Group Of Drugs Research Articles

Pattern of Adverse Drug Reactions in Extremes of Age Group Reported to a Tertiary Care Hospital

ABSTRACT Background: The World Health Organization (WHO), defined adverse drug reactions (ADRs) as “any noxious and unintended response to a drug, which occurs at doses normally used in humans for prophylaxis, diagnosis and treatment of the disease or for the modification of physiological functions.” Pediatrics (≤12 years) and geriatrics (≥65 years) are the extreme age groups that are more vulnerable for ADRs. Aim and Objectives: To determine ADRs time-plausible relationship, clinical spectrum, causality, and severity in extreme age group patients. Materials and Methods: All the ADRs reported to ADR monitoring center among geriatrics and pediatrics patients after Institutional Ethics Committee approval were collected from January 2015 to July 2022. The collected reports were analyzed for ADR pattern, drug groups, Causality (as per WHO-Uppsala Monitoring Centre scale) and severity (Modified Hartwig scale). Results: Out of 4705 ADRs, 176 (3.74%) were reported in geriatric and 181 (3.84%) in pediatric patients. In geriatric patients, anti-neoplastic drugs followed by cardiovascular drugs were the most commonly implicated drugs, erythematous rash and dyspnea were the most common ADRs. Erythematous rash and diarrhea were the most commonly ADRs and immunological agents followed by antimicrobials were implicated drugs in pediatric patients. In geriatric patients 84.1% were mild, 14.8% moderate, and 1.1% severe reactions whereas in pediatric group 91.2% were mild, 8.3% moderate, and 0.5% severe ADRs. Two cases of toxic epidermal necrolysis and one case of Steven–Johnson syndrome were reported in geriatric and pediatric patients respectively. Causality assessment of the majority of ADRs in geriatric age group was possible (79.5%) and in pediatric age group it was probable (61.3%). Conclusion: Extreme age group populations are more vulnerable to ADRs due to comorbidities, polypharmacy and drug interactions in elderly people and immature hepatobiliary and renal systems in pediatric age. Hence, active surveillance of drugs and education of prescribers will help to minimize the risk of ADRs in this susceptible population.

Employee Assistance Programs for Indigenous People in the Workplace

According to a survey regarding indigenous employment, in Taiwan, a high proportion of indigenous people are engaged in construction work compared with the overall population. However, among indigenous construction workers, 56.15% have received no occupational safety or health training, and 9.39% have encountered occupational accidents in their workplaces. Therefore, this study aimed to develop employee assistance programs (EAPs) for indigenous workers in Taiwan by focusing on three dimensions—namely work, life, and health—and by establishing corresponding implementation paths for these EAPs. A modified Delphi method was adopted to screen EAP measures for the workplaces of indigenous workers, and a formal evaluation followed. Subsequently, the analytic hierarchy process was employed to calculate the overall weights among the factors in order to discern the relative importance of each factor in achieving the target goal or to resolve target problems and establish an order of priority. The results indicated that health was the most important of the three dimensions of indigenous EAPs, followed by the life dimension and then the work dimension. Compared with previous studies regarding Han Taiwanese workers, mental health services in the health dimension were particularly important in the present study. Finally, regarding the health dimension, this study suggests developing mental health services that respect indigenous culture and therefore are appropriate for indigenous people, such as the establishment of drug and alcohol addiction support groups and mental health service systems. In addition, corresponding welfare measures can be offered to enhance people’s motivation to change.

Implementation of the pharmacovigilance database in the usage of antibiotics in a tertiary care hospital: A pilot study.

Antimicrobial resistance (AMR) has evolved into a severe public health issue that defies all current control strategies and needs multidisciplinary, creative solutions. Antimicrobial stewardship (AMS) activities demand a set of tools and abilities that can be used by health systems. In view of the growing AMR and the difficulty for the surveillance of it in the developing country, this study was conducted to incorporate pharmacovigilance (PV) in the AMS program. A cross-sectional pilot study was conducted to collect the PV database of antimicrobials induced adverse drug reactions (ADR) from the Adverse Drug Reactions Monitoring Center (AMC) of the institute for a period of 2 months from August 2022 to September 2022. The information from the database was analyzed to estimate the usage of antibiotics from the PV database from AMC and classified it under the Anatomical Therapeutic Chemical, to assess the rationality of the antimicrobial's usage based on "Access," "Watch," and "Reserve" (AWaRe) classification, and to assess the ADR of the antibiotics. The analysis was done by using the SPSS version 20.0 for Windows. The results showed that the prevalence of ADRs were more in adults' population with preponderance in female. The antibiotics usage was as per with World Health Organization standard and most of the antibiotics used were from the Access group of AWaRe classifications. Tetracyclines and penicillins were the most used antibiotic group of drugs. The number of patients included in the study was 70. Most of the causality assessment was "possible" (62.85%). In the study, almost 90% of the drug was withdrawn and 70% of the patients were in the recovering stage. Using existing PV approaches to address usage of antibiotics and AMR issues would allow PV to progress as a field, and governments will get a stronger return on their PV investments.

