Histological analysis of the intestinal wall of newborn rats submitted to hypoxia and reoxygenation to evaluate the protective effect of N-Acetylcysteine

Abstract Purpose To evaluate the effect of N-Acetylcysteine (NAC) in newborn rats submitted to hypoxia and reoxygenation (H/R) conditions in an experimental model of necrotizing enterocolitis. Methods Eight pregnant rats and their 70 cubs were used (5 groups) and exposed to H/R conditions and received NAC at different times. The animals in the H/R groups were placed in a gas chamber (100% CO2) for 10 minutes and then reoxygenated for 10 minutes (100% O2), twice a day for the first three days of life, with a six-hour span between events. On the third day of life, the animals were anesthetized, laparotomized and the intestines were resected. Results The H/R and NAC groups showed changes in the intestinal wall in relation to the number, height and width of the villi when compared to the control group (p<0.0001), but with better preservation of structures in the NAC group. There were no differences between groups regarding the number (%) of mitoses. Conclusion The administration of NAC decreased the lesions in the intestinal wall of rats submitted to H/R, therefore suggesting that this drug can be used to prevent the development of necrotizing enterocolitis in newborns.

Glabridin alleviates ischemia/reperfusion-induced functional failure of smooth muscle of rat ileum by upregulating the cAMP / Glabridin alivia la falla funcional inducida por isquemia/reperfusión del músculo liso de ileum murino regulando el incremento de cAMP

Despite the development of modern medicine, alternative medicine, which has not lost its timeliness, remains attractive for the treatment of various diseases. Glabridin, a major flavonoid of Glycyrrhiza glabra, is known for its antioxidant and anti-inflammatory activity. The aim of this study was: 1) to determine the possible protective role of glabridin against ischemia/reperfusion (I/R) injury of the intestine; 2) to evaluate the in vitrocontractile responses of ileum smooth muscles to acetylcholine after an intestinal I/R; and 3) to explain the underlying molecular mechanism of its effect. Rats were assigned to groups of six rats each; 1) I/R, 2) gla10, 3) gla20, 4) gla40, 5) N5-[imino(nitroamino)methyl]-L-ornithine, methyl ester monohydrochloride (L-NAME)+gla40, and 6) Sham group. The healing effect of glabridin was abolished by L-NAME. Glabridin did not cause contractility of the smooth muscles to acetylcholine-induced contractile responses in intestinal I/R. Yet, it increased to spontaneous basal activity.

A pesar del desarrollo de la medicina moderna, la medicina alternativa, sin perder su vigencia, sigue siendo atractiva para el tratamiento de varias enfermedades. Glabradina, el flavonoide mayoritario de Glycyrrhiza glabra, es conocido por su actividad antioxidante y antiinflamatoria. Los propósitos de este estudio fueron: 1) Determinar el posible rol protector de glabradina ante daños intestinales por isquemia/reperfusion (I/R) 2) Evaluar in vitrolas respuestas de contracción de los músculos lisos del ileum ante acetilcolina después de I/R intestinal; y 3) Explicar el mecanismo molecular subyacente de este efecto. Se asignaron grupos de seis ratas: 1) I/R, 2) gla10, 3) gla20, 4) gla40, 5) N5-[imino(nitroamino)metil]-L-ornithina, metil ester monohidrochloruro (L-NAME)+gla40, y 6) Grupo testigo. El efecto curativo de glabridina fue abolido por L-NAME. Glabridina no causó contracción en el músculo liso como respuesta acetilcolina-inducida I/R. Además, incrementa la actividad basal expontánea.

Intestinal inflammatory and redox responses to the perioperative administration of teduglutide in rats

