treatment were determined for all patients with the choice of the drug after acute pharmacological tests. Then, therapy with two antiarrhythmic drugs was initiated using multi-day ECG telemonitoring, the purpose of which was to control the efficacy, safety, choice of doses and time of drug administration. On days 5–6, combination therapy was effective in 25 patients (78 %). Conclusion. With the help of stress tests, it is possible to accelerate not only the search for the cause of ventricular arrhythmia, but also the choice of a personalized method of treatment. Supplementing the examination with pharmacological tests allows predicting the result of combined antiarrhythmic therapy with a beta-blocker and a class IС drug with an anticholinergic effect.

Differentiation of Horner Syndrome and Physiological Anisocoria by Automated Pupillometry.

The differentiation of Horner syndrome from physiological anisocoria is important yet clinically challenging. We investigated the diagnostic accuracy of pupillometry to discriminate Horner syndrome from physiological anisocoria compared to pharmacological testing with the alpha-2-agonist apraclonidine, which is considered the current gold standard. Forty-four adult patients, mostly referred to our neuro-ophthalmology service for evaluation of anisocoria, were included. Automated binocular pupillometry was performed under standardized light conditions before and >30 minutes after instillation of 1% apraclonidine eye drops. A positive apraclonidine test indicating unilateral Horner syndrome was defined as an increase of pupil size in the smaller pupil and decrease of size in the larger pupil. Receiver operator characteristic curves were calculated to find the best pupillometric parameter discriminating Horner syndrome from physiological anisocoria. We found that the parameters measuring the pupillary dilation lag using pupillometry could reliably discriminate Horner syndrome from physiological anisocoria compared to pharmacological testing. Calculating the change of anisocoria at 3-4 seconds after light-off relative to the anisocoria at the end of the light-on period (Δ3-4) may be most suitable to rule out Horner syndrome reaching a sensitivity of 95% and specificity of 68% using a cutoff of 0.35 mm. Our results indicate that pupillometry is a robust tool to measure the dilation lag in Horner syndrome and, therefore, to distinguish pathological from physiological anisocoria obviating pharmacological testing. The high sensitivity of the test will allow to identify the patients with Horner syndrome requiring further investigation.

Prognostic algorithm for risk assessment of retinal vein occlusion under geomagnetic perturbations

Aim. To develop a screening and prognostic algorithm for assessing the risk of retinal vein occlusion in patients with arterial hypertension under the conditions of geomagnetic disturbances. Material and methods. In total, 1512 patients with arterial hypertension of 1–4 stages were examined. Within the period of three years, 391 patients developed retinal venous occlusions. The parameters of systemic and regional hemodynamics in these patients, as well as ocular microcirculatory function, were compared both in a magnetically calm environment and during geomagnetic disturbances. To simulate the response of microcirculatory bed to stress, a functional pharmacological instillation test with a 10% Irifrin solution was performed. To assess the geomagnetic situation, the Кр index was used, which objectively characterizes fluctuations of the Earth’s magnetic field over a 3h time interval. The International Classification of Кр values was used. Results. For statistical analysis, 78 studied signs of systemic, regional hemodynamics, and microcirculation were selected. The prognostic significance of 30 studied signs was revealed. A training group (1434 people) and an examination group (78 people) were formed. Based on the training group, a predictive algorithm was formed. A number of regularities were established, which can be used to create a system for risk assessment of retinal vein thrombosis during geomagnetic disturbances in patients with hypertension. To determine the risk of retinal vein occlusion, a coefficient was developed. The algorithm showed the sensitivity and specificity of 89% and 94%, respectively. Conclusion. A prognostic algorithm with high sensitivity and specificity for assessing the risk of occlusive lesions of the retinal veins during geomagnetic disturbances in patients with arterial hypertension is proposed.

