Steroidal Anti-inflammatory Drugs Research Articles

Pseudophakic cystoid macular edema.

Pseudophakic cystoid macular edema (PCME) is the most common postoperative complication of cataract surgery, resulting in visual decline. In this review, we discuss its pathophysiology, epidemiology, clinical presentation, and the current available evidence on therapeutic management. Patients with diabetes mellitus have twice the risk of developing PCME as compared to nondiabetic individuals. Recent large database studies have revealed an increased risk among young, male, and black patients. A previous history of PCME is perhaps the strongest risk factor for fellow eye involvement. PCME generally occurs around 6 weeks postoperatively and is likely a consequence of postoperative inflammation with disruption of the blood-queous and blood-retina barriers. Optical coherence tomography of the macula servers as a key diagnostic tool. There is a lack of large controlled clinical trials to guide treatment approaches. We recommend a stepwise approach for PCME that includes observation if not visually significant versus treatment with topical nonsteroidal anti-inflammatory drugs and steroids if symptomatic. Refractory cases can be treated with a periocular steroid injection, followed by intravitreal steroids if still nonresponsive.

A rare occurrence of Vancomycin-induced gastrointestinal hemorrhage without thrombocytopenia: a case report and literature review

BackgroundVancomycin-induced bleeding has been reported, attributed to the mechanism of immune thrombocytopenia. A rare case of vancomycin-induced gastrointestinal hemorrhage in a young patient with no underlying disease, receiving intravenous vancomycin for methicillin-resistant Staphylococcus aureus (MRSA) infection, is presented. This occurrence occurred without thrombocytopenia. Relevant cases reported in the literature were also reviewed.Case presentationA 34-year-old male patient presented with maxillofacial multiple spaces infection accompanying left temporal abscess, bilateral lung abscesses. Culture results from both blood and secretion indicated that the infection was caused by MRSA. The patient received standard-dose vancomycin (1 g q12h intravenously guttae) for treatment. On the 5th day of therapy, he presented with bright red blood in his stool; however, vancomycin treatment was continued. By the 9th day, a decrease in hemoglobin level to 76 g/L and a platelet (PLT) count of 424 × 109/L raised concerns about gastrointestinal hemorrhage. The hemoglobin level decreased to 62 g/L on day 12. Due to the high tissue concentration of linezolid, administration of linezolid at a dose of 600 mg q12h intravenously guttae commenced on the 13th day as an alternative to vancomycin(D13-D17). Subsequently, on the 17th day, there was an improvement in hemoglobin level to 78 g/L. However, despite treatment with linezolid, the patient’s fever showed no significant improvement, prompting a switch back to vancomycin at a dosage of 1 g q12h intravenously guttae(D18-D22). On the 21st day, there was a recurrence of gastrointestinal hemorrhage, accompanied by a hemoglobin level of 42 g/L and a PLT count of 224 × 109/L. Gastroscopy revealed the presence of a gastroduodenal ulcer. The patient had no prior history of hemorrhoids, gastrointestinal ulcers, liver cirrhosis, or purpura. Prior to admission, he had not been administered non-steroidal anti-inflammatory drugs (NSAIDs) or steroids. During hospitalization, the only medications given were vancomycin, ambroxol and lidocaine. Additional tests ruled out immunological disorders as the cause of gastrointestinal ulcers, and a positive vancomycin rechallenge test indicated an association between vancomycin and bleeding. After discontinuation of vancomycin, no further bleeding occurred. This case highlights a rare occurrence of vancomycin-induced bleeding without thrombocytopenia, classified as “Certain” according to the World Health Organization-Uppsala Monitoring Centre (WHO-UMC) scale for standardized case causality assessment.ConclusionThis case represents the first documented instance of vancomycin-induced bleeding without thrombocytopenia, as confirmed by a positive rechallenge test. This discovery will aid in the early detection of this rare adverse reaction in future cases.

Teriflunomide Transdermal Cream: In-vitro And In-vivo Evaluation for the Treatment of Rheumatoid Arthritis.