Abstract Purpose: To investigate the inflammatory and redox responses to teduglutide on an animal model of laparotomy and intestinal anastomosis. Methods: Wistar rats (n=62) were allocated into four groups: "Ileal Resection and Anastomosis" vs. "Laparotomy", each one split into "Postoperative Teduglutide Administration" vs. "No Treatment"; and euthanized at the third or the seventh day. Ileal and blood samples were recovered at the baseline and at the euthanasia. Flow cytometry was used to study the inflammatory response (IL-1α, MCP-1, TNF-α, IFN-γ and IL-4 levels), oxidative stress (cytosolic peroxides, mitochondrial reactive species, intracellular glutathione and mitochondrial membrane potential) and cellular viability and death (annexin V/propidium iodide double staining). Results: Postoperative teduglutide treatment was associated with higher cellular viability index and lower early apoptosis ratio at the seventh day; higher cytosolic peroxides level at the third day and mitochondrial overgeneration of reactive species at the seventh day; higher tissue concentration of IL-4 and lower local pro-to-anti-inflammatory cytokines ratio at the seventh day. Conclusion: Those findings suggest an intestinal pro-oxidative and anti-inflammatory influence of teduglutide on the peri-operative context with a potential interference in the intestinal anastomotic healing.

Effects of quercetin-supplementation in NADH-diaphorase positive neurons subpopulations in the ileum of rats with experimental diabetes mellitus / Efectos de la suplementación con quercetina en subpoblaciones de neuronas NADH-diaforasa positivas en el Ileon de ratas con diabetes mellitus experimental

The effects of quercetin supplementation in NADH-diaphorase positive (NADH-d) neurons of streptozotocin-induced diabetic rats was carried in this study. Fifteen male rats were divided into three groups: normoglycemic (N), diabetic (D) and diabetic supplemented with quercetin (DQ). Whole mount preparations of the muscular layer of the ileum underwent NADH-d histochemistry for evidencing the NADH-d neuronal subpopulation. Quantitative analyzes were performed on 30 random fields, and morphometric analyzes in 100 neuronal bodies and nuclei per animal. The supplementation promoted a 44 % reduction in the neuronal density in D group when compared to N group (p <0.001); a 24.5 % reduction was observed in the DQ group when compared to N (p <0.01). Animals in D group presented an 18.7 % increase in the cell body areas of myenteric neurons when compared to N (p <0.001); DQ group showed a 14.2 % decrease in neuronal areas when compared to D (p <0.01); the nuclear area were similar among the three groups. We conclude that quercetin supplementation was positive for animals with diabetes mellitus.

Se estudiaron los efectos de la suplementación con quercetina en neuronas NADH-diaforasa positiva (NADH-d) de ratas diabéticas inducidas por estreptozotocina. Quince ratas machos se dividieron en tres grupos: normoglicémico (N), diabéticos (D) y diabéticos suplementados con quercetina (DQ). Las cortes montados de la capa muscular del íleon fueron sometidos a histoquímica de NADH-d para evidenciar la subpoblación neuronal NADH-d. Se realizaron análisis cuantitativos en 30 campos aleatorios y análisis morfométricos en 100 cuerpos y núcleos neuronales, por animal. La suplementación promovió una reducción del 44 % en la densidad neuronal en el grupo D cuando se comparó con el grupo N (p <0,001). Se observó una reducción del 24,5 % en el grupo DQ en comparación con N (p <0,01). Los animales del grupo D presentaron un aumento del 18,7 % en las áreas del cuerpo celular de las neuronas mientéricas cuando se compararon con N (p <0,001). El grupo DQ mostró una disminución de 14,2 % en las áreas neuronales en comparación con D (p <0,01). El área nuclear fue similar entre los tres grupos. Se concluye que la suplementación con quercetina fue positiva para animales con diabetes mellitus.

Verapamil and loperamide; to compare the inhibitory effects on isolated guinea pig ileum

In smooth muscle cells, an increase in cytosolic free calcium concentration is an essential step for the cells to contract. The increase in calcium concentration occurs by influx from the extra cellular medium through calcium ion channels. Calcium channels have potential role in regulation of motility in gastrointestinal tract so there is growing interest in calcium channel blockers as a potential pharmacological approach to the treatment of various gastrointestinal motor disorders. In this study we evaluate the inhibitory effects of verapamil on spontaneous contractions of isolated guinea pig ileum and compare them with inhibitory effects of loperamide. Isolated intestinal segments of sixteen guinea pigs were used in this study. Serial dilutions [10-18 -10-3 gm/ml] of loperamide and verapamil were administered; effects observed and recorded by 7B Grass Polygraph machine. We observed that at lower concentrations, loperamide showed more inhibitory effects than verapamil while at higher concentrations [10-4 and 10-3 gm/ml] verapamil showed more inhibitory effects than loperamide on the contractions of isolated guinea pig ileum. This study gave us a clue that verapamil found a potent inhibitor of small intestinal contractions as loperamide. However one can presume further that calcium channel blocker verapamil acting on calcium channel receptor on GIT will be developed with more specific effects on smooth muscle of intestinal tract

