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SARS-CoV-2 is a type of beta-CoV that develops acute pneumonia, which is an inflammatory condition. A cytokine storm has been recognized as one of the leading causes of death in patients with COVID-19. ALI and ARDS along with multiple organ failure have also been presented as the consequences of acute inflammation and cytokine storm. It has been previously confirmed that SARS-CoV, as another member of the beta-CoV family, activates NLRP3 inflammasome and consequently develops acute inflammation in a variety of ways through having complex interactions with the host immune system using structural and nonstructural proteins. Numerous studies conducted on Tranilast have further demonstrated that the given drug can act as an effective anti-chemotactic factor on controlling inflammation, and thus, it can possibly help the improvement of the acute form of COVID-19 by inhibiting some key inflammation-associated transcription factors such as NF-κB and impeding NLRP3 inflammasome. Several studies have comparably revealed the direct effect of this drug on the prevention of inappropriate tissue's remodeling; inhibition of neutrophils, IL-5, and eosinophils; repression of inflammatory cell infiltration into inflammation site; restriction of factors involved in acute airway inflammation like IL-33; and suppression of cytokine IL-13, which increase mucosal secretions. Therefore, Tranilast may be considered as a potential treatment for patients with the acute form of COVID-19 along with other drugs.

Choisya ternata Kunth (Rutaceae) is native to North America where it is popularly known as "Mexican orange". In this study, the anti-inflammatory effects of the essential oil (EO) obtained from the leaves of C. ternata, one of its minor components (ternanthranin-ISOAN) and its two synthetic analogues (methyl and propyl N-methylanthranilate--MAN and PAN) were evaluated. Mice pretreated with the EO (EO) obtained from C. ternata leaves (3-100 mg/kg, p.o.), ISOAN, MAN or PAN (1-30 mg/kg, p.o.) and the reference drugs, morphine (1 mg/kg, p.o.) and acetylsalicylic acid (ASA, 100 mg/kg, p.o.), were evaluated in inflammation models such as formalin and subcutaneous air pouch models, with measurement of cell migration, exudate volume, protein extravasation, nitric oxide and pro-inflammatory cytokines. The EO from C. ternata significantly inhibited the time that the animals spent licking the formalin-injected paw in the second phase of the model at their higher doses (30 and 100 mg/kg, respectively). An inhibition of the inflammatory reaction induced after subcutaneous carrageenan injection into air pouch was also observed. In this model, the EO significantly reduced cell migration, exudate volume, protein extravased, and the increase in levels of inflammatory mediators (nitric oxide, TNF-α and IL-1β). ISOAN, MAN and PAN behaved in the same fashion at much smaller doses. Also, these molecules were able to show significant effects in the reduction of paw edema (at all tested doses) when the phlogistic agent was carrageenan, bradykinin, 5-HT, PGE2, C48/80 or 12-O-tetradecanoylphorbol-acetate (TPA). None of the tested doses had any effect in reducing histamine-induced edema. Our results indicate that the EO from C. ternata and anthranilate derivatives demonstrates an anti-inflammatory effect.

