Search

Irradiation of the small intestine can result in depletion of the epithelial stem cell compartment and is often the dose-limiting factor for radiotherapeutic treatment of tumors in the abdominal and pelvic region. Since mitotic cells are most sensitive to radiation, significant radioprotection can be achieved by reducing the number of cells in mitosis at the time of irradiation. We have previously shown that administration of macrophage inflammatory protein (MIP) -1alpha induces a transient 50% reduction in the number of mitotic cells in small intestinal crypts, including the stem cell region, and therefore, MIP-1alpha pretreatment before radiation exposure could result in a substantial reduction of the side effects associated with radiotherapy. Groups of adult mice were exposed to different doses of radiation (6, 8, 10, or 12 Gy), with or without prior administration of 200 microg BB-10010/kg 3 hr before irradiation and radiation damage was assessed by means of the microcolony survival assay. MIP-1alpha pretreatment resulted in significantly increased numbers of surviving crypts (10%) when compared to untreated irradiated animals. The observed radioprotective effects of MIP-1alpha in the small intestine should translate into reduced side effects in a clinically relevant radiotherapy context and could allow larger doses of radiation to be delivered to patients with tumors in the abdominal or pelvic region. [ABSTRACT FROM AUTHOR]

BB10010/MIP-1 alpha reduces the number of proliferating cells in the small intestine, strongly suggesting a radioprotective potential in this organ. This study was designed to optimize BB10010 administration for maximal radioprotection. In single administration protocols 1 or 4 mg/kg of BB10010 was injected into mice 2, 4 or 10 hr before death. In double administration protocols an initial dose of either 0.4 or 200 microg/kg, and a second dose (2.5 hr apart) of 200 microg/kg 4 hr before death were administered. The number of vincristine-arrested metaphases were counted on individually microdissected crypts from the midpoint of the small intestine. When compared to the smaller doses of BB 10010 used in our previous studies, the higher doses used in these experiments did not result in any further reduction in the number of proliferating cells under any of the protocols assessed. Furthermore, some values were found to be above not only those observed with the smaller doses, but also above untreated controls. It is concluded that a single dose of 200 microg/kg of BB10010 offers the most consistent reduction of mitotic cells, and is, therefore, considered optimal for assessment of radioprotection. [ABSTRACT FROM AUTHOR]

Purpose: Irradiation of the small intestine in the mouse induces damaging structural alterations to the architecture of the enteric mucosa. There is growing interest in the possible relevance of underlying additional pathology when appreciating the total response of tissues to irradiation. The possibility that small intestinal mucosal abnormalities in the streptozotocin-induced diabetic mouse may exacerbate radiation-induced injury was tested by examining the combined effects of the two treatments. Materials and methods: Streptozotocin-diabetic and -non-diabetic mice were exposed to 10 Gy abdominal X-radiation. Profiles of mucosal epithelial cell populations were quantified and comparisons with corresponding groups of unirradiated mice made on the third day post-irradiation. Results: The histological appearances of the small intestinal mucosa were similar in both groups of irradiated mice, but the numbers of profiles of crypts and of columnar, goblet, Paneth and entero-endocrine cells were depressed in these groups when compared with values in corresponding groups of unirradiated mice. However, the expression of radiation damage in the diabetic mouse was less severe than in the non-diabetic mouse, particularly in the jejunum where the changes attendant on the onset of diabetes were most marked. Conclusion: These findings suggest that the response of mouse to radiation may be moderated by the presence of this type of pathophysiology. However, there is no evidence that the damage produced by streptozotocin-induced diabetes and radiation is additive. [ABSTRACT FROM AUTHOR]

