Polyhalide derivatives of poly[N-(2-aminoethyl)-acrylamido]triethylammonium resins as iodinating reagents

Poly[N-(2-aminoethyl)acrylamido]triethylammonium dichloroiodate, tetrachloroiodate and dibromoiodate resins have been developed as a new class of heterogeneous reagents. The use of the polyhalide derivatives for the selective iodination of aromatic amines and phenols is described. The influence of the various reaction parameters including nature of the solvent, effective molar concentration of the reagent and temperature were investigated to find out the optimum reaction conditions for achiveing selectivity for monoiodination.     

Tremorogenesis by physostigmine is unrelated to acetylcholinesterase inhibition: evidence for serotoninergic involvement

Studies were performed to bring out a serotoninergic involvement in physostigmine tremor, hitherto known to be working via the cholinergic system. 5-Hydroxytryptamine (5-HT) was estimated fluorimetrically after isolation on Sephadex G-10 and acetylcholinesterase (AChE) was assayed spectrophotometrically. The dose-dependent tremor was quantified by a double-blind study. No correlation (r = 0.01) existed between tremor and AChE inhibition since the non-tremoring dose of physostigmine caused the same degree of enzyme inhibition. An increase of 5-HT was found to be correlated (r = 0.59) with the duration and intensity of tremor. Cholinergic antagonists atropine (2 and 5 mg/kg, i.p.), scopolamine (0.5, 1.0, 2.0 mg/kg, i.p.) and mecamylamine (1 mg/kg, i.p.) failed to block the tremor while the 5-HT antagonists methysergide (5 mg/kg, i.v.) and cyproheptadine (10 and 30 mg/kg, s.c.) could afford more than 60% protection. These results suggest a serotoninergic rather than a cholinergic component in the genesis of physostigmine tremor.     

Use of cuprous ion and metallic copper as initiators of aqueous vinyl polymerization

Cuprous chloride and copper powder (in acid media) initiate the aqueous polymerization of certain vinyl monomers such as methyl methacrylate, ethyl methacrylate, methacrylic acid and styrene but it fails in case of acrylonitrile, methyl acrylate, and acrylic acid under identical conditions. Catalyst exponent of this initiator (in acid aqueous media) with respect to methyl methacrylate is 0.38. Quantitative determination of end-groups by dye techniques of the polymers obtained shows that about 2 hydroxyl end-groups per chain are present under acidic conditions in presence of slight traces of oxygen but in rigorous absence of oxygen, very little OH end-groups are found incorporated. The mechanism of initiation under different experimental condition is discussed.     

Prognostic performance of clinical assessment tools following hip fracture in patients with chronic kidney disease

International Urology and Nephrology - People living with chronic kidney disease (CKD) are at a higher risk of hip fracture with an associated increased mortality risk compared to individuals...     

Bile Salt–Fatty Acid Mixed Micelles as Nasal Absorption Promoters of Peptides. I. Effects of Ionic Strength,Adjuvant Composition,and Lipid Structure on the Nasal Absorption of [D-Arg2]Kyotorphin

Bile salts and synthetic surfactants have been used to promote nasal absorption of peptide drugs. Although a marked increase in nasal absorption has been achieved, this may not be adequate and the possibility of adjuvant-induced membrane toxicity exists. The present study employs a rat in situ nasal perfusion technique and mixed micelles between sodium glycocholate (NaGC) and various lipids as potential nasal absorption enhancers of a stable model dipeptide, [D-Arg²]kyotorphin. NaGC alone enhanced the nasal absorption of the dipeptide in a concentration-dependent manner. When linoleic acid was added to form mixed micelles with NaGC, the absorption was further enhanced (P < 0.01). The effect of mixed micelles was synergistic and much greater than with single adjuvants. Increasing ionic strength was found to increase the adjuvant activity of both NaGC and NaGC–lipid mixed micelles. Structure of the lipid component of the mixed micelles also affected the adjuvant potency. Oleic acid, a cis-unsaturated fatty acid, was more effective than elaidic acid, the trans-isomer, whereas cis-linoleic acid and trans-linolelaidic acid were equally effective ( = 0.05). Mixed micelles of mono-glycerides such as monoolein and monolinolein were also more effective than NaGC alone ( = 0.05). Micellar solubilization of these polar lipids by NaGC appears to be important for nasal absorption enhancement to occur. Reversal of the membrane permeability was also observed within approximately 20–40 min after removal of the adjuvants from the rat nasal cavity. These observations are similar to the effects of mixed micelles on the rectal mucosa and may involve the same mechanism.     