[Effect of hydroalcoholic extract of valeriana officinalis root on the ileum contraction on Guinea pig]

Valeriana Officinalis administrated for treatment of many gastrointestinal disorders traditionally and probably reduced smooth muscle contraction and bowel movement. The aim of this study was to determine the effect of Valeriana Officinalis extract on Ileum contraction of Guinea pig ileum in In Vitro model. This experimental study done on five male Guinea pigs. The animals were sacrificed and the pieces of ileum with 2-3 cm long [at least 6 pieces] dissected and established in normal Tyrod solution plus Carbogen gas in 37°C. Tissue fixed between of two electrodes that connected to stimulator apparatus. The contraction of ileum carried to physiograph by isotonic transducer and recorded. A solution with 5 concentration of Valeriana Officinalis extract was added to the organ bath during ileum stimulation with stimulator and the muscle contraction recorded in 7 responses. Hydroalcoholic extract of Valeriana Officinalis root in concentrations of 5, 15, 50, 150, 500 mg/ml during 0.1 Hz stimulation decreased Ileum contractions in a dose dependent manner. The percent of reduce contraction was 34.45%, 36.07%, 47, 53%, 56.42%, and 76.22% respectively. Also Ec50% of this effect of Valeriana Officinalis was found to be 50 mg/ml [P<0.05]. This study showed that Valeriana Officinalis extracts can decrease ileum contraction in dose dependent manner

Effect of Itopride Hydrochloride on the Ileal and Colonic Motility in Guinea Pig In Vitro

PURPOSE: Itopride hydrochloride (itopride) inhibits acetylcholinesterase (AChE) and antagonizes dopamine D(2) receptor, and has been used as a gastroprokinetic agent. However, its prokinetic effect on the small bowel or colon has not yet been thoroughly investigated. The aim of this study was to investigate the effects of itopride on motor functions of the ileum and colon in guinea pigs. MATERIALS AND METHODS: The distal ileum was excised and the activity of peristaltic contraction was determined by measuring the amplitude and propagation velocity of peristaltic contraction. The distal colon was removed and connected to the chamber containing Krebs-Henseleit solution (K-H solution). Artificial fecal matter was inserted into the oral side of the lumen, and moved toward the anal side by intraluminal perfusion via peristaltic pump. Colonic transit times were measured by the time required for the artificial feces to move a total length of 10cm with 2-cm intervals. RESULTS: In the ileum, itopride accelerated peristaltic velocity at higher dosage (10(-10)-10(-6)M) whereas neostigmine accelerated it only with a lower dosage (10(-10)-10(-9)M). Dopamine (10(-8)M) decelerated the velocity that was recovered by itopride infusion. Itopride and neostigmine significantly shortened colonic transit at a higher dosage (10(-10)-10(-6)M). Dopamine (10(-8)M) delayed colonic transit time that was also recovered after infusion of itopride. CONCLUSION: Itopride has prokinetic effects on both the ileum and colon, which are regulated through inhibitory effects on AChE and antagonistic effects on dopamine D(2) receptor.

Mechanism of spasmolytic activity of a fraction of Sarcostemma brevistigma Wight.

The effect of chloroform soluble fraction (F-A) of twigs of Sarcostemma brevistigma on contractions induced by KCl, histamine, and acetylcholine in the isolated guinea pig ileum and taenia coli smooth muscles has been evaluated. F-A (19.5 microg/ml) significantly inhibited the contraction induced by 40 mM KCl to the extent of 87.6% in the isolated guinea pig ileum. In the isolated guinea pig ileum, F-A (64.3 and 59.2 microg/ml) significantly inhibited the contractions induced by acetylcholine and histamine to the extent of 85 and 83% respectively. In the isolated guinea pig taenia coli, F-A (65.2 microg/ml) significantly inhibited the contraction induced by 40 mM KCl to the extent of 96.0%. The inhibitory effect of F-A (40 microg/ml) on the isolated guinea pig taenia coli was reduced by Bay K 8644 (10(-6) M) to the extent of 61.6 from 73.6%. These results suggest that the F-A may exhibit smooth muscle relaxant activity by blocking the Ca2+ channels.