During aging, chronic systemic inflammation increases in prevalence and antioxidant balance shifts in favor of oxidant generation. Avenanthramide (AVA) is a group of oat phenolics that have shown anti-inflammatory and antioxidant capability. The present study investigated whether dietary supplementation of avenanthramides (AVA) in oats would increase antioxidant protection and reduce inflammation after a bout of downhill walking (DW) in postmenopausal women. Women at age of 50-80 years (N = 16) were randomly divided into two groups in a double-blinded fashion, receiving two cookies made of oat flour providing 9.2 mg AVA or 0.4 mg AVA (control, C) each day for 8 weeks. Before and after the dietary regimen, each group of subjects walked downhill on a treadmill (-9% grade) for 4 bouts of 15 minutes at a speed of 4.0 km/h with 5 minutes rest between sessions. Blood samples were collected at rest, 24 h post-DW, and 48 h post-DW pre- and post-supplementation. Both DW sessions increased plasma creatine kinase activity (P < 0.05). Before supplementation, in vitro neutrophil respiratory burst (NRB) activity was increased at 24 h post-DW (P < 0.05) and C-reactive protein (CRP) was increased 48 h post-DW (P < 0.05). AVA supplementation decreased DW-induced NRB at 24 h (P < 0.05) and CRP level 48 h (P < 0.05). Plasma interleukin (IL)-1β concentration and mononuclear cell nuclear factor (NF) κB binding were suppressed at rest and during post-DW period in AVA but not C group (P < 0.05). Plasma total antioxidant capacity (P < 0.05) and erythrocyte superoxide dismutase activity were increased in AVA vs. C (P < 0.05), whereas glutathione redox status was elevated 48 h post-DW but not affected by AVA. Thus, chronic AVA supplementation decreased systemic and DW-induced inflammation and increased blood-borne antioxidant defense in postmenopausal women.

Tranilast (TL), an antiallergic agent, has been clinically used in the treatment of bronchial asthma, although its clinical use has been limited by its poor solubility in water, photodegradation and systemic side effects. In this study, we prepared a gel ointment containing TL nanoparticles (TLnano gel ointment), and investigated its usefulness. In addition, we demonstrated the preventive effects of the TLnano gel ointment on inflammation in adjuvant-induced arthritis (AA) rats. The TLnano gel ointment was prepared using Bead Smash 12 (a bead mill) and additives including sodium docusate, 2-hydroxypropyl-β-cyclodextrin, methylcellulose and Carbopol 934; the mean particle diameter of the TL nanoparticles was 71.0±25.4 nm. In in vitro skin penetration experiments, the amount of penetrated TL, the penetration rate (Jc) and the penetration coefficient through the skin (Kp) of the TLnano gel ointment were significantly higher than those of a gel ointment containing TL microparticles (TLmicro gel ointment; particle diameter 50.5±26.3 µm). The TL concentrations in the skin tissue and plasma of rats receiving the TLnano gel ointment were also higher than in rats receiving the TLmicro gel ointment. In addition, the application of the TLnano gel ointment attenuated the increase in paw edema of the hind feet of AA rats in comparison with AA rats treated with the TLmicro gel ointment. These results suggest that TL nanoparticles can be applied to the formulation of a transdermal system, and that a transdermal formulation using TL nanoparticles might be a delivery option for the clinical treatment of RA.

Aims/hypothesis: A key morphological feature of diabetic nephropathy is the accumulation and deposition of glycogen in renal tubular cells, known as Armanni-Ebstein lesions. While this observation has been consistently reported for many years, the molecular basis of these lesions remains unclear., Methods: Using biochemical and histochemical methods, we measured glycogen concentration, glycogen synthase and glycogen phosphorylase enzyme activities, and mRNA expression and protein levels of glycogenin in kidney lysates from control and transgenic (mRen-2)27 rat models of diabetes that had been treated with and without a new anti-fibrotic agent, FT011., Results: Diabetic nephropathy was associated with increased glycogen content, increased glycogen synthase activity and decreased glycogen phosphorylase activity. Glycogenin, the key protein responsible for initiating the synthesis of each glycogen particle, had very high levels in the diabetic kidney together with increased mRNA expression compared with control kidneys. Treatment with FT011 did not change glycogen synthase or glycogen phosphorylase enzyme activities but prevented both glycogenin mRNA synthesis and accumulation of Armanni-Ebstein lesions in the diabetic kidney., Conclusions/interpretation: Armanni-Ebstein lesions found in diabetic nephropathy are due to aberrant glycogenin protein levels and mRNA expression, providing an explanation for the increased glycogen concentration found within the diabetic kidney. FT011 treatment in diabetic rats reduced glycogenin levels and, subsequently, renal glycogen concentration.

