Determinants of under-five mortality in rural and urban Kenya.

INTRODUCTION: The disparity in under-five year-old mortality rates between rural and urban areas in Kenya (also reported in other in sub-Saharan African countries), is a critical national concern. The objective of this study was to investigate the influence of geographical location and maternal factors on the likelihood of mortality among under-five children in rural and urban areas in Kenya. METHODS: Data from the 2008-2009 Kenya Demographic and Health Survey were used to determine mortality among under-five children (n=16,162) in rural and urban areas in the 5 years preceding the survey. Multivariate analysis was used to compare the influence of key risk factors in rural and urban areas. RESULTS: Overall, the likelihood of death among under-five children in the rural areas was significantly higher than that in the urban areas (p<0.05). Household poverty was a key predictor for mortality in the rural areas, but the influence of breastfeeding was similar in the two areas. The likelihood of under-five mortality was significantly higher in the rural areas of Coast, Nyanza and Western Provinces than in Central Province. CONCLUSIONS: The study shows that the determinants of under-five mortality differ in rural and urban areas in Kenya. Innovative and targeted strategies are required to address rural poverty and province-specific sociocultural factors in order to improve child survival in rural Kenya.

Nimesulide alters cell recruitment into mitosis in murine intestinal crypts without influencing the cell production rate.

The use of nonsteroidal anti-inflammatory drugs (NSAIDs) that exhibit COX-2 selectivity is associated with fewer gastrointestinal side effects than seen with more traditional NSAIDs. To determine whether the early effects on cell kinetics in the intestinal mucosal epithelium described after COX-2 selective inhibition are sustained following continuous therapy with these inhibitors, assessments of morphometry and cryptal cell proliferation in the murine small intestinal mucosa were made at 24 hr after treatment with indomethacin, a dual COX inhibitor (10 mg/kg body weight intraperitoneally), nimesulide, a selective COX-2 inhibitor (15 mg/kg body weight intraperitoneally), or vehicle. Nimesulide-treated intestine was elongated beyond control values, in contrast to the shorter indomethacin-treated intestine, but anomalous villous forms were present in both treated groups. Both treatments induced expansion and contraction of proliferating compartments in the crypts in different regions of the intestine but nimesulide did not alter crypt cell production rates, in contrast to the down-regulation induced by indomethacin. These findings may provide some of the fundamental basis for the gut-sparing properties seen in patients treated with COX-2 selective inhibitors.

The Stimulatory Effect of Intragastric Administration of Crude Aqueous Extract of Ageratum Conyzoides on Gastric Acid Secretion in Rats

The effect of an aqueous leaf of Ageratum conyzoides on gastric acid secretion in rats was investigated in 18 albino rats of Wistar strain. The rats were divided into 2 groups of 9 each. Gastric acid output was determined by continuous perfusion in urethane anaesthetized rats. Control gastric acid output was obtained usign 0.9

Inhibitory effect of manganese on contraction of isolated rat aorta.

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.

Morinda lucida extract induces endothelium-dependent and -independent relaxation of rat aorta.

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.

Effects of diabetes and insulin resistance in pregnant rats on ex vivo vascular reaction to magnesium.

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.

Role of the endothelium in the vascular effects of vitamin C in rats.

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.

Chronic administration of aqueous extract of Hibiscus sabdariffa attenuates hypertension and reverses cardiac hypertrophy in 2K-1C hypertensive rats.

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.

Vitamin C lowers blood pressure and alters vascular responsiveness in salt-induced hypertension.

The present study was undertaken to investigate the effect of vitamin C treatment on blood pressure and vascular reactivity in salt-induced hypertension. Male Sprague-Dawley rats were fed a normal rat diet, a high-sodium (8% NaCl) diet, a normal rat diet plus vitamin C treament (100 mg x kg(-1) x day(-1)), or a high-sodium diet plus vitamin C treatment for 6 weeks. Salt loading significantly increased blood pressure, which was attenuated by vitamin C treatment. Aortic rings from the different groups were suspended for isometric-tension recording. The contractile response to noradrenaline was significantly increased in the salt-loaded rats. Vitamin C reduced the sensitivity of aortic rings to noradrenaline in rats on normal and high-sodium diets. In noradrenaline-precontracted rings, the relaxation response to acetylcholine, which was attenuated in the salt-loaded rats, was restored by vitamin C treatment. Pretreatment with N(G)-nitro-L-arginine methyl ester (L-NAME) abolished the enhanced response to acetylcholine caused by vitamin C. The results suggest that the antihypertensive effect of vitamin C is associated with a reduction in vascular sensitivity to noradrenaline and enhancement of endothelium-dependent relaxation due to increased nitric oxide bioavailability.