Antispasmodic effect of Tecoma stans [L.] Juss leaf extract on rat ileum

Tecoma stans [L.] Juss or Yellow bells from Bignoniaceae is a ornamental tropical shrub or small tree predominantly found in central, and south America and in Latin America is used traditionally for reducing blood glucose. However, its other pharmacological effects have not been yet elucidated. The aim of present study was to investigate the effect of its leaves extract on rat ileum contractility and involved mechanism[s]. Tecoma stans Juss hydroalcoholic leaf extract [TLE] was prepared by macerated method using 70% alcohol. Distal segment of ileum [2 cm] from male Wistar rat was mounted in an organ bath containing Tyrode solution [10 ml, pH 7, 37 °C] and pre-contracted by carbachol [CCh, 10 micro M] or by KCl [60 mM]. The antispasmodic effects of TLE [0.125-2 mg/ml] were studied prior and after 20-30 min incubation of ileum with propranolol [1micro M], naloxone [1micro M], L-NAME [100 micro M], or 5 min incubation with glibenclamide [10 micro M] and tetraethylammonium [TEA, 1mM]. The effect of TLE on CaCl[2]-induced contraction in Ca[2+] -free with high K[+] Tyrode solution was also studied. The CCh- and KCl-induced ileal contractions were reduced by TLE [P<0.0001]. This effect was not attenuated by propranolol, naloxone, L-NAME, glibenclamide and TEA. In Ca[2+]-free Tyrode solution with high K[+], cumulative concentrations of CaCl2 induced contractions which were inhibited by TLE dose-dependently. Our results indicate that the Tecoma stans [L.] Juss leaf extract induces its antispasmodic effects without involvement beta-adrenoceptors, opioid receptors, potassium channels and NO production. It seems that, the calcium channels are involved in this spasmolytic effect

[Anti spasmolytic effect of Glycyrrhiza glabra leaf on rat ileum contractions]

Glycyrrhiza glabra is a type of plant that a lot of researches have been carried out on components and properties of its licorice but the effect of its leaf extract has not been evaluated. Therefore, this study was aimed to investigate the effect of Glycyrrhiza glabra leaf extract on rat ileum contractions. In this experimental study, the terminal portion of ileum from male Wistar rat was contracted under 1 gram tension by 60 mM KCl and/or 10 micro M carbachol and then the effect of aquatic extraction of Glycyrrhiza glabra on the contractions was assessed. The new portions of the ileum were separately incubated with propranolol [1micro M], naloxone [1 micro M], inhibitor of nitric oxide synthetize [L-NAME] [100 micro M], glibenclamide [10mM] and tetraethyl ammonium [1 micro M] and the tissue spasm and antispasmodic effect of the extract were recorded. Data were analyzed using one and two way analysis of variance and post hoc LSD tests. Cumulative concentrations of the extract [0.0625-0.5mg/ml] reduced the ileum contractions induced by KCl and carbacole, dose-dependently [P<0.001]. Incubation of the tissue with propranolol, naloxone, L-NAME, and tetraethyl ammonium did not reduce the antispasmodic effect of the extract, but it was reduced by glibenclamide [0.125mg/ml]. In Tyrode-containing solution, without calcium and with high concentrations of potassium [60 micro M], the cumulative concentrations of CaCl[2] [0.5-8mM] contracted the ileum and the extract [0.0156-0.0625mg/ml] reduced the induced contractions [P<0.001]. Based on our results, the aqueous extract of Glycyrrhiza glabra inhibited the ileum contractions without involving beta-adrenergic, opioid, and tetraethyl ammonium receptors. Calcium channels were involved in the main part of this inhibitory effect and probably activation of ATP-dependent potassium channels partially was involved in this process

[Antispasmodic effect of Teucrium polium leaf extract on rat ileum]

