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Background:IgG4-related disease (IgG4-RD) is an often unrecognized, rare fibro-inflammatory condition that can involve various organ systems.Objectives:The aim of this study was to identify the different clinical patterns of this disease in a single centre in North India.Methods:70 patients were diagnosed on the basis of published diagnostic criteria for IgG4-RD. Patients’ presenting complaints, epidemiological profiles, laboratory, radiological and histological findings along with the treatment and outcomes were collated and analyzed from 2011 – 2019.Results:In a total of 70 patients who were diagnosed with the disease, the ratio of female to male ratio was 1:1. The mean age of patients was 41.4 years. Involvement of orbits and peri-orbital tissues was highest (52.9%) due to large number of referrals from ophthalmology services. 13% of patients had multiple organ involvement. Patients with involvement of retroperitoneal tissues and lymph nodes were 8.5% and 5.7%, respectively. Increased serum IgG4 levels were found in 74.3% of the patients. Histopathological examinations of the affected organs were performed in 44 (62.85%) patients and a diagnosis of possible (38.57), probable (32.85%) and definite (28.57%) IgG4-RD was made. Majority of the patients (94.3%) required immunosuppressive medications along with corticosteroids. Azathioprine was the most commonly used (72.8%) immunosuppressive medication. Rituximab was used in17.1% of the patients, of whom one had multisystem involvement.Conclusion:This study depicts the most common patterns of organ involvement along with the epidemiological, laboratory, histological, radiological data and response to treatment, in IgG4-RD, with a definite ophthalmology referral bias, in a tertiary care centre in North India.References:[1]Stone JH, Zen Y, Deshpande V. IgG4-related disease. N Engl J Med 2012; 366(6):539-51.[2]Khosroshahi A, CarruthersMN, Deshpande V, Unizony S, Bloch DB, Stone JH. Rituximab for the treatment of IgG4-related disease: lessons from 10 consecutive patients. Medicine 2012; 91(1):57-66.Table 1.Clinical and laboratory characteristicsCharacteristicsNumber of patients (N=70)Age (years)41.4Age group in years, n (%) >50 24 (34.28) <5046 (65.71)Sex, n (%) Male36 (51.42) Female34 (47.22) ESR (mm/hr)24.37 CRP (mg/dL)12.31 Serum IgG (mg/dL)1214.2 Serum IgE (IU/L)587.2Type of IgG4 related disease, n (%) Definite20 (28.57) Probable23 (32.85) Possible27 (38.57)Data represented as mean, unless otherwise specified.CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; Ig, immunoglobulin.Table 2.Distribution of patients according to organ involvement.Organ involvementNumber (%)Orbital and periorbital37(52.9)Retroperitoneum6 (8.5)Laryngotracheal tissue4 (5.7)Aorta and branches4 (5.7)Lymph nodes3(4.2)Paranasal sinus2 (2.8)Paravertebral tissue2 (2.8)Pancreas2 (2.8)Lung and bronchus2 (2.8)Eye (Scleritis)1 (1.4)Prevesical Mass1 (1.4)Ear polyp1 (1.4)Small Bowel1 (1.4)Primary sclerosing cholangitis1 (1.4)Musculoskeletal1(1.4)Submandibular gland1(1.4)Central nervous system1 (1.4)Multisystem involvement9 (12.86%)Figure 1.Right eye proptosisFigure 2.CT abdomen showing hydronephrosis due to retroperitoneal fibrosisDisclosure of Interests:None declared

An investigation of Ni–Cu alloys electrodeposited from aqueous bath, using bothdirect current (dc) and pulsed current (pc) deposition techniques, has revealed many interesting features: A modulated structure with typical layer thickness of 90 and75 nm of copper-rich and nickel-rich layers, respectively, is formed in dc plating. A surprising observation was that the modulation direction was parallel to the substrate, unlike in the case of artificial multilayers wherein it is along the growth direction. No such compositional modulations were observed in pc-plating in the present work. Spinodal phase separation, accompanied by L10 ordering, was found to have occurred in the as deposited samples in both the cases. The size of the deposited crystals in both the cases has been found to be in the range of 2.5–30 nm. Detailed high-resolution transmission electron microscopy has shown that the atomic arrangements are nearly perfect right upto the boundaries of the nanosized grains.