Phytochemical Analysis and Toxicity Test of Secondary Metabolite Compounds in Methanol Extract from Tuber of Belajang Keissi’ (Stephania venosa (Blume) Spreng)

The tuber of Stephania venosa (Blume) Spreng, locally known as Belajang Keissi’, belongs to the Menispermaceae family and is traditionally used in Indonesia for treating diabetes mellitus, as a nerve tonic, and as an anti-cancer remedy. This plant is recognized for its bioactive compounds with anti-inflammatory, analgesic, antioxidant, and anti-tumor properties. The objective of this study was to analyze the phytochemical content and evaluate the toxicity of the methanol extract of Stephania venosa tubers to explore its potential as an anticancer agent. The study involved sample preparation, extraction by maceration, phytochemical group testing using specific reagents, and toxicity assessment through the Brine Shrimp Lethality Test (BSLT) method. Phytochemical screening revealed the presence of alkaloids and flavonoids as the major secondary metabolites, while the toxicity test showed that the extract exhibited significant lethality to Artemia salina larvae, with an LC50 value of 14.92 ppm. This result indicates high toxicity, meeting the threshold of bioactivity for potential therapeutic applications (LC50 ≤ 1000 ppm). The mechanism of toxicity is hypothesized to involve the interference of alkaloids with the neural and digestive systems of the larvae. This study highlights the potential of Stephania venosa tubers as a source of bioactive compounds for antibacterial, antifungal, or anticancer development, warranting further isolation and advanced pharmacological testing to confirm its therapeutic applications.

Characterization of Human Melanoma Skin Cancer Models: A step towards Model-Based Melanoma Research

Advancing 3D in vitro human tissue models is crucial for biomedical research and drug development to address the ethical and biological limitations of animal testing. Recently, 3D skin models have proven to be effective for studying serious skin conditions, such as melanoma. For these advanced models to be applicable in preclinical studies, thorough characterization is essential to understand their applicability and limitations.In this study, we used bioimaging and RNA sequencing to assess the architecture and transcriptomic profiles of skin models, including models with melanoma. Our results indicated that these models closely mimicked skin morphology and gene expression patterns. The full-thickness (FT) model shows a superior resemblance to the human skin, particularly in basement membrane formation and cellular interactions.The integrity of the skin-like properties and gene expression signatures of both skin and melanoma cells were preserved upon the integration of melanoma cells, establishing these models as robust platforms for cancer research. The responsiveness of the FT melanoma models to vemurafenib treatment was successfully monitored, demonstrating their validity as a reliable, reproducible, and humane tool for pharmacological testing and drug development. Furthermore, the transcriptomic data showed that skin models with cancer spheroids had upregulated genes linked to aggressive and resilient cancer behavior compared to spheroids alone. This emphasizes the importance of the microenvironment in cancer progression and suggests that 3D skin models can serve to uncover mechanisms and therapeutic targets that are not detectable in simpler systems. Statement of SignificanceThis study introduces advanced, ethically sound skin and melanoma models as alternatives to animal testing in drug discovery. By thoroughly characterizing these models using bioimaging and RNA sequencing, we demonstrate their close resemblance to human skin, particularly in full-thickness models. These models not only replicate the complex cellular interactions and gene expression patterns of human tissue but also maintain robustness after melanoma integration. Our findings highlight the potential of these models in revealing cancer mechanisms and therapeutic targets, offering a significant impact on melanoma research and preclinical testing.

Phenotype heterogeneity of SCN5A mutations in Brugada syndrome

Abstract Introduction Although SCN5A is the main gene associated with Brs syndrome (Brs), rare variants in this gene only affect 20 to 30 % of patients. Additionally, associated phenotype may differ even among relatives sharing the same mutation emphasizing a phenotype heterogeneity that is poorly understood for now. Objective Here we aim to investigate the association between the presence of SCN5A mutations and the expression of a BrS phenotype in large families. Methods Among Brugada patients enrolled in our prospective cohort, we included patients from families with affected proband carrier of a SCN5A mutation and at least 4 relatives carriers of the same SCN5A mutation. Patient without a spontaneous type 1 ECG and no pharmacological provocative test were excluded. Results A total of 463 individuals from 45 large families were enrolled. Among them, 258 (56%) were mutation carriers of one of the 33 identified SCN5A mutations. After pharmacological test, 219 (47%) individuals were diagnosed with BrS, including 32 not carriers of the familial mutation. Seventy-five patients (30%), carriers of the familial SCN5A mutation, remain negative for Brugada syndrome after pharmacological test. The prevalence of genotype-phenotype mismatch was 24%, including 32 BrS patients non carrier of the familial mutation (phenocopy) and 75 patients with the familial mutation but without BrS (30% of uncomplete penetrance). Conclusion Our data strongly suggest that SCN5A mutation is not either necessary nor sufficient to explain the occurrence of BrS phenotype. We now aim to identify which associated factors might interfere, focusing first on the genetic background of phenotype/genotype mismatched individuals.

