Steroidal Anti-inflammatory Drugs Research Articles

EFFICACY AND SAFETY OF DR. ORTHO OIL IN THE TREATMENT OF JOINT PAIN, STIFFNESS, AND INFLAMMATION: AN OPEN-LABEL, NON-RANDOMISED CLINICAL STUDY

Background: Joint pain or inflammation is a common complaint among the elderly and is conventionally treated with steroidal or non-steroidal anti-inflammatory drugs (NSAIDs). Because of the adverse effects of these drugs, the present herbal formulation is being developed for the long-term control of pain and inflammation. Objective: The objective of this study was to assess the efficacy and safety of Dr. Ortho Oil in patients with knee pain, low back pain, joint stiffness, sports injuries, and joint inflammations. Methods: This was a single-centre, open-label, non-randomised study. 120 participants were selected based on the inclusion and exclusion criteria. All individuals were instructed to use Dr. Ortho Oil for 60 days. The primary outcome was a change in the frequency of subjects with a significant reduction in joint pain, stiffness, and inflammation. Secondary outcomes were improvements in investigator assessment scale (IAS) and subject self-assessment questionnaire (SAQ) scores at successive administrations compared with the baseline. Results: The study indicated that topical use of Dr. Ortho Oil for 30 days reduced all dimensions of pain. SAQ and IAS scores also decreased significantly.

The role of pharmaceutical analysis in ensuring the safety of drug radiation sterilization

Radiation sterilization is a widely used method for ensuring the sterility of medical and pharmaceutical products. The process involves exposing the products to ionizing radiation, which destroys microorganisms such as bacteria, viruses, and fungi, rendering the products sterile. The most commonly used ionizing radiation sterilization methods are highly penetrating with low dose rate gamma-irradiation from isotopic sources and less penetrating but with high dose rate e-beam from accelerators. This review provides an overview of the principles and applications of radiation sterilization, including the types of radiation sources used, the differences between them that may affect the efficacy of the process, and the regulatory requirements for radiation sterilization of active pharmaceutical ingredients and drug dosage forms. This review focuses on the analytical methods used to evaluate the effect of irradiation on drug substances. Finally, it discusses studies on radiation sterilization of various groups of drugs, including anthracyclines, β-lactam antibiotics, chloramphenicol and its derivatives, sulphonamides, antifungal drugs, β-blockers, nonsteroidal anti-inflammatory drugs, steroids, and others, and drug dosage forms.

Effect of Diclofenac Sodium in Developing Chick Embryo, Gallus Gallus domesticus (Linn, 1758)

Diclofenac sodium, a non steroidal anti-inflammatory drug (NSAID) is an acetic acid derivative with generic name Diclofenac. NSAIDs represent some of the oldest medicines with recorded history of use of people. However, it is also known to inhibit implantation and embryonic development in rats and mammals. It is widely prescribed in India to women of child bearing age for the treatment of various conditions including arthritis, masculo-skeletal pain etc. Research has shown that it also crosses human placenta readily and potentially teratogenic. The present study focuses on assessing the embryonic development in chick under varied dosages of diclofenac sodium at different developmental stages. The results showed teratogenic effects such as omphlaocoele, reduced body size, delay in hatchability and angiogenesis with irregular heartbeats.