Storage beyond three hours at ambient temperature alters the biochemical and nutritional qualities of breast milk.

The effect of storage on stability of human breast milk was investigated in 30 lactating mothers. Samples stored for 3, 6 and 24 hours at ambient temperature of 302K (29 degrees) were analysed for protein, lactose, pH, and microbial content. There were significant (p < 0.01) decreases in protein, lactose and pH upon storage for 6 and 24 hours, compared with storage for 3 hours as control. The mean +/- SEM values for protein for 6 and 24 hours were 15.56 +/- 0.48 and 13.27 +/- 0.50, compared with 17.26 +/- 0.41 for 3 hours. For lactose, corresponding values for 6 and 24 hours were 0.08 +/- 0.005 and 0.07 +/- 0.006, compared with 3 hours (0.09 +/- 0.005). The pH values were 6.1 +/- 0.09, 5.9 +/- 0.07 in 3, 6 and 24 hour samples rspectively. The skin floras investigated were Streptococcus viridians, Straphylococcus aureus and Staphylococcus albus. The microbial content increased with increase in storage time from 3 to 24 hours. The predominant bacterial specie was S. Albus, followed by S.viridians and S. aureus. A positive correlation (r = 0.453, p < 0.01) between lactose level and pH were obtained. These results suggest that breast milk is stable for 3 hours, beyond which significant changes occur in its biochemical composition and nutritional quality. The implications of these findings are discussed with respect to its consequences on their child's survival.

BB-10010, an analog of macrophage inflammatory protein-1alpha, protects murine small intestine against radiation.

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.

Gastric anti-secretory and anti-ulcerogenic effects of Dombeya buettneri in rats.

The effects of an aqueous extract of the leaves of Dombeya buettneri on gastric acid secretion and ethanol-induced gastric mucosal damage were studied in rats. Gastric acid secretion was measured by continuous perfusion in urethane-anaesthetised rats. Intragastric perfusion with the extract caused significant reduction in basal and histamine-stimulated gastric acid secretion. Pretreatment with the extract also reduced the extent of gastric mucosal damage induced by oral ethanol (75% v/v), but had no effect on mucus secretion. It is suggested that the consumption of an extract of the leaves of D. buettneri may be beneficial in the prevention and treatment of peptic ulcer disease.

Radiation effects in the small bowel of the diabetic mouse.

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.

Dose-effect relationship of BB-10010/MIP-1 alpha on proliferation in murine small intestinal epithelium: single and double administration protocols.

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.

The influence of kolanut (cola nitida) on exploratory behaviour in rats.

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.

BB-10010, an analogue of macrophage inflammatory protein-1 alpha, reduces proliferation in murine small-intestinal crypts.

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 microg/kg or 200 microg/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 microg/kg of BB-10010 2 h and 4 h before death (P < 0.0001). The animals that received 0.4 microg/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.

Caffeine and theobromine levels in selected Nigerian beverages.

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.

A morphological study of the enteric mucosal epithelium in the streptozotocin-diabetic mouse.

In the acutely diabetic rat, the polyphagia-induced increase in the weight of the small intestine is associated with reported increases in mucosal mass. Whereas, some of the individual mucosal components in the rat have been studied, comparable information for the acutely streptozotocin-diabetic mouse is lacking. A detailed morphological comparison of the epithelium of the small intestinal mucosa in control and untreated streptozotocin-diabetic mice was therefore undertaken. Samples from three small intestinal sites were examined by light and scanning electron microscopy and quantitative data obtained from histological sections. Although the morphological appearance of the small intestine in acutely diabetic mice was similar in many respects to literature accounts for the diabetic rat, infestation with filamentous microorganisms was present in the jejunum and ileum. The quantitative data showed that these sites also contained distorted villi, fewer crypt profiles, more goblet and Paneth cell profiles and a smaller epithelial volume in comparison to controls. These findings may represent differences between the rat and mouse models of streptozotocin-induced diabetes mellitus.

Morphometric analysis of the small intestinal epithelium in the indomethacin-treated mouse.

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.

Ultrastructural observations on the peritoneum in the mouse.

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.