Construction and Evaluation of BAL-PTX Co-Loaded Lipid Nanosystem for Promoting the Anti-Lung Cancer Efficacy of Paclitaxel and Reducing the Toxicity of Chemotherapeutic Drugs.

The present study aimed to develop a lipid nanoplatform, denoted as "BAL-PTX-LN", co-loaded with chiral baicalin derivatives (BAL) and paclitaxel (PTX) to promote the anti-lung cancer efficacy of paclitaxel and reduce the toxicity of chemotherapeutic drugs. BAL-PTX-LN was optimized through central composite design based on a single-factor experiments. BAL-PTX-LN was evaluated by TEM, particle size, encapsulation efficiency, hemolysis rate, release kinetics and stability. And was evaluated by pharmacokinetics and the antitumor efficacy studied both in vitro and in vivo. The in vivo safety profile of the formulation was assessed using hematoxylin and eosin (HE) staining. BAL-PTX-LN exhibited spherical morphology with a particle size of 134.36 ± 3.18 nm, PDI of 0.24 ± 0.02, and with an encapsulation efficiency exceeding 90%, BAL-PTX-LN remained stable after 180 days storage. In vitro release studies revealed a zero-order kinetic model of PTX from the liposomal formulation. No hemolysis was observed in the preparation group. Pharmacokinetic analysis of PTX in the BAL-PTX-LN group revealed an approximately three-fold higher bioavailability and twice longer t1/2 compared to the bulk drug group. Furthermore, the IC50 of BAL-PTX-LN decreased by 2.35 times (13.48 μg/mL vs 31.722 μg/mL) and the apoptosis rate increased by 1.82 times (29.38% vs 16.13%) at 24 h compared to the PTX group. In tumor-bearing nude mice, the BAL-PTX-LN formulation exhibited a two-fold higher tumor inhibition rate compared to the PTX group (62.83% vs 29.95%), accompanied by a ten-fold decrease in Ki67 expression (4.26% vs 45.88%). Interestingly, HE staining revealed no pathological changes in tissues from the BAL-PTX-LN group, whereas tissues from the PTX group exhibited pathological changes and tumor cell infiltration. BAL-PTX-LN improves the therapeutic effect of poorly soluble chemotherapeutic drugs on lung cancer, which is anticipated to emerge as a viable therapeutic agent for lung cancer in clinical applications.

Cutibacterium species: An Underestimated Pathogen in Chronic Infections

Cutibacterium speciesis a member of the skin micro biota, found predominantly in regions rich in sebaceous glands, involved in various chronic infections that led to its emergence as an opportunistic pathogen. The present study is a retrospective study to determine the prevalence and antibiotic sensitivity pattern of Cutibacterium species recovered from chronic infections over a period of 4.5 years. The identification of the colonies grew on the Robertson’s Cooked Meat media plate was done using VITEK 2. The antibiotic sensitivity tests were put by pour plate method using Epsilometer strips (E-strip).Out of 400, 17.75% (n=71) were confirmed as anaerobic bacteria by VITEK 2. Out of 71 positive anaerobic organisms, 21% (n=15/71) were confirmed as Cutibacteriumspecies.Cutibacterium species recorded prevalenceof 3.75% (15/400) among clinical specimens. High sensitivity was observed with beta lactam group of drugs whereas metronidazole drug was found ineffective against Cutibacteriumspecies. Due to prolonged culture time for anaerobic bacteria there is a high need in new diagnostic methods. In the recent times Cutibacterium species has been reported from various clinical samples which depicts shift of Cutibacterium species as a potential pathogen in the upcoming time.