Rheumatoid Arthritis (RA) is an incurable long-term disease that requires continuous safe treatment. Currently, many antiinflammatory agents and steroids are used to manage the diseases and are associated with a variety of side effects. There is a great need for a formulation that addresses the root cause of the disease and can be used for prolonged periods without any side effects. Hence, an attempt was made to develop a formulation of an alternative to steroid formulations that can be used for prolonged periods without/minimal side effects, i.e., teriflunomide topical dosage form. Teriflunomide tablet was approved for multiple sclerosis. It is the primary metabolite of leflunomide which is approved to treat RA. When leflunomide is administered orally converts to teriflunomide to elicit its action as such, leflunomide has no anti-rheumatoid effect. Both leflunomide and teriflunomide have different GIT side effects such as diarrhea, nausea, and hepatotoxicity on oral administration. To avoid these oral side effects of leflunomide and teriflunomide and to improve RA treatment compliance, teriflunomide was formulated as a topical cream. The developed topical cream is designed to be applied at night on the affected joints. It is intended to release the drug during the night, provide higher localized concentrations of the drug in the synovial joint and reduce GI and systemic side effects improving treatment compliance.

Trismus in cold-stunned Kemp's ridley (Lepidochelys kempii) and loggerhead (Caretta caretta) sea turtles.

To describe the presentation, clinical findings, diagnosis, treatment, and outcome of cases of trismus (lockjaw) in cold-stunned sea turtles. 4 Kemp's ridley (Lepidochelys kempii) and 1 loggerhead (Caretta caretta) sea turtle. Cold-stunned sea turtles that presented with difficulty or inability to open their jaw between 2009 and 2023 were included. Information retrieved from medical records included signalment, physical exam findings, diagnostic information, definitive diagnosis via either advanced imaging or histopathology, treatment, and clinical outcome. Turtles presented between 4 and 48 days into rehabilitation. Three were diagnosed by advanced imaging (CT or MRI), and 2 were diagnosed based on clinical signs and postmortem histopathology. Treatment was multimodal and consisted of antibiotics (5/5), nonsteroidal anti-inflammatories (5/5), vitamin E (3/5), intralesional steroid therapy (3/5), acupuncture (3/5), antifungals (2/5), anti-inflammatory parenteral steroids (2/5), physical therapy (2/5), therapeutic laser (2/5), and supportive feeding via either total parenteral nutrition (1/5), or tube feedings (2/5). Two animals were released, 2 died naturally, and 1 was euthanized. Trismus (lockjaw) is an uncommon finding in stranded cold-stunned sea turtles that can have a significant impact on animal welfare if not diagnosed and treated. This report describes the condition to aid clinical case management and resource allocation in rehabilitation facilities.

Effects of the anti-inflammatory drug budesonide on the gut microbiota and cytokine production of 13-lined ground squirrels during prehibernation fattening.

The gut microbiome is essential for maintaining organismal health. Gut microbiota may be disrupted through external factors like dietary change, which can lead to gut inflammation, resulting in obesity. Hibernating mammals develop low-grade gut inflammation when they accumulate fat deposits in preparation for hibernation, making them useful models for studying the relationship between the microbiome, inflammation, and weight gain. Nonsteroidal anti-inflammatory drugs and steroids are commonly used in humans to target gut inflammation, but how these drugs affect the gut microbiome and its stability is unclear. We investigated the effect of the glucocorticoid drug budesonide on the gut microbiome and cytokine levels of an obligate hibernator, the 13-lined ground squirrel, during the fattening season. We used 16S rRNA gene sequencing to characterize bacterial communities in the lumen and mucosa of the cecum and colon and measured proinflammatory [tumor necrosis factor-α (TNF-α)/interleukin 6 (IL-6)] and anti-inflammatory (IL-10) cytokine levels. Budesonide affected the microbiome only in the cecum lumen, where bacterial diversity was higher in the control group, and communities significantly differed between treatments. Across gut sections, Marvinbryantia and Enterococcus were significantly higher in the budesonide group, whereas Sarcina was higher in the control group. TNF-α and IL-6 levels were higher in control squirrels compared with the budesonide group, but there was no difference in IL-10 levels. Overall, budesonide treatment affected the microbial community and diversity of 13-lined ground squirrels in the cecum lumen. Our study presents another step toward developing ground squirrels as a model for studying the interaction between the microbiota and host inflammation.NEW & NOTEWORTHY Disruptions of gut microbiota can lead to inflammation, resulting in weight gain. Inflammation can be treated with budesonide, but how budesonide affects gut microbiota is unclear. Thirteen-lined ground squirrels experience low-grade gut inflammation during prehibernation fattening, which compares with human inflammation-weight gain mechanisms. We showed that budesonide treatment decreased microbiome diversity and lead to a shift in community in the cecum lumen. Our study supports developing ground squirrels as a model for studying microbiome-inflammation interactions.

