Combination Of NSAIDs Research Articles

Methylene Blue as an Adjuvant Analgesic Postoperative Anal Fistula: A Randomized Clinical Trial

Introduction. Anal fistula is a pathological condition that connects the anorectal mucosa to the perianal skin, requiring various types of surgical procedures. However, surgery often causes postoperative pain. The use of methylene blue is being studied as a potential analgetic adjuvant in anal fistula surgery. Previous studies have shown that methylene blue can effectively reduce postoperative pain in various types of anorectal surgery. This study aims to determine methylene blue's clinical efficacy as an analgetic adjuvant. Methods. A double-blind, randomized controlled trial was conducted. Subjects consisting of subjects with simple anal fistula to undergo fistulectomy were randomly allocated into two groups. The first group received adjuvant analgesics in the form of methylene blue and NSAIDs, while the second group only received NSAIDs. Methylene blue 4 mL 1% was administered subcutaneously to the edge of the wound, sprayed on the surgery site, and intravenously administered ketorolac 3 x 30 mg. Randomization was done using the double-blind method. Pain levels were evaluated on the first, second, third, and seventh postoperative days using a visual analog scale (VAS). Results. Thirty-four subjects were enrolled (17 subjects in each group). Significant differences in pain levels (VAS values) were recorded between the group receiving the combination of methylene blue and NSAIDs compared to the group receiving only NSAIDs on days 1 to 3 after surgery (p <0.05). This difference was no longer significant between the two groups on the seventh postoperative day (p >0.05). Conclusion. The use of methylene blue in subjects undergoing anal fistula surgery as an adjuvant analgesic along with NSAIDs may reduce the intensity of pain better than NSAIDs alone.

Discovery of Novel Diesters Incorporating Kojic Acid With NSAIDs and Palmitic Acid as Dual Inhibitor of Melanogenesis and Inflammation

Our study focuses on creating hybrid compounds and assessing their suitability for use in skincare products. The synergistic combination of Kojic acid, NSAIDs, and Palmitic acid proved to be an effective approach in inhibiting melanin production, making it a promising solution for individuals with hyperpigmentation concerns with Kojic acid (KA) Ibuprofen monoester (IBUM) and Ibuprofen-Kojic acid-Palmitic acid diester (IBUD) exhibiting a potential tyrosinase (38 % and 49 % inhibition at 200 µM) and anti-melanogenesis activity (77 % and 79 % inhibition at 100 µM). Furthermore, these compounds exhibited potent anti-inflammatory effects, Kojic acid-Diclofenac monoester (DICM) and Diclofenac-Kojic acid-Palmitic acid diester (DICD) offering potential benefits for inflammation by lowering the paw volume. A stability study under chemical conditions and enzymatic conditions was also performed, wherein DICM and DICD showed a better half-life of 515, 593 h under chemical stability and 6.3, 7.5 h under enzymatic stability studies respectively. The diester hybrids IBUD, DICD, Naproxen-Kojic acid-Palmitic acid diester (NAPD) showed a better permeation and penetration profiles compared to their parent drugs. In-vitro cell line studies were conducted to assess the safety and efficacy of these hybrid esters, with promising results. The dual inhibitor demonstrated minimal cytotoxicity and remarkable anti-melanogenic and anti-inflammatory activities, showing its potential as a versatile agent in addressing both melanogenesis and inflammation.

Determining the Effect of Different Combinations of NSAIDs on Hemato-Immunological Parameters and the Association with Heat Shock Protein-70 in Broilers

Determining the Effect of Different Combinations of NSAIDs on Hemato-Immunological Parameters and the Association with Heat Shock Protein-70 in Broilers