T-cell signature cytokines distinguish pulmonary sarcoidosis from pulmonary tuberculosis

Sarcoidosis is a systemic inflammatory disorder characterized by tissue infiltration due to mononuclear phagocytes and lymphocytes and associated noncaseating granuloma formation. Pulmonary sarcoidosis (PS) shares a number of clinical, radiological, and histopathological characteristics with that of pulmonary tuberculosis (PTB). Due to this, clinicians face issues in differentiating between PS and PTB in a substantial number of cases. There is a lack of any specific biomarker that can diagnose PS distinctively from PTB. We compared T-cell-based signature cytokines in patients with PS and PTB. In this study, we proposed a serum biomarker panel consisting of cytokines from cells: T helper (Th) 1 [interferon-gamma (IFN-γ); tumor necrosis factor-alpha (TNF-α)], Th9 [interleukin (IL)-9], Th17 [IL-17], and T regulatory (Treg) [IL-10; transforming growth factor-beta (TGF-β)]. We performed the principal component analysis that demonstrated that our serum cytokine panel has a significant predictive ability to differentiate PS from PTB. Our results could aid clinicians to improve the diagnostic workflow for patients with PS in TB endemic settings where the diagnosis between PS and PTB is often ambiguous.     

Mechanistic insight of interleukin-9 induced osteoclastogenesis

Interleukin (IL)-9 is an emerging player in the pathogenesis of various chronic inflammatory diseases including bone disorders like rheumatoid arthritis (RA) and psoriatic arthritis. Recently, IL-9 was shown to enhance the osteoclast formation and their function in RA. However, the mechanisms by which IL-9 influences osteoclastogenesis are not known. Therefore, in this study we aimed to unravel the direct and indirect ways by which IL-9 can influence osteoclast formation. We used mouse bone marrow precursor cells for checking the effect of IL-9 on osteoclast differentiation and its function. Next, IL-9 induced signalling pathway were checked in the process of osteoclastogenesis. T cells play an important role in enhancing osteoclastogenesis in inflammatory conditions. We used splenic T cells to understand the impact of IL-9 on the functions of T effector (Teff) and regulatory T (Treg) cells. Furthermore, the effect of IL-9 mediated modulation of the T cell response on osteoclasts was checked using a coculture model of T cells with osteoclast precursors. We showed that IL-9 enhanced osteoclast formation and its function. We found that IL-9 activates STAT3, P38 MAPK, ERK1/2, NFκB and we hypothesize that it mediates the effect on osteoclastogenesis by accelerating mitochondrial biogenesis. Additionally, IL-9 was observed to facilitate the functions of pro-osteoclastogenic IL-17 producing T cells, but inhibits the function of anti-osteoclastogenic Treg cells. Our observations suggest that IL-9 can influence osteoclastogenesis directly by modulating the signalling cascade in the precursor cells; indirectly by enhancing IL-17 producing T cells and by reducing the functions of Treg cells.     

Bile-duct diameter at the porta hepatis and liver biopsies in Indian children with biliary atresia

Fibrous remnants from the porta hepatis and wedge biopsies of the liver were studied in 60 patients with biliary atresia. The patients were divided into three groups on the basis of bile duct diameter — I: no ducts; II: <50 m; III: >50 m. The liver damage was classified into three grades on the basis of ductular and parenchymal histopathologic changes and extent of inflammatory pathology. There was no correlation between severity of hepatic damage and duct diameter, although the levels of serum bilirubin and alkaline phosphatase varied in direct proportion to the degree of hepatic damage. There was an inverse relationship between age and duct diameter, but neither correlated with bile flow at surgery or in the postoperative period. The data suggest that Indian children with biliary atresia follow a different clinical course compared to those from Japan and Western countries. Correspondence to: V. Bhatnagar