Photocatalytic Decarboxylative Fluorination by Quinone-Based Isoreticular Covalent Organic Frameworks.

The strategic incorporation of fluorine atoms into molecules has become a cornerstone of modern pharmaceuticals, agrochemicals, and materials science. Herein, we have developed a covalent organic framework (COF)-based, robust photocatalyst that enables the photofluorodecarboxylation reaction of diverse carboxylic acids, producing alkyl fluorides with remarkable efficiency. The catalytic activity of an anthraquinone-based COF catalyst TpAQ outperforms other structurally analogous β-ketoenamine COFs. Through comprehensive control experiments, photoluminescence, and electrochemical studies, we have elucidated the unique features of the material and the mechanistic pathway. This in-depth understanding has paved the way for optimizing the reaction conditions and achieving high yields of alkyl fluorides. The versatility of this protocol extends to a broad range of aliphatic acids with diverse functional groups and heterocycles. It also enabled the late-stage diversification of anti-inflammatory drugs and steroid derivatives. This opens up exciting possibilities for synthesizing novel pharmaceuticals and functionalized molecules. The methodology was also generalized to other light-mediated decarboxylative halogenation reactions. Furthermore, our method demonstrates scalability under both batch and continuous flow conditions, offering a promising approach for large-scale production. Additionally, the TpAQ catalyst exhibits exceptional durability and can be reused multiple times without significant activity loss (>80% yield after the eighth cycle), making it a sustainable and cost-effective solution. This work lays the foundation for developing efficient and sustainable light-driven synthesis methods using COFs as photocatalysts with potential applications beyond alkyl halide synthesis.

A combined treatment for self-traumatic chronic skin lesions associated with post-surgical neuropathic pain in a domestic cat: a pharmacological and cold atmospheric plasma approach.

Cold atmospheric plasma (CAP) has been employed as a therapy against both acute and chronic skin lesions, contaminated or not, and has effects on angiogenesis and reepithelialization promoting healing. In this context, the present study aimed to evaluate the effects of a CAP jet associated with pharmacological treatment described by the 2015 AAHA/AAFP pain management guidelines and the 2022 WSAVA guidelines for the recognition, assessment, and treatment of pain, on the healing of chronic skin lesions caused by a pruritic reaction resulting from post-surgical neuropathic pain. To this end, a single CAP application was performed on a feline patient with a 6months old recurrent contaminated cervical skin lesions along with administration of ketamine (10µg/kg/min) following the prescription of prednisone (1mg/kg, SID, 6days), gabapentin (8mg/kg, BID, 60days) and amitriptyline (0.5mg /kg, SID, 60days). A single application of plasma associated with an NMDA antagonist, anti-inflammatory steroid, tricyclic antidepressant and gabapentinoid thus provided a significant improvement in the macroscopic appearance of the lesion within 10days, and the owner reported the cessation of intense itching within the first four hours after treatment and a consequent improvement in the animal's quality of life. The medical treatment was finished almost a year since the writing of this paper, without clinical or reported recurrent signs of the condition. Therefore, we observed that single dose CAP application associated with ketamine, gabapentin, amitriptyline and prednisone leads to significant healing of chronically infected skin lesions resulting from post-surgical neuropathic pain.

