Elevated cytosolic calcium of adipocytes in chronic renal failure

Elevated cytosolic calcium of adipocytes in chronic renal failure. Chronic renal failure (CRF) is associated with increased calcium content of, and impaired lipase release from lipid cells. This has been attributed to a rise in the cytosolic calcium ([Ca2+]i) of these cells. However, data on [Ca2+]i of lipid cells in CRF and on the mechanisms responsible for such an abnormality are lacking. To study this issue we examined the [Ca2+]i and ATP content of lipid cells and Vmax of Na+-K+-ATPase and Ca2+ ATPase of membrane preparation and Na+-Ca2+ exchange of membrane vesicles of adipocytes from normal rats, 6 week CRF, CRF normocalcemic parathyroidectomized (CRF-PTX) and CRF, and normal rats treated with verpamil (CRF-V, normal-V). [Ca2+]i in adipocytes of CRF rats was higher (199 ± 8.5 nM) and ATP lower (2.9 ± 0.31 nmol/106 cells) than in normal (120 ± 4.3 nM; 5.7 ± 0.27 nmol/106 cells), CRF-PTX (128 ± 4.7 nM; 5.8 ± 0.39 nmol/106 cells), normal-V (121 ± 3.2 nM; 5.3 ± 0.36 nmol/106 cells), CRF-V (123 ± 7.4 nM; 5.5 ± 0.30 mnol/106 cells). Vmax Ca2+ATPase and the activity of Na+-K+-ATPase and of Na+-Ca2+ exchanger were reduced in CRF rats as compared to the other four groups of rats. The values in normal, CRF-PTX, CRF-V and normal-V rats were not different. These results indicate that: (1) in CRF, adipocytes are overloaded by calcium; (2) this abnormality is mediated by the secondary hyperthyroidism of CRF since PTX of CRF rats or interference with the action of PTH by a calcium channel blocker prevented these changes; and (3) the elevation in [Ca2+]i is due to both increased entry of calcium into adipocytes and a decreased extrusion out of these cells

Elevation of cytosolic calcium of rat cardiac myocytes in phosphate depletion

Elevation of cytosolic calcium of rat cardiac myocytes in phosphate depletion. Phosphate depletion is associated with a rise in cytosolic calcium ([Ca2+]i) of cells and such a derangement is responsible in major part for organ dysfunction in phosphate depletion (PD). Cardiac function is impaired in PD, and it is possible that PD is also associated with rise in [Ca2+]i of cardiac myocytes. The present study examined the effect of PD on [Ca2+]i of cardiac myocytes and explored the mechanisms that may lead to the rise in their [Ca2+]i. The [Ca2+]i of cardiac myocytes began to rise and ATP content began to fall at the third week of PD. After six weeks of PD, the values of [Ca2+]i were significantly higher (P < 0.01) and those of ATP content were significantly lower (P < 0.01) than in control (PW) rats. The Vmax of Ca2+-ATPase and Na+,K+-ATPase as well as the Na+-Ca2+ exchange were significantly lower (P < 0.01) in PD than in PW animals. The data of the present study are consistent with the notion that the rise in [Ca2+]i of cardiac myocytes of PD rats is due to a decrease in calcium efflux out of them

Chronic Kidney Disease Causes Disruption of Gastric and Small Intestinal Epithelial Tight Junction