Teucrium polium [locally called as chez or kalporeh in Khuzestan Province, Iran] is used traditionally as a remedy for treatment of headache, convulsion and dysmenorrhea and moreover, its hypoglycemic, hypolipidemic and antibacterial effects have been reported in recent researches. In addition, it is also used traditionally to treat gastrointestinal disorders. The aim of the present study was to investigate the effects of Teucrium polium aqueous leaf extract on rat ileum contractions evoked by receptor and non-receptor stimulants and also to study the mechanism[s] involved. Freshly dried leaves of Teucrium polium were extracted with boiling water. Pieces of ileum from adult male Wistar rat were mounted in an organ bath containing Tyrode solution and an isotonic transducer recorded contractile responses under 1g initial tension. Data indicate that cumulative concentrations of the extract [0.25, 0.5, 1, 2, 4 and 8 mg/ml] reduced the ileum contractions induced by KCl [60 mM] and acetylcholine [1 microM] in a dose-dependent manner [P<0.0001]. The spasmolytic effect of the extract on KCl-induced contraction was more potent than on the ACh-induced contractions. The spasmolytic effect of extract was totally reversible. The spasmolytic effect of the extract was not affected by L-NAME [100 microM, 20min] in KCl-induced contractions. Spasmolytic effect of extract was not reduced by ileum incubation [30 min] with propranolol, phentolamine and naloxone [all at 1microM] in KCl-induced contractions. The cumulative concentrations of calcium evoked contractions in a dose dependent manner in Ca[2+]-free Tyrode solution with high potassium. These contractions were attenuated by the extract, significantly. The results suggested that the voltage dependent calcium channels might be involved in spasmolytic effects of Teucrium polium aqueous leaf extract. In this inhibitory effect, however, neither NO, opioid receptors, nor adrenoceptors [alpha and beta] were involved

Spasmolytic effect of Cuscuta pentagona fruit aqueous extract on rat ileum

Cuscuta pentagona [convolvulaceae] has been used in Iran for gastrointestinal disorders. The aim of the present study was to investigate the effect of Cuscuta pentagona fruit aqueous extract [CPE] on rat ileum contractility. The fruit extract was prepared according to the traditional method by boiling the fruits in distilled water. Ileum was dissected from adult male Wistar rat, mounted in an organ bath [10 ml] containing Tyrode solution [37°C, pH 7.4]. I leal contractions were recorded under 1 g initial tension, by an isotonic transducer. In many in-vitro studies, potassium chloride and acetyl cholin induced contractions of rat ileum in the absence or presence of some antagonists had been assessed. In some in vivo studies gastrointestinal transit time in different groups of rats after administration of saline, three doses of fruit extract or atropine, had been measured. Cumulative concentrations of CPE [0.5-8 mg/ml] reduced the ileal contractions induced by KC1 [60 mM] and ACh [1 microM] revealing a dose dependent effect [p<0.0001]. The spasmolytic effect of CPFAE was not reduced after 20-30 minutes of tissue incubation with phentolamine [ImicroM], propranolol [lmicroM] L-NAME 100 microM] and naloxone [1 microM]. In.a Ca[2+]-free Tyrode solution the ileum depolarized by KC1, 120 mM was contracted by addition of cumulative concentration of CaCl[2] [0.225 to 3.6 mM] but CPE [2 and 4 mg/ml] reduced the contractions in a dose dependent manner [p<0.0001]. Furthermore, fruit extract in concentrations of 250, 500 and 750 mg/kg [p.o.] reduced the transit time of charcoal meal in small intestine in a dose dependent manner. Our results suggest that the CPE spasmolytic effect is mediated via calcium channels without involvement of adrenoceptors [alpha and beta] or opioid receptors or any influence on NO synthesis. The results of the present study showed that Cuscuta pentagona fruit aqueous extract reduces rat ileum motility in both in vivo and in vitro studies

Inhibitory effects of thymoquinone, the major component of Nigella sativa l. seeds, on spontaneous and evoked contractions of guinea pig isolated ileum