Role of the Agnikarma in the Management of Frozen Shoulder

Shoulder joint discomfort and stiffness are indicators of frozen shoulder, which is also referred to as adhesive capsulitis. Symptoms and signs usually begin gradually subsiding before getting more severe. Frozen shoulder is a condition that is more prevalent in women than in men, particularly those between the ages of 40 and 60. Furthermore, individuals with diabetes are at an increased risk of developing frozen shoulder. Inflammation is the most common cause of frozen shoulder, which is characterized by swelling, pain, and irritation of the tissues surrounding the joint. The underlying cause of this ailment is not yet definitively understood. It is estimated that 2 to 5 percent of the general population will experience frozen shoulder at some point in their lives, with 8.2 percent of males and 10.1 percent of working-age women affected by it. This condition can affect one or both shoulders, and typically resolves on its own within one to two years. Depending on the severity of the disease, a combination of NSAIDs, steroids, physiotherapy, and surgical intervention may be recommended by modern medicine. Ayurveda has suggested Agnikarma as a potential treatment for frozen shoulder, as it was believed to be an effective therapy for Avbahuka. Frozen shoulder and Avbahuka may present with similar symptoms and indicators. Agnikarma, a distinct technique described in Ayurvedic texts, is used to treat Avbahuka that is caused by Dhatukshayajanya vata prakopa. Therefore, the aim of this research was to examine the therapeutic effects of Agnikarma in cases of frozen shoulder in Avabahuka.

Identification of Risk Factors for Sickle Cell Crisis Readmissions: A Community Center Experience

Introduction: Sickle cell disease (SCD) exerts a significant morbidity and mortality burden worldwide, with 300,000 infants being diagnosed with SCD annually. The term sickle cell crisis (SCC) encompasses several acute conditions under its umbrella, namely vaso-occlusive crisis, aplastic crisis, splenic sequestration crisis, dactylitis, and acute chest syndrome. SCC has been established to be a known cause of readmissions across the year with studies showing 17% of the population returning two to three times annually. This has resulted in a high mean length of stay for this diagnosis (5.3 days) in comparison to an index hospitalization (4.9 days), with a mean cost of $8485 per admission. Readmissions owing to SCC have relayed a significant burden of 95,445 hospitalization days and a total charge of $609 million in the US. Despite the high morbidity and financial burden it imposes, limited studies have been performed studying the risk factors for readmissions in these patients. Despite the establishment of a framework of recommendations and guidelines, there appears to be a high incidence of readmissions and discrepancies in adherence to evidence based recommendations. We performed a retrospective study to evaluate the risk factors for patients hospitalized in three community hospitals between October 2021 and August 2022. Methods: The admissions database of a community health system across three hospitals was scanned for admissions with SCC between the time period October 2021 and August 2022. ICD9 and ICD-10 codes of SCC were used. 50 patients found with the admitting diagnosis code of SCC and 103 encounters were included. After excluding patients who left against medical advice before initiation of treatment, those with the wrong diagnosis and incomplete documentation, a cohort of 47 patients with 100 encounters was attained. Patient charts were reviewed and demographic variables such as age, gender and race were studied. Readmissions and the length of stay were assessed for risk factors with the help of a chi square test. Risk factors assessed included use of pain medications (opioids with non-steroid anti-inflammatory medications versus monotherapy), use of IV Fluid Boluses, placement of Hematology consult, having an established primary care physician and the use of hydroxyurea as a home medication. Results: 87% of the patient population was African American with equal gender distribution (Males 51%; Females 49%). 59% of the patient population lay in the age group of 18-35. 49% of the patient population was noted to have readmissions within the time frame studied with 29% of the patient population having a length of stay of more than 3 days. 100% of the patients without an established primary care physician (PCP) were noted to have readmissions in comparison to 3.6% of the patients with an established PCP (p< 0.01). Length of stay was less than 3 days for 91.3% of the patients treated with the combination of opioids and NSAID's for pain in comparison to 64.9% of the patients that were not treated with this combination (p= 0.014). It was noted however, that 37% of the population was on hydroxyurea outpatient and 44% of the cases had involved hematology for the inpatient management of these patients. IV Fluid boluses and their association with length of stays in our patient population was unequivocal. 52.7% of the patients on hydroxyurea had readmissions within 30 days as opposed to 28.6% of the patients not on the drug. This was likely explained by non-compliance to the medication. No deaths were reported in this patient cohort. Conclusion: Several risk factors for readmissions in SCC patients exist in the community setting. Our findings reported that lack of close outpatient follow up is associated with higher readmission rates. In addition, we also observed that the type of medical pain management (combination vs monotherapy) played a role in length of stay with combination therapy being linked to shorter hospitalization stay. Integrated education for various medicine specialties regarding management guidelines should be instituted. In addition, maximum utilization of social work and case management for ensuring close follow ups for this patient population may further mitigate readmissions of SCC patients in the community setting.