BackgroundIntegrity of the tight junction (TJ) which seals the gap between the epithelial cells of the gastrointestinal tract is critical in preventing the entry of the microbial toxins, antigens, and other harmful products in the subepithelial tissues and the internal milieu. By enabling the absorption of these products, impairment of the intestinal epithelial barrier leads to local and systemic inflammation. We have recently found depletion of the key protein constituents of colonic epithelial TJ in animals with chronic kidney disease (CKD). Postmortem studies have revealed the presence of inflammation throughout the gastrointestinal tract in uremic humans. This observation suggests that uremia may cause disruption of the epithelial barrier in all segments of the gastrointestinal tract including the stomach, jejunum, and ileum. The present study was undertaken to explore this possibility.MethodsSprague-Dawley rats were randomized to CKD or control groups. The CKD group was subjected to 5/6 nephrectomy while the control group underwent a sham operation. The animals were observed for 10 weeks at which time they were euthanized and their stomachs, jejunums, and ileums were removed and processed for measurement of TJ proteins.ResultsThe CKD rats showed marked azotemia, systemic oxidative stress, and marked depletion of the key protein constituents of the epithelial TJ (claudin-1, occludin, and ZO1) in the stomach, jejunum, and ileum.ConclusionsThe present study extends the earlier finding of uremia-induced disruption of colonic epithelial TJ by documenting the involvement of the stomach, jejunum, and ileum as well

Life Cycle Costs Analysis of Reclaimed Asphalt Pavement (RAP) Under Future Climate

Reclaimed asphalt pavement (RAP) has received wide application in asphalt pavement construction and maintenance and it has shown cost-effectiveness over virgin hot mix asphalt (HMA). HMA with a high content of reclaimed asphalt (RA) (e.g., 40%) is sometimes used in practice, however, it may have significant adverse effects on the life cycle performance and related costs. In particular, challenges may arise as the life cycle performance of RAP is also affected by local climatic conditions. Thus, it is important to investigate whether it is still economic to use RAP under future local climate, with consideration of life cycle performance. A case study was conducted for various road structures on Interstate 95 (I-95) in New Hampshire (NH), USA for the investigation. The case study utilized dynamic modulus testing results for local virgin HMA and HMA with 40% RA (as major material alternatives) to predict life cycle performance of the selected pavement structures, considering downscaled future climates. Then, a life cycle cost analysis (LCCA) was considered to estimate and compare the life cycle cash flow of the investigated road structures. Responsive maintenance (overlay) and effectiveness were also considered in this study. It was found that using 40% RA in HMA can reduce agency costs by up to approximately 18% under the 2020–2040 predicted climate and NH should consider this practice under predicted future climate to reduce agency costs

Role of Nrf2 Dysfunction in Uremia-Associated Intestinal Inflammation and Epithelial Barrier Disruption

Aims: To study the expression profile of inflammatory and tight junction proteins in the colon from CKD rats compared to healthy controls, and demonstrate the role of Nrf2 (transcription factor nuclear factor erythroid 2-related factor 2) using a potent Nrf2 activator

Chronic kidney disease causes disruption of gastric and small intestinal epithelial tight junction.

BackgroundIntegrity of the tight junction (TJ) which seals the gap between the epithelial cells of the gastrointestinal tract is critical in preventing the entry of the microbial toxins, antigens, and other harmful products in the subepithelial tissues and the internal milieu. By enabling the absorption of these products, impairment of the intestinal epithelial barrier leads to local and systemic inflammation. We have recently found depletion of the key protein constituents of colonic epithelial TJ in animals with chronic kidney disease (CKD). Postmortem studies have revealed the presence of inflammation throughout the gastrointestinal tract in uremic humans. This observation suggests that uremia may cause disruption of the epithelial barrier in all segments of the gastrointestinal tract including the stomach, jejunum, and ileum. The present study was undertaken to explore this possibility.MethodsSprague-Dawley rats were randomized to CKD or control groups. The CKD group was subjected to 5/6 nephrectomy while the control group underwent a sham operation. The animals were observed for 10 weeks at which time they were euthanized and their stomachs, jejunums, and ileums were removed and processed for measurement of TJ proteins.ResultsThe CKD rats showed marked azotemia, systemic oxidative stress, and marked depletion of the key protein constituents of the epithelial TJ (claudin-1, occludin, and ZO1) in the stomach, jejunum, and ileum.ConclusionsThe present study extends the earlier finding of uremia-induced disruption of colonic epithelial TJ by documenting the involvement of the stomach, jejunum, and ileum as well

Cause Analysis of Hindering On-Site Lean Construction for Prefabricated Buildings and Corresponding Organizational Capability Evaluation