It has been recently shown that essential oil of Nigella sativa seeds and its major constituent, thymoquinone [TQ], possess relaxant activity on isolated trachea and ileum. Several mechanisms have been suggested to explain the smooth muscle relaxant effects of the essential oil of Nigella sativa seeds. But, only in one study, it has been shown that TQ exerts its relaxant activity probably through the inhibition of histaminergic and serotonergic receptors. Objective: This study was carried out in order to further evaluating the mechanism [s] of muscle relaxant activity of TQ. Tension recording technique using an isometric transducer connected to a physiograph in an organ bath set up was used. The spontaneous contractions of isolated ileum and contractile responses evoked by acetylcholine [Ach], histamine [His], potassium chloride [KC1], and repetitive electrical field stimulation [EFS], were recorded. ACh [10 pM], His [100 HM], KC1 [10 mM], and EFS [20 Hz, 0.2 ms, 130 V], were applied before and after adding TQ [10, 20, 40, 80,100 micro M]. Moreover, in order to evaluate the role of Ca[2+]-channels in TQ-induced relaxation of ileum, the amplitude of contractions evoked by EFS were recorded in the presence and absence of TQ [80 micro M], in Ca[2+]-free Krebs solution, as well as following adding of cumulative concentrations of CaCl[2] [0.1, 0.2, 0.4,1,2 mM]. The results showed that TQ at the minimum concentration of 20

decreased the amplitude of spontaneous contractility [p<0.01] and His- and EFS- evoked contractions [p<0.05]. Also, the amplitude of ACh- and KC1 - evoked contractions were decreased by TQ at the minimum concentration of 40 micro M [p<0.01 and p<0.001, respectively]. The maximum inhibitory effects of TQ against ileum contractility were achieved by the concentration of 100 micro M. Furthermore, the cumulative concentrations of CaCl[2] in the presence of TQ [80 micro M], failed to increase the amplitude of contractions induced by EFS, which were suppressed in Ca[2+]-free medium. These findings indicated that TQ possesses inhibitory effects on contractility of guinea pig isolated ileum, and that effects may be responsible for the smooth muscle relaxant activity of Nigella sativa seeds. The mechanism by which TQ relaxes ileum contractility was exerted, at least in part, through an antagonistic activity on calcium channels in guinea pig ileum smooth muscle cells

Intraluminal injection of short chain fatty acids diminishes intestinal mucosa injury in experimental ischemia-reperfusion

OBJETIVO: Investigou-se o efeito de ácidos graxos de cadeia curta (SCFA) na mucosa intestinal na presença de lesão por isquemia e reperfusão (IRI). MÉTODOS: Foram criados seis sacos fechados no intestino delgado (três no jejuno e três no íleo) em 10 ratos Wistar. Ao sacos laterais de ambas as regiões intestinais foram submetidos a IRI (15/15 minutos) enquanto que o saco medial não sofreu interrupção do suprimento sanguíneo. Nos sacos laterais ambas as regiões injetou-se SCFA ou solução fisiológica na luz intestinal. Nos sacos mediais não se injetou nenhuma solução. RESULTADOS: Tanto no jejuno quanto no íleo o escore de injuria da mucosa intestinal foi mais alto nos sacos tratados com solução salina do que nos controles. Os sacos que receberam SCFA apresentaram menor escore inflamatório no íleo (p=0.03) porém sem diferença no jejuno (p=0.083) quando comparados com os sacos injetados com solução salina. Observou-se um significante maior acumulo de neutrófilos nos sacos tratados com solução salina (p < 0.01) do que nos outros dois sacos em ambas as regiões. CONCLUSAO: Os SCFA protegem a mucosa intestinal distal e diminuem o acumulo de neutrófilos na lamina própria após IRI.

Role of 5HT in the modification of intestinal motility, in vitro study

To determine with the mechanism of action involved in the therapeutic potential of serotonin and its blocker on gastrointestinal motility. The standard method was used for obtaining the longitudinal and circular muscles strip of rabbit ileum for in vitro studies. Each muscle strip was exposed to serotonin and its blocker and the result obtained was recorded on polygraph apparatus. The effects were recorded in vice versa fashion i.e. agonist v/s antagonist and antagonist v/s agonist on longitudinal and circular muscle strip separately. Serotonin had depressant effect on the force of contraction. On addition of antagonist in the presence of agonist, the effects were increased. Longitudinal muscle showed more pronounced effect i.e. 52.7% with methysergide in comparison to circular muscle, which was 15.6%. Circular muscle showed reduction in the force of contraction with serotonin, which was increased on addition of antagonist, but still below the level of base line contraction. Serotonin when given from external source in vitro, decreased the force, however, there was minimal increase in the rate of contraction. Hence, serotonin decreases the intestinal motility giving an impression of having antispasmodic effect. The results of this study can be utilized in the development of new drug related to G.I. motility mediated through 5HT receptors