Indicators of quality of life, anxiety-depressive symptoms and severity of dysmenorrhea in adolescent girls with peritoneal endometriosis during conservative therapy for a year

Introduction. Delayed diagnosis and treatment of endometriosis lead to impaired quality of life and pain chronification in young female patients.Aim. To study indicators of quality of life, anxiety, depression and pain syndrome in adolescents with peritoneal endometriosis (PE) over a one-year period of conservative therapy.Materials and methods. A total of 45 girls aged 13 to 17 years with a confirmed diagnosis of PE were enrolled in a prospective longitudinal study. Pain syndrome (VAS, McGill Pain Questionnaire), anxiety-depressive symptoms (Beck Depression Inventory (BDI), Hospital Anxiety and Depression Scale (HADS), Spielberger State-Trait Anxiety Inventory (STAI)), quality of life indicators (SF-36) were assessed before and after one year of treatment in female patients (dienogest administered continuously, NSAIDs and drotaverine for immediate pain relief only).Results. One year of therapy resulted in a significant decrease in the severity of dysmenorrhea and chronic pelvic pain, gastrointestinal symptoms and dysuria, daily activity and productivity impairment (p < 0.001) in girls with PE. In addition, the study demonstrated decreased indicators of anxiety and depressive disorders (BDI depression, HADS anxiety and depression, STAI reactive and personal anxiety (p < 0.001)) and an improvement in quality-of-life indicators (physical and psychological component, average index (p < 0.001)). There was a declining trend in blood hormone and inflammation test results within the reference range during treatment. The estradiol level has been shown to be a risk factor for high levels of affective disorder symptoms in adolescents with PE: STAI reactive anxiety (p = 0.046), HADS anxiety and depression (p = 0.044 and 0.033, respectively).Conclusion. The one-year therapy of PE in adolescents (dienogest administered continuously, a combination of NSAIDs and drotaverine in pain syndrome only) was associated with significantly improved quality of life, decreased severity of anxietydepressive disorders and pain, which confirms the need to start therapy when symptoms of the disease begin to show them-selves in adolescence.

ID: 194317 Prolonged Dorsal Root Ganglion (DRG) Trial Adequately Treats Neuropathic Pain Due to Malignant Lumbosacral Mass

63-year-old female with PMH significant for Stage 1a endometrial adenocarcinoma s/p robotic total hysterectomy, had a fall 2 months prior to presentation, with subsequent development of left gluteal and labial numbness. She presented with subacute onset of urinary retention, constipation, weight loss, and radiating left lower extremity pain associated with dysesthesia and impaired gait. Conservative measures were ineffective (combination of NSAIDs, opioids and gabapentin). Typically, the diagnosis of Lumbosacral plexopathy (LSP) requires a thorough clinical evaluation due to a wide differential. However, our patient’s diagnosis was rather brisk due to an aggressive carcinoma causing severe localized pain. In cases of tumor compression, the L4-S1 segment is commonly affected (>50% of cases) followed by L1-L4 segment (31%) and pan-plexopathy (about 10%). At 42-month follow-up, 86% of patients diagnosed with malignancy-induced LS plexopathy had expired. DRG stimulation is approved for CRPS, persistent post-surgical pain syndrome, and peripheral neuropathy for T10-below. To our knowledge, this is the first report of successful application of DRG stimulation trial in the acute malignant pain crisis and palliative care setting.

Effects of combined use of steroidal and non-steroidal anti-inflammatory drugs on endometrial condition after artificial insemination