#3572 CLINICAL AND GENETIC CHARACTERISTICS OF CHILDREN WITH BARTTER SYNDROME: A SINGLE CENTER LONG-TERM EXPERIENCE

Abstract Background and Aims Bartter syndrome is an autosomal recessive renal tubular disorder. Clinical diagnosis can be challenging due to rarity and phenotypic overlap. Little information is available on a long term follow-up in Bartter syndrome. Our aim was to describe clinical -genetic correlations as well as our experience from the long term follow up of these patients. Method Clinical and genetic characteristics of patients with Bartter syndrome at diagnosis and long term follow up are reported in 19 children. Genetic testing (whole exome sequencing, WES) was done in 14/19 patients. The study period was 17 years (January 1, 2006 to December 31, 2022). Results 16 Caucasian and 3 of gipsy origin (13 boys, 68%) were included. The median age at diagnosis was 0,52 yrs. Median follow up time was 9.8yrs (IQR 6.86-13.8). WES revealed 6 mutations in KCNJ1 genes, 5 in SLC12A1 and 3 in CLCNKB genes. 4 new mutations were identified (3 in KCNJ1 genes and 1 in SLC12A1. 18/19 children were born pre-term (including 2/3 patients with CLCNKB). Nephrocalcinosis was present in 18/19 patients (included the 3 patients with CLCKNB mutations). 4/6 patients with KCNJ1 mutations presented initially with hyperkalemia. Medical treatment in the last follow up included supplementation with potassium in 18, non -steroidal anti-inflammatory agents in 15 and gastroprotective drugs in 13, ramipril in 2. 2/19 received recombinant growth hormone. At last follow up body weight and height were within normal ranges in 16/19 (84%) patients. Hyperparathyroidism (median time of PTH 151.5 pg/ml) have 6/11 (56%) of patients with Bartter I (ΚCNJ1mutation) and Bartter II (SLC12A1 mutation) and only 1/3 with Bartter III (CLCNKB mutation). 2/19 patients have proteinuria. Chronic kidney disease (CKD) occurred in 7/19 (37%) suggesting that the long term prognosis can be unfavorable (4 CKD stage II, 3 CKD stage III). Of note 2 patients with CKD had impaired renal function since diagnosis while the remaining 5 progressed gradually during followup. Conclusion WES is useful in dealing with the phenotypic heterogeneity of Bartter syndrome. Our results emphasize the need for early diagnosis, regular followup and appropriate treatment in order to maintain normal renal function and achieve normal final height and weight.

LOW POWER LASER THERAPY AS A COADJUNCT IN THE TREATMENT OF BELL'S PALSY IN POST-PARTUM - CASE REPORT

This case report presents a post-partum woman, three days after delivery, who tasted blood in her mouth, a sensation of a dead tongue, and nasal bleeding. After these symptoms, she also noted paralysis in the left hemiface, difficulties to close the left eye, earaches, and stiffening of the affected hemiface. Herobstetrician subsequently prescribed steroidal anti-inflammatory drugs and referred her to a neurologist, who confirmed the diagnosis of Bell's palsy. She underwent nine sessions of physical therapy; however, only discrete changes were noted. A licensed dentist began a laser therapy protocol as a therapeutic treatment, using low power laser with different wavelengths. The patient underwent weekly sessions, and the protocol varied from 1-3 Joules. The red beam was applied to muscle points and an infrared beam to the nervous facial line. As of the sixth session, facial asymmetry was no longer observed, although she still reported feeling some stiffening in some regions; therefore, an additional 11 sessions were applied to reduce these symptoms. This case report presents a post-partum woman, three days after delivery, who tasted blood in her mouth, a sensation of a dead tongue, and nasal bleeding. After these symptoms, she also noted paralysis in the left hemiface, difficulties to close the left eye, earaches, and stiffening of the affected hemiface. Herobstetrician subsequently prescribed steroidal anti-inflammatory drugs and referred her to a neurologist, who confirmed the diagnosis of Bell's palsy. She underwent nine sessions of physical therapy; however, only discrete changes were noted. A licensed dentist began a laser therapy protocol as a therapeutic treatment, using low power laser with different wavelengths. The patient underwent weekly sessions, and the protocol varied from 1-3 Joules. The red beam was applied to muscle points and an infrared beam to the nervous facial line. As of the sixth session, facial asymmetry was no longer observed, although she still reported feeling some stiffening in some regions; therefore, an additional 11 sessions were applied to reduce these symptoms.

Effects of Intracerebroventricular Injection of the Steroidal and Non-Steroidal Anti-Inflammatory Drugs on the Seizures during the Estrous Cycle in Rat.