Inclisiran Usage in Very High-Risk Patients with Dyslipidemia Resistant to Statins and Ezetimibe Therapy

Background. Complications of systemic atherosclerosis (myocardial infarction, ischemic stroke) are the main causes of mortality and disability in the modern world. The relevance of this problem is determined by its scale: the number of deaths from cardiovascular disease has gradually increased from 12.1 million in 1990 to 18.6 million in 2019 and is on the rise. Today, the standard treatment regimen for dyslipidemia includes statins and ezetimibe. For patients who do not achieve the required lipid lowering, intensification of therapy with a relatively new group of drugs – PCSK9 inhibitors – is available. The aim. To study the effectiveness of inclisiran in the complex therapy of dyslipidemia in patients with very high cardiovascular risk. Materials and methods. The study design was a series of clinical cases, the data of which are described for comparison in dynamics. On the basis of the Department of Cardiometabolic Diseases of the Ukrainian Children’s Cardiac Center, a group of 7 patients with very high cardiovascular risk who did not achieve the target lipid parameters on standard therapy with rosuvastatin and ezetimibe was selected. Results. All the patients in the study group of very high cardiovascular risk with dyslipidemia resistant to standard combination treatment who took inclisiran as part of complex lipid-lowering therapy achieved a significant reduction in total cholesterol, but more importantly, they reached the target low-density lipoprotein cholesterol values. We did not find any side effects when using inclisiran. Conclusions. The present series of clinical cases demonstrates high efficacy of inclisiran as part of complex lipid-lowering therapy in patients with very high cardiovascular risk, who have a combination of coronary heart disease and type 2 diabetes mellitus. These results suggest the possibility of wider use of inclisiran in patients with very high cardiovascular risk to reduce cardiovascular morbidity and mortality.

Effects of Konjac Glucomannan and Its Oligosaccharides on Improvement of Lactose Intolerance as Gut Prebiotics.

Lactose intolerance (LI) is a widespread health issue affecting almost 70% of the world population. This study evaluates the potential prebiotic benefits of konjac glucomannan (KGM) and konjac oligogalactomannan (KOGM) in improving LI. Colonic fermentation results indicate that lactase groups of healthy subjects showed lower pH, higher lactic acid content, and lactase activity in fermentation broth compared with LI subjects. Total short-chain fatty acid (SCFAs) content reached 1.71 mmol/L in healthy subjects, whereas it was 1.49 mmol/L in LI subjects. In vivo studies demonstrated that KGM and KOGM intake reduced total cholesterol (T-CHO) and triglyceride (TG) levels in the liver and significantly increased immunoglobulin G (lgG) and immunoglobulin A (lgA) values, while KOGM inclusion led to a significant 23.04% increase in serum free fatty acid (FFA) levels compared to the Blank group (p < 0.05). Furthermore, ileal tissue analysis revealed a marked increase in villus height and intestinal wall thickness (p < 0.05) as well as a decrease in crypt depth (p < 0.05). The composition and proportion of gut microbiota have improved with KGM and KOGM use, notably increasing the abundance of Lactobacillus and Lachnospiraceae_NK4A136_group, respectively (p < 0.05). Compared with the Blank group, Lactobacillus abundance increased by approximately 25.82% in the Drug group, 18.23% in the KGM group, and 8.67% in the KOGM group. These findings suggest that KGM and KOGM can be utilized as prebiotics to alleviate LI symptoms.

Pharmacology and pharmacotherapy of antimicrobials

The history of medicine has witnessed a remarkable breakthrough with the discovery and development of antimicrobials, a group of essential drugs for the treatment of bacterial, fungal, viral and parasitic infections. From early antibiotics to modern antiviral and antifungal agents, these drugs have played a crucial role in reducing morbidity and mortality associated with infectious diseases. According to Goodman &amp; Gilman (2021), "antimicrobials represent one of the most significant milestones in the history of medicine, radically transforming the treatment of previously fatal infections." Rang et al. (2019) corroborate, emphasizing that "the discovery and clinical use of antimicrobials are testaments to the ability of pharmaceutical science to positively impact global health."