From Zero to Overwhelm: PANS and PANDAS as Culprits Behind Sudden OCD in Pediatrics

Pediatric autoimmune neuropsychiatric disorders (PANDAS) and patient neuropsychiatric syndrome (PANS) are psychiatric illnesses characterized by a rapid onset of symptoms, including obsessive-compulsive disorder (OCD), behavioral symptoms and poor motor functions in children. The rapid onset and severity of OCD symptoms prompted investigations to provide an evidence-based intervention. This case series investigates the causes, diagnosis and treatment of the disease among children presenting with neuropsychiatric symptoms and acute-onset OCD. The diagnostic procedures provided grounds for the indication of medication. Methods: Bacterial infections, autoimmune cases and viral infections among 12 children with PANDAS and PANS were retrospectively studied. Pre- and post-treatment symptomatology were examined to monitor the effectiveness of interventions, following laboratory diagnostic approaches, including the Cunningham panel, serology, stool sample analysis, polymerase chain reaction (PCR), and bacterial cultures to determine the cause of the disorder. Diagnostic results informed treatments like non-steroidal anti-inflammatory drugs (NSAIDs), intravenous immunoglobulin (IVIG), fluid therapy, antibiotics, antivirals, steroids, and selective serotonin reuptake inhibitors (SSRIs) in each child. Post-treatment diagnostic results revealed remarkably improved symptoms of PANDAS and PANS, like inflammation and viral or bacterial infection. A combined therapy of antibiotics and NSAIDs or steroids was used to clear bacterial infections and manage inflammation. SSRIs and antiviral or fluid therapy were indicated for OCD and viral infections, respectively. Conclusions: OCD is a common comorbid disorder among children with PANS and PANDAS. Despite the severity and prevalence, OCD in children raises health concerns. The case series demonstrated the effectiveness of antibiotic therapy, RRIs, cognitive behavioral therapy, IVIG, steroids and NSAIDs in managing OCD in PANDAS and PANS, with a unique rationale of indication to every child. Keywords: PANS, PANDAS, Sudden Onset OCD, Pediatric OCD, Autoimmune Neuropsychiatric Disorders

Preemptive oral analgesia with steroidal and nonsteroidal anti-inflammatory drugs in periodontal surgery: a systematic review.

Introduction: Periodontal procedures can promote prolonged intense pain, particularly in clinical situations requiring surgical procedures. In this context, preemptive analgesia has also been assessed for its utility in controlling post-operative pain and discomfort in patients undergoing periodontal invasive procedures. This study assessed the efficacy and safety of preemptive oral analgesia with steroidal and non-steroidal anti-inflammatory drugs in periodontal surgeries. Methods: This systematic review performed a search in the following electronic sources: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (via PubMed), EMBASE (via Ovid), Web of Science, Virtual Health Library and in clinical trials electronic databases for relevant randomized clinical trials (RCTs); published up to July 2023. Primary outcomes assessed were post-operative pain, edema and trismus. A narrative synthesis of the findings was carried out. Results: Six RCTs, involving a total of 250 participants, were included. The studies reviewed had a high risk of bias, particularly due to allocation concealment and blinding of participants and personnel. The RCTs reported only the outcome pain. The preemptive use of dexamethasone 8mg, etoricoxib 90mg or 120mg and ketorolac 20mg seems to be more effective for controlling post-operative pain than placebo. Discussion: The anti-inflammatory drugs evaluated proved to be effective for controlling post-operative pain. However, given the limitations regarding lack of studies, methodological biases, disparities in drugs and doses, report restricted the pain outcome; further RCTs confirming the effectiveness and safety of these drugs in periodontal surgical procedures are warranted.

Management of Amavata w.s.r. to Rheumatoid Arthritis

Vitiated Vata Dosha, weakened Agni, and accumulation of Ama at Shleshmic Sthana mainly at Sandhi (joints) are responsible for the development of Aamvata. Amavata can be correlated with Rheumatoid Arthritis due to similarities in clinical symtoms. Rheumatoid arthritis is one among the autoimmune diseases causing chronic symmetrical polyarthritis. The treatment in Modern science includes the use of NSAID’s (Non steroidal anti-inflammatory drugs), DMARD’s (Disease-Modifying Antirheumatic Drugs), glucocorticoids, and immune-suppressants, long-term use of which causes several side effects. Ayurveda treatment procedures and medication used for the treatment of Amavata have Agni Deepana, Ama Pachana, Vata Shamaka, Sroto shodhana actions which are helpful to retard disease process and reduce signs and symptoms of the disease. In the present case, 65-year female patient presented with, complaints of multiple joint pain with swelling and morning stiffness, restricted joint movements, loss of appetite, fatigue, weakness, fever (on and off), migratory pain, and symmetrical joint involvement. Patient was administered with Phalatrikadiguggulu, Shwadanshtradi guggulu. Mahayograjguggulu, Rasapachak vati, Sameerpannag rasa and Gandharvaharitaki churna added as Nitya Virechana. Ruksha Swedan with Valukapottali had also been given. The therapeutic interventions adopted in the study have shown beneficial effects in the patients of Aamvata.

