51 research outputs found
Botanical Knowledge and its Differentiation by Age, Gender and Ethnicity in Southwestern Niger
Indigenous knowledge is unevenly distributed. Individual knowledge level may be affected by many factors such as gender, age, ethnicity, profession, religious and cultural beliefs, abundance and usefulness of the species. This study documents indigenous knowledge of herbaceous and woody plant species of farmers and herders in southwestern Niger. Specifically, we examine the effects of age, gender, and ethnicity on knowledge of local vegetation. Results from the study showed that on average a higher proportion of woody species was identified by the respondents compared to herbaceous species. Both gender and ethnicity had a significant effect on the identification of herbaceous species but no effect on identification of woody species. Respondents in lower age group (10 to 30 years) identified lower number of species compared to other age classes. There seems to be a curvilinear relationship between age of respondents and number of plant species identified. Results from this study reaffirm the uneven distribution of indigenous knowledge within a given area due to social factors. The main challenge is how to incorporate these social differences in knowledge of native plant species into sustainable management and conservation of community natural resources
Efficacy and Safety of Prucalopride in Patients with Chronic Noncancer Pain Suffering from Opioid-Induced Constipation
Opioid-induced constipation (OIC) has negative effects on quality of life (QOL). Prucalopride is a new, selective 5-HT4 agonist and enterokinetic with strong clinical data in chronic constipation. This study investigated the efficacy, safety, and tolerability of prucalopride in patients with noncancer pain and OIC. A phase II, double-blind, placebo-controlled study of 196 patients randomized to placebo (n = 66), prucalopride 2 mg (n = 66) or 4 mg (n = 64), for 4 weeks, was carried out. The primary endpoint was the proportion of patients with increase from baseline of a parts per thousand yen1 spontaneous complete bowel movement (SCBM)/week. Secondary endpoints [proportion of patients with a parts per thousand yen3 SCBM/week, weekly frequency of (SC)BM, severity of constipation, and efficacy of treatment], adverse events (AEs), and safety parameters were also monitored. More patients had an increase from baseline of a parts per thousand yen1 SCBM per week (weeks 1-4) in the prucalopride groups [35.9% (2 mg) and 40.3% (4 mg)] versus placebo (23.4%), reaching statistical significance in week 1. Over weeks 1-4, more patients in the prucalopride groups achieved an average of a parts per thousand yen3 SBM per week versus placebo (60.7% and 69.0% versus 43.3%), reaching significance at week 1. Prucalopride 4 mg significantly improved patient-rated severity of constipation and effectiveness of treatment versus placebo. Patient Assessment of Constipation-Symptom (PAC-SYM) total scores and Patient Assessment of Constipation-Quality of Life (PAC-QOL) total and satisfaction subscale scores were improved. The most common AEs were abdominal pain and nausea. There were no clinically relevant differences between groups in vital signs, laboratory measures or electrocardiogram parameters. In this population with OIC, prucalopride improved bowel function and was safe and well tolerated
Increased cholinergic contractions of jejunal smooth muscle caused by a high cholesterol diet are prevented by the 5-HT(4 )agonist – tegaserod
BACKGROUND: Excess cholesterol in bile and in blood is a major risk factor for the respective development of gallbladder disease and atherosclerosis. This lipid in excess negatively impacts the functioning of other smooth muscles, including the intestine. Serotonin is an important mediator of the contractile responses of the small intestine. Drugs targeting the serotonin receptor are used as prokinetic agents to manage intestinal motor disorders, in particular irritable bowel syndrome. Thus, tegaserod, acting on 5-HT(4 )receptor, ideally should obviate detrimental effects of excessive cholesterol on gastrointestinal smooth muscle. In this study we examined the effect of tegaserod on cholesterol-induced changes in the contractile responses of intestinal smooth muscle. METHODS: The effects of a high cholesterol (1%) diet on the in vitro contractile responses of jejunal longitudinal smooth muscle from Richardson ground squirrels to the cholinergic agonist carbachol were examined in the presence or absence of tetrodrodotoxin (TTX). Two groups of animals, fed either low (0.03%) or high cholesterol rat chow diet, were further divided into two subgroups and treated for 28 days with either vehicle or tegaserod. RESULTS: The high cholesterol diet increased, by nearly 2-fold, contractions of the jejunal longitudinal smooth muscle elicited