THE SIMULTANEOUS SPECTRAL DETERMINATION OF CANDESARTAN CILEXETIL AND HYDROCHLOROTHIAZIDE IN TABLETS USING THE TRIVARIATE CLASSICAL LEAST SQUARES METHOD

Objective: Candesartan cilexetil (CDS) is a member of the sartan group of drugs and is widely used to lower blood pressure. Hydrochlorothiazide (HCT) is the most commonly used diuretic group of drugs and is prescribed together with candesartan cilexetil in cases where blood pressure cannot be reduced. Pharmaceutical preparations containing these two active compounds in combination are preferred today to provide a more effective pharmacological effect. Therefore, it is of great importance to determine the quantities of these combined pharmaceutical preparations with new analytical methods that are fast, easy, and sensitive in quality control and routine analysis. In this study, a new trivariate classical least squares calibration method (TCLS) was developed for the simultaneous quantification of candesartan cilexetil (CDS) and hydrochlorothiazide (HCT) in binary mixtures and commercial tablets without using a preliminary separation step. Material and Method: CDS and HCT compounds were kindly donated by National Pharm Ind., Turkey. HPLC-grade methanol (J.T. Baker, Netherlands) was used as a solvent for the spectrophotometric analysis. In the application of the TCLS method, the determination and quantification of CDS and HCT were carried out using UV spectrophotometric measurements with 1 cm quartz cells in the 200-310 nm spectral region (slit range 2 nm). The newly developed TCLS method was tested using a validation set consisting of eight synthetic mixture solutions within the working ranges of 4.0-20.0 μg/ml for CDS and HCT. Simultaneous quantification analyses of CDS and HCT were performed on ATACAND PLUS® Tablet supplied by Astra Zeneca İlaç Ltd Şti. Result and Discussion: The method is based on the application of TCLS to the absorbance measurements at three different wavelength points (223.5, 240.0, and 268.5 nm). The absorptivity values (µg-1mlcm-1) of pure CDS and pure HCT were 6.67x10-2, 2.76x10-2, 2.33x10-2, and 11.41x10-2, 0.46x10-2, 6.42x10-2 at the selected wavelengths, respectively. Recovery values and relative standard deviation values were calculated as 97.2% and 1.61% for CDS and 99.7% and 3.67% for HCT, respectively. This method was successfully applied to the spectrophotometric quantitative analysis of tablets containing CDS and HCT, and then, a good agreement was reported.

Protective Effects of Aqueous Extract of Piper nigrumWhole Fruits Against Tramadol-induced Hepato-and Nephrotoxicity in Wistar Rats

Tramadol, a widely used analgesic, is becoming more abused in most countries. Hence, this study aims to investigate the protective effects of aqueous extract of Piper nigrum whole fruits on tramadol-induced toxicity in male Wistar rats. Six groups (A-F) of male Wistar rats were exposed to a 14-day oral treatment. Specifically, the control group, induced group (tramadol at 60 mg/kg), reference drug group (Vitamin C at 250 mg/kg) and the extract groups (250, 500, and 1000 mg/kg). The levels of liver cellular markers ALT, AST and ALP as well as the kidney function parameters (urea, creatinine and uric acid) showed a significant(p&lt;0.05) increase following the administration of 60 mg/kg of tramadol and a significant reversal was observedfollowing the administration of extract in a dose dependent manner. However, K+and HCO3-showed a significant(p&lt;0.05) decrease and were also reversed following the administration of extract in a dose dependent manner. Tramadol also showed a significant(p&lt;0.05) increase inthe concentration of WBC and LYM, and a significant(p&lt; 0.05) decrease inthe levels of RBC, HGB, HCT, RDW-SD, RDW-CV, and MPV. The reference drug and the extract showed significant (p&lt; 0.05) reversal inthe levels of these biochemical parameters. Histological examination revealed normal liver and kidneyarchitecture in all groups, indicating no signs of inflammation or damage. These findings revealed that the aqueousextracts from whole fruits of P. nigrum at concentrations of 250 and 500 and 1000 mg/kg may potentially offer protection and general improvement in the overall health status and function of the hematopoietic system.

Predicting Drugs Suspected of Causing Adverse Drug Reactions Using Graph Features and Attention Mechanisms.