Transplant-associated thrombotic microangiopathy in pediatrics: incidence, risk factors, therapeutic options, and outcome based on data from a single center.

Transplant-associated thrombotic microangiopathy (TA-TMA) is a critical complication of hematopoietic stem cell transplantation. Awareness about TA-TMA has increased in recent years, resulting in the implementation of TA-TMA screening in most centers. Retrospective analysis of children who underwent autologous or allogeneic hematopoietic stem cell transplantation at our center between January 2018 and December 2022 was conducted to evaluate the incidence, clinical features, and outcomes of TA-TMA following the administration of different therapeutic options. A total of 45 patients comprised the study cohort, of whom 10 developed TA-TMA with a cumulative incidence of 22% by 100 days after transplantation. Patients with and without TA-TMA in our cohort displayed an overall survival of 80% and 88%, respectively (p = 0.48), and a non-relapse mortality of 0% and 5.7%, respectively (p = 0.12), at 1 year after transplantation. Risk factors for TA-TMA development included allogeneic transplantation and total body irradiation-based conditioning regime. Among the 10 patients with TA-TMA, 7 did not meet the high-risk criteria described by Jodele and colleagues. Of these seven patients, two responded to calcineurin-inhibitor withdrawal without further therapy and five developed multiorgan dysfunction syndrome and were treated with anti-inflammatory steroids (prednisone), and all responded to therapy. The three patients with high-risk TA-TMA were treated with complement blockade or prednisone, and all responded to therapy. TA-TMA is a multifactorial complication with high morbidity rates. Patients with high-risk TA-TMA may benefit from complement blockade using eculizumab. No consensus has been reached regarding therapy for patients who do not meet high-risk criteria. Our analysis showed that these patients may respond to anti-inflammatory treatment with prednisone.

EXPERIMENTAL RESEARCH OF THE PHARMACOLOGICAL EFFECT OF CARBON DIOXIDE IN THE CORRECTION OF INFLAMMATION

Osteoarthritis is considered one of the leading causes of chronic disability and is a significant problem on human health and the economy. Chronic pain is the dominant symptom that prompts patients to seek medical attention. Pain mechanisms in osteoarthritis remained unknown for a long time. However, it is known that chronic inflammation of the joint can be a key factor in the occurrence and exacerbation of pain or changes in the perception of pain. Pharmacological therapy is often based on the use of steroidal and non-steroidal anti-inflammatory drugs, but their long-term use or large doses can cause side effects. That is why the development of new methods of treatment of inflammatory processes is the object of active research, as they can affect various mechanisms. In this context, carboxytherapy is an interesting alternative or addition to existing treatment regimens aimed at reducing pain in patients with osteoarthritis. This method involves the administration of medical carbon dioxide (CO2) to improve blood supply to tissues, which can contribute to humoral, biochemical and tissue mechanisms. Studying the effects of carboxytherapy in animal models of inflammation is important for understanding its potential benefits and mechanisms of action. Objective. Study of anti-inflammatory properties of carboxytherapy both in monotherapy and in its combined use. Methods. Carboxytherapy is the injection of carbon dioxide in monotherapy and when used in combination on the formalin model of inflammation in animals. Results. The obtained research results prove the anti-inflammatory properties of carbon dioxide on the model of formalin inflammationin animals. Conclusions. The combined use of carboxytherapy enhanced the effect of conventional drugs on the formalin model of inflammation in animals. The establishment of an anti-inflammatory effect of carboxytherapy indicates the therapeutic value of CO2, while emphasizing the need for further in-depth studies to explore its mechanisms and confirm the efficacy for clinical use.