Post-breeding endometritis is a physiological reaction to semen and should resolve within 36 to 48 hours. Failure of uterine defense mechanisms to eliminate antigens and inflammatory products from the uterus effectively results in persistent endometritis with a detrimental effect on fertility (Canisso et al. Internal Journal of Molecular Sciences. 2020; 21(4), 1432). This study was designed to evaluate the effect of combinations of systemic NSAIDs on the uterine inflammatory response in mares after AI. Twenty-eight females were used. They were submitted to four treatments (n=7) randomly distributed: TAIE - AIE (0.1 mg/kg of Dexamethasone; IM); TAINE - AINE (1.1 mg/kg Phenylbutazone; IV); TAIE+AINE - two classes of associated anti-inflammatory drugs (0.1 mg/kg of Dexamethasone and 1.1 mg/kg of Phenylbutazone; IV) and TC – Control (NaCl 0.9% saline solution; IV). Gynecological examinations were performed three times a week and when follicles with a diameter of ≥ 35 mm were detected, ovulation was induced using 500 mg of histrelin acetate (Strelin®). The mares were inseminated 36 hours after ovulation induction with refrigerated semen. Immediately after AI, treatments were applied to each experimental group. Eight and 24 h post-AI, samples were collected foruterine cytology and ultrasound was performed to verify the presence of intrauterine fluid. The standard for considering the presence of endometritis was >5% PMN/endometrial cells or >5 PMN/field, in addition to the presence of intrauterine fluid greater than 2 cm. All mares underwent pregnancy diagnosis by transrectal ultrasound 25 days after AI. There was a difference between TAIE and the other treatments eight hours after AI in relation to PMN/endometrial cells (p <0.0001). However, in relation to the number of PMN/field there was a difference only between TAIE and TAIE+AINE (p<0.05). Twenty-four hours after AI, for PMN/endometrial cells, there was a difference between TAIE and TAINE (p<0.01), TAIE and TC (p<0.01), TAINE and TAIE+AINE (p<0.05), TAIE+AINE and TC (p<0.01) and for PMN/field between TAIE and TC (p<0.01) and TAIE+AINE and TC (p<0.01). The results obtained between the two evaluation criteria were discrepant and greater reliability was observed in the evaluation of PMN/endometrial cells. IN conclusion, the combined use of two anti-inflammatory classes (TAIE+AINE) was effective in improving the endometrial condition at 24 hours post-AI in normal mares.

PHARMACOKINETIC STUDY IN HUMANS AND IN VITRO EVALUATION OF BIOENHANCED BILAYER SUBLINGUAL FILMS FOR THE MANAGEMENT OF ACUTE MIGRAINE

Objective: Long-lasting migraine pain is one of the most disabling neurological disorders and requires a quick onset of action from the administered dosage form. This study aimed to provide sublingual administration of the frequently used combination of NSAID and triptan in order to trigger their action immediately by escaping the first-pass metabolism, simultaneously improving patient compliance. Methods: In the present research, sublingual bilayer films were developed by joining the two loaded layers with zolmitriptan and piroxicam, respectively. Each layer was prepared and loaded separately using the traditional solvent casting method. Mechanical support was provided by the 1:1 combination of HPMC E-15 and pullulan, which were used as water-soluble film-forming polymers with polyethylene glycol 400 as a plasticizer. Films were evaluated for various physicochemical and mechanical properties. Finally, a pharmacokinetic study was performed on six healthy human volunteers to compare the PK parameters of the best formulation, BSTF-3, with those of a commercially available formulation. Sepitrap 80 and Sepitrap 4000 were used as bio-enhancers to achieve faster systemic delivery. Results: The thin, flexible bilayer films were observed to provide quick action alone with increase patient compliance by preventing the first-pass metabolism and dysphagia. Sepitrap 80 successfully increased the permeation of both drugs. Approximately 92 percent of zolmitriptan was released from the formed bilayer sublingual thin films within 3 min, whereas 92 percent of piroxicam was released within 4.5 min from the best formulation. Within 30 min of the commencement of the pharmacokinetic investigation, plasma concentrations of the active component began to rise rapidly. Conclusion: When compared to commercial formulations, the developed films had a greater AUC and Cmax with a shorter Tmax, indicating a faster trigger of action and higher bioavailability.

Impact of Canine Amniotic Mesenchymal Stem Cell Conditioned Media on the Wound Healing Process: In Vitro and In Vivo Study.

The aim of this study was to provide a beneficial treatment effect of mesenchymal stem cell products derived from the canine amniotic membrane (AM-MSC) on the complicated wound healing process in dogs. AM-MSCs were characterized in terms of morphology, phenotypic profile, and multilineage differentiation potential. The in vitro study of the effect of canine amniotic mesenchymal stem cell conditioned media (AMMSC-CM) on a primary skin fibroblast cell culture scratch assay showed a decrease in the measured scratch area of about 66.39% against the negative control (Dulbecco's Modified Eagle's Medium-32.55%) and the positive control (Dulbecco's Modified Eagle's Medium supplemented with FGF2, N2, B27, and EGF-82.077%) after 72 h treatment. In the experimental study, seven dogs with complicated nonhealing wounds were treated with a combination of antibiotics, NSAIDs, and local AMMSC-CM application. After 15 days of therapy, we observed a 98.47% reduction in the wound surface area as opposed to 57.135% in the control group treated by conventional therapy based on debridement of necrotic tissue, antibiotic therapy, pain management, and change of wound dressing.