Prevalence and characteristics of the catecholamine induced QT prolongation syndrome

Abstract Background We have recently described large families of idiopathic ventricular fibrillation characterised by catecholamine-induced QT interval prolongation (CIQTP). The patient presented with a normal QT duration at rest but an abnormal QT prolongation during a mental stress test (MST). Objective The aim of this study was to investigate the role of this new syndrome in inherited arrhythmic diseases. Methods Consecutive patients and their relatives, identified after unexplained familial sudden cardiac death or sudden cardiac arrest, were enrolled in the study in the presence of: - no other diagnosis after cardiac ultrasound, stress test, pharmacological test with adrenaline and ajmaline. - positive MST defined by a prolongation of the QT interval (>-11ms) during MST (as previously published). Results 134 families with unexplained SCD were examined. CIQTP was diagnosed in 15 families, representing a prevalence of 11.2%. Family screening of these 15 families identified a total of 43 individuals. Seven (16%) had symptoms prior to diagnosis, including sudden cardiac arrest in one. At baseline, the QTc interval was measured at 440+/-23 ms. MST increased the QTc interval by 49+/-33 ms. The identification of QT interval prolongation was less important in the exercise test (delta QTc 17+/-52 ms at 4 minutes after exercise) and the epinephrine test (delta QTc 19+/-36 at 1 minute according to the Krahn protocol). Treatment with beta-blockers was initiated in 19 patients (44%) on the basis of symptoms and major prolongation of the QT interval during the MST. After a mean follow-up of 7+/-2 years, only one patient developed ventricular fibrillation. This episode occurred during a short period when he was no observant for the treatment. Since then, there has been no recurrence of the arrhythmia on beta-blocker therapy. All other patients, including those who were previously symptomatic remained symptom-free on treatment. Conclusion CIQTP may explain a significant part of sudden cardiac arrest or syncope in young patients. Conventional screening using ECG, exercise test and epinephrine challenge may not be able to unmask CIQTP. Then MST may be systematically proposed for the screening of patient and their family. In CIQTP patients beta blocker therapy appears to be highly efficient to prevent symptoms.

High Detectability of Prehospital 12-Lead Electrocardiogram in Diagnosing Spasm-Induced Acute Coronary Syndrome.

The importance of prehospital (PH) electrocardiograms (ECG) recorded by emergency medical services (EMS) for diagnosing coronary artery spasm-induced acute coronary syndrome (CS-ACS) remains unclear. We enrolled 340 consecutive patients with ACS who were transported by EMS within 12 h of symptom onset. According to Japanese Circulation Society guidelines, CS-ACS (n=48) was diagnosed with or without a pharmacological provocation test (n=34 and n=14, respectively). Obstructive coronary artery-induced ACS (OC-ACS; n=292) was defined as ACS with a culprit lesion showing 99% stenosis or >75% stenosis with plaque rupture or thrombosis observed via angiographic and intravascular imaging. Ischemic ECG findings included ST-segment deviation (elevation or depression) and negative T and U waves. In CS-ACS, the prevalence of ST-segment deviation decreased significantly from PH-ECG to emergency room (ER) ECG (77.0% vs. 35.4%; P<0.001), as did the prevalence of overall ECG abnormalities (81.2% vs. 45.8%; P<0.001). Conversely, in OC-ACS, there was a similar prevalence on PH-ECG and ER-ECG of ST-segment deviations (94.8% vs. 92.8%, respectively; P=0.057) and abnormal ECG findings (96.9% vs. 95.2%, respectively; P=0.058). Patients with abnormal PH-ECG findings that disappeared upon arrival at hospital without ER-ECG or troponin abnormalities were more frequent in the CS-ACS than OC-ACS group (20.8% vs. 1.0%; P<0.001). PH-ECG is valuable for detecting abnormal ECG findings that disappear upon arrival at hospital in CS-ACS patients.