Because of the mutual relationship between neural inflammation and seizure, this study aimed to determine the effects of intracerebroventricular (ICV) injection of the steroidal and non-steroidal anti-inflammatory drugs on pentylenetetrazol (PTZ)-induced seizures during the estrous cycle in rats. A total of 105 adult female Wistar rats were selected and divided into seven groups, including the control (saline), ketorolac tris salt (7.5, 15, and 30 µg), and methylprednisolone acetate (0.15, 0.3, and 0.6 µg), each with four subgroups (proestrus, estrus, metestrus, and diestrus) and three replicates (n=5). After a week of acclimatization, the estrous phase determination and synchronization were performed. Acute epilepsy was inspired by the intraperitoneal injection of 80 mg/kg of PTZ 30 min after the ICV injection of ketorolac and methylprednisolone acetate. The initiation time of myoclonic seizures (ITMS), the initiation time of tonic-clonic seizures (ITTS), seizure duration (SD), and mortality rate (MR) were measured for 30 min. Data were shown as mean±SD and analyzed using One-way ANOVA followed by Tukey-Kramer multiple comparison post hoc test (P<0.05). According to the results, ketorolac (15 and 30 µg) and methylprednisolone acetate (0.3 and 0.6 µg) significantly increased the ITTS and ITMS but decreased SD during the estrous cycle, compared to the control (P<0.05). Moreover, MR and SD were significantly decreased by ketorolac (7.5, 15, and 30 µg) and methylprednisolone (0.3 and 0.6 µg), compared to the control during the estrous cycle (P<0.05). Therefore, it seems that both ketorolac and methylprednisolone possess dose-dependent anticonvulsant effects that may decrease neural inflammation.

Comment on: The Effect of Intra-articular Hyaluronic Acid Injections and Payer Coverage on Total Knee Arthroplasty Procedures: Evidence From Large US Claims Database.

Comment on: The Effect of Intra-articular Hyaluronic Acid Injections and Payer Coverage on Total Knee Arthroplasty Procedures: Evidence From Large US Claims Database.

Diclofenac and dexamethasone modulate the effect of cannabidiol on the rat colon motility ex vivo.

Due to the growing interest in the use of cannabinoids in supportive therapies, they are increasingly used together with anti-inflammatory drugs. Cannabinoids inhibit gastrointestinal motility, while steroidal and nonsteroidal anti-inflammatory drugs influence motility in other ways. The aim of the research was to study the interactions between cannabidiol (CBD) and these two classes of anti-inflammatory drugs in the context of gastrointestinal motility. Dexamethasone (DEX) was selected as a steroidal drug and diclofenac (DCF) as a nonsteroidal counterpart. The experiments were performed on isolated rat colon strips in isometric conditions. The contractile response to acetylcholine (ACh) (1 μM) was measured with no substance applied as a control value and was measured after application of CBD (80 μM), DEX (100 μM), DCF (100 μM), or a combination of these substances. Cannabidiol strongly inhibited intestinal motility mediated by ACh application, DCF inhibited it non-significantly, while DEX intensified it. When CBD was co-administered with DEX, the combination inhibited intestinal motility non-significantly relative to the ACh-only control. Co-administration of CBD with DCF inhibited motility more than when these substances were administered separately. Inhibition of the intestinal response to ACh is likely due to the synergistic effect of CBD and endogenous cannabinoids. Dexamethasone lessened the inhibitory effect of CBD, likely because of diminished availability of the arachidonic acid necessary for endogenous cannabinoid synthesis. However, diclofenac may increase endogenous cannabinoid synthesis, because of the greater availability of arachidonic acid caused by DCF blocking the cyclooxygenation pathway.

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.

Anti-inflammatory compounds reduce equine herpesvirus type 1 replication and cell-to-cell spread.