Value of Urinary NGAL for Predicting Acute Kidney Injury Secondary to Decompensated Cirrhosis

Abstract Background Physicians caring for patients with cirrhosis should recognize the acute or chronic character of renal disease; the causes of renal injury; the clinical conditions leading concomitantly to acute kidney injury (AKI) and liver dysfunction, and the prognostic factors associated with the progression of AKI. Hypovolemia (due to diuretics, hemorrhage, diarrhea), acute tubular necrosis, sepsis, nephrotoxic agents (such as non steroidal anti-inflammatory drugs, aminoglycosides radiological contrasts) and hepatorenal syndrome-type 1 are the most common causes of AKI in cirrhotic patients. Aim of the Work The aim of this study was to evaluate urinary Neutrophil Gelatinase-Associated Lipocalin (uNGAL) as a diagnostic biomarker for different causes of acute kidney injury in liver cirrhosis. Patients and Methods This was a cross sectional study done in patients with liver cirrhosis hospitalized at the Gastroenterology Department of the Ain shams university hospital. Results We found that in the comparison between HRS and AKI regarding HB, WBCs, Platelets, ALT, AST, Albumin, INR, Bilirubin, Urea, Creatinine, Na, Urinary Cr, Urinary Na and FeNa%, there was highly statistically significant difference found between two groups regarding Urinary Na and Fe Na%, Platelets, AST, Bilirubin and Na, and there was no statistically significant difference found between two groups regarding HB, WBCs, ALT, Albumin, INR, Urea, Creatinine and Urinary Cr. While in the Correlation between NGAL With Age, HB, WBCs, Platelets, ALT, AST, Albumin, INR, Bilirubin, Urea, Creatinine, Na, Urinary Cr, Urinary Na and FeNa%, we found that there was Non statically significant correlation Between NGAL, Age, HB, WBCs, Platelets, ALT, Albumin, INR, Bilirubin, Urea, Creatinine, Na and Urinary Cr, and there was statically significant Negative correlation Between NGAL, Urinary Na and FeNa%, and there was statically significant positive correlation Between NGAL and AST. Conclusion It is well known that development of acute kidney injury (AKI) increases mortality in hospitalized cirrhotic patients; therefore many novel markers have been studied for early detection, differential diagnosis and prognosis in cirrhotic patients with AKI. NGAL is a newly identified member of the lipocalin family that is signifcantly expressed in injured epithelial cells. It can lead to rapid increases in NGAL secretion from glomeruli, thus increasing NGAL concentrations in the urine. In addition, its concentration often increases within 2 h of kidney injury. Urinary NGAL has the ability to differentiate between AKI types in patients with cirrhosis. This could improve risk stratification for patients admitted to the hospital with cirrhosis, perhaps leading to early ICU admission, transplant evaluation, and prompt initiation of HRS therapy and early management of AKI. These findings, if confirmed in larger cohorts, could lead to the development of biomarker algorithms to rapidly identify patients with HRS and ATN and accurately predict prognosis.

Treatment Strategies for Filamentous Fungi Keratitis.

This research aims to describe clinical findings, epidemiology and treatment outcomes in patients with filamentous fungi keratitis of a tertiary centre in Germany over a 7-year period and to compare the efficacy of different antifungal treatments and the effect of additive topical steroids. This retrospective study included 25 eyes of 23 patients from October 2013 to December 2020 with cultural isolates of filamentous fungi and corresponding keratitis. Best-corrected visual acuity (BCVA), clinical signs, symptoms, risk factors and outcome were extracted from medical records. Improvement of BVCA was noted in 68% of eyes. Mean BCVA of the study population increased from 0.75 logMAR [median 0.40, standard deviation (SD) 0.82, range 0-2.3] to 0.48 logMAR (median 0.10, SD 0.88, range - 0.1 to 3). The most commonly used antifungal topical treatment was a combination of natamycin 5% and voriconazole 2% (44% of eyes), followed by voriconazole 2% in 36% of cases. An antiinflammatory topical steroid was applied in 52%. In 16% of the eyes, penetrating keratoplasty (pKP) was performed. Diagnosis of filamentous fungi keratitis is often difficult or delayed. Outcomes can be poor even with intensive treatment because of high resistance to common antifungals. Access to natamycin 5% seems to lead to favourable outcomes in filamentous fungi keratitis.