The treatment of coronary artery disease has reached many milestones - from balloon angioplasty to drug-eluting stents. The last decade witnessed the revolution of bare metal stents with new designs, alloys and strut thicknesses. Yet restenosis, the aphorismic 'Achilles heel', remains to be conquered. The restenosis rates with balloon angioplasty alone are 30-40% and are reduced to 20-30% with stents. Although intravascular brachytherapy proved to be a durable and safely used technique to treat in-stent restenosis, clinical event rates were not reduced to single digits.Drug-eluting stents are showing positive results in this direction, but it is too early to predict their efficacy in various subsets of lesions. With the increased usage of these stents, there are reports of problems such as late stent malapposition, subacute and late thromboses, and aneurysm formations due to the vessel toxicity associated with this method of treatment. Furthermore, when multivessel stenting is considered, the cost of drug-eluting stents is a significant problem given the fact that these are no longer 'zero restenosis' devices. There is a definite need for a simple, safe and durable solution to restenosis. Oral agents are an alternative delivery strategy that can target multiple coronary lesions, which are targets for catheter-based revascularisation with any approved metal stent and with potentially lower cost. Although oral agents have been an interesting option to treat restenosis and several agents have been tested in trials since the 1980s, the results were disappointing. The development of devices such as intravascular ultrasound has led to a greater understanding of restenosis mechanisms, and the focus on pathophysiological mechanisms, which centred mainly on platelets, growth factors and lipids, has changed to inflammation, endothelium and smooth muscle cell proliferation.Accordingly, the targets of pharmaceutical agents have shifted from platelets to cell cycle inhibition, smooth muscle cell proliferation and migration, synthesis of extra cellular matrix, and inflammatory mediators. Initial encouraging results with oral drugs such as cilostazol, sirolimus (rapamycin) and thiazolidinediones indicate a definite place for this strategy to reduce restenosis. A desirable oral agent would be anti-inflammatory, inhibit smooth muscle cell migration and proliferation, promote endothelial growth, and be well tolerated and free from significant adverse effects. It may be useful to start with a high loading dose before stent implantation and then follow with a short-term lower maintenance dose. Future trials should be aimed at finding an ideal agent, effective loading dose, maintenance dose and optimum duration of therapy.

Background and Objectives: Triptans are effective drugs for the acute treatment of migraine. However, 30-40% of the patients commonly present recurrence before 24 hours therefore requiring another dose. Nonsteroidal anti-inflammatory drugs (NSAID) such as tolfenamic acid and naproxen sodium combined with sumatriptan have demonstrated efficacy in reducing recurrence observed with the single use of this drug. Steroids also have been suggested to treat refractory migraine and status migranosus. The aim of this study was to evaluate whether patients presenting frequent recurrence with the combination triptan plus NSAID, would decrease it with the association of dexamethasone., Method: Twenty three patients, 17 women and 6 men with migraine according to IHS criteria were prospectively studied. All patients presented frequent recurrence (> or= 60%, mean recurrence rate 74,8%) with the single use of sumatritpan 100 mg or zolmitriptan 2,5 mg or rizatriptan 10mg in at least 5 consecutive attacks, and didn't present a reduction of the recurrence rate superior than 20% with the combination of tolfenamic acid 200 mg or rofecoxib 25 mg in at least 5 other consecutive attacks (mean recurrence rate 60%). The patients had to treat 6 consecutive moderate or severe migraine attacks with their usual combination plus 4 mg of dexamathasone with a maximum of twice a week, and fill out a diary reporting headache parameters., Results: Twenty patients, 16 women and 4 men completed the study. Of those who completed the study, 11 took rizatriptan plus rofecoxib, 4 rizatriptan plus tolfenamic acid, 3 zolmitriptan plus rofecoxib, 1 zolmitriptan plus tolfenamic acid and 1 patient took sumatriptan plus tolfenamic acid, having the 20 patients taken as a third medication, a single tablet of 4 mg of dexamethasone. All patients took oral formulations and none presented vomiting after that. Among all 20 patients, one female and one male patient presented recurrence in 3 out of the 6 attacks (50%) while the remaining 18 patients revealed recurrence in 1 or 2 treated attacks (mean 23,4%) (p<0,001)., Conclusion: We concluded that the judicious use of oral dexamethasone might be useful for a limited population of migraine patients still presenting recurrence with the combination of a triptan and a NSAID. Case-control studies and studies with a randomized double-blind design are necessary to confirm these observations.