Background: The small-intestinal epithelium, a rapidly proliferating tissue, is highly sensitive to cycle-specific agents such as radiation. Macrophage inflammatory protein (MIP)-1 alpha has been shown to reduce cell proliferation in bone marrow, seminiferous epithelium, and skin. The current work investigates the activity of an MIP-1 alpha variant, BB-10010, in the gut. Methods: A single dose of either 0.4 μg/kg or 200 μg/kg was administered to mice 2, 4, 6, 8, 10, 12, or 14 h before animal death. Fifteen crypts from the midpoint of the small intestine were dissected from each animal and squashed, and the numbers of vincristine-arrested metaphases was counted for each fifth of the crypts. Results: A 40%-50% reduction of accumulated metaphases throughout all crypt segments was observed in animals injected with 200 μg/kg of BB-10010 2 h and 4 h before death (P < 0.0001). The animals that received 0.4 μg/kg showed a similar effect at 4 h (P < 0.0001). Conclusions: The results provide evidence of a significant reduction in numbers of intestinal cryptal cells passing through mitosis at specific time periods after a single administration of BB-10010. By putting these cells temporarily out of the mitotic phase of the cell cycle this protein might reduce the side effects of radiation therapy to patients undergoing abdominal or pelvic treatments. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the effects of diabetes and insulin resistance during pregnancy on the ex vivo vascular reaction to magnesium. Female Sprague-Dawley rats were made diabetic by intravenous injection of alloxan, or insulin resistant by fructose feeding. The rats were allowed to mate and sacrificed on Day 19 of pregnancy. Aortic rings were isolated and mounted in organ baths for measurement of isometric tension. The rings were contracted with 10(-7) M phenylephrine and cumulative concentration-response curves for magnesium (1-12 mM) were determined in the presence and absence of 10(-4) M Nomega-nitro-L-arginine methyl ester (L-NAME) or 10(-5) M indomethacin. The relaxation response to magnesium was significantly decreased in pregnant rats compared with non-pregnant rats. Pregnant rats with diabetes or insulin resistance had greater impairment in the relaxation responses to magnesium compared with normal pregnant rats. The effects of diabetes and insulin resistance on magnesium-induced relaxation in pregnant rats were not altered in the presence of L-NAME and indomethacin. The results suggest that diabetes and insulin resistance aggravate the alteration in magnesium-induced vascular relaxation observed in pregnancy, and this may be due in part to impairment to mechanisms other than the nitric oxide-cyclic guanosine monophosphate and cyclooxygenase pathways.

The effect of an aqueous extract of Morinda lucida (ML) on vascular tone was tested using rat aortic rings precontracted with noradrenaline (10(-7) mol/l). Relaxation responses were determined with endothelium-intact, L-NAME-treated, methylene blue-treated and endothelium-denuded tissues. In the concentration range of 0.25-9.0 mg/ml, ML elicited vasorelaxation in noradrenaline-precontracted rings. This relaxation response was partially attenuated by removal of the endothelium, and completely inhibited by pretreatment of rings with L-NAME and methylene blue. Thus, ML-induced relaxation of vascular smooth muscle occurs via endothelium-dependent and -independent mechanisms, the former of which involves the nitric oxide-cGMP pathway., (Copyright 2004 Elsevier B.V.)

The effects of MnCl2 on vascular smooth muscle contraction induced by noradrenaline (NA) and KCl were investigated. Rings segments from rat aorta were isolated and changes in isometric tension recorded. MnCl2 (10 microM and 1 mM) significantly attenuated the contractile responses to NA and KCI. There were also reductions in the contractile responses to CaCl2 in NA- and KCl-stimulated rings, after pretreatment with MnCl2. The magnitude of the phasic contraction to NA was significantly reduced in presence of MnCl2. The results suggest that MnCl2 inhibits vascular smooth muscle contraction by influencing a Ca2+-mediated mechanism.

The effect of aqueous extract of petals of Hibiscus sabdariffa (HS) on the established stages of 2-Kidney, 1-Clip renovascular hypertension was investigated in Sprague-Dawley rats. Renovascular hypertension was induced by subjecting the animals to left renal artery clamping using a 0.2mm silver clip under ether anesthesia. Sham-operated (Sh-Op) rats served as controls. Six weeks after renal artery clamping, one group of hypertensive rats (blood pressure (BP) >140 mmHg) received HS (250 mg/kg/day) in drinking water (2K-1C+HS). The second group (2K-1C) and the sham-operated (Sh-Op) controls, received drinking water. BP was monitored weekly using rat-tail plethysmography. After 8 weeks, 2K-1C+HS had a reduction in systolic BP (139.6+/-1.6 mmHg) compared to 2K-1C (174+/-2.4 mmHg, n=5; P<0.001). No significant difference was found in BP of 2K-1C+HS and Sh-Op (139.6+/-1.6 mmHg versus 132+/-3.4 mmHg). A reduction in heart rate in 2K-1C+HS was observed (388+/-3.7 bpm versus 444+/-6.8 bpm in 2K-1C and 416+/-9.3 in Sh-Op, n=5; P<0.001). The hearts of 2K-1C were heavier than those of 2K-1C+HS (0.74+/-0.03 g versus 0.66+/-0.03 g, n=5; P<0.05). Cardiac weight of 2K-1C+HS was comparable to those of Sh-Op (0.57+/-0.04 g). Serum creatinine and plasma electrolytes were not different from controls. This study suggests that HS exhibits antihypertensive and cardioprotective effects in vivo and supports the public belief that HS may be a useful antihypertensive agent.

