Rabbit Intestine Research Articles

Development of Low Density Microspheres of Metformin Hydrochloride Using Ethyl Cellulose and HPMC K4M: In Vitro and in Vivo Characterization

Polymeric floating microspheres of metformin hydrochloride were prepared by a modified solvent evaporation method using ethyl cellulose and HPMC K4M. Microspheres were characterized by SEM, particle size, drug content, in vitro swelling, in vitro buoyancy, in vitro drug release and in vivo X-ray imaging. Formulation D exhibited in vitro swelling, about 48.28 ± 1.03% and the desired floating time and with retention in the upper small intestine of rabbits for 8 h and with release for 12 h. We conclude that ethyl cellulose and HPMC K4M at 0.40:1.50 w/w ratios could be an effective carrier for multiparticulate controlled drug delivery.

Prostaglandins, not the leukotrienes, regulate Cl−/HCO3− exchange (DRA, SLC26A3) in villus cells in the chronically inflamed rabbit ileum

Previously studies have demonstrated that Cl−/HCO3− exchange was inhibited during chronic intestinal inflammation secondary to decrease in the affinity of the exchanger for Cl− rather than the number of transporters. Arachidonic acid metabolites (AAM) are elevated in the mucosa of the chronically inflamed small intestine. However, their role in the alteration of Cl−/HCO3− during chronic enteritis was unknown. Inhibition of AAM formation with arachidonyl trifluoro methylketone (ATMK) in chronically inflamed rabbit intestine reversed the diminished Cl−/HCO3− exchange activity. Kinetics studies showed that the reversal was secondary to restoration of the altered affinity of transporter. Downstream regulation of Cl−/HCO3− inhibition by AAM was determined to be by the cyclooxygenase pathway since only inhibition of cyclooxygenase with piroxicam treatment reversed the inhibited Cl−/HCO3− exchange. Further, DRA was shown to be the primary Cl−/HCO3− exchanger in villus cells. Kinetics and molecular studies indicated that the mechanism of inhibition of Cl−/HCO3− exchange by cyclooxygenase pathway metabolites was secondary to diminished affinity of the transporter for Cl− without a change in DRA BBM expression. Thus our data indicated that cyclooxygenase pathway metabolites mediate the inhibition of DRA during chronic intestinal inflammation.

Hypoglycemic effects of the aqueous extract of African Mistletoe, <em>Tapinanthus sesselifolius</em> (P. Beauv) van Tiegh (Loranthaceae)

The hypoglycemic effect of the aqueous extract of African mistletoe, Tapinanthus sesselifolius, was investigated in-vivo and in-vitro. Studies were carried out on normoglycemic and alloxan-induced hyperglycemic rabbits, and glucose uptake studies were done using the isolated intestine of normal rabbits. The safety studies (acute toxicity test) were carried out in mice. The results revealed that the aqueous extract of Tapinanthus sesselifolius exhibited transient reduction of blood glucose in normoglycemic rabbits and significantly lowered blood glucose level in hyperglycemic rabbits. The extract significantly decreased the level of glucose in serosal fluid dose dependently. The intraperitoneal (i.p.) LD50 of Tapinanthus sesselifolius was found to be 2000 – 2650 mg/kg within 95% confidence limits. The preliminary phytochemical screening showed positive test for biologically active substances such as saponins, tannins, flavonoids, terpenoids and glycosides. The data showed that Tapinanthus sesselifolius contain biologically active substances that may be useful in treatment of diabetes and thus gave a scientific basis for its use in herbal traditional medicine as an antidiabetic agent.Keywords: Phytomedicine, alloxan-induced hyperglycemia, glucose uptake

Effects of feed-borne Fusarium mycotoxins on performance, serum chemistry, and intestinal histology of New Zealand White fryer rabbits1