Abstract 5112: Immune biomarkers of clinical response after NSAID treatment in combination with vaccination targeting EGFR-COX2-CDC25B in the APC(Min/+) mouse model

Abstract Studies from our group have shown that administration of NSAIDs in mouse models of Familial Adenomatous Polyposis (FAP) results in a decrease in the development in small intestinal polyps with a significant increase in CD8 tumor infiltrating lymphocytes (TIL) and downregulation of PD-L1 on tumors. Furthermore, we have demonstrated that NSAIDs could be used in combination with vaccination to even further reduce the development of intestinal polyps. We questioned what tissue specific biomarkers could define the efficacy of response with the combination treatment. APC(Min/+) male and female mice (4-6 weeks old) were immunized with a multi-antigen (EGFR, COX2, CDC25B) peptide vaccine with CFA/IFA as an adjuvant. Control mice received immune adjuvant alone. Regular chow or chow containing 400 ppm naproxen was provided intermittently (3 weeks on, 3 weeks off for 3 cycles) or continuously (18 weeks on) at the initiation of the vaccine regimen. Animals were euthanized at 22 weeks and tumors quantified. TIL were evaluated by flow cytometry. Since intermittent naproxen treatment was just as effective at inhibiting tumor development as continuous naproxen treatment, with or without vaccine, we did not differentiate between NSAID regimens. We observed an increase in CD8+ (83%; p&amp;lt;0.0001), Tbet+CD4+ (94%; p&amp;lt;0.001), effector memory (EM) CD4+ (76%; p&amp;lt;0.0001) and EM CD8+ (94%; p&amp;lt;0.0001) TIL in the tumors that did develop in the mice treated with the combination NSAID and vaccination as compared to control. There was increased CD8+ (Pearson correlation coefficient: −0.506, p&amp;lt;0001), Tbet+CD4+ (Pearson correlation coefficient: -0.6222, p&amp;lt;0.001), EM CD4+ (Pearson correlation coefficient: 0.-6074, p&amp;lt;0.001) and EM CD8+ (Pearson correlation coefficient: -0.7155, p&amp;lt;0.001) in mice with greater tumor inhibition than those with less protection. Receiver operator curves revealed that CD8+ (AUC: 0.7623; p=0.002), Tbet+CD4+ (AUC 0.7273; p=0.008), EM CD4+ (AUC 0.6782; p=0.04) and EM CD8 (AUC 0.7897; p&amp;lt;0.001) TIL can differentiate mice receiving the combination of NSAID and vaccination as compared to either monotherapy alone. These data define potential biomarkers of response that can guide human clinical trials of NSAIDs +/- vaccination in patients with FAP. Citation Format: Denise L. Cecil, Ying Liu, Lauren Corulli, Mary L. Disis. Immune biomarkers of clinical response after NSAID treatment in combination with vaccination targeting EGFR-COX2-CDC25B in the APC(Min/+) mouse model. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5112.

Evolution in the choice of therapies used to treat latrodectism: Redback spider antivenom or standard analgesic medications. Nothing to rave about.

Redback spider (RBS) antivenom (RBSAV) use appears to have decreased since the results of the RAVE-2 antivenom efficacy study were released. The aims of this study were to assess change in RBSAV use over time and compare responses to treatment for antivenom and other analgesics. Retrospective audit of RBS bite referrals to a toxicology unit, from January 2010 to January 2022. Data included demographics, pain severity, treatment (analgesia or RBSAV), response to treatment, re-presentation rate, adverse events, change in antivenom use over time. Of 270 presentations, 157 with moderate or severe pain were included (RBSAV n= 51, analgesia n= 106). Median age was 39 years, n= 81 (51%) female. Those receiving antivenom were more likely to report severe pain n= 46/51 (84%) versus n= 68/106 (58%) (P= 0.006). Eighty-three percent of antivenom doses were administered between 2010 and 2013. Analgesia-only group received various combinations of paracetamol, NSAIDs, and opioids. In those receiving RBSAV, 17/48 (35%), 26/48 (54%), 5/48 (10%) reported a partial, complete or no reduction in pain, respectively, versus 30/77 (39%), 43/77 (58%) and 4/77 (5%), for analgesia-only group. Post-treatment pain was not recorded in three RBSAV and 28 analgesia-only patients. Pain reduction was no different for intravenous and intramuscular antivenom. Re-presentation for ongoing pain was more common in the analgesia-only group, 16/106 (15%) versus 1/51 (2%) for antivenom (P= 0.013). Antivenom use fell over the study period. There was no difference in pain relief between RBSAV and analgesia-only groups. RBSAV, regardless of route of administration, was no better than standard analgesics in pain reduction in the present study.