Equine herpesvirus type 1 (EHV-1) is a highly transmissible pathogen that leads to a variety of clinical disease outcomes in infected horses. A major sequela that can occur after an EHV-1 infection is a neurological disease termed equine herpesvirus myeloencephalopathy (EHM). Clinical manifestations of EHM include fever, ataxia, incontinence, and partial to full paralysis, which may ultimately lead to the euthanization of the infected horse. To develop an effective treatment strategy for EHM, it is critical that the specific virus-host interactions that lead to EHM be investigated so that safe and effective therapeutic interventions can be developed and delivered. In this study, we examined the ability of four non-steroidal anti-inflammatory drugs (NSAIDs), a steroidal anti-inflammatory drug (dexamethasone), a Rho-kinase (ROCK) inhibitor, and a JAK/STAT inhibitor (AG490) to reduce EHV-1 virus yields and cell-to-cell spread. We show that the NSAID, flunixin meglumine (FM), and the JAK/STAT inhibitor, AG490, significantly reduced virus yields in endothelial and epithelial cell lines, and this inhibition was similar for two neurologic and two non-neurologic EHV-1 strains. In addition to reducing virus yields, AG490 and FM also significantly reduced the ability of EHV-1 to spread laterally from cell to cell.

P23 A STRANGE CASE OF CERVICALGIA

Abstract 65–year–old patient with a history of Type 2 Diabetes Mellitus on oral hypoglycaemic therapy, hypercholesterolemia, previous diagnosis of non–secreting K–chain micronodular myeloma undergone heterologous marrow transplantation. From January 2022, he presented persistent mild–moderate neck pain and feverish episodes, therefore he started empiric antibiotic therapy at home. Since June 2022, he complained a worsening of the neck pain partially controlled by non–steroidal anti–inflammatories. Magnetic resonance imaging was therefore performed which highlighted findings consistent with spondylitis of probable infectious nature and subsequent start of empiric antibiotic. A bone marrow biopsy was also performed which showed no recurrence of myelopathy. In July 2022 new feverish episode with shaking chills lasting about 3 days. In this circumstance he underwent a blood culture which resulted positive for the presence of Str. Bovis. In addition, a transthoracic echocardiogram was performed and showed evident floating serpiginous vegetation on the anterior mitral leaflet measuring approximately 1.2 cm x 2.5 cm with a mild mitral regurgitation. Targeted antibiotic therapy was set up and abdominal ultrasound and brain MRI were performed which excluded splenic and brain embolization. A close echocardiographic follow–up showed no reduction of the vegetation. So the patient underwent cardiac surgery in thoracotomy to remove the vegetation adhered to the anterior mitral flap in A2 on the atrial side (3 cm x 1.5 cm x 0.5 cm), and also removal of millimetric lesions on the posterior flap and abrasion of the implantation areas. The post–surgery clinical course passed without any complications, the patient remained stably afebrile with a progressive reduction of the inflammation indexes. Approximately 10 days post–surgery, the patient was then discharged with indications for echocardiographic follow–up.

Modeling Early Heterogeneous Rates of Progression in Boys with Duchenne Muscular Dystrophy.

Duchenne muscular dystrophy (DMD) exhibits substantial variability in rates of disease progression and response to treatment. This has hindered treatment development and complicated interpretation of drug effects in clinical trials. We hypothesized that a multivariate combination of early-age clinical outcome measurements can explain differential disease progression. Data on boys with DMD (ages 4-<10 years), both treated with steroidal anti-inflammatories and untreated, were obtained from CINRG Duchenne Natural History Study (n = 209) and vamorolone VBP15-002/003/LTE (n = 46) studies. Velocities from three timed function tests (TFTs; stand from supine, run/walk 10 meters, and climb 4 stairs) were simultaneously modeled in a longitudinal latent class analysis. Three classes of differentially progressing early age DMD motor trajectories were identified. Quicker decline/progression was associated with lower baseline TFT velocities, earlier loss of ability to finish a TFT, and lower predicted velocities. Earlier substantial steroid exposure was associated with greater TFT velocities while the moderate progression class was observed to have the largest difference in performance between boys treated early with steroids vs. not. Sample size calculations with the class showing the largest treatment response showed a large reduction in required sample size as compared to using summaries from all participants. Gene mutations were also investigated in post-hoc analyses, with mutations near the beginning of the DMD gene (Dp427 absent and Dp140/Dp71 present) found to be enriched in the slowest progressing class. This study provides insight into the variation in DMD progression through a latent class analysis. Our findings show class-related trajectories of motor outcomes and pharmacological response to corticosteroids, and suggest that enrichment strategies and/or subgroup analyses could be considered further in design of therapeutic interventions in DMD.

