Bombesin Receptor Subtype-3 in Human Diseases.

This review summarizes the recent findings of the roles of bombesin receptor subtype-3 (BRS-3) in various patho-physiological conditions. Studies have demonstrated that two mammalians bombesin-like peptides, GRP and NMB, exhibit a large range of functions by binding to three receptors. Knockout studies showed that the mice BRS-3 has important effects on tumor growth, energy homeostasis, glucose regulation, satiety, and lung development (1,7). BRS-3 is an orphan receptor whose natural ligand is unknown. However, several agonists and antagonists have been synthesized which facilitate its characterization, (D-Tyr6, ß-Ala11, Phe13, Nle14) Bn-(6-14) and MK-5046 are agonists, whereas ML-18 and Bantag-1 are antagonists. With the development of several selective, high-affinity BRS-3 agonists and antagonists, recent studies provided some insights into the biological effects of BRS-3 in several disease states including lung cancer, obesity, diabetes mellitus, asthma, and kidney diseases.

Functional and structural alterations of peritoneum and secretion of fibrotic cytokines in rats caused by high glucose peritoneal dialysis solutions.

OBJECTIVE: To determine functional and structural alterations of peritoneum and fibrotic cytokines expression in peritoneal dialysis (PD) rats. METHODS: 28 Sprague-Dawley (S-D) rats were randomly divided into four groups and dialyzed with various solutions daily for four weeks: (1) no solution (CON group), (2) 0.9% Saline solution (NS group), (3) 1.5% Dianeal (LG group), (4) 4.25% Dianeal (HG group). Peritoneal equilibration tests, ultrafiltration function and effluent protein quantification were measured. Peritoneum morphology was studied and immunohistochemistry were performed for detection of transforming growth factor ß1 (TGF-ß1), connective tissue growth factor (CTGF), and fibronectin (FN) proteins. Reverse transcriptional-polymerase chain reaction was used to analyze the expression of TGF-ß1, CTGF mRNA. RESULTS: Administration of 4.25% Dianeal caused functional and structural changes of peritoneum, including protein loss through the transport process, decrease of peritoneal solute transport rate and ultrafiltration capacity. The collagen of peritoneum in the HG group was thicker than the other groups. The levels of CTGF, TGF-ß1, and FN proteins were significantly the highest in the HG group, followed by the LG group. The liner correlation analysis showed positive correlations between the levels of CTGF, TGF-ß1, and FN proteins and the collagen thickness. The expression of TGF-ß1 and CTGF mRNA in the HG group were significantly higher than those in the other groups and were indicated positive correlation. CONCLUSION: Using high glucose peritoneal dialysis solutions in rats may not only lead to processing of peritoneal fibrosis, which is promoted by ectopic expression of TGF-ß1, but also increase the expression of CTGF. CTGF is an important fibrotic media of peritoneal fibrosis in PD rats.

Aged rats are susceptible to nephrotoxicity induced by iodinated contrast media.

OBJECTIVE: The objective of this study is to evaluate the effect and mechanism of aging on iodinated-contrast-media-induced nephropathy in male rats. METHODS: Twenty-four healthy male rats were initially divided into 12-month-old and 24-month-old age groups (adult and older age groups, respectively; n = 12/group); subsequently, each age group was randomly divided into saline control (NS) and contrast media (CM) groups (n = 6/group). CM (76% diatrizoate, 10 mL/kg b.w.) was given through the caudal vein. Urinary creatinine (Ucr) and serum creatinine (Scr) were detected by an automatic biochemical analyzer. The activities of renal malondialdehyde (MDA), superoxide dismutase (SOD), angiotensin-converting enzyme (ACE), angiotensin II (Ang II), and reduced form of nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase) were determined by spectrophotometric assays with commercially available kits according to the manufacturers' protocols. Renal histological changes were observed by hematoxylin and eosin staining and scored semiquantitatively. RESULTS: In diatrizoate-injected aged rats, Scr, the activities of ACE, Ang II, MDA, and NADPH oxidase in renal tissues were significantly increased (p < 0.01). The histologic scores were higher in the aged animals with CM treatment than those of control or adult rats (p < 0.01). There was an increasing trend but no significant statistical difference in renal ACE, Ang II, MDA, and NADPH oxidase or histologic scores in adult CM-injected rats compared with control animals (p > 0.05). CONCLUSIONS: Older age is an aggravating factor of iodinated-contrast-media-induced nephropathy in male rats. Oxidative stress and the renin-angiotensin system (RAS) may play an important role in nephrotoxicity induced by iodinated contrast media, especially in aged male rats.