Quercetin ameliorates depressive-like phenotypes and memory deficits in hypoxia-induced murine model of stress

BackgroundHypoxia is believed to induce a form of stress that contributes to the exacerbation of certain disease conditions such as heart diseases. Most of these conditions revolve around the central nervous system (CNS) since the brain consumes a significant percentage of oxygen. PurposeThis study aims to determine the specific effect of hypoxia on mood and cognitive behaviours using behavioural assessment and histological methods in mice. Additionally, this study investigated the counter effect of quercetin (QCN) on the hypoxia-induced changes. MethodsA total of thirty (30) mice were equally divided into five (5) groups. Group 1 and 2 received 5 % DMSO while only the latter was subjected to the hypoxia protocol. Groups 3–5 received graded doses of quercetin (10, 20 and 40 mg/kg), respectively. Approximately 24 h after a consecutive seven-day treatment, the mice were tested for depressive-like symptoms as well as dysfunctional memory function using recognized pharmacological tests. Afterwards, histology of specific brain regions was conducted. Finally, the data were analysed by one-way ANOVA and statistical significance was set at p<0.05. ResultsIn comparison with the normal control, mice of the model control group scored significantly (p<0.05) higher in the tests that assess depression and significantly (p<0.05) lower in the tests that assessed memory function, both indicators of adverse effects of hypoxia. Also, the contributing brain regions were also negatively affected by hypoxia. However, a significant attenuation of these effects was observed in the groups that received quercetin. ConclusionIn conclusion, quercetin is a nutritional flavonoid that possesses the ability to improve behaviour and cognition in individuals regularly exposed to hypoxia or suffering from conditions that affect oxygen delivery within the body.

A Mechanistic Approach on Structural, Analytical and Pharmacological Potential of Beta-sitosterol: A Promising Nutraceutical

Abstract: Phytosterols are bioactive substances that are found spontaneously in the cell membranes of plants and have an atomic composition similar to cholesterol produced by vertebrate cells. They are widely distributed in dietary lipids from plants such as nuts, seeds, and beans with olive oil. β-sitosterol has a variation of pharmacological belongings, with analgesic, immunomodulatory, antiseptic, antineoplastic, anti-inflammatory, cholesterol decreasing, hepatoprotective, and protecting action concerning respiratory and non-alcoholic fatty liver disease illnesses, antioxidant, and anti-diabetic activity. Clinical studies on humans have shown that it works against prostate cancer and has anti-inflammatory and anti-cancer properties. Pharmacological testing of β-sitosterol demonstrated a range of actions including antibacterial, anti-inflammatory, antinociceptive, anticancer, antifertility, angiogenic, antioxidant, immunomodulatory, diabetes-fighting, and anticancer without significant toxicity. Several formulations have been created by numerous authors, but there are few scholarly reviews of the analytical, pharmacology, and phytochemistry methodologies for this molecule. In this review the literature on β-sitosterol, its biosynthesis, pharmacology, nutraceutical applications, toxicity, formulations, and analytical techniques are all highlighted.

A mathematical multiple-dimensional strategy for Q-markers identification based on “five principles”: Tianshu Capsule for migraine treatment as an example