Adverse drug reactions (ADRs) refer to an unintended harmful reaction that occurs after the administration of a medication for therapeutic purposes, which is unrelated to the intended pharmacological action of the drug. In the United States, ADRs account for 6% of all hospital admissions annually. The cost of ADR-related illnesses in 2016 was estimated at USD 528.4 billion. Increasing the awareness of ADRs is an effective measure to prevent them. Assessing suspected drugs in adverse events helps to enhance the awareness of ADRs. In this study, a suspect drug assisted judgment model (SDAJM) is designed to identify suspected drugs in adverse events. This framework utilizes the graph isomorphism network (GIN) and an attention mechanism to extract features based on patients' demographic information, drug information, and ADR information. By comparing it with other models, the results of various tests show that this model performs well in predicting the suspected drugs in adverse reaction events. ADR signal detection was conducted on a group of cardiovascular system drugs, and case analyses were performed on two classic drugs, Mexiletine and Captopril, as well as on two classic antithyroid drugs. The results indicate that the model can accomplish the task of predicting drug ADRs. Validation using benchmark datasets from ten drug discovery domains shows that the model is applicable to classification tasks on the Tox21 and SIDER datasets. This study applies deep learning methods to construct the SDAJM model for three purposes: (1) identifying drugs suspected to cause adverse drug events (ADEs), (2) predicting the ADRs of drugs, and (3) other drug discovery tasks. The results indicate that this method can offer new directions for research in the field of ADRs.

Quantitative assessment of baseline imbalances in evolocumab and alirocumab trials: a meta-epidemiological study

BackgroundBaseline imbalances have been identified in randomized trials of evolocumab and alirocumab. Our aim was to quantitatively assess (1) the presence of systematic baseline differences, and (2) the relationship of baseline differences with effects on low-density lipoprotein-cholesterol (LDL-c) and clinical outcomes in the trials.MethodsWe performed a meta-epidemiological study. PubMed, Embase, regulatory reports, ClinicalTrials.gov and company websites were searched for trials. Seven baseline characteristics (mean age, LDL-c, BMI, percentage males, diabetics, smokers, and hypertensives) and five outcomes (LDL-c, major adverse cardiac events, serious adverse events, any adverse events, all-cause mortality) were extracted. We calculated (1) range and distribution of baseline imbalances (sign-test), (2) pooled baseline differences and heterogeneity (meta-analysis), (3) differences in SDs around continuous variables (sign-test and pooling), and (4) the relationship of baseline differences with outcomes (meta-regression). The comparisons of PCSK9-inhibitor groups with either placebo or ezetimibe were analysed separately and combined.ResultsWe identified 43 trials with 63,193 participants. Baseline characteristics were frequently missing. Many trials showed small baseline imbalances, but some large imbalances. Only baseline BMI showed a statistically significant lower pooled mean for the drug versus placebo groups (MD -0.16; 95% CI -0.24 to -0.09). Heterogeneity in baseline imbalances was present in six placebo- and five ezetimibe-comparisons. Heterogeneity was statistically significant for BMI, males, diabetics and hypertensives in the combined comparisons. There was a statistically significant preponderance for larger SDs in the PCSK9-inhibitor versus control groups (sign-test age 0.014; LDL-c 0.014; BMI 0.049). Meta-regression showed clinically relevant relationships of baseline imbalances in age, BMI and diabetics with the risk of any adverse events and the risk of mortality. Two relationships were statistically significant: A higher mean BMI in the drug versus control group with a decreased risk of mortality (beta − 0.56; 95% CI -1.10 to -0.02), and a higher proportion of diabetics with an increased risk of any adverse events (beta 0.02; 95% 0.01 to 0.04).ConclusionsHeterogeneous baseline imbalances and systematically different SDs were present in evolocumab and alirocumab trials, so study groups cannot be assumed to be comparable. These findings raise concerns about the design and conduct of the randomization procedures.

Predictive value of the controlling nutritional status (CONUT) score to assess long-term mortality (10 Years) in patients with hypertension