The objective of the present study was to determine the effects of feeding diets containing grains naturally contaminated with Fusarium mycotoxins to fryer rabbits. The efficacy of a glucomannan mycotoxin adsorbent (GMA) was also examined. Thirty 5-wk-old male New Zealand White rabbits were fed a control diet, a contaminated diet, or a contaminated diet + 0.2% GMA for 21 d. Experimental diets contained deoxynivalenol (DON; vomitoxin) at a concentration of 0.25, 4.3, and 4.9 μg/g, respectively. Feed intake was measured daily and water intake was measured every 3 d. At the end of the feeding period, blood was collected for evaluation of serum chemistry and hematology. Visceral organs were excised, weighed, and processed for histopathological examination. Body weight gain and water intake were greater in rabbits fed the contaminated diet (P = 0.075 and 0.020, respectively) and those fed the contaminated + GMA diet (P = 0.026 and 0.002, respectively) compared with controls. Rabbits fed the contaminated + GMA diet had significantly increased serum urea concentrations (P = 0.023) and decreased serum alkaline phosphatase activity (P = 0.020) compared with controls. Increase in BW gain of rabbits fed the contaminated diets was caused by increased water consumption. There was no effect (P > 0.05) of diet on relative organ weights, but decreased infiltrations with eosinophilic granulocytes were observed in different regions of the intestine in rabbits fed the contaminated or the contaminated + GMA diet. It was concluded that rabbits could be adversely affected by feed-borne Fusarium mycotoxins but appear to be less sensitive than other mammalian species. Supplementation with GMA did not reduce many of the effects of feed-borne mycotoxins.

An Animal Model of Necrotizing Enterocolitis (NEC) in Preterm Rabbits

Creation of an animal model of necrotizing enterocolitis (NEC) allowing adjustment of severity and potential recoverability is needed to study effectiveness of prevention and treatment strategies. This study describes a novel model in preterm rabbits capable of adjusting severity of NEC-like histologic changes. Rabbit pups (n = 151) were delivered by cesarean section 2 days preterm. In the treatment groups, tissue adhesive was applied to anal openings to simulate the poor intestinal function and dysmotility of preterm neonates. Pups were placed into five groups: 3INT (3 day intermittent block), 4INT (4 day intermittent block), 3COM (3 day complete block), 4COM (4 day complete block), based on differences in type of anal blockage and day of life sacrificed. The fifth group, 4CON, was comprised of a control arm (n = 28) without anal block, with sacrifice of subjects on day 4. All pups were gavage fed with formula contaminated with Enterobacter cloacae, ranitidine, and indomethacin. Following sacrifice, the intestines were harvested for pathologic evidence of NEC. A blinded pathologist graded histologic changes consistent with NEC using a grading scale 0–4 with 4 being most severe. Fifty-seven pups (57/123) (46%) in the research arm survived to sacrifice, compared to 26/28 (93%) in the control arm of the investigation, p < 0.0001. The incidence and severity of NEC-like damage increased with the duration and completeness of the anal blockage. 44/57 (77%) of survivors revealed various degrees of NEC-like damage to large and small bowel, and 3/26 (12%) exhibited early NEC-like mucosal injury in the research and control arms, respectively. This animal model produces NEC-like pathologic changes in both small and large intestine in preterm rabbits. Because incidence and severity of damage increases with duration and completeness of intestinal dysmotility, this allows future effectiveness studies for nonsurgical treatment and prevention of NEC.

Fimbriation and curliation in Escherichia coli O157

Shiga toxin-producing Escherichia coli (STEC) serotypes, particularly E. coli O157:H7, possess a variety of fimbrial and afimbrial adhesins which have emerged as important contributors to intestinal colonization. E. coli O157:H7 possesses two chromosomal operons encoding long polar fimbriae (Lpf), which have been found to influence adherence in vitro and colonization in vivo. In a recent Infection and Immunity paper, we further explored the role of Lpf in E. coli O157:H7 intestinal colonization by using the infant rabbit model of STEC infection. We found that an E. coli O157:H7 Lpf-deficient mutant was outcompeted in the rabbit intestine by its parental strain, which may suggest that Lpf contributes to colonization. In contrast, the Lpf-deficient mutant showed an increased adherence to cultured intestinal epithelial cells, and we discovered that this strain overexpressed curli fibers. In this addendum article, we provide a continued perspective on the predicted roles of Lpf and curli, both in vivo and in vitro.

