Receptor Tyrosine Kinases in Kidney Development

The kidney plays a fundamental role in the regulation of arterial blood pressure and fluid/electrolyte homeostasis. As congenital anomalies of the kidney and urinary tract (CAKUT) constitute one of the most common human birth defects, improved understanding of the cellular and molecular mechanisms that lead to CAKUT is critical. Accumulating evidence indicates that aberrant signaling via receptor tyrosine kinases (RTKs) is causally linked to CAKUT. Upon activation by their ligands, RTKs dimerize, undergo autophosphorylation on specific tyrosine residues, and interact with adaptor proteins to activate intracellular signal transduction pathways that regulate diverse cell behaviours such as cell proliferation, survival, and movement. Here, we review the current understanding of role of RTKs and their downstream signaling pathways in the pathogenesis of CAKUT

Emergency Management of Hypertension in Children

Systemic arterial hypertension in children has traditionally been thought to be secondary in origin. Increased incidence of risk factors like obesity, sedentary life-styles, and faulty dietary habits has led to increased prevalence of the primary arterial hypertension (PAH), particularly in adolescent age children. PAH has become a global epidemic worldwide imposing huge economic constraint on health care. Sudden acute increase in systolic and diastolic blood pressure can lead to hypertensive crisis. While it generally pertains to secondary hypertension, occurrence of hypertensive crisis in PAH is however rare in children. Hypertensive crisis has been further subclassified depending on presence or absence of end-organ damage into hypertensive emergency or urgency. Both hypertensive emergencies and urgencies are known to cause significant morbidity and mortality. Increasing awareness among the physicians, targeted at investigation of the pathophysiology of hypertension and its complications, better screening methods, generation, and implementation of novel treatment modalities will impact overall outcomes. In this paper, we discuss the etiology, pathogenesis, and management of hypertensive crisis in children. An extensive database search using keywords was done to obtain the information

Design and Validation of an Accurate Low-Cost Data Acquisition System for Structural Health Monitoring of a Pedestrian Bridge

Structural health monitoring (SHM) is an effective operating technique devoted to enhance the robustness of an infrastructure, and to validate its safety requirements. The aim of SHM is to determine a structure’s reaction when subjected to any type of excitation, by means of identifying modifications in basic vibration measurements and modal parameters such as natural frequencies, damping and mode shapes. Consequently, sensors are mounted on a structure intending to record data on equal time intervals basis prior to, during and after an induced stimulation. Therefore, the necessity to adopt a computer-based data acquisition (DAQ) technique is required in this analytical approach in order to evaluate vibrational signals collected by sensors placed on a structure. In this work an accurate microcontroller-based DAQ system is proposed to monitor a pedestrian bridge located in Athens Greece for the purpose of characterizing the system state and evaluate the modal properties of the investigated structure. Four low-cost yet accurate triaxial accelerometers were systematically placed along the bridge intending to report the system response toward different generated perturbations. The proposed monitoring and computational system was tested in laboratory conditions prior to the bridge assessment. Three triaxial accelerometer were installed on a steel cantilever beam. A comparative analysis between the results of the suggested DAQ system and that of the standard laboratory DAQ system National Instrument DAQ was performed to test the accuracy of the suggested framework

Ontogeny of bradykinin B2 receptors in the rat kidney: Implications for segmental nephron maturation

Ontogeny of bradykinin B2 receptors in the rat kidney: Implications for segmental nephron maturation. Kinins modulate renal function, yet their role in the developing kidney is largely unknown. To explore the developmental role of the kallikrein-kinin system, we examined the postnatal ontogeny and intrarenal localization of B2 receptors in the rat. Northern blot analysis and RT-PCR documented the expression of B2 receptor mRNA in the kidney and extrarenal tissues of fetal, neonatal and adult animals. The abundance of B2 receptor mRNA is 10- to 30-fold higher in neonatal than adult tissues in the following order: kidney > heart > aorta > lung > brain. Receptor autoradiography revealed a gradual shift in the localization of bradykinin binding sites from the outer cortex in the newborn to the outer medulla in weanling and maturing rats. The almost complete displacement of [125I]tyr0-bradykinin by HOE-140 indicates that the majority of kinin receptors in the developing kidney belong to the B2 type. Immunolocalization studies using antipeptide antibodies directed against various portions of the receptor revealed that B2 receptors are first expressed on the luminal aspect of the upper limb of S-shaped bodies and differentiating cortical collecting ducts. In marked contrast, the metanephric mesenchyme, pretubular aggregates and glomeruli display weak or no B2 receptor immunoreactivity. Following completion of nephrogenesis, B2 receptor expression shifts to both luminal and basolateral aspects of connecting tubules and collecting ducts. The results demonstrate that bradykinin B2 receptor gene expression is activated in the developing kidney and cardiovascular system. The spatially restricted expression of B2 receptors in the differentiating epithelium of the distal nephron, the site of kinin formation, supports the hypothesis that kinins are paracrine modulators of segmental nephron maturation

Impact of weight loss on oxidative stress and inflammatory cytokines in obese type 2 diabetic patients.

