Supplement With Calcium or Alendronate Suppresses Osteopenia Due to Long Term Rabeprazole Treatment in Female Mice: Influence on Bone TRAP and Osteopontin Levels.

BACKGROUND AND PURPOSE: Rabeprazole, a proton pump inhibitor (PPIs) is much endorsed to patients with increased gastric acidity. PPIs were accused to have osteoporotic effects on patients who chronically use them. The point of the current investigation was to decide the impact of rabeprazole on osteoporosis and to explore the modulatory effects of dietary calcium or alendronate on this side effect. METHODS: 80 female mice were alienated into four groups maintained for 18 weeks: [1] Vehicle group: given distilled water in 12 ml/kg, P.O. [2] Rabeprazole control group: given rabeprazole in a dose equals 10 mg/kg every 48 h, P.O. [3] Rabeprazole + calcium: given rabeprazole (10 mg/kg every 48 h) along with calcium supplement. [4] Rabeprazole + alendronate: given rabeprazole (10 mg/kg every 48 h) and alendronate (1 mg/kg per week, i.p.). Serum calcium, phosphorus and parathyroid hormone were measured. Both femurs were kept in paraformaldehyde, and then the right one was used for X-ray examination with analysis by Digora software and the left one for histopathological examination (H&E) and immunohistochemical stains for osteopontin and tartrate resistant acid phosphatase (TRAP). RESULTS: Calcium supplementation or administration of alendronate along with rabeprazole significantly restored the mean bone density as shown by X-ray analysis. Femurs from mice received rabeprazole showed widely separated, thin-walled bone trabeculae and increased number of osteoclasts. Calcium or alendronate with rabeprazole showed thick bone trabeculae without full recovery from rabeprazole induced damage. Adding calcium supplementation to rabeprazole did not affect the histological abnormalities related to osteoclasts meanwhile alendronate produced inactivation of osteoclasts. Both calcium and alendronate decreased the rabeprazole-induced increment in the femur osteopontin level. CONCLUSION: Calcium or alendronate can be recommended for female patients on PPI therapy who are at risk of osteopenia.

Exenatide suppresses 1,2-dimethylhydrazine-induced colon cancer in diabetic mice: Effect on tumor angiogenesis and cell proliferation.

Colon cancer is the third leading cause of cancer mortality worldwide, which results from interactions of different factors. It is frequently a pathological consequence of persistent inflammation. Diabetes affects several cancers and is positively correlated with the incidence of colon cancer. This study aimed to study the effect of exenatide in ameliorating inflammation, angiogenesis and cell proliferation in 1,2-dimethyl hydrazine (DMH) induced colorectal carcinoma in diabetic mice. Mice were randomly allocated into six groups, 8 mice each. Group 1: vehicle control group. Group 2: diabetic control group. Group 3: DMH control group: diabetic mice treated with DMH (20mg/kg/week,s.c.) for 15 week. Group 4: DMH-cisplatin group: mice received cisplatin (4mg/kg/week, i.p.). Groups 5 & 6: DMH-exenatide (10 and 20µg/kg) group: mice received exenatide (10 or 20µg/kg/day,s.c.), respectively. The present results highlighted an increase in angiogenic markers and cell proliferation in the DMH-diabetic group in comparison with the control group with greater expression of endothelial marker (CD34) and Ki-67 in colon tissue. Monotherapy with cisplatin or exenatide (10 and 20µg/kg) downregulated these markers to different extents. The current results provided evidence that exenatide represents a promising chemopreventive effect against DMH-induced colon carcinogenesis in diabetic mice, at least in part, attributed to its anti-angiogenic and anti-proliferative mechanisms.

Effect of human umbilical cord blood progenitor cells versus mononuclear cells on acute renal failure rat model.

BACKGROUND: Acute renal failure (ARF) resulting from ischemic or toxic insults remains a major health care problem because of its grave prognosis and the limited effectiveness of available treatment modalities. Current treatment options for ARF are limited to supportive measures and preventive strategies, none of which have been definitively shown to alter mortality. AIM: To assess the ability of human umbilical cord blood CD34(+) (HUCB CD34(+)) cells and mononuclear (HUCB MNC) cells to improve renal function of nephrotoxic kidney. METHODS: ARF was induced in 30 rats by glycerol. After 24 hours, ARF was confirmed by increased blood urea nitrogen (BUN), serum urea and creatinine levels. The rats were divided into 3 groups, group one included 10 rats treated with HUCB CD34(+) cells, group two included 10 rats treated with HUCB MNC and group three included 10 rats treated with normal saline. Five rats were included in the study as a normal control group. Serial measurement of BUN, serum urea and creatinine levels were done every three days throughout the study. To proof homing of HUCB CD34(+) into renal tissue, Y chromosome detection in renal tissue was carried out using Real time polymerase chain reaction (PCR) technique. RESULTS: Four days after the therapy, the renal function of CD34(+) and MNC treated rats improved in comparison to saline treated rats. After 2 weeks of therapy and at the end of the study (28 days), ANOVA test revealed that, there was significant difference between the four studied groups (P=.000). Y chromosomes were detected in kidneys of CD34(+) treated rats and MNC treated rats. CONCLUSION: HUCB CD34(+) cells and HUCB MNC improve renal function of nephrotoxic kidney with superiority to the HUCB MNC.