Effects of angiotensin II on NaPi-IIa co-transporter expression and activity in rat renal cortex

AbstractThe kidney plays a major role in reabsorption of phosphate with the majority occurring in the proximal tubule (PT). The type IIa sodium-phosphate co-transporter (NaPi-IIa) is the main player in PT. The purpose of current study was to determine the effect of angiotensin II (A-II) on membrane expression of NaPi-IIa in the rat renal cortex. A-II (500 ng/kg/min) was chronically infused into the Sprague–Dawley rats by miniosmotic pump for 7 days. The arterial pressure and circulating plasma A-II level along with urine output were markedly increased in A-II rats. There was diuresis but no natriuresis. The phosphate excretion increased sevenfold on day 4 and 5.7-fold on day 7. There was no change in Na-dependent Pi uptake in brush-border membrane (BBM) vesicles between A-II-treated group and control on day 4, however, there was a 43% increase on day 7. Western blot analysis of NaPi-IIa protein abundance showed a parallel pattern: no change after 4 days of treatment and a 48% increase after 7 days of treatment. However, Northern blot analysis of cortical RNA showed no change in NaPi-IIa mRNA abundance on day 7. A-II stimulation of Na/Pi co-transport activity is a result of increases in the expression of BBM NaPi-IIa protein level and that stimulation is most likely mediated by posttranscriptional mechanisms

Intramural Duodenal Haematoma after Endoscopic Biopsy: Case Report and Review of the Literature

The development of intramural duodenal haematoma (IDH) after small bowel biopsy is an unusual lesion and has only been reported in 18 children. Coagulopathy, thrombocytopenia and some special features of duodenal anatomy, e.g. relatively fixed position in the retroperitoneum and numerous submucosal blood vessels, have been suggested as a cause for IDH. The typical clinical presentation of IDH is severe abdominal pain and vomiting due to duodenal obstruction. In addition, it is often associated with pancreatitis and cholestasis. Diagnosis is confirmed using imaging techniques such as ultrasound, magnetic resonance imaging or computed tomography and upper intestinal series. Once diagnosis is confirmed and intestinal perforation excluded, conservative treatment with nasogastric tube and parenteral nutrition is sufficient. We present a case of massive IDH following endoscopic grasp forceps biopsy in a 5-year-old girl without bleeding disorder or other risk for IDH, which caused duodenal obstruction and mild pancreatitis and resolved within 2 weeks of conservative management. Since duodenal biopsies have become the common way to evaluate children or adults for suspected enteropathy, the occurrence of this complication is likely to increase. In conclusion, the review of the literature points out the risk for IDH especially in children with a history of bone marrow transplantation or leukaemia

Bowel Obstruction Caused by an Intramural Duodenal Hematoma: A Case Report of Endoscopic Incision and Drainage

Complications associated with an intramural hematoma of the bowel, is a relatively unusual condition. Most intramural hematomas resolve spontaneously with conservative treatment and the patient prognosis is good. However, if the symptoms are not resolved or the condition persists, surgical intervention may be necessary. Here we describe internal incision and drainage by endoscopy for the treatment of an intramural hematoma of the duodenum. A 63-yr-old woman was admitted to the hospital with hematemesis. The esophagogastroduodenoscopy (EGD) showed active ulcer bleeding at the distal portion of duodenal bulb. A total of 10 mL of 0.2% epinephrine and 2 mL of fibrin glue were injected locally. The patient developed diffuse abdominal pain and projectile vomiting three days after the endoscopic treatment. An abdominal computed tomography revealed a very large hematoma at the lateral duodenal wall, approximately 10×5 cm in diameter. Follow-up EGD was performed showing complete luminal obstruction at the second portion of the duodenum caused by an intramural hematoma. The patient's condition was not improved with conservative treatment. Therefore, 21 days after admission, endoscopic treatment of the hematoma was attempted. Puncture and incision were performed with an electrical needle knife. Two days after the procedure, the patient was tolerating a soft diet without complaints of abdominal pain or vomiting. The hematoma resolved completely on the follow-up studies

Protective effects of dietary curcumin in mouse model of chemically induced colitis are strain dependent:

Curcumin (diferulolylmethane) has been shown to have a protective role in mouse models of inflammatory bowel diseases (IBD) and to reduce the relapse rate in human ulcerative colitis (UC), thus making it a potentially viable supportive treatment option. Trinitrobenzene sulfonic acid (TNBS) colitis in NKT-deficient SJL/J mice has been described as Th1-mediated inflammation, whereas BALB/c mice are believed to exhibit a mixed Th1/Th2 response

Pharmacodynamics of bisphosphonates in arthritis.