Design and in vitro and in vivo characterization of mucoadhesive matrix pellets of metformin hydrochloride for oral controlled release: A technical note

The aim of the current work was to design and develop matrix pellets of hydroxy propyl methyl cellulose K200M and microcrystalline cellulose in an admixture for a mucoadhesive gastroretentive drug delivery system. Pellets containing metformin hydrochloride (500 mg) were prepared by the pelletization technique using an extruder-spheronizer. Pellets were characterized by differential scanning calorimetry (DSC), x-ray diffraction (XRD), scanning electron microscopy (SEM), circularity, roundness, percent drug content, percent production yield, in vitro swelling, ex vivo mucoadhesion, in vitro drug release and in vivo x-ray imaging studies. Optimized pellets were sufficiently porous spheroids, free flowing, had smooth surfaces, had yields up to 75.45 ± 0.52% and had drug content up to 96.45 ± 0.19%. The average particle size of formulations MF2 and MF6 were 1.13 ± 0.41 mm and 1.22 ± 0.18 mm, respectively. Formulation MF6 exhibited strong adhesion, about 94.67%, to goat mucosal tissue, and the desired in vitro swelling, with a sustained drug release profile for 12 h and with retention in the upper small intestine of rabbits for 10 h. We conclude that hydroxy propyl methyl cellulose K200M and microcrystalline cellulose at a 2.80:1.00 w/w ratio could be an effective carrier for multiple unit controlled delivery of metformin hydrochloride.

Vaccinia viruses isolated from skin infection in horses produced cutaneous and systemic disease in experimentally infected rabbits

The susceptibility of rabbits to two isolates of Vaccinia virus (VACV) recovered from cutaneous disease in horses in Southern Brazil was investigated. Rabbits were inoculated in the ear skin with both VACV isolates, either in single or mixed infection. All inoculated animals presented local skin lesions characterized by hyperaemia, papules, vesicles, pustules and ulcers. Infectious virus was detected in the lungs and intestine of rabbits that died during acute disease. Histological examination of the skin revealed changes characteristic of those associated with members of the genus Orthopoxvirus. These results demonstrate that rabbits develop skin disease accompanied by systemic signs upon intradermal inoculation of these two equine VACV isolates, either alone or in combination, opening the way for using rabbits to study selected aspects of the biology and pathogenesis of VACV infection.

Synthesis and characterization of peroxotungsten(vi) complexes bound to water soluble macromolecules and their interaction with acid and alkaline phosphatases

A set of peroxotungsten(VI) complexes in a macroligand environment has been prepared and characterized by elemental analysis (CHN and energy dispersive X-ray spectroscopy), spectral studies (UV–vis, IR, 13C NMR) and thermal gravimetric analysis (TGA), as well as SEM studies. The compounds were obtained by anchoring of peroxotungsten species to the pendant functional groups of water soluble polymers, such as poly(vinyl sulfonate) (PVS), poly(acrylate) (PA), poly(methylacrylate) (PMA) and poly(acrylamide) (PAm). The stability of the compounds in solutions of pH values ranging between 1.2 to 8.0 has been ascertained. The polymeric compounds, as well as a pair of previously reported monomeric and dinuclear pW complexes, were screened for their effect on two different membrane bound phosphatases viz., wheat thylakoid membrane acid phosphatase (ACP) and rabbit intestine alkaline phosphatase (ALP). Each of the tested complexes behaved as active inhibitors of the enzymatic function of the model enzymes. The two classes of enzymes exhibited significantly different sensitivity towards the inhibitors. The IC50 and Ki values were more than 50 orders of magnitude lower for ACP than for ALP, which shows the greater affinity of the complexes for the enzyme binding site of ACP compared to ALP. The kinetic data enabled us to group the complexes into two classes on the basis of their mechanistic preferences. The group comprised of polymeric pW complexes behave as classic non-competitive inhibitors of ACP and ALP, while the free heteroligand pW compounds show mixed inhibition, combining competitive and non-competitive pathways.