Isothiocyanate-Corticosteroid Conjugates against asthma: Unity makes strength

Asthma is a major noncommunicable disease, affecting both children and adults, and represents one of the major causes leading to high health care costs due to the need for chronic pharmacological treatments. The standard gold therapy of inflammation in asthmatic patients involves the use of glucocorticoids even if their chronic use is often related to serious adverse effects. Growing evidence suggests the biological relevance of hydrogen sulfide (H2S) in the pathogenesis of airway diseases. Hence, aiming to associate the beneficial effects of steroidal anti-inflammatory drugs (SAIDs) to H2S biological activity, we designed and synthesized novel multi-target molecules by chemically combining a group of glucocorticoids, usually employed in asthma treatment, with an isothiocyanate moiety, well-known for its H2S releasing properties. Firstly, the synthesized compounds have been screened for their H2S-releasing profile using an amperometric approach and for their in vitro effects on the degranulation process, using RBL-2H3 cell line. The physicochemical profile, in terms of solubility, chemical and enzymatic stability of the newly hybrid molecules, has been assessed at different physiological pH values and in esterase-rich medium (bovine serum albumin, BSA). The selected compound 5c, through both its corticosteroid and H2S releasing component, has been evaluated in vivo in experimental model of asthma. The compound 5c inhibited in vivo all asthma features with a significative effect on the restoration of pulmonary structure and reduction of lung inflammation.

Potential of natural products in inflammation: biological activities, structure-activity relationships, and mechanistic targets.

A balance between the development and suppression of inflammation can always be found in the body. When this balance is disturbed, a strong inflammatory response can damage the body. It sometimes is necessary to use drugs with a significant anti-inflammatory effect, such as nonsteroidal anti-inflammatory drugs and steroid hormones, to control inflammation in the body. However, the existing anti-inflammatory drugs have many adverse effects, which can be deadly in severe cases, making research into new safer and more effective anti-inflammatory drugs necessary. Currently, numerous types of natural products with anti-inflammatory activity and distinct structural features are available, and these natural products have great potential for the development of novel anti-inflammatory drugs. This review summarizes 260 natural products and their derivatives with anti-inflammatory activities in the last two decades, classified by their active ingredients, and focuses on their structure-activity relationships in anti-inflammation to lay the foundation for subsequent new drug development. We also elucidate the mechanisms and pathways of natural products that exert anti-inflammatory effects via network pharmacology predictions, providing direction for identifying subsequent targets of anti-inflammatory natural products.

Subacute Thyroiditis Following COVID-19 and COVID-19 Vaccination

ObjectiveCOVID-19 infection and immunizations have been implicated in developing a range of thyroid diseases, including subacute thyroiditis (SAT). This study aimed to evaluate the association between COVID-19 infection and/or COVID-19 vaccination with SAT. MethodsA population of 3 million adults insured by Clalit Health Services was evaluated from March 2020 to September 2022. Patients with a new diagnosis of SAT were identified and matched in a 1:10 ratio to a control group. Each control was assigned an index date that was identical to that of their matched case, defined as the date of SAT diagnosis. Multivariate conditional logistic regression models were used to evaluate the association between COVID-19 infection, vaccine, and thyroiditis. ResultsA total of 3221 patients with SAT were matched with 32 210 controls. Rates of COVID-19 vaccination (first, second, or third dose) and COVID-19 infection were evaluated prior to the date of SAT diagnosis (disease group) or index date (control group) to detect a possible association. No difference was detected between the groups in relation to vaccinations at the 30 days, 60 days, and 90 days of time points (P = .880/0.335/0.174, respectively). No difference was found between groups in relation to COVID-19 infection at these time points (P = .735/0.362/0.956, respectively). There was higher use of medications for the treatment of thyroiditis, including nonsteroidal anti-inflammatory drugs (28.6% vs 7.9%, P < .01), steroids (10.3% vs 1.8%, P < .01), and beta-blockers (18.3% vs 5.4%, P < .01). ConclusionBased on this large population study, no association was found between COVID-19 infection and/or the COVID-19 vaccine and SAT.

Assessing Pharmacogenomic loci Associated with the Pharmacokinetics of Vamorolone in Boys with Duchenne Muscular Dystrophy.