Evaluation of renal clinicopathological changes in IgA nephropathy by urinary podocytes excretion and podocalyxin expression.

OBJECTIVE: To explore the association of urinary podocyte excretion and renal expression of podocyte-specific marker podocalyxin (PCX) with clinicopathological changes in immunoglobulin A nephropathy (IgAN). METHODS: Morning urine samples from IgAN patients and healthy controls were collected. The expression of glomerular PCX was quantified in 50 IgAN patients diagnosed by renal biopsy. IgAN was classified based on the Lee's Grading system and scored according to the Katafuchi semiquantitative criteria. Morphological evaluation of podocyte was determined by electron microscopy. RESULTS: The amount of urinary podocytes in the IgAN patients was significantly higher than that in the healthy controls (p < 0.01). Pairwise comparison among Lee's grades of IgAN showed that the median of urinary podocytes in Lee's I-II group was lower than that in Lee's III, IV, and V groups (p < 0.05); group III lower than group V (p < 0.05). The positive rate of urinary podocytes was the highest in Lee's IV and V groups (100%), and lowest in Lee's I-II group (55%). Multiple comparison among groups of Lee's grades of IgAN showed that the glomerular PCX expression in Lee's I-II group was higher than that in Lee's III, IV, and V groups (p < 0.05); groups III and IV higher than group V (p < 0.05). The amount of urinary podocytes in IgAN patients was negatively correlated with PCX expression (r = -0.702, p < 0.01), but positively correlated with 24-h urinary protein (r = 0.465, p < 0.01) and glomerular (r = 0.233, p < 0.01) and renal tubular pathological scores (r = 0.307, p < 0.05). The glomerular PCX expression was negatively correlated with 24-h urinary protein (r = -0.367, p < 0.05) and glomerular (r = -0.560, p < 0.05) and tubular pathological scores (r = -0.377, p < 0.05). Electron microscopy showed significant changes in podocytes of IgAN, especially in the foot process. CONCLUSION: The amount of urinary podocyte can reflect the loss of podocytes in renal tissue, which may be a marker of IgAN progression.

[Prognosis comparison in middle and later stage severe hepatitis B patients treat with plasma exchange or unified medicine therapy].

OBJECTIVE: To observe the influence on the prognosis of the patients with severe hepatitis B in middle and later stage treated with plasma exchange or unified medicine therapy, and search the therapy methods on the middle and later stage severe hepatitis B. METHODS: To observe the liver function, complications and prognosis of the patients treated with plasma exchange on the basis of unified medicine therapy. To compare with that of the corresponding period patients with unified medicine therapy and analysis the clinical data with statistics methods. RESULTS: 36 cases of the plasma exchange group, 18 cases survived and 18 cases died. 32 cases of the unified medicine therapy group, 13 cases survived and 19 cases died. The survival rates between the two groups patients does not appear statistics difference;liver function index (ALT, AST, SB, ALB, TC, ChE) and PT also appear the same results in statistics. CONCLUSIONS: Compare with unified medicine therapy, plasma exchange on the basis of the unified medicine therapy does not appear to improve survival rate of the patients with the middle and later stage severe hepatitis B. The prognosis of these patients determined by the liver failure extent itself.

[Influence of plasma exchange on serum cytokines in severe viral hepatitis patients].

OBJECTIVE: To evaluate the changes of serum cytokines vary with plasma exchange (PE) therapy in patients with severe viral hepatitis. METHODS: Forty patients suffering from severe liver failure were randomized and treated by PE therapy. The tumor necrosis factor-alpha (TNF-alpha), interleukin-4 (IL-4) levels and liver function before and after PE therapy were examined. Moreover, the relation of TNF-alpha, IL-4 levels and the efficacy of PE, liver function and the compliment were also observed. RESULTS: It showed that the TNF-alpha and IL-4 level of the serum were decreased after PE therapy. The TNF-alpha level of the serum was(79.32+/-22.39) ng/L before treatment and (20.01+/-22.25) ng/L after treatment (P<0.001), IL-4 was(0.61+/-0.07) ng/L before treatment and (0.57+/-0.06) ng/L after treatment (P<0.01). There were more differences between recovering patients and worsen ones (P<0.05 or P<0.01). There was remarkable difference between recovering patients and worsen ones in the liver function improvement (P<0.05 or P<0.01), the severe symptom ( P<0.01 and P<0.05) and the complication (P<0.01). CONCLUSION: PE therapy can effectively purge or reduce TNF-alpha, IL-4 and is a method treating and preventing the complication. The worsen patients have continuous inflammation and higher level of TNF-alpha and IL-4.