Effects of the combined use of glutamine and growth hormone in the intestinal adaptation after massive resection of the small bowel in rats

OBJETIVO: Investigar os efeitos do uso combinado da glutamina (GL) e do hormônio do crescimento (GH) no intestino de ratos submetidos a ressecção de 80% do intestino delgado. MÉTODOS: Vinte e quatro ratos Wistar foram randomizados para receber uma a dieta padrão- grupo controle (GC, n=12) ou a mesma dieta adicionada de glutamina 4% (isocalórica, isoproteica) - grupo glutamina- hormônio do crescimento (GL-GH, n=12) após a enterectomia à 80%. Este último grupo recebeu por via sub-cutânea, 0,6 UI/dia de GH. Grupos de seis ratos cada foram sacrificados no 5º e 14º dias. As seguintes variáveis foram estudadas: peso corporal, peso de mucosa, histomorfometria e conteúdo de DNA no segmento ressecado inicialmente e no intestino adaptado coletado após o sacrifício. RESULTADOS: Todos os animais perderam peso até o 5º dia, estabilizando-se após esta data em ambos os grupos. Não houve diferença estatística no peso da mucosa associada a grupos ou datas. O peso da mucosa do íleo diminuiu dos dados iniciais para os finais, quando comparados a mucosa jejunal (p<0.02). O conteúdo de DNA aumentou dos dados iniciais para os finais (p=0.001) em ambos os grupos, porém, o aumento foi maior nos animais do grupo GL-GH (CG = 0.53 [95% CI, 0.44-0.62] g/cm-1 vs. GL-GH= 0.85 [95%CI, 0.76-0.94] g/cm-1; p<0.01), especialmente no 14º dia. O conteúdo de DNA no íleo foi significativamente maior que no jejuno (p=0.01). Houve um aumento significativo na espessura da parede e na profundidade da cripta, no grupo controle (p<0.01). CONCLUSÃO: A adaptação intestinal após ressecção extensa é melhorada com o uso combinado de glutamina e GH.

Modulatory effect of diclofenac on antispasmodic effect of pitofenone in cholinergic spasm.

Biliary, ureteric and intestinal colic are extremely common clinical conditions associated with smooth muscle spasm. In the present study, antispasmodic activity was carried out against acetylcholine (10-640 ng/ml)-induced contractions on guinea pig ileum. Acetylcholine (10-640 ng/ml) induced concentration-dependent contraction of smooth muscle. Diclofenac, in varying concentration (9.4 x 10(-5) mol/l and 14.1 x 10(-5) mol/l) shifted the concentration response curve of acetylcholine to the right without suppressing the maximal response. However, in higher concentration diclofenac (18.9 x 10(-5) mol/l) blocked the response in an unsurmountable fashion. Further, analgin (11.09 x 10(-5), 16.63 x 10(-5) and 22.18 x 10(-5) mol/l) in equimolar concentrations did not alter the concentration response curve of acetylcholine, but in higher concentration analgin (44.36 x 10(-5) mol/l) also blocked the response in an unsurmountable fashion. Pitofenone (2.5 x 10(-6) mol/l) also, shifted the concentration response curve of acetylcholine to right in a parallel fashion with no change in maximal response. The present study confirms the potent antispasmodic activity of diclofenac-pitofenone combination in comparison to analgin-pitofenone in molar equivalent concentration (in comparison to diclofenac) against acetylcholine-induced contractions of guinea pig ileum.

Antispasmodic effects of curcuminoids on isolated guinea-pig ileum and rat uterus.