The effects of anti-rheumatic drugs (lobenzarit (CCA); 10 and 50mg/kg, cyclophosphamide (CP); 5 mg/kg and dexamethasone (DM); 0.25mg/kg) were evaluated immunologically and histopathologically on DBA/1J mice that develop polyarthritis after immunization by the intradermal injection of type II collagen. Serum anti-type II collagen IgG levels in the groups treated with CP and DM were significantly suppressed to 1/2 and 1/10 as compared to those of the positive control group, respectively. Those of both groups treated with CCA were not different from those of the positive control group. Histopathological examination revealed that treatment with CP and DM markedly reduced or suppressed inflammatory changes and resulted in low incidence of arthritis. From the standpoint mentioned above, treatment with anti-rheumatic drugs suppressed the development of arthritis in this model, and we could confirm that this model was useful for evaluation of the effect of anti-rheumatic drugs.

The effect of 9 nonsteroidal anti-inflammatory drugs on the renal excretion of uric acid was studied in patients with normal renal function. Diflunisal, Azapropazone and Indomethacin caused an increase and Piroxicam a decrease in the uric acid excretion. Other drugs studied had no significant influence.

In the face of deficiencies in our present system of introducing new drugs, clinicians must be committed to monitoring patients carefully. They must not be caught up in the hyperbole and excitement of the latest new drug, but instead should allow the crucible of time to teach them and the rest of the medical community the ultimate truths about this drug in all situations. They must not let the package circular be their only guide to therapy, for it reflects only what has been accomplished under limited conditions. By knowing their patients well and by learning to proficiently use selected drugs that they have become familiar and comfortable with, conscientious practitioners will approach the present state of the art in meeting the needs of their patients.

Cutaneous reactions to medications probably represent the most common manifestation of drug reactions. The diversity of cutaneous eruptions produced by drugs provide a challenge in searching for the mechanisms producing the reaction. Many eruptions are due to a form of allergic hypersensitivity, while others may be idiosyncratic, due to a metabolic abnormality, or represent a cumulative phenomenon. This article discusses the diagnosis of drug-induced cutaneous reactions by reviewing specific drugs commonly used in rheumatologic therapy.

The elimination of ionized urinary fluorine was studied in groups of eight subjects treated during several days with niflumic acid, flufenamic acid, sulindac, antrafenine and floctafenine. Sulindac and floctafenine do not changes this elimination. After administration of niflumic acid, flufenamic and antrafenine, the urinary elimination of ionized fluorine increase in all the subjects. This increase is manifested from the start of treatment and persists for several days after it has been stopped. The administration of three drugs also results in an elevated level of ionized plasmic fluorine the duration of treatment. The results prove the existence in the human organism of a metabolic process capable of effecting the ionization of the organic fluor contained in the drugs studied. This biotransformation causes a fluorine impregnation of endogenous origin that is permanent and relatively stable, and whose consequences are examined (risk of fluorine osteosis and possibility of therapeutic application).

Etoclofene, the ethoxy methyl ester of N-(2,6-dichloro-m-tolyl)anthranilic acid, showed potent anti-inflammatory, anti-pyretic and peripheral analgesic activity in several experimental models of inflammation. There was no evidence of adrenal dependence or corticoid-like effects at effective and non-toxic dose levels. Etoclofene showed a low level of toxicity and was well tolerated in animals.