Reactive oxygen species (ROS, free radicals) produced during cardiac ischemia and reperfusion can damage the contractile functions of arteries. The sarcoplasmic reticulum (SR) Ca2+ pump in coronary artery smooth muscle is very sensitive to ROS. Here we show that contractions of de-endothelialized rings from porcine left coronary artery produced by the hormone Angiotensin II and by the SR Ca2+ pump inhibitors cyclopiazonic acid and thapsigargin correlate negatively with the tissue weight. In contrast, the contractions due to membrane depolarization by high KCl correlate positively. Peroxide also produces a small contraction which correlates negatively with the tissue weight. When artery rings are treated with peroxide and washed, their ability to contract with Angiotensin II, cyclopiazonic acid and thapsigargin decreases. Thus, the SR Ca2+ pump may play a more important role in the contractility of the smaller segments of the coronary artery than in the larger segments. These results are consistent with the hypothesis that ROS which damage the SR Ca2+ pump affect the contractile function of the distal segments more adversely than of the proximal segments.

The aim of this study was to quantify the glucose modulation of the plasma membrane calcium pump (PMCA) function in rat pancreatic islets. Ca2+-ATPase activity and levels of phosphorylated PMCA intermediates both transiently declined to a minimum in response to stimulation by glucose. Strictly dependent on Ca2+ concentration, this inhibitory effect was fully expressed at physiological concentrations of the cation (less than 0.5 muM), then progressively diminished at higher concentrations. These results, together with those previously reported on the effects of insulin secretagogues and blockers on the activity, expression and cellular distribution of the PMCA, support the concept that the PMCA plays a key role in the regulation of Ca2+ signaling and insulin secretion in pancreatic islets.

Bright and smooth nanocrystalline Monel-type Ni-Cu alloy gets deposited from complex citrate electrolyte by pulse electrolysis. Transmission electron microscopy studies have revealed that the deposited Ni-Cu alloy was nanocrystalline in nature and it comprised a two-phase (fcc+Ll,) mixture. The presence of twins could be seen in the nanocrystals. The Ni-Cu alloys prepared by pulse electrolysis were finer grained (- 2.5-28.5 nm) than those deposited by direct current method. Nelson-Riley function has been used to calculate the lattice parameters for both the pulse current-plated and direct current-plated alloys from x-ray diffraction analysis. The microhardness values for pulse current-plated alloys were higher than for the direct currentplated alloys. The internal stresses of both the pulse current-deposited and the direct currentdeposited alloys have also been measured; the values were lower for pulse current-plated alloys. Potentiodynamic polarisation studies were carried out in aerated and deaerated neutral 3.0 Wt per cent NaCl solution and instantaneous corrosion current density of the plated alloy was determined and compared with the Monel-400 alloy. It was found that nanocrystalline pulse current-N,-35 8 Wt p;r cent copper alloy uxh~bitedlo wer instantaneous value of corros~onc urrent densirv than that of soeclrnens with direct current method and Monel-400 allov The d~ssolut~on ~ ~~~-~ behaviour ofthe deposited nanocrystalline material was found to be more like general corrosion rather than localised corrosion as in the case of Monel-400 alloy.

Iron-cadmium interactions are important in cadmium toxicity. Dietary iron supplements may decrease cadmium retention after oral cadmium exposure but the underlying mechanism is not known. Using a CdS/AgS ion selective electrode to measure [Cd2+] in physiological saline solution at pH 7.4, we show that Fe2+ promotes Cd2+ binding to citrate thereby decreasing the availability of free Cd2+. This suggests the formation of high molecular weight Cd2+-Fe2+-citrate complexes. We confirm this suggestion by showing that 109Cd2+ is retained by 1 kDa cut off filters when present with total 50 microM Fe2+ plus 1 mM citrate but not when present with citrate alone. The formation of high molecular weight complexes may prevent Cd2+ absorption. As citrate is part of the diet, we suggest that these iron-cadmium interactions may contribute to the protective effect of iron against cadmium toxicity.