Ethnopharmacological relevanceQuality control is a critical element for Traditional Chinese medicine (TCM). Due to the varied chemical components, mechanisms of action, and pharmacological functions in TCM, ensuring quality is more challenging compared to chemical drugs. Then, the concept of quality markers (Q-markers) was proposed and ideal Q-markers for TCM prescriptions need to compliant with “five principles”, including pharmacological effectiveness, specificity, transfer and traceability, measurability, and prescription compatibility. Aim of the studyTo establish a mathematical multiple-dimensional “spider-web” strategy and identify the Q-markers of Tianshu capsule (TSC), a Chinese patent medicine for the treatment of migraine, following the “five principles” rules. Materials and methodsQ-marker candidates of TSC were firstly screened according to the HPLC fingerprints. Their contents in 10 batches of TSC and stabilities under high temperature, high humidity and in work solutions were determined quantitatively by HPLC-UV (measurability). Their existences in Gastrodiae Rhizoma, Chuanxiong Rhizoma, TSC, rat plasma and brain samples were investigated using HPLC-Q-TOF/MS (transfer and traceability). Their anti-migraine efficacies were evaluated by network pharmacology and mice hot-plate analgesia test; and their relationships with the property (flavor) of Gastrodiae Rhizoma or Chuanxiong Rhizoma were studied by molecular docking (effectiveness). Their contributions were defined based on their herb source according to the compatibility theories of Da Chuan Xiong Fang (compatibility). Their biosynthetic pathways were studied, and their frequencies detected in different plant families were calculated (specificity). Finally, an eight dimensional “spider-web” mode was developed for 10 components, and the regression area (RA) and the coefficient variation (CV) of each candidate were calculated after data normalization. ResultsTen components including gastrodin, parishin E, chlorogenic acid, ferulic acid, isochlorogenic acid A, senkyunolide I, H, A, Z-ligustilide and levistilide A were selected and evaluated as the Q-marker candidates. The results showed that gastrodin, senkyunolide I, and senkyunolide A had the higher RA and lower CV than other compounds with the established “spider-web” mode, indicating that they could be used as the Q-markers of TSC. ConclusionThe multi-dimensional “spider-web” mode based on “five principles” was firstly applied to identify the Q-markers of TSC, and it can be used as a practical strategy to discover Q-markers of other compounded prescriptions.

The Analgesic Activity Study of Ethanol Extract of Plantago Major L. in Mice (Mus Musculus L.) using Writhing Test Method

Plantago major L. are known as weeds on plantations. Plantago major L. is effective to overcome pain because they contain secondary flavonoid metabolites that have the potential as pain relievers. The purpose of the experiment was to determine the analgesic effect of ethanol extract on Plantago major L. plant on male white mice. The experiment, phytochemical screening of ethanol and powder extracts from Plantago major L. plant, powder of simplicia characterization examination and analgesic effect using writhing test were carried out. As a pain inducer, 0.5% acetic acid is used intraperitoneally injected the lower abdomen of the mice and the amount of stretching is calculated with an interval of 5 minutes for 1 hour. The suspension of ethanol extract of Plantago major L. was given at a dose of 500, 1000 and 2000 mg / kg BW, 2% methampyron suspension as a positive control and 0.5% CMC suspension as a negative control. Pharmacological test results based on ANOVA test found that the amount of stretching between treatment groups was significantly different (p &lt;0.05). The results of the analgesic effectiveness percentage obtained that the EEPM (Ethanol Extract of Plantago Major L.) suspension dose 500, 1000 and 2000 mg / kg BW had the highest analgesic power at a dose of 2000 mg / kg BW of 85.84%, EEPM suspension group 1000 mg / kg BW of 74.96 % and in the EETDS suspension group 500 mg / kg BW 62.37%.

High-Throughput Bioprinting Method for Modeling Vascular Permeability in Standard Six-well Plates with Size and Pattern Flexibility.

Vascular permeability is a key factor in developing therapies for disorders associated with compromised endothelium, such as endothelial dysfunction in coronary arteries and impaired function of the blood-brain barrier. Existing fabrication techniques do not adequately replicate the geometrical variation in vascular networks in the human body, which substantially influences disease progression; moreover, these techniques often involve multi-step fabrication procedures that hinder the high-throughput production necessary for pharmacological testing. This paper presents a bioprinting protocol for creating multiple vascular tissues with desired patterns and sizes directly on standard six-well plates, overcoming existing resolution and productivity challenges in bioprinting technology. A simplified fabrication approach was established to construct six hollow, perfusable channels within a hydrogel, which were subsequently lined with human umbilical vein endothelial cells to form a functional and mature endothelium. The computer-controlled nature of 3D bioprinting ensures high reproducibility and requires fewer manual fabrication steps than traditional methods. This highlights VOP's potential as an efficient high-throughput platform for modeling vascular permeability and advancing drug discovery.

