Point mutations of the human parathyroid calcium receptor gene are not responsible for non-suppressible renal hyperparathyroidism

Point mutations of the human parathyroid calcium receptor gene are not responsible for non-suppressible renal hyperparathyroidism. The calcium-dependent secretion of parathyroid hormone (PTH) is mediated through an extracellular G protein-coupled calcium receptor (CaR). Inactivating point mutations of this receptor have been found in familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism. These diseases feature a decreased calcium sensitivity of the parathyroid glands, resulting in a rightward shift of the Ca2+-PTH relationship. Severe, non-suppressible renal hyperparathyroidism (rHPT) is often characterized by similar setpoint shifts to the right. Thus, point mutations of the CaR gene could contribute to non-suppressible rHPT. We examined genomic DNA of hyperplastic or mainly nodular tissues of 39 parathyroids from 25 rHPT-patients with resistance to calcitriol therapy. Amplification of the six exons of the CaR gene was followed by single-strand conformation polymorphism (SSCP) analysis. DNA sequencing was performed where band shifts were observed. No point mutations in the coding sequence of the CaR gene were detected using the PCR-SSCP strategy. Point mutations in the coding regions of the CaR gene probably play no role in the evolution of renal HPT and are not responsible for the calcitriol resistance of PTH secretion

Effect of flosulide, a selective cyclooxygenase 2 inhibitor, on passive Heymann nephritis in the rat

Effect of flosulide, a selective cyclooxygenase 2 inhibitor, on passive Heymann nephritis in the rat.BackgroundNonsteroidal anti-inflammatory drugs (NSAIDs) induce an inhibition of cyclooxygenase (COX), an enzyme that makes prostaglandins. Two isoforms of COX exist: COX-1 represents the constitutively expressed enzyme, whereas COX-2 is the inducible isoform. This study investigated the role of COX-2 in the inflammatory processes of the kidneys of rats with passive Heymann nephritis (PHN), and focused of the effect of a selective COX-2 inhibitor, flosulide. COX-2–selective inhibitors are thought to represent potent anti-inflammatory agents without major renal side effects.MethodsPHN was induced by injecting heterologous Fx1A antiserum into female Wistar rats. Two treatment groups, each consisting of 12 rats with PHN, received either 3 or 9 mg of flosulide/kg body wt/day and were compared with untreated controls. After four weeks, the generation of thromboxane B2 (TxB2) and 6-keto-PGF1α were determined in renal tissue and in urine. COX-2 protein expression was investigated by Western blotting using a selective antibody.ResultsRats with PHN exhibited a marked proteinuria of 71 ± 8 mg/24 hr as compared with 2.0 ± 0.3 mg/24 hr in healthy controls (P < 0.01). Treatment with flosulide reduced the proteinuria to 26.1 ± 9 mg/24 hr at 3 mg flosulide/kg body wt/day and 35.5 ± 6 mg/24 hr at 9 mg/kg body wt/day, which was equivalent to a reduction of proteinuria by a maximum of 65% (P < 0.05). This was accompanied by an increase in glomerular TxB2 from 3073 ± 355 to 5255 ± 1041 pg/mg glomerular protein and 6-keto-PGF1α from 1702 ± 161 to 2724 ± 770 pg/mg glomerular protein in rats with PHN. COX-2 protein expression was also highly elevated in comparison to healthy controls. Low-dose flosulide treatment had no effect on COX protein expression and renal prostaglandin formation. High-dose flosulide treatment reduced renal prostaglandin production and caused a marked decline in COX-1 and COX-2 protein expression. Urine prostanoid excretion remained unchanged in all therapeutic groups. There was a small though significant reduction in renal creatinine clearance from 0.86 ml ± 0.2/min in untreated controls to 0.6 ml ± 0.1/min in flosulide-treated rats with PHN (P < 0.01) after four weeks.ConclusionsUnder the influence of flosulide, a highly COX-2–selective inhibitor, we observed an antiproteinuric drug effect. The inflammation in PHN induced COX-2 protein expression that was not affected by low-dose flosulide. COX-1 and COX-2 protein expression was affected by high-dose flosulide, which therefore might lose its selectivity. High-dose flosulide induced a decrease in glomerular prostanoid production possibly because of COX-1 inhibition. Our results suggest that the therapeutic use of flosulide in proteinuria seems advantageous and deserves further studies because the basal prostaglandin levels remain unchanged in the low-dose–treated group, indicating that the compensatory capacity of prostaglandin production, which is essential for the regulation of renal hemodynamics, is maintained

Техническое перевооружение сливо-наливной эстакады для продуктов переработки нефти

Объектом исследования является сливоналивная эстакада продуктов переработки нефти". Цель работы – провести техническое обоснование перевооружения перевооружение сливоналивной эстакады продуктов переработки нефти. В процессе исследования проводились литературный обзор, анализ технологии слива и налива нефтепродуктов, технико-экономического обоснование перевооружения сливоналивной эстакады. В результате, исследования был проведен расчет и подбор насосного оборудования для сливоналивной эстакады переработки нефтепродуктов. Область применения: нефтегазовое производство.The object of the study is the overflow loading rack of oil refining products. The purpose of the work is to conduct a technical justification for the re-equipment of the re-equipment of the loading rack of oil refining products. In the course of the study, a literature review was carried out, an analysis of the technology for draining and filling oil products, a feasibility study for the re-equipment of the loading rack. As a result of the study, calculation and selection of pumping equipment for a loading ramp for oil products processing was carried out. Scope: oil and gas production

Геоэкологическая характеристика и элементный состав листьев тополя территории г. Тюмень

Работа направлена на изучение элементного состава листьев тополя как биогеохимического индикатора состояния окружающей среды городов с выраженной специализацией. Исследование проведено на примере города Тюмень.The work is directed at studying the elemental composition of poplar leaves as a biogeochemical indicator of the state of the environment of cities with a pronounced specialization. The study was conducted on the example of the city of Tyumen