Pig left descending coronary artery (main artery) and its next branch (branch arteries) differ in many properties. Here we report on the receptor types and the Ca^sup 2+^ pools utilized for endothelin (ET) contraction in 3 mm long de-endothelialized rings of the main (weight 7.38 ± 0.38 mg) and the branch (1.07 ± 0.03 mg) arteries. KCl (60 mM) contracted the main and the branch arteries with force of 41.8 ± 3.1 and 16.9 ± 1.0 mN (millinewton), respectively. Force of contraction for all the other agents was normalized taking the KCl value as 100%. We determined the total ET-induced responses using ET-1 and those mediated by ET^sub B^ using IRL1620. In Ca^sup 2+^-containing solutions, ET-1 contracted the main arteries with pEC^sub B^ = 8.2 ± 0.1 and a maximum force of 98 ± 5%. The branch arteries also gave similar values of pEC^sub 50^ (8.4 ± 0.1) and maximum force (99 ± 14%). IRL1620 contracted the main and the branch arteries with pEC^sub 50^ = 7.9 ± 0.1 but the maximum force was significantly higher in the branch arteries (44 ± 3%) than in the main (15 ± 2%). In Ca^sup 2+^-free solutions, the pEC^sub 50^ values for ET-1 or IRL-1620 did not change but the maximum force of contraction was diminished considerably in both main and branch arteries. Thus, the left coronary artery and its next branch differ in that the role of ET^sub B^ receptors is greater in the latter.[PUBLICATION ABSTRACT]

Endothelin is one of the most potent vasoconstrictors known. It plays an important role in the regulation of vascular tone and in the development of many cardiovascular diseases. This study focuses on the receptor types and the Ca^sup 2+^ mobilization responsible for endothelin-1 (ET-1) contraction in de-endothelialized pig coronary artery rings. ET-1 contracted the artery rings with an EC^sub 50^ = 6.5 ± 1 nM and a maximum contraction which was 98.6 ± 9% of the contraction produced by 60 mM KCl. BQ123 (5 µM), an ET^sub A^ antagonist, reversed 78 ± 3% of the ET-1 contraction (50 nM). IRL1620, a selective ET^sub B^ agonist, produced 23 ± 3% of the total ET-1 contraction with an EC^sub 50^ = 12.7 ± 2 nM. More than 85% of the contraction due to 100 nM IRL 1620 was inhibited by 200 nMBQ788, an ET^sub B^ antagonist. Therefore, approximately 80% of the ET-1 contraction in this artery occurred via ET^sub A^ receptors, and the other 20% was mediated by ET^sub B^ receptors. To assess the Ca^sup 2+^ pools utilized during the ET-1 response, ET-1 contraction was also examined in medium containing an L-type Ca^sup 2+^ channel blocker nitrendipine, and in Ca^sup 2+^ free medium containing 0.2 mM EGTA. In Ca^sup 2+^ containing medium the contraction elicited by ET-1 was 98.6 ± 9% of the KCl contraction, however, in the presence 10 µM nitrendipine the ET-1 induced contraction was 54 ± 7% of the KCl contraction, and in Ca^sup 2+^-free medium it was 13 ± 2%. Similarly, the IRL 1620 contractions in Ca^sup 2+^ containing medium, in the presence of nitrendipine and in Ca^sup 2+^-free medium were 22.4 ± 3%, 12 ± 3% and 11 ± 2% of the KCl response respectively. Thus, both ET^sub A^ and ET^sub B^ contractions utilize extracellular Ca^sup 2+^ pools via L-type Ca^sup 2+^ channels and other undefined route(s), as well as intracellular Ca^sup 2+^ pools. In the pig coronary artery smooth muscle, ET-1 contractions occur predominantly via ET^sub A^ receptors, with ET^sub B^ receptors using similar Ca^sup 2+^ mobilization pathways, but the ET^sub B^ receptors appear to use the intracellular Ca^sup 2+^ stores to a greater extent.[PUBLICATION ABSTRACT]