As prefabricated buildings play a significant role in the global fight against the new coronavirus “COVID-19,” they attract more global attention than other types of buildings. Lean construction helps to improve the benefits of enterprises and the working environment of workers. However, prefabricated buildings are encountering various challenges in implementing on-site lean construction. According to a cause-and-effect relationship, it will be more meaningful to explore the critical causes hindering on-site lean construction, namely, the critical barriers. Hence, this paper establishes a research methodology framework based on multimethod collaboration, including the exploratory factor analysis model regarding critical barriers, the exploratory factor evaluation model regarding organizational capabilities, and the important findings and suggestions. Thirty-one critical barriers of on-site lean construction for prefabricated buildings are identified via literature analysis, field survey, and semistructured interview. After pre-exploratory factor analysis, thirty critical barriers are finally retained and prioritized, and six common components are extracted and nominated. A large-scale project using the Engineering, Procurement, and Construction (EPC) mode is selected as a case study to evaluate its construction organizational capability to deal with the six common components. The important findings indicate that the inadequate professional management capability of managers is the most critical barrier, and the construction organization from the project case is fully capable of dealing with the common components during on-site lean construction. Six corresponding substantive suggestions are also proposed according to domain experts, and the most prioritized one of them is that an internal training or external recruitment is suggested to solve the inadequate professional management capability of managers. The internal training should take the form of seminars and training courses that invite senior prefabricated project management experts to participate. The external recruitment needs to focus on the management experience, lean skills, and leadership of managers in prefabricated projects. The established methodology framework proposes a new idea for the barrier analysis and corresponding organizational capability evaluation of on-site lean construction from the perspective of the specific prefabricated construction industry rather than the entire construction industry. Due to the special construction mode of prefabricated buildings, it further expands the current boundary of lean construction methodology. The findings and suggestions will provide a valuable reference and guidance for the prefabricated construction industry to solve the barriers regarding on-site lean construction

Abnormalities in Hepatic Lipase in Chronic Renal Failure Role of Excess Parathyroid Hormone

Post-heparin hepatic lipase activity is reduced in chronic renal failure (CRF). This could be due to reduced synthesis, decreased activity, and/or impaired secretion of the enzyme. Further, the factor(s) responsible for such derangements are not elucidated. We examined hepatic lipase metabolism in normal, 6-wk-old CRF rats, CRF-PTX (parathyroidectomized) rats, and CRF and normal rats treated with verapamil (CRF-V, normal-V) using liver homogenate, hepatic cell culture for 8 h, and in vitro liver perfusion. The V max of hepatic lipase in liver homogenate was significantly (P � 0.01) reduced and the K m was significantly (P � 0.01) increased in CRF rats, but the values were normal in CRF-PTX, CRF-V, and normal-V rats. Culture of hepatic cells for 8 h was associated with an increase in hepatic lipase activit

Reversal of biochemical and behavioral parameters of brain aging by melatonin and acetyl L-carnitine.

The potential utility of dietary supplementation in order to prevent some of the oxidative and inflammatory changes occurring in the brain with age, has been studied. The cerebral cortex of 27-month-old male B6C3F1 mice had elevated levels of nitric oxide synthase 1 (EC 1.14.13.39) (nNOS) and peptide nitrotyrosine relative to cortices of younger (4-month-old) animals. After 25-month-old mice received basal diet together with 300 mg/l acetyl L-carnitine in the drinking water for 8 weeks, these levels were fully restored to those found in younger animals. A partial restoration was found when old animals received basal diet supplemented with 200 ppm melatonin in the diet. Levels of mRNA (messenger RNA) for nNOS were unchanged following these treatments implying translational regulation of nNOS activity. Behavioral indices indicative of exploratory behavior were also depressed in aged animals. Dietary supplementation with melatonin or acetyl L-carnitine partially reversed these changes. These findings suggest that dietary supplementation cannot merely arrest but indeed reverse some age-related increases in markers of oxidative and inflammatory events occurring with the cortex