DRUG MISUSE AND SELF-MEDICATION AMONG PHARMACY STUDENTS IN JORDAN

Aim: To estimate risks and prevalence of self-medication and potential abuse risk among pharmacy students in Jordanian Universities. Materials and Methods: A cross-sectional study design was conducted with 450 students, selected using multistage sampling methods, from seven different universities. Data was collected by self-administrated questionnaires covering demographic and academic information, health-related information, use of self-medication, and pattern of self-medication among pharmacy students. Results: Out of 394 students who answer the questions, 76.9% reported that they had usually treated themselves in case of simple cases without physician or pharmacist consultation. Most commonly used drugs among the surveyed students were Paracetamol 60%, multivitamins supplement 74.25%, and herbal products 37.2%, combination of NSAIDs and Paracetamol 20.6%, and laxatives 19.4%. Cold and flu 25.5%, headache 22.3%, abdominal pain 7.9%, gastric pain 7.9%, cold and flu, headache, abdominal pain, and gastric pain 14.9% were the main conditions which contribute to self-medication practice. It was also found that Pharmacy students were over-confident with the type of cases they could treat without referral to a specialist physician, despite knowing that some of the symptoms may be due to serious health problems. Misuse of analgesics and laxatives was clear, and there was a weakness in knowledge of the indications for the use of the most common drug. Conclusions: The prevalence of self-medication among pharmacy students in Jordan is high, and medical teaching institutions need to educate students about the proper use of medicines. Strict legislation and more education on self-medication are necessary for effective use of medicines.

Rationale for the use of NSAIDs with antiseptic action for sore throat in the complex therapy of infectious and inflammatory diseases

Sore throat is one of the most common symptoms with which patients seek an appointment with an otorhinolaryngologist, and also serve as the main subjective symptom of infectious and inflammatory diseases of the pharynx. Pain in the throat, making it difficult to swallow, colloquial speech can drastically reduce the quality of life of patients, almost completely turning them off from active personal, work and social life. At the same time, the increase in the intensity of pain in the throat serves as a diagnostic criterion for the growth of the local inflammatory process, leading to its complications (peritonsillitis, paratonsillar abscess, etc.). Given that the main etiopathogenetic factors of the infectious and inflammatory pathology of the throat are viral, bacterial infection and inflammation, antibacterial and anti-inflammatory therapy are the main points of application in the complex treatment of these diseases. The economic and practical inconveniences of the need to purchase a large number of drugs justify the relevance and practical significance of the use of drug release forms, including a combination of etiopathogenetically targeted substances. This article discusses the effectiveness and feasibility of using a combination of NSAIDs and an antiseptic in one preparation. The studied materials allow us to state that the use of both individual components of the drug and its combined composition in the treatment of infectious and inflammatory diseases of the throat is justified, which manifests itself in a fairly quick and complete relief of the symptoms of the disease without complications and side effects of the drug. A comparative evaluation of the effectiveness of mono and complex therapy indicates a significant advantage of complex treatment, which includes two active ingredients of NSAIDs and an antiseptic.

Abstract 15317: An Unusual Case of Recurrent Chest Pain: Lymphocytic Myocarditis

Case Presentation: A 42-year-old male with a past medical history of recurrent myopericarditis treated with a combination of NSAIDs, colchicine, and steroids presented for left-sided chest pain. The pain first recurred when he attempted a prednisone taper and he was started on Anakinra. Upon presentation, physical examination and laboratory findings were within normal limits. Echocardiography and electrocardiogram were within normal limits. Cardiac magnetic resonance imaging (CMR) showed transmural enhancement of the basal-mid inferolateral segments and patchy mid-myocardial enhancement in the basal-mid anterolateral segments. Nuclear medicine PET showed FDG uptake in the basal anteroseptal, anterolateral, inferolateral, inferior, and apical segments suggestive of active inflammation. Initially, the diagnosis was thought to be recurrent myopericarditis of unknown etiology. Subsequent right heart catheterization with endomyocardial biopsy (EMB) showed mononuclear infiltrates in the interstitium associated with myocyte infiltration and focal moderate interstitial fibrosis. Due to his clinical, imaging, and pathologic findings, he was diagnosed with lymphocytic myocarditis. His anti-inflammatory therapy regimen was reinstated, and he was started on Mycophenolate Mofetil. On follow-up, the patient had significant symptomatic improvement. Discussion: Lymphocytic myocarditis is a pattern of myocardial inflammation that is typically associated with autoimmune and idiopathic causes. Myocarditis frequently manifests with signs and symptoms of heart failure, including chest pain, dyspnea, and arrhythmias. Diagnosis of myocarditis is often supported by CMR and FDG-PET findings, however, EMB is the gold standard for the diagnosis of myocarditis. Treatment is generally supportive, though immunomodulatory therapies have gained increased popularity due to benefits in treating symptoms and preventing complications of heart failure.

