Experimental inflammation of the joints of ankles and feet in rats ('polyarthritis') can be induced by local injections of irritants ( 1 ) , or by remote injections of systemically active agents such as micro-organisms( l-s), hormones ( 1 ) , or immunological agents ( 1,6-9) .We have not found in the literature any report of an orally active agent. Inflammation of the periarticular connective tissue of ankles and feet in rats following oral administration of 6-sulfanilylindazole was originally observed by T. J. Becker and J. 0. Hoppe at this Institute during a routine toxicity test (unpublished) in 1946. This. report describes the pathology and pathogenesis of this phenomenon. &faterials and methods. Male albino Sprague-Dawley rats weighing 100, 300, or 500 g were used. A total of 445 rats were medicated with 6-sulfanilylindazole ( designated as SAI hereafter) by gavage 6 times weekly for various periods. The doses were 62.5, 125, 250, or 500 mg/kg given as a suspension in 1% gum tragacanth. Twelve rats received SAI subcutaneously at 125 mg/kg, and 61 control rats received the gum tragacanth vehicle by gavage.Inflammation was recorded daily by measuring the width of the ankles (distance from lateral to median malleoli). The rats were sacrificed and autopsied at various intervals from the 5th to the 36th days of medication. Feet and portions of the major organs were processed for microscopic examination.To determine whether the SAI induced inflammation was species-specific, SAI was also administered by gavage to mature male rhesus monkeys (Macaca mulatta) and to mature male albino Swiss mice. The doses of SAI were 62.5, 125, and 250 mg/kg; each dose was administered to 3 monkeys 25 times in 29 days, and to 10 mice 18 times in 21 days. Control groups of 4 monkeys and 10 mice received only the vehicle, 1% gum tragacanth. All animals were observed daily for changes in appearance and behavior. Blood urea nitrogen determinations were done on monkeys weekly as an indicator of kidney toxicity due to the sulfonamide. All mice that died during the experiment were autopsied.Subcutaneous connective tissue of feet and cardiac blood from 3 rats with inflamed feet and 3 control rats were cultured for bacteria and PPLO ( pleuropneumonia-like organisms). Blood-agar plates, beef heart broth, and thioglycollate broth were used for bacteriological cultures, and pancreatic digest medium ( 10) containing 2 5 % sterile normal horse serum was used for PPLO cultures. PPLO growths were identified when stained according to Dienes' method ( 1 1 ) .

BACKGROUND: Programmatic management of TB infection is a critical component of the WHO End TB Strategy. Interferon-gamma release assays (IGRAs) overcome some limitations of the tuberculin skin test, but implementation of IGRA testing in low-resource settings is challenging.METHODS: In this feasibility study, we evaluated performance of a novel digital lateral-flow assay, the QIAreach® QuantiFERON® TB (QIAreach-QFT) test, against the QuantiFERON®-TB Gold Plus (QFT-Plus) assay. A population with a mix of risk factors for TB infection (111 donors) were sampled over multiple days. A total of 207 individual blood samples were tested according to the manufacturer´s instructions.RESULTS: The overall percentage agreement was 95.6% (two-sided 95% CI 91.8–98), with a positive percentage agreement (i.e., sensitivity) of 100% (95% CI 94.7–100) and a negative percentage agreement (i.e., specificity) of 95.6% (95% CI 90.6–98.4). All QFT-Plus positive specimens with TB1-Nil and TB2-Nil values less than 1 IU/ml tested positive on QIAreach-QFT.CONCLUSIONS: QIAreach QFT is a deployable, accurate testing solution for decentralised testing. It has the potential to overcome key hurdles for TB infection screening in high-burden settings thus helping to achieve the WHO End TB programme goals.

Recent evidence suggests that fibronectin (Fn), a high molecular weight glycoprotein, may be used as an indicator protein in rats with adjuvant‐induced arthritis. Rocket immunoelectrophoresis, using purified goat anti‐rat Fn, provided a specific and sensitive means of measuring plasma Fn in rats during the development of various inflammatory disease states. It was shown that normal rat plasma Fn levels of approximately 400 μg/ml double within 24 hours after injection of adjuvant. Plasma Fn levels in this model of chronic systemic inflammatory joint disease were tracked for more than 4 months and remained significantly higher than normal. On the other hand, a carrageenan‐induced inflammatory response in the pleural cavity of rats resulted in a large local accumulation of leukocytes, but no change in plasma Fn levels. A carrageenan‐induced model of acute inflammation resulted in increased paw swelling within 6 hours and enhanced plasma Fn levels within 24 hours; plasma Fn levels returned to normal within 1 week. Quantitation of plasma Fn levels in the rat may provide a useful biochemical parameter for the study of chronic systemic inflammatory diseases.

The sizes of passive cutaneous anaphylaxis (PCA) reactions, mediated by reagin or hyperimmune antibodies, were directly related to the degree of sensitization and, to a lesser degree, to the dose of the challenging antigen. Inhibition by anti-anaphylactic drugs of both types of PCA was inversely related to the degree of sensitization. Anti-anaphylactic drugs shifted the diameter-antibody concentration slopes to the region of higher antibody concentration in a parallel manner which suggests a possible competitive nature of the inhibitory mechanisms of these drugs. Disodium cromoglycate and methysergide were effective against reagin-mediated PCA but they were ineffective against hyperimmune antibody-mediated PCA. Then-yldiamine and chlorpheniramine had marginal activities against both PCA systems. Aminophylline was effective against both systems and it had similar potencies and efficacies against both types of PCA. Three β-adrenergic sympathomimetic drugs were more efficacious against hyperimmune antibody-mediated PCA than against reagin-mediated PCA.

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Oxarbazole, 9-benzoyl-2,3,4,9,-tetrahydro-6-methoxy-1H-carbazole-3-carboxylic acid, inhibited bronchoconstriction induced by a crude SRS-A preparation or by bradykinin in dose-related manner in anesthetized guinea pigs. Oxarbazole was ineffective against bronchoconstriction induced by histamine, carbachol, serotonin, or PGF_2α. Inhibition of bronchoconstriction induced by the crude SRS-A preparation by oxarbazole was unimpeded by the presence of β-adrenergic- or cholinergic-blocking agents, but it could be overcome by increased doses of the crude SRS-A preparation.

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Bronchoconstriction was induced in nonsensitized dogs by intravenous injections of soluble immune complexes. Immune complex-induced bronchoconstriction was associated with a drop in blood pressure and a drop in the circulating complement levels. Different antiasthmatic agents were compared for their effects in dogs against bronchoconstriction induced by intravenous injections of immune complexes or histamine. Bronchodilators (isoproterenol, aminophylline, and bitolterol) inhibited both types of bronchoconstriction, whereas disodium cromoglycate, prednisone, and oxarbazole inhibited only bronchoconstriction induced by immune complexes. Thenyldiamine and atropine inhibited histamine- and carbachol-induced bronchoconstriction, respectively, but they were ineffective at the same doses against immune complex-induced bronchoconstriction.