by carbachol. These cholinergic contractions were mediated by muscarinic receptors since they were blocked by scopolamine, a muscarinic receptor antagonist, but not by the nicotinic receptor antagonist, hexamethonium. Tegaserod treatment, which did not affect cholinergic contractions of tissues from low cholesterol fed animals, abrogated the increase caused by the high cholesterol diet. With low cholesterol diet TTX enhanced carbachol-evoked contractions, whereas this action potential blocker did not affect the augmented cholinergic contractions seen with tissues from animals on the high cholesterol diet. Tegaserod-treatment removed the effects of a high cholesterol diet on neuronal muscarinic receptors, as the potentiating effect of TTX on carbachol-elicited contractions was maintained in these animals. CONCLUSION: A high cholesterol diet causes significant changes to cholinergic neurotransmission in the enteric nerves of the jejunum. The mechanisms by which these effects of cholesterol are reversed by tegaserod are unknown, but relate to removal of an inhibitory effect of cholesterol on enteric nerves
Energy Efficient Branch Prediction for the Cell BE SPU
We propose a power e?cient branch predictor for the Cell SPU, which normally depends on compiler inserted hint instructions to predict taken branches. We designed four predictors all using Branch History Table (BHT) to store the Branch Target Address and the prediction, which is computed using a bimodal counter. The Simple Bimodal Predictor (SBP) predecodes instructions in the Instruction Line Bu?er and accesses the BHT only for a branch instruction and ignores hints. For the second design, four ways to combine hints with the SBP are studied, by not or partially overruling hints by the predictor. We also introduce Branch Warnings (BW). The SPU only accesses the predictor when a BW or a hint is executed and hints can be overruled. The Aggressive Bimodal Predictor is an aggressive implementation of the SBP that starts predicting when instructions are fetched from local store. It is not designed for energy e?ciency but to investigate the maximum possible speedup for a branch predictor not using hints. Results show that a SBP in combination with overruling hints (SBP-OH-NLS) and a 256-entry BHT can have a speedup of 18.8%. The Branch Warning predictor is the fastest in some occasions, however a non optimal compiler makes it the worst for others. The SBP has the lowest performance overall. The estimated extra power needed for the SBP and SBP-OH-NLS is about 1% of the total SPE power and even less for the BW-OH-NLS. The energy-delay product is reduced the most for the SBP-OH-NLS.Computer EngineeringElectrical Engineering, Mathematics and Computer Scienc
Pharmacological characterization of 5-HT(4) receptors mediating relaxation of canine isolated rectum circular smooth muscle
1. This study aimed to characterize for the first time in vitro 5-HT(4) receptors in the canine gastrointestinal tract. For this purpose, we used circular muscle strips of the canine isolated rectum. 2. In the presence of methysergide (60 μM), 5-HT induced relaxation of methacholine (1 μM)-precontracted muscle strips, yielding a monophasic sigmoidal concentration-relaxation curve (pEC(50) 7.2±0.07). 3. Tetrodotoxin (0.3 μM) did not affect the curve to 5-HT, suggesting the inhibitory 5-HT receptor is located on the smooth muscle. Granisetron (0.3 μM) did also not affect the curve to 5-HT, which excludes the 5-HT(3) receptor mediating the relaxation to 5-HT. The presence of methysergide rules out the involvement of 5-HT(1), 5-HT(2) or 5-HT(7) receptors. 4. 5-HT, the selective 5-HT(4) receptor agonists R076186, prucalopride (R093877) and SDZ HTF-919 and the 5-HT(4) receptor agonists cisapride and 5-MeOT relaxed the muscle strips with a rank order of potency R076186=5-HT>cisapride>prucalopride⩾SDZ HTF-919>5-MeOT. 5. The selective 5-HT(4) receptor antagonists GR 125487, RS 39604 and GR 113808 competitively antagonized the relaxations to 5-HT, yielding pK(B) estimates of 9.7, 7.9 and 9.1, respectively. The selective 5-HT(4) receptor antagonist SB 204070 shifted the curve to 5-HT rightward and depressed the maximal response (apparent pA(2) 10.6). GR 113808 (10 nM) produced a parallel rightward shift of the curve to the selective 5-HT(4) receptor agonists R076186 (pA(2) 8.8). 6. It is concluded that 5-HT induces relaxation of the canine rectum circular muscle through stimulation of a single population of smooth muscle 5-HT(4) receptors. For the first time, a non-human species was shown to exhibit relaxant 5-HT(4) receptors in the large intestine
An improved in vitro bioassay for the study of 5-HT(4) receptors in the human isolated large intestinal circular muscle