Combination of NSAIDs with donepezil as multi-target directed ligands for the treatment of Alzheimer’s disease

To search for multi-target directed ligands for the treatment of Alzheimer’s disease (AD), eight hybrid compounds from the combination of non-steroidal anti-inflammatory drugs with donepezil were designed and synthesized. The enzyme test revealed that the synthesized compounds had remarkable inhibitory activity towards both AChE and BChE. The IC50 values of the most active compound 3a reached 0.015 and 0.80 μM for AChE and BChE, respectively, much lower than that of donepezil. Besides, the anti-inflammatory assays showed that the target compounds could effectively inhibit COX-1 and COX-2, and prevent the secretion of proinflammatory cytokines (TNF-α and IL-1β) induced by LPS. Moreover, the target compound could also protect the neuron cells from the damage caused by Aβ42 in vitro. All the results suggest that the hybrid compounds, in particular compound 3a, can be considered as potential candidates for the treatment of AD.

The impact of clamp castration on the behaviour and body temperature of reindeer (Rangifer tarandus tarandus) – Effects of local anesthesia and non-steroidal anti-inflammatory drug.

Yearly, 2500–4000 reindeer (Rangifer tarandus tarandus) bulls are castrated in Finland, mostly without pain alleviation. No previous research exists concerning pain-related behaviours during castration in reindeer. Our aims were to investigate the effects of Burdizzo clamp castration on reindeer behaviour and rectal temperature during the procedure, and how these are affected by handling, local anaesthesia (LA) with lidocaine, and a non-steroidal anti-inflammatory (NSAID) drug meloxicam. A total of 44 1.5-year-old-reindeer were clamp castrated with either no pain alleviation (TRAD), perioperative meloxicam (NSAID), local lidocaine anaesthesia (LA), or with a combination of LA and NSAID (LA+NSAID), n = 11 in each treatment group. The fifth group was a non-castrated control (CONTROL), n = 11. We scored the reindeer behaviours, i.e., head, neck, and leg movements, nostril closure, panting, defecation, abdominal muscle contractions, and respiratory rate, from video recordings prior to and during castration and LA injection. We measured rectal temperatures (T) during the experiment and scored the number of reindeer reaching a T of at least 39.5ºC. Differences between treatments were analysed with the Kruskal-Wallis and chi square tests and differences between sampling intervals with the Wilcoxon signed rank and Friedman tests. During castration, nostril closures and abdominal muscle contractions occurred more often and for longer duration in the TRAD, NSAID, LA, and LA+NSAID groups than in the CONTROL group (p < 0.05 for all) or prior to castration (p < 0.001 for all). T increased during the experiment for all treatments. Overall, a total of 25 animals reached T 39.5ºC and treatments differed (p < 0.05): a larger number reached T 39.5ºC in the LA+NSAID group (11/11) than in the TRAD (2/10), NSAID (3/11), LA (4/11), or CONTROL (5/11) groups. The median respiratory rates decreased overall during the experiment for all treatments. During castration, TRAD had the highest median respiratory rate, differing from LA (38(40) vs. 32(20) breaths per min, n = 10 and 11, respectively, p = 0.003). Reindeer appear to express pain during clamp castration by closing their nostrils and contracting their abdominal muscles. Local lidocaine anaesthesia failed to significantly reduce the pain-related behaviours, at least with the 5-minute effect time used in this study. Moreover, a long handling time increased the rectal temperature of reindeer, especially when combined with other stressors such as injecting NSAIDs.