Virtual screening of zinc compounds similar to NSAIDS with better pharmacodynamic and pharmacokinetic profiles

BACKGROUND: Pain is a common symptom that is managed in both outpatients and inpatients. There are many side effects associated with opioids such as respiratory depression, constipation, hyperalgesia, and tolerance. Non- steroidal anti-inflammatory drugs cause gastrointestinal tract (GIT) irritation and may be a risk factor for developing peptic ulcer disease. This study aimed to generate active analgesic agents from known analgesics, determine the docking scores of these agents to their receptors, determine the pharmacokinetic properties of these agents, and evaluate their toxicity profiles. METHODS: PubChem was used to download smiles for ibuprofen, aspirin and celecoxib. Avogadro optimized the ligands. The smiles were copied to SwissSimilarity and were used as query compounds to generate zinc compounds. DrugBank and Protein Data Bank were used to download cyclooxygenase 1 and 2. Molecular docking was done using Chimera and Autodock Vina. Smiles for both query compounds and generated zinc compounds were pasted onto the Protox II webserver and SwissADME for toxicity and pharmacokinetics properties determination. The data was presented in tabular forms with textual descriptions of the contents in the tables. RESULTS: Aspirin, ibuprofen and celecoxib’s zinc compounds were generated and the first 20 compounds were docked to COX-1 and COX-2 enzymes. Seven, one, and four of the docked compounds showed better binding energies to COX-2 than COX-1. The zinc compounds were analyzed for toxicity profiles. ZINC01680731 and ZINC33823423 were predicted to have LD50 of 1240 mg/kg as compared to aspirin’s 250mg/kg. Ibuprofen and ZINC39120409 showed LD50 of 299mg/kg and they were hepatoactive. Celecoxib and four of its zinc compounds showed LD50 of 1400mg/kg. All compounds had high GIT absorption and they conformed with Lipinski rule of five. CONCLUSIONS: ZINC01680731 0.994 and ZINC00600558 0.988 were identified as the best compounds as they showed better binding affinities, toxicities and pharmacokinetics properties compared to standard compounds.

Optical Coherence Tomography-guided intravitreal bevacizumab in the treatment of refractory pseudophakic cystoid macular edema – case study

One of the serious vision threatened complications of cataract surgery is refractory PCME. That is why this complication has to be managed in time and adequately. Non steroidal and steroidal antiinflammatory and anti VEGF agents like bevazicumab are useful for refractory PCME. OCT has an important role in detecting PCME and measurement of central macular thickness to control the treatment of PCME. In this case study patient after rutin uncomplicated FACO surgery with refractory PCME at postop 4-th week is described. Despite of using of topical NSAID+steroidal antiinflammatory treatment there was no improvement in decreased vision and CMT was remained stable increased (811 mmk). Vision was increased only after 2 week of i/v bevazicumab injection, macular edema resolved and CMT decreased (280 mmk) which was revealed by OCT. In conclusion, OCT quided i/v bevacizumab is safe and well tolerated treatment option for refractory PCME.

Anti-inflammatory steroids from the stems of Solanum nigrum L.