A double-blind crossover study compared sodium meclofenamate (300 mg daily) and ibuprofen (900 mg daily) in thirty patients with osteoarthritis. Each treatment period was of 3 weeks duration. Both drugs were effective in reducing the severity of joint symptoms and in improving the range of motion, with the exception of spine movement which did not show any changes from the baseline. Tolerance was good.

Floctafenine has been studied in comparison with acetyl-salicylic acid, indomethacin and d-propoxyphene in a series of tests for analgesic and anti-inflammatory activity. It is very active in the acetic acid-induced writhing test and on the inflamed paw in the Randall and Selitto test. Furthermore, like acetylsalicylic acid and indomethacin, but unlike d-propoxyphene, it has no effect on the non-inflamed paw, and similarly it is inactive in the tail flick and in the hot plate test. Floctafenine is also very effective in some acute inflammations such as naphtoylheparamine-induced oedema or in UV erythema, but it is distinctly less active in carrageenin-induced oedema or in adjuvant arthritis. In rat gastric and intestinal mucosa its tolerance is excellent. It has no action on the central and autonomous nervous systems. The pharmacological profile of this compound thus places it amongst the non-narcotic analgesics. It has an exceptionally high therapeutic index, much higher than that of acetylsalicylic acid and indomethacin.

The analgesic effect of 10 anti-inflammatory drugs was compared using a single-blind method in 90 patients with rheumatoid arthritis. Each patient received two different drugs, for three days each and each drug was evaluated in 18 patients. After the trial, the patients considered which of the drugs they preferred. The greatest relief from pain was achieved by diclofenac, indomethacin, naproxen and tolfenamic acid, each of these being preferred by the majority of patients and being significantly (p less than 0.01) better than the least effective drugs ketoprofen and proquazone. Acetylsalicylic acid, azapropazone, carprofen and ibuprofen were considered intermediate in efficacy.

The physiology of primary dysmenorrhea and its treatment with nonsteroidal anti-inflammatory agents are reviewed. Primary dysmenorrhea involves incapacitating pelvic pain associated with nausea, vomiting, and diarrhea. Currently, it is thought to be caused by an overproduction of prostaglandins that are released as the endometrium degenerates. Since the nonsteroidal anti-inflammatory agents are one class of antiprostaglandin agents, they are frequently prescribed for the relief of dysmenorrhea. Naproxen and naproxen sodium have both been shown to be superior to placebo in subjective and objective assessments of dysmenorrheic patients when administered at the onset of symptoms. Indomethacin studies demonstrate its efficacy over placebo, but the frequency of side effects at the doses used (25-50 mg t.i.d.) diminish its usefulness. Few placebo-controlled studies have been published on ibuprofen, but the studies that have been performed show that ibuprofen is more beneficial than placebo for treating dysmenorrhea with a low incidence of side effects. The fenamates appear to be effective in dysmenorrhea, although they were not studied extensively with placebo and previous experience with mefenamic acid has led to warnings about side effects. Phenylbutazone and oxyphenbutazone have been found to be effective; however, their use has been less frequent since the introduction of the newer less toxic nonsteroidal agents. Comparative studies of the nonsteroidal anti-inflammatory agents have not indicated that one agent is more effective than the others. Until further well-controlled comparative research is performed, any of the agents reviewed would be an appropriate choice in the treatment of primary dysmenorrhea.

The effects of one-day treatment with nine nonsteroidal anti-inflammatory drugs and prednisolone on human synovial fluid concentrations of prostanoids were studied. The doses were calculated so as to be approximately equipotent according to clinical experience and the recommendations of the manufacturers. Most of the drugs used reduced clearly PGE2 and TxB2 levels in synovial fluid, but only a slight diminution in 6-keto-PGF1 alpha values was found. Carprofen, diclofenac, indomethacin, naproxen and tolfenamic acid reduced significantly the synovial fluid PGE2 concentrations. Diclofenac and indomethacin also reduced significantly the synovial TxB2 concentrations.