Accelerated Growth, Differentiation, and Ploidy with Reduced Proliferation of Right Ventricular Cardiomyocytes in Children with Congenital Heart Defect Tetralogy of Fallot

The myocardium of children with tetralogy of Fallot (TF) undergoes hemodynamic overload and hypoxemia immediately after birth. Comparative analysis of changes in the ploidy and morphology of the right ventricular cardiomyocytes in children with TF in the first years of life demonstrated their significant increase compared with the control group. In children with TF, there was a predominantly diffuse distribution of Connexin43-containing gap junctions over the cardiomyocytes sarcolemma, which redistributed into the intercalated discs as cardiomyocytes differentiation increased. The number of Ki67-positive cardiomyocytes varied greatly and amounted to 7.0–1025.5/106 cardiomyocytes and also were decreased with increased myocytes differentiation. Ultrastructural signs of immaturity and proliferative activity of cardiomyocytes in children with TF were demonstrated. The proportion of interstitial tissue did not differ significantly from the control group. The myocardium of children with TF under six months of age was most sensitive to hypoxemia, it was manifested by a delay in the intercalated discs and myofibril assembly and the appearance of ultrastructural signs of dystrophic changes in the cardiomyocytes. Thus, the acceleration of ontogenetic growth and differentiation of the cardiomyocytes, but not the reactivation of their proliferation, was an adaptation of the immature myocardium of children with TF to hemodynamic overload and hypoxemia.

Allergic Reaction Following Implantation of a Blood Glucose Sensor.

Increasing incidence and onset at a younger age has changed the treatment strategy of diabetes mellitus (DM) towards prevention, delaying the onset, and minimizing disease complications. Self-monitoring blood glucose systems and continuous glucose monitoring systems are routinely preferred in diabetic children.Flash glucose monitoring system has come as an entirely new concept in glucose monitoring by providing much greater data than blood glucose testing while being more affordable than the continuous glucose monitors. The FreeStyle Libre provides ‘flash glucose monitoring’ with glucose readings by scanning a sensor rather than pricking the patient’s finger. The sensor measures interstitial tissue glucose levels every minute via a disposable round sensor with a small catheter inserted under the skin that can be worn for up to 14 days. The entire system’s on-body sensor patch worn on the back of the upper arm is disposable. However, the mild erythema may occur on the skin and disappear spontaneously after 24 hours from the detachment of the sensor. Similar skin lesions were observed in diabetic patients, and there was moderate to severe itching in 0.5% of the cases and moderate erythema in 4% of cases

INTERSTITIAL RENAL NECROSIS SYNDROM OF CALVES

Interstitial renal necrosis syndrom (IRNS) was diagnosed in calves sloughtered in Mosul sloughter house. Gross and microscopical picture of 33 affected animals were described. The lesions were identified according topathomorpholgy of tissue reaction. Two patterns of tissue rections were observed. The lesions of the first pattern showed grossly an oval, greyish white translucent nodules on the surface of kidney. Microscopically, cells like lymphocytes and few plasma cells were aggregated in the interstitial tissue. The lesions of the second pattern comprised grossly a milliary yellowish-white nodules on the surface of the kidney and on cut sectionforming extention in the depth of the renal cortex. Microscopically, the infiltrated cells were mainly neutrophils, macrophages and few lymphocytes, the possible causes of this syndrom was discussed.

Effect of Lycopene on Histological Alterations of Basement Membrane & Fibrosis in Renal Interstitial Tissue of Celebrex Induced Albino Rats; An Experimental Study

Objective: To assess the histological alterations in basement membrane and fibrosis in renal interstitium of albino rats due to celebrex with enhancement by lycopene. Study Design: Experimental study. Abode of Study: Animal House of Jinnah Postgraduate institute, Karachi, Materials and Methods: COX-2 inhibitor and antioxidant medicines were used in this research work. These medications were orally administered in 40 male albino rats weighing 200-220gm for experimentation. Rats were housed in separate pens at 23ºC. Rats were arranged into 4 groups including control horde and three experimental hordes. The medications were dose up orally by gastric tube daily for one month. At completion of experiment, animals were dissected and tissues were well-preserved for staining. Results: In second horde PAS stained kidney segments showed disrupted basement membrane of distended proximal convoluted tubules & ill-defined brush border and fibrosis in renal interstitium, but 3rd horde had intact basement membrane & well-define brush border at the luminal surface of proximal tubular epithelium and there was mild fibrosis in renal interstitium. Conclusion: This study divulges that lycopene convalesce the disrupted basement membrane and fibrosis in second horde.

Vascular-tissue relations in the lungs in experimental superinvasive opisthorchiasis

Structural changes in the lungs in superinvasive opisthorchiasis at various stages of invasion were studied. The morphology of permanent epithelial proliferation at the initial stage and their decrease in the late period were revealed. With the formation of granulomas in the interstitial tissue of the respiratory organs, with changes in the chronic period towards the formation of sclerotic foci. Key words: superinvasive opisthorchiasis (CO), metacercariae, acinus, terminal bronchioles (TB), cell infiltrates, pneumocytes.