Background and aimsMalnutrition is associated with poor outcomes in patients with chronic diseases. The aim of this study is to investigate the prevalence of malnutrition in patients with hypertension and relationship between malnutrition severity and long-term mortality in these patients. Methods and resultsThe study included 11,278 patients with hypertension from the National Health and Nutrition Examination Survey database. The degree of malnutrition was assessed using the Controlled Nutritional Status score, with patients divided into normal, mild, and moderate-to-severe groups. After 10 years of follow-up, the results showed that patients who died had higher CONUT scores, poorer nutritional status, and lower albumin, total cholesterol, and lymphocytes than those who survived (P < 0.05). The Kaplan–Meier analysis revealed that patients with poor nutritional status had a significantly higher risk of all-cause death. In the Non-Lipid Lowering Drugs group, the CONUT score (hazard ratio (HR): 1.225; 95% confidence interval (CI): 1.162–1.292; P < 0.0001), as well as mild (HR: 1.532; 95% CI 1.340–1.751; P < 0.0001) and moderate-to-severe malnutrition (HR: 2.797; 95% CI: 1.441–5.428; P = 0.0024), were independent predictors of long-term mortality. The competing risk regression models showed that cardiovascular and cerebrovascular mortality increased with increasing CONUT scores. The results were robust in both subgroup and sensitivity analyses. ConclusionsMalnutrition significantly impacts long-term mortality in hypertensive patients. The CONUT score may be a useful tool for assessing the nutritional status of patients with hypertension in the non-lipid-lowering population and for predicting their long-term mortality.

Efficacy of superficial cervical plexus block in the management of neck pain due to surgical positioning in patients undergoing burr-hole craniotomy for unilateral chronic subdural hematoma under scalp block: A prospective randomized control trial

: Alternatives to general anesthesia technique, pain management of surgical sites have been discussed at length in various studies for burr-hole evacuation in geriatric patients. This is the first study addressing the management of pain that occurs due to extreme contra-lateral side neck rotation to access the surgical site. : This trial was conducted (from January 2021 to January 2022) on 60 patients of age ≥ 18 years with ASA grade I/I/III undergoing unilateral burr hole craniotomy for evacuation of chronic subdural hematoma (CSDH) under scalp block. Group D (n=30) received 5 ml of 0.5% bupivacaine by ultrasound-guided superficial cervical plexus block (SCPB), and group P (n=30) received SCPB with placebo (normal saline). The primary outcome was the numerical rating pain score (NRS) pain score during neck movement in the postoperative period. Secondary objectives were muscle spasm assessed by the modified Ashworth scale (MAS), consumption dosage of rescue analgesia, modified Ramsay sedation score (MRSS), and hemodynamic parameters.: NRS scores were significantly lower at 8 hours in the SCPB with drug (D) group compared to the SCPB with placebo group (p-value = 0.019). MAS were higher in group P compared to group D until 12 (&amp;#60;0.001). Consumption of rescue analgesia was higher in group P than group D (&amp;#60;0.001). MRSS was significantly higher in group D compared to group P throughout the intra-operative period (&amp;#60;0.001).: Preoperative superficial cervical plexus block decreases postoperative neck pain and facilitates neck rotation.

A comprehensive pharmacognostical study of Charakokta Shonitasthapana Varga Dravyas

Shonitasthapana Varga Dravyas of Charaka consists of Audhbida (Madhuka, Lodhra, Mocharasa, Priyangu, Kunkuma), Jangama (Madhu), Parthiva (Gairika, Mritkapala) and Ahara Dravya (Laja, Sharkara). Potent pharmacological action of the drug depends on proper identification authentication and purity of the drug. Majority of the drugs of Shonitasthapana Varga are subjected to extensive adulteration commercially. Detailed pharmacognostic analysis of the group of drugs is indispensable before its utility in therapeutics. Samples of Shonitasthapana Varga Dravyas were collected, procured or purchased from authentic sources and analyzed for their organoleptic, macroscopic, microscopic and physicochemical characteristics. The results of Madhu, Madhuka, Lodhra, Mocharasa, Priyangu, Gairika, Kunkuma and Sharkara were within the limits of Indian Pharmacopieal standards; Laja as per the Indian Council for Medical research guidelines. The Pharmacognostic analysis of Shonitasthapana Varga Dravyas helps in standardization and safe use of the drugs clinically on human subjects for its maximum therapeutic effects.