Human genetic variation (polymorphisms) in genes coding proteins involved in the absorption, distribution, metabolism, and elimination (ADME) of drugs can have a strong effect on drug exposure and downstream efficacy and safety outcomes. Vamorolone, a dissociative steroidal anti-inflammatory drug for treating Duchenne muscular dystrophy (DMD), primarily undergoes oxidation by CYP3A4 and CYP3A5 and glucuronidation by UDP-glucuronosyltransferases. This work assesses the pharmacokinetics (PKs) of vamorolone and sources of interindividual variability (IIV) in 81 steroid-naïve boys with DMD aged 4 to <7 years old considering the genetic polymorphisms of CYPS3A4 (CYP3A4*22, CYP3A4*1B), CYP3A5 (CYP3A5*3), and UGT1A1 (UGT1A1*60) utilizing population PK modeling. A one-compartment model with zero-order absorption (Tk0, duration of absorption), linear clearance (CL/F), and volume (V/F) describes the plasma PK data for boys with DMD receiving a wide range of vamorolone doses (0.25-6 mg/kg/day). The typical CL/F and V/F values of vamorolone were 35.8 L/h and 119 L, with modest IIV. The population Tk0 was 3.14 h yielding an average zero-order absorption rate (k0) of 1.16 mg/kg/h with similar absorption kinetics across subjects at the same vamorolone dose (i.e., no IIV on Tk0). The covariate analysis showed that none of the genetic covariates had any significant impact on the PKs of vamorolone in boys with DMD. Thus, the PKs of vamorolone is very consistent in these young boys with DMD.

RECENT ADVANCES IN NANOTECHNOLOGY - BASED DRUG DELIVERY SYSTEMS FOR DELIVERY OF PHYTOCONSTITUENTS WITH SPECIAL EMPHASIS ON PSORIASIS MANAGEMENT

Psoriasis is an inflammatory, autoimmune disorder characterized by thick and silvery lesions of the skin. Beyond its physical dimension, this disease has a significant adverse effect on quality of life and represents a huge social health burden. Based on symptoms, psoriasis may be characterized from mild to severe. A range of therapeutic agents are available to treat the disease, but none is able to provide permanent cure of the disease. The most commonly used medicines for treatment of psoriasis include anti-inflammatory drugs, steroids, biological and immunosuppressants. Though these drugs cure the disease to an extent, they are associated with many contra-indicative manifestations. Hence, an alternative system of medicine could be an excellent approach in the management of this disease, and numerous studies proved that bio-actives derived from natural sources have potential anti-psoriatic activity. Further, the therapeutic actions of these natural products can be enhanced by incorporating them in nano-formulations. The present era of medicine is focusing on implementation of natural product based nanotechnology to overcome the drawbacks of conventional treatment. This review primarily aims to focus on the recent advances in the field of natural product based nanomedicines for the effective management of psoriasis.

Equine Musculoskeletal Pathologies: Clinical Approaches and Therapeutical Perspectives-A Review.

Musculoskeletal injuries such as equine osteoarthritis, osteoarticular defects, tendonitis/desmitis, and muscular disorders are prevalent among sport horses, with a fair prognosis for returning to exercise or previous performance levels. The field of equine medicine has witnessed rapid and fruitful development, resulting in a diverse range of therapeutic options for musculoskeletal problems. Staying abreast of these advancements can be challenging, prompting the need for a comprehensive review of commonly used and recent treatments. The aim is to compile current therapeutic options for managing these injuries, spanning from simple to complex physiotherapy techniques, conservative treatments including steroidal and non-steroidal anti-inflammatory drugs, hyaluronic acid, polysulfated glycosaminoglycans, pentosan polysulfate, and polyacrylamides, to promising regenerative therapies such as hemoderivatives and stem cell-based therapies. Each therapeutic modality is scrutinized for its benefits, limitations, and potential synergistic actions to facilitate their most effective application for the intended healing/regeneration of the injured tissue/organ and subsequent patient recovery. While stem cell-based therapies have emerged as particularly promising for equine musculoskeletal injuries, a multidisciplinary approach is underscored throughout the discussion, emphasizing the importance of considering various therapeutic modalities in tandem.