Volume-Independent Sodium Toxicity in Peritoneal Dialysis: New Insights from Bench to Bed

Sodium overload is common in end-stage kidney disease (ESKD) and is associated with increased cardiovascular mortality that is traditionally considered a result of extracellular volume expansion. Recently, sodium storage was detected by Na23 magnetic resonance imaging in the interstitial tissue of the skin and other tissues. This amount of sodium is osmotically active, regulated by immune cells and the lymphatic system, escapes renal control, and, more importantly, is associated with salt-sensitive hypertension. In chronic kidney disease, the interstitial sodium storage increases as the glomerular filtration rate declines and is related to cardiovascular damage, regardless of the fluid overload. This sodium accumulation in the interstitial tissues becomes more significant in ESKD, especially in older and African American patients. The possible negative effects of interstitial sodium are still under study, though a higher sodium intake might induce abnormal structural and functional changes in the peritoneal wall. Interestingly, sodium stored in the interstial tissue is not unmodifiable, since it is removable by dialysis. Nevertheless, the sodium removal by peritoneal dialysis (PD) remains challenging, and new PD solutions are desirable. In this narrative review, we carried out an update on the pathophysiological mechanisms of volume-independent sodium toxicity and possible future strategies to improve sodium removal by PD.

MiR-224 ameliorates inflammation and symptoms in mouse model of allergic rhinitis by targeting CDK9

Objectives: To explore the regulatory effects of microRNA (miRNA)-224 and its potential target gene, cyclin dependent kinase 9 (CDK9), in the pathological process of allergic rhinitis (AR). Methods: To investigate the role of miR-224 and CDK9, it was screened by bioinformatics prediction software and verified by dual-luciferase reporter assay. The mouse model of AR was established by ovalbumin (OVA).The animal models were intervened with miR-224 agomir, negative control agomir, and saline respectively. The symptoms of sneezing and nasal rubbing were recorded. The expressions of miR224, CDK9, and cytokines in the nasal mucosa of different groups were analyzed by rt-PCR or western blotting. Enzyme-linked immunoassay (ELISA) was used to evaluate the levels of IgE and Histamine (HA) in the serum. The infiltration of inflammatory cells in the nasal mucosa was studied by immunohistochemistry. The expression and distribution of CDK9 in the nasal mucosa of mice were revealed by immunofluorescence. Results: In the nasal mucosa of the animal models, the level of miR-224 was downregulated, while that of CDK9 was upregulated. The upregulation of miR-224 by miR-224 agomir reduced the frequencies of nasal rubbing and sneezing, the expression of CDK9, the levels of cytokines, and the concentrations of IgE and HA. Moreover, miR-224 appeared to attenuate the infiltration of inflammatory cells and hypersecretion of glands in the nasal mucosa. The expression of CDK9, which was distributed under the mucosa, especially in the submucosa interstitial tissue, was significantly reduced.Conclusion: MiR-224 affected the pathogenesis of AR by targeting CDK9. It proves that miR-224 could be a novel potential therapeutic target for AR.

Fibroblast Differentiation and Matrix Remodeling Impaired under Simulated Microgravity in 3D Cell Culture Model

Exposure to microgravity affects astronauts’ health in adverse ways. However, less is known about the extent to which fibroblast differentiation during the wound healing process is affected by the lack of gravity. One of the key steps of this process is the differentiation of fibroblasts into myofibroblasts, which contribute functionally through extracellular matrix production and remodeling. In this work, we utilized collagen-based three-dimensional (3D) matrices to mimic interstitial tissue and studied fibroblast differentiation under simulated microgravity (sµG). Our results demonstrated that alpha-smooth muscle actin (αSMA) expression and translocation of Smad2/3 into the cell nucleus were reduced upon exposure to sµG compared to the 1g control, which suggests the impairment of fibroblast differentiation under sµG. Moreover, matrix remodeling and production were decreased under sµG, which is in line with the impaired fibroblast differentiation. We further investigated changes on a transcriptomic level using RNA sequencing. The results demonstrated that sµG has less effect on fibroblast transcriptomes, while sµG triggers changes in the transcriptome of myofibroblasts. Several genes and biological pathways found through transcriptome analysis have previously been reported to impair fibroblast differentiation. Overall, our data indicated that fibroblast differentiation, as well as matrix production and remodeling, are impaired in 3D culture under sµG conditions.

Studies on Postnatal Development of Testis of Guinea Pig (Cavia porcellus)

The histology and histochemistry of the testis of guinea pig of various postnatal age groups was conducted. A total of 24 guinea pigs of four different postnatal ages with six male animals each were collected from the Department of Laboratory Animal Medicine, Madhavaram Milk Colony, Chennai as per the Ethical committee approval. After collection, animals were euthanized as per CPCSEA norms and testis was dissected out and was cut into small pieces, fixed and processed for paraffin embedding. Sections of 4–5 µm thickness were cut and used for the routine and special histological and histochemical staining techniques. Testes wereencapsulated by tunica vaginalis and tunica albuginea. Septa from the capsule divided the testicular parenchyma into lobules. Each lobule consisted of seminiferous tubules which consisted of spermatogenic cells in stratified layers and sertoli cells. Pre-weaning and weaning group of guinea pigs seminiferous tubules showed wide lumen with only type 1 and type 2 spermatogonia and sertoli cells. Young and adult animals seminiferous tubules showed narrow lumen with type 1 and type 2 spermatogonia, primary spermatocytes in various stages of differentiation, secondary spermatocytes, spermatids (early and late) and sertoli cells. Sertoli cells were large oval shaped cells with lightly stained irregular shaped nucleus. Interstitial tissue contained leydig cells in all ages.Leydig cells appeared as varied in shape. In all the age groups studied, PAS activity was noticed in the capsule and basement membrane. The micrometrical parameters increased as age advanced in both right and left testis.