Development of a glycine-MWCNT nanohybrid via electropolymerization for enhanced electrochemical detection of diclofenac

In this study, electropolymerization of glycine (Gly) was carried out to enhance the sensitivity of the carbon paste electrode (CPE) blended with multi-walled carbon nanotubes (MWCNTs) for electroanalysis of diclofenac (DCF). Analytical applications and electrochemical performance were examined using various voltammetric methods, including differential pulse voltammetry and cyclic voltammetry. Atomic force, scanning electron microscopy, dispersive X-ray, X-ray diffraction, and Raman spectroscopy were used to ascertain the surface topology of the modifier. The modified sensor with high electrocatalytic properties could electrochemically oxidize DCF, resulting in an enhanced current compared to the bare CPE when an anodic peak was detected at 0.77 V peak potential for the bare CPE, consisting of 0.1 mM DCF and 2.11 µA peaks current. The working electrode CPE was then modified with MWCNT and glycine. For MWCNT/CPE, a peak was seen at 5.20 µA and 0.75 V, and a more intense peak was observed for poly(Gly)-MWCNT/CPE at 11.52 µA and 0.74 V. The poly(Gly)-MWCNT/CPE exhibited a five-fold enhancement of peak current compared to bare CPE. The modified electrode displayed fast electron transfer, reproducibility, and repeatability. The study explored how factors like immersion time, pH variation, scan speed, and substance concentration could influence the peak current of DCF. Methods such as differential pulse voltammetry and cyclic voltammetry were utilized to examine the electrochemical oxidation behavior of DCF. The concentration variation is 0.5 µM to 7.0 µM, and the detection limit was 7.96 × 10-8 M. The rate constant (ks) for the electrochemical process was 1.710 s-1. The DCF of pharmacological and biological test substances was measured using the constructed modified electrode.

Objective Ischemia, Subjective Angina, and Psychological Distress in Angina With No Obstructive Coronary Disease.

Angina with no obstructive coronary disease (ANOCA) and ischemia with no obstructive coronary disease, prevalent yet underrecognized conditions, mostly affect women. Previous studies rarely distinguished between them. We aimed to compare the prevalence of objective ischemia through various examinations in women with ANOCA and assess the impact of objective and subjective ischemia on their mental health. A total of 84 eligible women with ANOCA and 42 controls underwent mental stress, pharmacological stress, exercise stress, and Holter testing. Objective evidence of myocardial ischemia was assessed by positron emission tomography-computed tomography and ECG, and subjective symptoms were graded using the Canadian Cardiovascular Society scale (CCS). Psychological assessments were conducted using 6 scales. Among 84 women with ANOCA, 37 (44%) received a diagnosis of ischemia with no obstructive coronary disease following mental stress testing, 20 (28.6%) through pharmacological stress testing, 14 (21.2%) via exercise stress testing, and 24 (32.9%) from Holter. Mental stress-induced myocardial ischemia was more prevalent (P<0.05). Among 54 patients with ANOCA who completed all tests, 30% showed no ischemia, and only 1 (1.9%) showed ischemia in all tests. In addition, patients with ANOCA had higher psychological scores than controls (P<0.01). No significant differences was observed in psychological scores between ANOCA with positive and negative ischemia test results (P>0.05). However, ANOCA with milder angina (CCS I) exhibited higher scores across the Hospital Anxiety and Depression Scale, State-Trait Anxiety Inventory, Perceived Stress Scale, and Posttraumatic Stress Disorder Checklist-Civilian Version and a higher prevalence of Type D personality traits (P<0.05). In patients with ANOCA, the positive rate of myocardial ischemia exhibits variability among several noninvasive tests. A worsened psychological state is more closely linked to milder angina symptoms than to ischemia performance, highlighting the importance of focusing on symptom management in their psychological care. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03982901.