Inflammatory arthritis is a group of autoimmune diseases characterized by chronic inflammation of the joints. Rheumatoid arthritis, the most common form of arthritis, is associated with local joint destruction and systemic bone loss. Osteoclasts, the only cells of the body able to resorbe bone, are key players in these two types of bone loss. Bisphosphonates are analogs of pyrophosphate that inhibit osteoclast action and bone resorption. They are indicated in pathology associated with excess resorption. Besides their effect on bone they also exhibit extra-osseous properties, acting on tumor cells, inflammation and angiogenesis. As a result, they have been trialed in the context of arthritis. It is now clear that they do not have any significant direct effect on disease activity or pain. If their indication in the prevention of glucocorticoid-induced osteoporosis is clear, any beneficial effects on bone erosions are still controversial but interesting preliminary results warrant further investigations

Post-Translational Loss of Renal TRPV5 Calcium Channel Expression, Ca2+ Wasting, and Bone Loss in Experimental Colitis

Dysregulated Ca2+ homeostasis likely contributes to the etiology of IBD-associated loss of bone mineral density (BMD). Experimental colitis leads to decreased expression of Klotho, a protein which supports renal Ca2+ reabsorption by stabilizing TRPV5 channel on the apical membrane of distal tubule epithelial cells

Rapid Downregulation of DAB2 by Toll-Like Receptor Activation Contributes to a Pro-Inflammatory Switch in Activated Dendritic Cells

Dendritic cells (DCs) are pivotal in regulating tolerogenic as well as immunogenic responses against microorganisms by directing both the innate and adaptive immune response. In health, phenotypically different DC subsets found in the gut mucosa are maintained in their tolerogenic state but switch to a pro-inflammatory phenotype during infection or chronic autoinflammatory conditions such as inflammatory bowel disease (IBD). The mechanisms that promote the switch among the mucosal DCs from a tolerogenic to an immunogenic, pro-inflammatory phenotype are incompletely understood. We hypothesized that disabled homolog 2 (DAB2), recently described as a negative regulator of DC immunogenicity during their development, is regulated during intestinal inflammation and modulates mucosal DC function. We show that DAB2 is highly expressed in colonic CD11b+CD103− DCs, a subset known for its capacity to induce inflammatory Th1/Th17 responses in the colon, and is downregulated predominantly in this DC subset during adoptive T cell transfer colitis. Administration of Dab2-deficient DCs (DC2.4Dab2−/− cells) modulated the course of DSS colitis in wild-type mice, enhanced mucosal expression of Tnfa, Il6, and Il17a, and promoted neutrophil recruitment. In bone-marrow derived dendritic cells (BMDC), DAB2 expression correlated with CD11b levels and DAB2 was rapidly and profoundly inhibited by TLR ligands in a TRIF- and MyD88-dependent manner. The negative modulation of DAB2 was biphasic, initiated with a quick drop in DAB2 protein, followed by a sustained reduction in Dab2 mRNA. DAB2 downregulation promoted a more functional and activated DC phenotype, reduced phagocytosis, and increased CD40 expression after TLR activation. Furthermore, Dab2 knockout in DCs inhibited autophagy and promoted apoptotic cell death. Collectively, our results highlight the immunoregulatory role for DAB2 in the intestinal dendritic cells and suggest that DAB2 downregulation after microbial exposure promotes their switch to an inflammatory phenotype

Downregulation of aging-related Klotho gene in experimental colitis: the role of TNF and IFN-γ

Klotho deficiency in hypomorphic KL mice leads to premature senescence and phenotype consistent with impaired mineral homeostasis. Klotho has anti-inflammatory properties protecting from NO-induced endothelial dysfunction, reduces the expression of endothelial adhesion molecules, and may contribute to T-cell dysfunction. Since defective Ca2+/Pi homeostasis leading to osteopenia/osteoporosis is frequently associated with human IBD, we investigated the changes in Klotho gene expression as a consequence of experimental colitis

The Role of Curcumin in Modulating Colonic Microbiota During Colitis and Colon Cancer Prevention:

Intestinal microbiota influences the progression of colitis-associated colorectal cancer (CAC). With diet being a key determinant of the gut microbial ecology, dietary interventions are an attractive avenue for the prevention of CAC. Curcumin is the most active constituent of the ground rhizome of the Curcuma Longa plant, which has been demonstrated to have anti-inflammatory, anti-oxidative and anti-proliferative properties