Sixteen previously undescribed steroidal sapogenins along with two known ones were isolated from the stems of Solanum nigrum L. (Solanaceae). Their structures were identified using a combination of 1D and 2D NMR, HR-ESI-MS spectroscopy, the Mosher method, and X-ray diffraction analysis. Compounds 1–8 have an unusual F ring and 9–12 have a derived A ring, both of which are rare skeletons found in natural products. The biological evaluation showed that the isolated steroids exhibited inhibition of nitric oxide in the LPS-induced RAW 264.7 macrophages with IC50 values from 7.4 to 41.3 μM. Further studies revealed that compounds 6 and 10 exhibited anti-inflammatory activity by blocking the nuclear translocation of NF-κB, and down-regulating the expression of iNOS, COX-2, IL-1β, and IL-6 in a concentration-dependent manner. These results suggest that the stems of S. nigrum may serve as a source of anti-inflammatory agents for use in healthy or medicinal products.

A Review of Recent Innovations in Cartilage Regeneration Strategies for the Treatment of Primary Osteoarthritis of the Knee: Intra-articular Injections.

The pathology of primary osteoarthritis (OA) begins with structural cartilage damage, which initiates a self-propagating inflammatory pathway that further exacerbates cartilage deterioration. Current standard of care for knee primary OA involves treating the inflammatory symptoms to manage pain, which includes intra-articular (IA) injections of cortisone, an anti-inflammatory steroid, followed by a series of joint-cushioning hyaluronic acid gel injections. However, these injections do not delay the progression of primary OA. More focus on the underlying cellular pathology of OA has prompted researchers to develop treatments targeting the biochemical mechanisms of cartilage degradation. Researchers have yet to develop a United States Food and Drug Administration (FDA)-approved injection that has been demonstrated to significantly regenerate damaged articular cartilage. This paper reviews the current research on experimental injections aimed at achieving cellular restoration of the hyaline cartilage tissue of the knee joint. Narrative review. The authors conducted a narrative literature review examining studies on primary OA pathogenesis and a systematic review of non-FDA-approved IA injections for the treatment of primary OA of the knee, described as "disease-modifying osteoarthritis drugs" in phase 1, 2, and 3 clinical trials. New treatment approaches for primary OA investigate the potential of genetic therapies to restore native cartilage. It is clear that the most promising IA injections that could improve treatment of primary OA are bioengineered advanced-delivery steroid-hydrogel preparations, ex vivo expanded allogeneic stem cell injections, genetically engineered chondrocyte injections, recombinant fibroblast growth factor therapy, injections of selective proteinase inhibitors, senolytic therapy via injections, injectable antioxidant therapies, injections of Wnt pathway inhibitors, injections of nuclear factor-kappa β inhibitors, injections of modified human angiopoietin-like-3, various potential viral vector-based genetic therapy approaches, and RNA genetic technology administered via injections.

Targeted Therapies in Chronic Kidney Disease

About a millions of glomeruli, or filtration units, found in the kidney linked to the tubules where water and solutes from the primary urine are selectively reabsorbed. Both the glomerular and tubular compartments are eventually affected by acute and chronic kidney diseases, but circulating substances like antibodies or cytokines frequently target the glomeruli first. A minimum of three months must pass before there are any abnormalities in renal function in order for the patient to be diagnosed with chronic kidney disease (CKD). Twenty million people in the US have CKD. Despite being a major global health burden, chronic and acute kidney illness still lack effective treatments. Current treatments, like anti-inflammatory steroids, have systemic side effects and cannot halt the disease's development. Although efforts have been made to create renally pursued treatments, no such strategy exhibits yet entered the clinic. At this time, we provide a critical overview of the state of drugs and delivery methods that specifically target the kidneys [1].&#x0D; Functional results fall into two categories: (i) Targeting the kidney causes the renal-to-liver ratio to rise. This is referred to as explicit targeting; (ii) the medication accumulates more in the kidneys while the kidney verses liver proportion stays the same, which allows the carrier to boost uptake generally. Overall, targeting that was focused on receptors and transporters was the most successful. The biggest task for nanoparticulate formulations is to reach glomerular cells and prevent liver accumulation [2].&#x0D; Long-term contact with a carrier may be necessary to treat chronic kidney illnesses. Evidence on frequency, quantity, and application as well as the kinetics of degradation must be converted crazy about kinetic models of degradation and uptake in order to determine whether possibly lethal accumulation is to be predictable for decomposable polymers.