THERAPEUTIC APPROACH IN COEXISTENCE OF AVOIDANT PERSONALITY DISORDER AND PSYCHOTIC STRUCTURE IN ITS EARLY MANIFESTATIONS: A CASE REPORT

Introduction: The first manifestations of a psychotic structure, generally in adolescence or early adulthood, are an important milestone in an individual's life. But, considering the concomitant signs and symptoms of an avoidant personality disorder can appear since childhood, there is a demand for more targeted and delicate attention from the team of healthcare professionals. Case summary: During the monitoring of the patient, a series of clinical signs and symptoms appeared that met the criteria of two simultaneous psychic conditions, one of them structural and the other personality related. With the aforementioned diagnoses, specific new pharmacological treatment tests were carried out, carrying positive effects and improving the patient's quality of life (introduction of antipsychotics instead of antidepressants as the pivot of therapy). Discussion: the onset of a psychotic condition in the trema phase associated with pre-existing avoidant/avoidant personality disorder demands balanced management between both conditions, using the strategies offered by both pharmacotherapies and psychotherapies. Conclusion: in order to adopt an appropriate treatment and management of the case, due to the complexity of diagnostic simultaneity, constant attention is required from the assistant team, so that continuous reassessments of hypotheses are made and, therefore, adjustments whenever necessary.

Optimizing Treatment Strategies of Prostate Adenoma through Analytical Urodynamics

Aim: To investigate the role of urinary obstruction in determining surgical indications based on analytical urodynamics.Materials and methods. To collect observational data, a cohort of patients was selected from those receiving treatment at the Urination Pathology Centre in Vladivostok due to urinary disorders and prostate adenoma. This cohort consisted of patients aged 50 to 73 years (mean age 60.5 ± 8.2 years), with observation periods ranging from 2 to 29.3 months (mean duration 15.5 ± 13.5 months). During a two-day home uroflow monitoring session, the severity of urinary symptoms was assessed using the IPSS questionnaire prior to each monitoring event. The study utilized a domestically designed two-sensor SIGMA uroflowmeter in conjunction with LEVELEST software.Results. The study demonstrated that in patients from all three groups undergoing therapy with an alpha-1 adrenergic blocker, there was a significant reduction in clinical symptoms as measured by the IPSS questionnaire and an increase in the average effective volume of urination. However, despite these improvements, the groups exhibited differing dynamics in urinary obstruction, which ultimately determined the indications for surgical intervention.Conclusion. Home uroflow monitoring with the Sigma uroflowmeter provides an objective assessment of the lower urinary tract function in patients with bladder outlet obstruction, focusing on the urinary obstruction indicator dynamics. Repeated pharmacological testing in patients with prostate adenoma shows potential for long-term patient management, aiming to prevent detrusor failure and evaluate the efficacy of conservative therapy. Analytical urodynamic methods enable the establishment of surgical treatment indications based on uroflow monitoring outcomes.

A new 3D model of L929 fibroblasts microtissues uncovers the effects of Bothrops erythromelas venom and its antivenom.

In Brazil, around 80% of snakebites are caused by snakes of the genus Bothrops. A three-dimensional culture model was standardized and used to perform treatments with Bothrops erythromelas venom (BeV) and its antivenom (AV). The MRC-5 and L929 cell lines were cultured at increasing cell densities. Morphometric parameters were evaluated through images obtained from an inverted microscope: solidity, circularity, and Feret diameter. L929 microtissues (MT) showed better morphometric data, and thus they were used for further analysis. MT viability was assessed using the acridine orange and ethidium bromide staining method, which showed viable cells in the MT on days 5, 7, and 10 of cultivation. Histochemical and histological analyses were performed, including hematoxylin/eosin staining, which showed a good structure of the spheroids. Alcian blue staining revealed the presence of acid proteoglycans. Immunohistochemical analysis with ki-67 showed different patterns of cell proliferation. The MT were also subjected to pharmacological tests using the BeV, in the presence or absence of its AV. The results showed that the venom was not cytotoxic, but it caused morphological changes. The MT showed cell detachment, losing their structure. The antivenom was able to partially prevent the venom activities.