The present study was undertaken to determine whether vascular responsiveness and endothelial function were altered in rats after 8 weeks of vitamin C treatment. Thoracic aortae were isolated from control and vitamin C-treated rats and analysed for changes in vascular reactivity. Vitamin C treatment attenuated the contractile response of aortic rings to noradrenaline and KCl. Removal of the endothelium increased the sensitivity of control rings but did not alter the effect of vitamin C. Endothelium-dependent relaxation to acetylcholine was significantly (P<0.05) enhanced by vitamin C, but the endothelium-independent relaxation response to sodium nitroprusside was not affected by vitamin C. The results suggest that the endothelium is not involved in the reduction in vascular sensitivity to contractile agonists caused by vitamin C. In addition, the enhancement of endothelium-dependent relaxation may be due to protection of nitric oxide against inactivation by oxygen free radicals.

The effect of oral administration of an aqueous extract of kolanut ( Cola nitida ) on exploration of a Y-maze was investigated in rats. The number of entries made into all the arms of the maze and the frequency of rearing following administration of the extract was determined over 20 min, and repeated 24 h later without administration of the extract. Both the extract (400 and 800 mg/kg) and caffeine (15 mg/kg) caused significant increases in the number of entries, but reduced the frequency of rearing. The extract did not significantly reduce the number of entries after 24 h. It is suggested that kolanut stimulates exploratory locomotor activity due to its caffeine content, but does not enhance habituation.

Caffeine and theobromine contents (mg/g) were determined in samples of selected Nigerian beverage products. The beverages were cocoa (Milo, Bournvita, Rosevita and Enervita), coffee (Nescafe, Bongo, and Maxwell House decaffeinated) and tea (Lipton). The theobromine contents of samples of Milo, Bournvita, Rosevita, Enervita, Nescafe, Bongo, Maxwell House decaffeinated coffee and Lipton were 62.10+/-5.21, 64.80+/-6.72, 82.80+/-4.43, 80.37+/-6.80, 27.00+/-4.31, 14.67+/-2.90, 23.46+/-3.13 and 12.60+/-1.52, respectively. The corresponding caffeine contents of these samples were 2.78+/-0.43 (Milo), 3.17+/-0.36 (Bournvita), 0.92+/-0.51 (Rosevita), 1.05+/-0.68 (Enervita), 93.66+/-8.91 (Nescafe), 6.47+/-2.42 (Bongo), 37.22+/-5.34 (Lipton), and 0.21+/-0.11 (Maxwell House decaffeinated coffee). Semi-processed cocoa beverages (Rosevita and Enervita) had significantly (p < 0.05) higher levels of theobromine compared with the finished cocoas (Milo and Bournvita). Similarly, Nescafe contained significantly (p < 0.05) higher levels of caffeine compared to Maxwell House (decaffeinated coffee) and Bongo. Levels of caffeine in Lipton tea were moderate.

To obtain a clearer understanding of the changes which are induced in the small intestine of the mouse by an ulcerogenic dose of indomethacin, a quantitative analysis of the nonulcerated small intestinal mucosa was performed in mice that were given 2 injections of indomethacin at a dose of 85 mg/kg body weight. At 20 h after the administration of the drug, values were obtained for epithelial volume, whole crypt number, and for the number of profiles of columnar, Paneth, entero-endocrine and goblet cells and cryptal mitotic figures in the small intestine. Comparison of the values obtained from indomethacin-treated mice with those from control mice showed that there were fewer whole crypts and a reduced epithelial volume in the jejunum and ileum in indomethacin-treated mice. The numbers of columnar and Paneth cell profiles and of mitotic figures were significantly greater in the jejunal and ileal crypts in indomethacin-treated mice than in controls. These findings suggest that the administration of high-dose indomethacin in the mouse leads to crypt losses and increased mitotic activity in the nonulcerated parts of the small intestine.

The serous mesothelium of the serosa and mesentery of the small intestine in the mouse were examined by scanning and transmission electron microscopy. The serosa consisted of a single layer of flattened microvilli-bearing cells containing nuclei, caveolae and micropinocytotic vesicles. The observations in this study differed from previous reports on mesothelial surfaces in two respects. A surface layer of amorphous material was present over parts of the serosa. This layer probably represents serous fluid trapped by the mesothelial microvilli but is unaffected by prefixation rinsing in saline or ultrasonic cleaning. The layer is lost following osmication and routine processing for transmission electron microscopy. The possibility that a serous fluid layer may be preserved in this way may be useful in assessing changes in the peritoneum. Stomata were observed in the mesentery but there was no evidence of a connection with the lymphatic system. The presence of mesenteric stomata may explain the difference in permeability reported between parietal peritoneum and mesentery.