In-Vitro Anti-inflammatory Activity of Traditionally reported Poly Herbal Combination

Inflammatory diseases are still one of the most important heath-problems in the world. Most of anti-inflammatory drugs such as non–steroidal anti-inflammatory drugs (NSAIDS) have number of adverse effects hence there are a need to develop safe and new anti-inflammatory formulation with minimum side effects. Present study focused on investigating and comparing anti-inflammatory potential of hydroalcoholic extracts of Tinospora cordifolia, Boerhavia diffusa, Tribulus terrestris and their combinations. Inhibition of heat induced HRBC membrane lysis was taken as a measure of the anti-inflammatory activity. The combination ratio of hydroalcoholic extracts of Tinospora cordifolia, Boerhavia diffusa, Tribulus terrestris (2:5:3) showed the most significant membrane stabilizing action on HRBC membrane as compare tohydroalcoholic extracts of individual drugs and theirother combinations. The present study revealed that the proper combination of Tinospora cordifolia, Boerhavia diffusa, Tribulus terrestris gives more effective anti-inflammatory activity than any of the individual drug.

Transition metal(II) complexes with the non–steroidal anti–inflammatory drug oxaprozin: Characterization and biological profile

A series of copper(II), nickel(II) and cobalt(II) complexes with the non–steroidal anti–inflammatory drug oxaprozin (Hoxa) have been synthesized and characterized by diverse techniques. The crystal structures of two copper(II) complexes, namely the dinuclear complex [Cu2(oxa)4(DMF)2] (1) and the polymeric complex {[Cu2(oxa)4]·2MeOH·0.5MeOH}2 (12) were determined by single–crystal X–ray diffraction studies. In order to evaluate in vitro the antioxidant activity of the resultant complexes, their scavenging ability towards 1,1–diphenyl–picrylhydrazyl (DPPH), hydroxyl and 2,2′–azinobis(3–ethylbenzothiazoline–6–sulfonic acid) (ABTS) radicals was investigated revealing their high effectiveness against these radicals. The binding of the complexes to bovine serum albumin and human serum albumin was examined and the corresponding determined albumin–binding constants showed a tight and reversible interaction. The interaction of the complexes with calf–thymus DNA was monitored by diverse techniques including UV–vis spectroscopy, cyclic voltammetry, DNA–viscosity measurements and competitive studies with ethidium bromide. Intercalation may be proposed as the most possible DNA–interaction mode of the complexes.

Extracellular vesicles and their cells of origin: Open issues in autoimmune diseases.

The conventional therapeutic approaches to treat autoimmune diseases through suppressing the immune system, such as steroidal and non-steroidal anti-inflammatory drugs, are not adequately practical. Moreover, these regimens are associated with considerable complications. Designing tolerogenic therapeutic strategies based on stem cells, immune cells, and their extracellular vesicles (EVs) seems to open a promising path to managing autoimmune diseases' vast burden. Mesenchymal stem/stromal cells (MSCs), dendritic cells, and regulatory T cells (Tregs) are the main cell types applied to restore a tolerogenic immune status; MSCs play a more beneficial role due to their amenable properties and extensive cross-talks with different immune cells. With existing concerns about the employment of cells, new cell-free therapeutic paradigms, such as EV-based therapies, are gaining attention in this field. Additionally, EVs' unique properties have made them to be known as smart immunomodulators and are considered as a potential substitute for cell therapy. This review provides an overview of the advantages and disadvantages of cell-based and EV-based methods for treating autoimmune diseases. The study also presents an outlook on the future of EVs to be implemented in clinics for autoimmune patients.