Curcuminoids, a yellow constituent isolated from Curcuma longa Linn. rhizomes was studied for its antispasmodic activity in isolated guinea-pig ileum and rat uterus. Curcuminoids at the concentration of 12 microg/ml significantly inhibited the ileum pre-contracted with acetylcholine (ACh) 5 x 10(-7) M and histamine 5 x 10(-7) M. (Force of contraction was 62.84 +/- 4.66% and 75.60 +/- 4.66% respectively) and the effects were prominently observed when the concentration of curcuminoids was increased to 36 microg/ml. (Force of contraction was 44.93 +/- 4.33% and 42.79 +/- 1.98%). In potassium depolarizing Tyrode solution, curcuminoids 4 microg/ml and 20 microg/ml reduced the contraction induced by calcium chloride (CaCl2) 1.8 mM. (The contraction was 63.31 +/- 1.80% and 36.87 +/- 3.25%). In rat uterus smooth muscle preparation, curcuminoids 8 microg/ml and 16 microg/ml significantly reduced force and frequency of contraction induced by oxytocin 1 x 10(-2) IU/ml. Curcuminoids 8 microg/ml produced 54.68 +/- 3.34 per cent force of contraction and 79.09 +/- 2.29 per cent frequency of contraction. Curcuminoids 16 microg/ml caused more relaxation of rat uterus smooth muscle. (Force of contraction was 43.38 +/- 3.56%, frequency of contraction was 49.96 +/- 5.20%). Curcuminoids 8 and 16 microg/ml significantly reduced force of contraction induced by KCl 50 mM. (Force of contraction was 54.10 +/- 4.92% and 36.60 +/- 2.99%). The results obtained from this study concluded that curcuminoids produced a smooth muscle, relaxation effect on isolated guinea-pig ileum and rat uterus by receptor-dependent and independent mechanism.

An experimental and clinical evaluation of anti-asthmatic potentialities of Devadaru compound (DC).

Devadaru compound was shown to be beneficial in Tamak Swasa (bronchial asthma). Clinical findings revealed higher percentage of relief in cardinal and general symptoms with decrement in the pulse rate and in the respiration rate. A significant linear increase in PEFR value was observed before and after treatment and an increase in FEV1 values measured in Group I subjects. There was relief of all symptoms in a significant number of patients. Occurrence of relief was observed only among patients who suffer less than 10 years duration with Tamak Swasa and among those the frequency of attacks of Tamak Swasa was at fortnightly or monthly intervals. Antispasmodic activity of Devadaru Compound (DC) on acetylcholine (Ach) induced contractions using rat ileum preparation was studied. The results demonstrated that DC inhibits Ach-induced contractions significantly and bears a dose-response relationship. This suggests that DC has got anti-spasmodic activity and corroborates the clinical findings. The clinical findings and experimental studies show that DC is of significant use in the treatment of Tamak Swasa (Bronchial Asthma) and superior to the standard and placebo therapy.

Investigation into the Effects of Mosapride on Motility of Guinea Pig Stomach, Ileum, and Colon

Mosapride citrate (Mosapride) is a new prokinetic agent that enhances the gastrointestinal (GI) motility by stimulation of 5-HT4 receptors. This agent stimulates acetylcholine release from enteric cholinergic neurons in the GI wall. It was reported in several studies that mosapride selectively enhanced the upper, but not lower, GI motor activity. However, in these studies other 5-HT4 receptor agonists exerted stimulating effects on the motility of the colon. Moreover, it is well known that the receptors of 5-HT4 are also located in the colon. The purpose of this study was to estimate the effect of mosapride on the motility of the stomach, ileum and colon in the guinea pig and to investigate whether or not mosapride influenced the colonic motility. Mosapride significantly increased the amplitude of the contraction waves in the guinea pig stomach by electrical stimulation. In addition, it significantly increased the number of peaks, the area under the curve and the propagation velocity of the peristaltic contraction of the guinea pig ileum in a concentration dependent fashion. Mosapride also significantly shortened the transit time of the guinea pig colon. Accordingly, we concluded that mosapride exerted prokinetic effect on the entire GI tract of the guinea pig. Based on the possibility of similar results in humans, we suggest the potential use of mosapride for lower GI motor disorders such as constipation and upper GI motor disorders such as gastroesophageal reflex disease or gastroparesis.