Background: Type 2 diabetes mellitus is associated with abnormal markers of inflammatory cytokines and oxidative stress markers. Although, these abnormalities could be modulated with weight reduction; there is limitation in clinical studies that have addressed the beneficial effects of weight reduction in modulating biomarkers of inflammatory cytokines and oxidative stress for obesity associated with type 2 diabetes mellitus. Objective: This study was designed to detect the effects of weight loss on the inflammatory cytokines, oxidative stress markers in obese type 2 diabetic patients. Material and Methods: Eighty obese patients with type 2 diabetes mellitus, their age ranged from 35-57 years and their body mass index ranged from 31-35 kg/m2 were equally assigned into 2 groups: the weight reduction group received aerobic exercises, diet regimen, where as the control group received medical treatment only for 12 weeks. Results: The mean values of body mass index (BMI), tumor necrosis factor\u2013alpha (TNF-\u3b1), interleukin-6 (IL-6), C-reactive protein (sCRP), conjugated dienes (CD) and malondialdehyde (MDA) were significantly decreased, while the mean values of glutathione peroxidase (GPx), superoxide dismutase (SOD) and glutathione (GSH) were significantly increased in patients of group (A), while changes were not significant in group (B). Also, there were significant differences between mean levels of the investigated parameters in group (A) and group (B) at the end of the study. Conclusion: Weight loss ameliorates inflammatory cytokines and oxidative stress markers in obese type 2 diabetic patients

A química verde e os plásticos ambientalmente degradáveis

O estudo de impacto ambiental é um dos mais importantes instrumentos de defesa do meio ambiente, e se fundamenta na obrigatoriedade de se respeitar o meio ambiente e no direito dos cidadãos à participação e à informação. Com o enfoque mundial na preocupação ambiental foram desenvolvidos os bioplásticos, que são plásticos biodegradáveis, que não utilizam o petróleo como matéria–prima e por isso sua síntese é uma atividade sustentável com diminuição da emissão de gases de efeito estufa. Em outra categoria estão os plásticos verdes, que são uma nova geração de plásticos, cujos componentes são também derivados de matérias–primas renováveis, e que contribuem para a preservação das fontes fósseis não renováveis tais como, petróleo e gás natural. Este trabalho teve como objetivo, realizar um estudo mercadológico simplificado dos principais biopolímeros, como também avaliar as tendências tecnológicas deste segmento, com base em informações extraídas de documentos de patentes, de modo a mapear os principais setores, evolução ao longo dos anos, tipos de depositantes, empresas e áreas de aplicação. No estudo mercadológico foi possível analisar os biopolímeros que possuem maior chance de sucesso de desenvolvimento de tecnologia local, tendo se destacado em ordem decrescente, o polihidroxialcanoato, com propriedades semelhantes a xantana; os polímeros de amido e o polilactato. Os biopolímeros com maior potencial de receitas foram em ordem decrescente, o polilactato e, praticamente no mesmo nível, o polihidroxialcanoato, xantana e os polímeros de amido. Para o estudo de prospecção tecnológica foram utilizados os bancos de patentes da United Patents and Trademark Office (USPTO) e do Instituto Nacional de Propriedade Intelectual (INPI), onde foram compiladas cerca de 1431 patentes, tomando como base o período de 1970 a 2007. Em ambos os bancos, a supremacia Norte- Americana em registro de patentes ficou evidente. O Brasil é o segundo do ranking em depósitos no banco do INPI, não havendo registro de depósitos brasileiros no banco da USPTO no período estudado. Em relação aos tipos de depositantes compilados, tanto no banco norte-americano como no nacional, os maiores depositantes são as empresas. Este fato está relacionado com a constante busca por inovações tecnológicas e maior competitividade por parte dessas empresas. No Brasil, se percebe uma maior ligação entre P&D e a academia, caracterizada pelo segundo lugar das Universidades como depositantes de patentes

Weight loss improves biomarkers endothelial function and systemic inflammation in obese postmenopausal Saudi women.

Background: Although postmenopausal associated disorders are important public health problems worldwide, to date limited studies evaluated the endothelial function and systemic inflammation response to weight loss in obese postmenopausal women. Objective: This study was done to evaluate the endothelial function and systemic inflammation response to weight loss in obese postmenopausal Saudi women. Material and methods: Eighty postmenopausal obese Saudi women (mean age 52.64\ub16.13 year) participated in two groups: Group (A) received aerobic exercise on treadmill and diet whereas, group (B) received no intervention. Markers of inflammation and endothelial function were measured before and after 3 months at the end of the study. Results: The values of body mass index(BMI), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-\u3b1), C-reactive protein (CRP), inter-cellular adhesion molecule (ICAM-1), vascular cell adhesion molecule (VCAM-1) and plasminogen activator inhibitor- 1 activity (PAI-1:Ac) were significantly decreased in group (A), while changes were not significant in group (B). Also, there were significant differences between mean levels of the investigated parameters in group (A) and group (B) after treatment. Conclusion: Weight loss ameliorates inflammatory cytokines and markers of endothelial function in obese postmenopausal Saudi women

Impact of weight reduction program on serum alanine aminotransferase activity and immunologic response in obese hepatitis B patients.