Steroid-induced dermatoses: a challenge for modern dermatology

The aim of this work is to determine the variability and significance of motivating and provoking factors associated with the uncontrolled use of topical glucocorticosteroids, psychological features of this condition. Materials and methods. 50 patients with exacerbation of inflammatory dermatoses after long-term topical application of drugs with glucocorticosteroids as an active substance were examined. The key diagnostic measures were a clinical examination, an anamnesis collection with clarification of the activity class of the used agent, duration and potential reason for its systematic or periodic use. Assessment of the psycho-emotional state in relation to self-perception of one’s own body was carried out using the dermatological version of the dysmorphic disorder questionnaire – BDDQ-DV. Results. The main pathology for which patients of both sexes used this group of drugs were rosacea, perioral dermatitis, and seborrheic dermatitis. Taking into account anamnestic data, the mean duration of application of topical corticosteroids in creams, ointments or lotions was 10.25 ± 3.50 months for women and 8.3 ± 1.6 months for the male cohort. Most patients received information about the need to use a topical steroid from acquaintances / friends and pharmacists. The most frequent pharmacological agent was betamethasone dipropionate. Analyzing the psychopathological aspect of the studied group, dysmorphic manifestations are prevalent and the most well argued. 32 individuals (64 %) from the cohort met the criteria for concern about the body or its parts. Conclusions. Regional clinical features of steroid-induced dermatoses, which are mostly represented by chronic inflammatory conditions located in aesthetically significant areas, have been determined. 64 % of patients with steroid-induced dermatoses develop a psychopathological profile. An important aspect remains the necessity to raise the awareness of medical, pharmaceutical workers, and the public about the need and correct use of topical corticosteroids.

Adolescent stress differentially modifies dopamine and norepinephrine release in the medial prefrontal cortex of adult rats

Adolescent stress (AS) has been associated with higher vulnerability to psychiatric disorders such as schizophrenia, depression, or drug dependence. Moreover, the alteration of brain catecholamine (CAT) transmission in the medial prefrontal cortex (mPFC) has been found to play a major role in the etiology of psychiatric disturbances. We investigated the effect of adolescent stress on CAT transmission in the mPFC of freely moving adult rats because of the importance of this area in the etiology of psychiatric disorders, and because CAT transmission is the target of a relevant group of drugs used in the therapy of depression and psychosis. We assessed basal dopamine (DA) and norepinephrine (NE) extracellular concentrations (output) by brain microdialysis in in the mPFC of adult rats that were exposed to chronic mild stress in adolescence. To ascertain the role of an altered release or reuptake, we stimulated DA and NE output by administering either different doses of amphetamine (0.5 and 1.0 mg / kg s.c.), which by a complex mechanism determines a dose dependent increase in the CAT output, or reboxetine (10 mg/kg i.p.), a selective NE reuptake inhibitor. The results showed the following: (i) basal DA output in AS rats was lower than in controls, while no difference in basal NE output was observed; (ii) amphetamine, dose dependently, stimulated DA and NE output to a greater extent in AS rats than in controls; (iii) reboxetine stimulated NE output to a greater extent in AS rats than in controls, while no difference in stimulated DA output was observed between the two groups. These results show that AS determines enduring effects on DA and NE transmission in the mPFC and might lead to the occurrence of psychiatric disorders or increase the vulnerability to drug addiction.

Diagnosis and treatment of migraine: an analysis of the latest diagnostic and therapeutic guidelines

Introduction Migraine is a common disease that a large part of the population struggles with. Stressful work and poor eating habits increase the risk of headaches. The basic therapy is lifestyle change, and when this does not bring results, medications are used. The choice of the appropriate preparation depends on the characteristics of the pain and the patient's condition. Knowledge about different treatment methods can improve patients' lives. Aim of the study The aim of the article was to present current guidelines for migraine therapy depending on the individual patient's requirements. Materials and methods The article is the result of a review of recent scientific literature using PubMed, Scopus and Google Scholar databases. The literature was reviewed using the keywords. Results Many clinical trials have examined the effects of different classes of drugs on migraine headaches. The final effect depends on the dose used, the moment of drug administration, and the patient's age, gender and health condition. Doctors often have to modify therapy within the same group of drugs to find a drug that will work for a given patient. Conclusions Clinical trials have proven the effectiveness of, among others, non-steroidal anti-inflammatory drugs, triptans and botulinum neurotoxin. A clinically significant analgesic effect is sometimes characterized by side effects, therefore careful selection of the preparation and patient observation are important.