Combination of Anlotinib and Celecoxib for the Treatment of Abdominal Desmoid Tumor: A Case Report and Literature Review

Desmoid tumor is a rare disease, which is histologically characterized by local invasion, monoclonality, and fibroblast proliferation; and clinically characterized by a variable and often unpredictable course. The treatment of desmoid tumor is mainly surgical resection, but the recurrence rate is high. In recent years, a variety of treatment methods, including endocrine therapy, surgery, radiotherapy, chemotherapy, non-steroidal anti-inflammatory drugs, targeted drugs, interferon and more, have been used and achieved certain curative effects. In addition, in view of the inertia characteristics of desmoid tumor, observation is also a first-line scheme recommended by multiple guidelines. In the past, the research progress of targeted therapy for desmoid tumor is relatively slow and the curative effect is limited. Thus, targeted therapy is usually used as a remedial treatment after the failure of other conventional treatment methods. However, in recent years, with the rapid progress in the basic research of targeted therapy, some new targeted drugs are increasingly used for the clinical treatment of desmoid tumor and have achieved good results. Herein, we described a patient with aggressive fibromatosis in the abdominal cavity. Following a combined treatment using anlotinib and celecoxib, the patient achieved a partial response with mild toxicity. Simultaneously, the patient’s pain symptoms completely disappeared. This case indicates that the combination of anlotinib and NSAIDs could be an effective treatment for desmoid tumor.

Патогенетическое обоснование применения комбинированного препарата с анальгетическим действием для купирования болевого синдрома при первичной дисменорее

Dysmenorrhea is a complex of symptoms that most commonly occurs a day before or on the first day of menstruation. This paper describes in detail risk factors and prevalence of the primary and secondary dysmenorrhea. The authors discuss the etiology and pathogenesis of period pain, the mechanism of analgesic action of combined analgesic, and its use for primary dysmenorrhea depending on its severity. Systematic reviews of the comparative analysis of the efficacy of management strategies for primary dysmenorrhea have demonstrated that NSAIDs are beneficial for moderate-to-severe pelvic pain. A broad effect of NSAIDs on pain relief is mediated by reducing the production of prostaglandins (inflammatory mediators). NSAIDs or antispasmodics are most commonly used to reduce dysmenorrhea symptoms. Russian scientists focus on fixed-dose combinations of NSAIDs and myotropic antispasmodics, e.g., ibuprofen, pitofenone hydrochloride (myotropic antispasmodic), and fenpiverinium bromide (M-cholinoblocker with central and peripheral action). The pathogenic basis for the use of this combination for primary dysmenorrhea is addressed. KEYWORDS: primary dysmenorrhea, pelvic pain, NSAIDs, menstrual pain, myotropic antispasmodic, M-cholinoblocker, fixed-dose combination. FOR CITATION: Chebotareva Yu.Yu., Petrov Yu.A. Pathogenic basis for the use of a combined analgesic for pain relief in primary dysmenorrhea. Russian Journal of Woman and Child Health. 2022;5(2):146–152 (in Russ.). DOI: 10.32364/2618-8430-2022-5-2-146-152.

A triple-blind randomized clinical trial of different associations between dexamethasone and non-steroids anti-inflammatories for preemptive action in third molar extractions

The aim of this study is to evaluate the preemptive analgesic effects of dexamethasone (DEX) alone or combined with non-steroidal anti-inflammatory drugs (NSAIDs) in third molar surgeries. The subjects were divided into five groups (n = 20 teeth/group); subjects received only 8 mg of dexamethasone 1 h before the surgical procedure (DEX group), or in combination with etodolac (DEX + ETO), ketorolac (DEX + KET), ibuprofen (DEX + IBU), loxoprofen (DEX + LOX). Paracetamol 750 mg was provided as the number of rescue analgesics (NRA). Salivary PGE2 expression was measured preoperatively and at 48 h. Edema and Maximum mouth opening (MMO) were measured postoperatively at 48 h and 7 days. A visual analog scale (VAS) was performed postoperatively at 6, 12, 24, 48, 72 h, and 7 days. Salivary expression of PGE2 showed a decrease only for the DEX group. Edema and MMO and NRA consumption showed no significant differences among the groups (P > 0.05). The VAS showed a significantly lower pain perception at 6 h after the surgery for the DEX + ETO and DEX + KET groups (P < 0.05). The combination of DEX and NSAIDS should be considered for preemptive acute postsurgical pain management in third molar surgery. In some drug associations such as dexamethasone 8 mg + NSAIDS (ETO and KET) in the pre-operative time, only a few rescue analgesics are necessary.