Background: Globally, chronic B viral hepatitis (HBV) is a major health problem. Obesity is a common problem among patients with HBV. Several studies have reported that obesity is an important risk factor that alters immune system response in individuals with no underlying cause of liver disease. However, there is a strong association between BMI and the human immune system among HBV patients. Objective: This study was to examine the correlation between body mass index, serum alanine aminotransferase activity (ALT) and immunologic response in obese hepatitis B patients. Material and methods: One hundred fifty male patients with chronic hepatitis B virus, their age ranged from 30 to 45 (38.64 \ub1 7.12) years and their BMI ranged from 30-35 kg/m2. All Subjects were included in two groups: The first group received weight reduction program in the form of treadmill aerobic exercises in addition to diet control whereas the second group received no therapeutic intervention. Parameters of serum alanine aminotransferase (ALT), CD3, CD4 and CD8 were quantified; Leukocyte, differential counts and body mass index (BMI) were measured before and after 3 months at the end of the study. Results: There was a 24.7%, 36.8%, 30.8%, 40.7%, 28.6%, 25.9%, 33.3% and 14.3 % reduction in mean values of alanine aminotransferase (ALT), white blood cells, total neutrophil count, monocytes, CD3, CD4 ,CD8 and BMI respectively in group (A) at the end of the study. In addition, there were significant differences between mean levels of the investigated parameters in groups. Conclusion: Based on our findings, weight loss modulates serum alanine aminotransferase and immune system parameters of patients with hepatitis B virus infection

Premature differentiation of nephron progenitor cell and dysregulation of gene pathways critical to kidney development in a model of preterm birth

Preterm birth is a leading cause of neonatal morbidity. Survivors have a greater risk for kidney dysfunction and hypertension. Little is known about the molecular changes that occur in the kidney of individuals born preterm. Here, we demonstrate that mice delivered two days prior to full term gestation undergo premature cessation of nephrogenesis, resulting in a lower glomerular density. Kidneys from preterm and term groups exhibited differences in gene expression profiles at 20- and 27-days post-conception, including significant differences in the expression of fat-soluble vitamin-related genes. Kidneys of the preterm mice exhibited decreased proportions of endothelial cells and a lower expression of genes promoting angiogenesis compared to the term group. Kidneys from the preterm mice also had altered nephron progenitor subpopulations, early Six2 depletion, and altered Jag1 expression in the nephrogenic zone, consistent with premature differentiation of nephron progenitor cells. In conclusion, preterm birth alone was sufficient to shorten the duration of nephrogenesis and cause premature differentiation of nephron progenitor cells. These candidate genes and pathways may provide targets to improve kidney health in preterm infants

Gene length is a pivotal feature to explain disparities in transcript capture between single transcriptome techniques

The scale and capability of single-cell and single-nucleus RNA-sequencing technologies are rapidly growing, enabling key discoveries and large-scale cell mapping operations. However, studies directly comparing technical differences between single-cell and single-nucleus RNA sequencing are still lacking. Here, we compared three paired single-cell and single-nucleus transcriptomes from three different organs (Heart, Lung and Kidney). Differently from previous studies that focused on cell classification, we explored disparities in the transcriptome output of whole cells relative to the nucleus. We found that the major cell clusters could be recovered by either technique from matched samples, but at different proportions. In 2/3 datasets (kidney and lung) we detected clusters exclusively present with single-nucleus RNA sequencing. In all three organ groups, we found that genomic and gene structural characteristics such as gene length and exon content significantly differed between the two techniques. Genes recovered with the single-nucleus RNA sequencing technique had longer sequence lengths and larger exon counts, whereas single-cell RNA sequencing captured short genes at higher rates. Furthermore, we found that when compared to the whole host genome (mouse for kidney and lung datasets and human for the heart dataset), single transcriptomes obtained with either technique skewed from the expected proportions in several points: a) coding sequence length, b) transcript length and c) genomic span; and d) distribution of genes based on exons counts. Interestingly, the top-100 DEG between the two techniques returned distinctive GO terms. Hence, the type of single transcriptome technique used affected the outcome of downstream analysis. In summary, our data revealed both techniques present disparities in RNA capture. Moreover, the biased RNA capture affected the calculations of basic cellular parameters, raising pivotal points about the limitations and advantages of either single transcriptome techniques