ERβ activation improves nonylphenol-induced depression and neurotransmitter secretion disruption via the TPH2/5-HT pathway

The aim of this study is to investigate the role of estrogen receptor β (ERβ) in nonylphenol (NP) - induced depression - like behavior in rats and its impact on the regulation of the TPH2/5-HT pathway. In the in vitro experiment, rat basophilic leukaemia cells (RBL-2H3) cells were divided into the four groups: blank group, NP group (20 μM), ERβ agonist group (0.01 μM), and NP＋ERβ agonist group (20 μM＋0.01 μM). For the in vivo experiment, 72 adult male Sprague-Dawley rats were randomly divided into following six groups: the Control, NP (40 mg/kg) group, ERβ agonist (2 mg/kg, Diarylpropionitrile (DPN)) group, ERβ inhibitor (0.1 mg/kg, 4-(2-phenyl-5,7-bis(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-3-yl) phenol (PHTPP)) group, NP+ERβ agonist (40 mg/kg NP ＋ 2 mg/kg DPN) group, and NP+ERβ inhibitor (40 mg/kg NP + 0.1 mg/kg PHTPP) group, with 12 rats in each group. Each rat in drug group were given NP by gavage and/or received a single intraperitoneal injection of DPN 2 mg/kg or PHTPP 0.1 mg/kg. Both in vivo and in vitro, NP group showed a decrease in the expression levels of ERβ, tryptophan hydroxylase (TPH1), and tryptophan hydroxylase-2 (TPH2) genes and proteins, and reduced levels of DA, NE, and 5-hydroxytryptophan (5-HT) neurotransmitters. RBL-2H3 cells showed signs of cell shrinkage, with rounded cells, increased suspension and more loosely arranged cells. The effectiveness of the ERβ agonist stimulation exhibited an increase exceeding 60% in RBL-2H3 cells. The application of ERβ agonist resulted in an alleviation the aforementioned alterations. ERβ agonist activated the TPH2/5-HT signaling pathways. Compared to the control group, the NP content in the brain tissue of the NP group was significantly increased. The latency to eat for the rats was longer and the amount of food consumed was lower, and the rats had prolonged immobility time in the behavioral experiment of rats. The expression levels of ERβ, TPH1, TPH2, 5-HT and 5-HITT proteins were decreased in the NP group, suggesting NP-induced depression-like behaviours as well as disturbances in the secretion of serum hormones and monoamine neurotransmitters. In the NP group, the midline raphe nucleus showed an elongated nucleus with a dark purplish-blue colour, nuclear atrophy, displacement and pale cytoplasm. ERβ might ameliorate NP-induced depression-like behaviors, and secretion disorders of serum hormones and monoamine neurotransmitters via activating TPH2/5-HT signaling pathways.

Molecular mechanism of the treatment of lung adenocarcinoma by Hedyotis Diffusa: an integrative study with real-world clinical data and experimental validation.

With a variety of active ingredients, Hedyotis Diffusa (H. diffusa) can treat a variety of tumors. The purpose of our study is based on real-world data and experimental level, to double demonstrate the efficacy and possible molecular mechanism of H. diffusa in the treatment of lung adenocarcinom (LUAD). Phenotype-genotype and herbal-target associations were extracted from the SymMap database. Disease-gene associations were extracted from the MalaCards database. A molecular network-based correlation analysis was further conducted on the collection of genes associated with TCM and the collection of genes associated with diseases and symptoms. Then, the network separation SAB metrics were applied to evaluate the network proximity relationship between TCM and symptoms. Finally, cell apoptosis experiment, Western blot, and Real-time PCR were used for biological experimental level validation analysis. Included in the study were 85,437 electronic medical records (318 patients with LUAD). The proportion of prescriptions containing H. diffusa in the LUAD group was much higher than that in the non-LUAD group (p < 0.005). We counted the symptom relief of patients in the group and the group without the use of H. diffusa: except for symptoms such as fatigue, palpitations, and dizziness, the improvement rate of symptoms in the user group was higher than that in the non-use group. We selected the five most frequently occurring symptoms in the use group, namely, cough, expectoration, fatigue, chest tightness and wheezing. We combined the above five symptom genes into one group. The overlapping genes obtained were CTNNB1, STAT3, CASP8, and APC. The selection of CTNNB1 target for biological experiments showed that the proliferation rate of LUAD A549 cells in the drug intervention group was significantly lower than that in the control group, and it was concentration-dependent. H. diffusa can promote the apoptosis of A549 cells, and the apoptosis rate of the high-concentration drug group is significantly higher than that of the low-concentration drug group. The transcription and expression level of CTNNB1 gene in the drug intervention group were significantly decreased. H. diffusa inhibits the proliferation and promotes apoptosis of LUAD A549 cells, which may be related to the fact that H. diffusa can regulate the expression of CTNNB1.