1. Recently, it was demonstrated that 5-HT induces relaxation of human colon circular muscle through activation of 5-HT(4) receptors and 5-HT(7) receptors. The aim of the current study was to develop a new in vitro bioassay of human colon that would facilitate the pharmacological analysis of 5-HT responses mediated solely by 5-HT(4) receptors. 2. Contracting circular muscle strips with KCl (80 mM) yielded a stable contractile tension and, in contrast to muscarinic cholinoceptor agonists and histamine, a profound reduction of spontaneous contractility. This allowed the establishment of reproducible, fully-defined, agonist concentration-response curves by cumulative dosing. Under these conditions, 5-HT induced a concentration-dependent relaxation (pEC(50) 7.31, Hill slope 0.91). 3. Neither methysergide (10 μM) nor granisetron (1 μM) affected the 5-HT-induced relaxation, suggesting that 5-HT(1), 5-HT(2), 5-HT(3), 5-ht(5), 5-HT(6) or 5-HT(7) receptors are not involved. The lack of effect of tetrodotoxin (0.3 μM) indicated a direct effect of 5-HT on the smooth muscle. 4. The selective 5-HT(4) receptor antagonists GR 113808, GR 125487 and RS 39604 competitively antagonized the 5-HT-induced relaxation (pK(B) 9.43, 10.12 and 8.53, respectively). SB 204070 (1 nM) produced a rightward shift (pA(2) 10.34) and depression of the 5-HT curve. These affinity estimates are similar to those previously reported for 5-HT(4) receptors. 5. The selective 5-HT(4) receptor agonists, prucalopride and R076186, induced relaxations (pEC(50) 7.50 and 7.57, respectively), that were blocked by GR 113808 (3 nM), yielding pA(2) estimates of 9.31 and 9.21, respectively. 6. To summarise, in KCl (80 mM)-contracted muscle strips, 5-HT induces relaxation through activation of a homogeneous smooth muscle 5-HT(4) receptor population. This new bioassay allows the focused, pharmacological characterization of human colonic 5-HT(4) receptors in vitro
Botanical knowledge and its differentiation by age, gender and ethnicity in southwestern Niger
Indigenous knowledge is unevenly distributed. Individual knowledge level may be affected by many factors such as gender, age, ethnicity, profession, religious and cultural beliefs, abundance and usefulness of the species. This study documents indigenous knowledge of herbaceous and woody plant species of farmers and herders in southwestern Niger. Specifically, we examine the effects of age, gender, and ethnicity on knowledge of local vegetation. Results from the study showed that on average a higher proportion of woody species was identified by the respondents compared to herbaceous species. Both gender and ethnicity had a significant effect on the identification of herbaceous species but no effect on identification of woody species. Respondents in lower age group (10 to 30 years) identified lower number of species compared to other age classes. There seems to be a curvilinear relationship between age of respondents and number of plant species identified. Results from this study reaffirm the uneven distribution of indigenous knowledge within a given area due to social factors. The main challenge is how to incorporate these social differences in knowledge of native plant species into sustainable management and conservation of community natural resources
Nitric oxide is involved in 5-HT-induced relaxations of the guinea-pig colon ascendens in vitro.
1. In the guinea-pig colon ascendens, 5-hydroxytryptamine (5-HT) induces contractions, mediated by 5-HT2, 5-HT3 and 5-HT4 receptors, and relaxations, through a 5-HT1 receptor subtype, that triggers the release of an inhibitory neurotransmitter. Nitric oxide (NO) is one of the main candidates of NANC inhibitory neurotransmission in the gut. The aim of this study was to establish whether NO is involved in 5-HT-induced relaxations of the guinea-pig colon ascendens. 2. Antagonists to block the contractile responses to 5-HT via 5-HT2, 5-HT3 and 5-HT4 receptors were present throughout the experiments and methacholine was administered to precontract the strips. Under these conditions, 5-HT concentration-dependently induced relaxations from 10 nM onwards (EC50 = 258 (172-387) nM). The relaxations were inhibited by metergoline (10 nM) and methiothepine (100 nM) and abolished by tetrodotoxin (TTX, 320 nM). Guanethidine (3.2 microM) did not affect them. 3. NG-nitro-L-arginine (L-NNA) inhibited the responses to 5-HT (IC50 = 18.7 (13.3-26.3) microM); at the highest 5-HT concentration a maximum inhibition of about 75% was observed with 320 microM L-NNA. This inhibition was reversed with L-arginine. Relaxations to glyceryl trinitrate (GTN) were not inhibited by L-NNA. 4. Haemoglobin (32 microM) inhibited the relaxations to 5-HT and GTN, but not those to isoprenaline (Iso). Methylene blue (10 microM) inhibited the relaxations to 5-HT but did not affect those caused by GTN or Iso. 5. It is concluded that 5-HT induces relaxations that involve NO.(ABSTRACT TRUNCATED AT 250 WORDS
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