Phytopharmacological assessment of medicinal properties of Psoralea corylifolia

Psoralea corylifolia (Leguminosae) is traditionally used for the treatment of skin conditions, fever and as anthelmintic. The aim of present study was to standardize the crude extract of P. corylifolia and determine its pharmacological activities. The crude extract of P. corylifolia was standardized by high performance liquid chromatography (HPLC), Fourier transform infra red (FT-IR), Fourier transform near infra red (FT-NIR) and ultra violet (UV) spectrophotometric methods. Pharmacological study of the crude extract of P. corylifolia and its fractions were carried out on smooth muscle of rabbit intestine. The results revealed quick decrease in the normal intestinal movement followed by a gradual dose dependant increase in the rhythmic activity of intestine. The antispasmodic response of the crude extract was found most significant at 20 mg/ml (78.13%). The chloroform fraction of the crude extract exhibited maximum antispasmodic response at 10 mg/ml (45.16%). n-butanol and aqueous fractions produced 39.29 and 13.79% antispasmodic effect, respectively, whereas, ethyl acetate fraction produced spasmogenic effect (21.9%). The crude extract of P. corylifolia exhibited positive antifungal activity against Candida albicans and positive antibacterial activity againstStaphylococcus aureus. Significant analgesic effect was also observed with 300 and 500 mg/kg dose at P < 0.05. The analgesic effect of the plant extract (500 mg/kg) was found to be higher than that of diclofenac sodium (50 mg/kg; positive control). Brine shrimp lethality assay was performed and the plant extract did not exhibit any toxicity. Key words: Psoralea corylifolia, high performance liquid chromatography (HPLC), standardization, smooth muscles, analgesic, antibacterial, antifungal.

Na-glutamine co-transporters B0AT1 in villus and SN2 in crypts are differentially altered in chronically inflamed rabbit intestine

Glutamine is a major nutrient utilized by the intestinal epithelium and is primarily assimilated via Na-glutamine co-transport (NGcT) on the brush border membrane (BBM) of enterocytes. Recently we reported that B0AT1 (SLC6A19) mediates glutamine absorption in villus while SN2 (SLC38A5) does the same in crypt cells. However, how B0AT1 and SN2 are affected during intestinal inflammation is unknown. In the present study it was shown that during chronic enteritis NGcT was inhibited in villus cells, however, it was stimulated in crypt cells. Our studies also demonstrated that the mechanism of inhibition of NGcT during chronic enteritis was secondary to a reduction in the number of B0AT1 co-transporters in the villus cell BBM without a change in the affinity of the co-transporter. In contrast, stimulation of NGcT in crypt cells was secondary to an increase in the affinity of SN2 for glutamine without an alteration in the number of co-transporters. Thus, glutamine assimilation which occurs via distinct transporters in crypt and villus cells is altered in the chronically inflamed intestine.

Morphometric Features and Glycoconjugate Pattern of Rabbit Intestine are Affected by Particle Size of Pelleted Diets

Feed particle size effects on morphology and glycoconjugate pattern was investigated in the rabbit intestine. Rabbits fed with fine particles (2 mm) displayed more irregularly shaped, higher duodenal villi and deeper crypts in distal colon as well as higher number of goblet cells than coarse (8 mm) fed ones. Brush border expressed: (i) in duodenum, neutral/sulfated glycoconjugates and glycans binding MAL II, SNA, Con A than KOH-sialidase-PNA and DBA reactivity in fine and coarse fed rabbits, respectively, (ii) in cecum, mainly sulfoglycans in coarse fed rabbits, MAL II and PNA staining in all samples, and (iii) in distal colon few sulfoglycans and MAL II reactivity. Enterocytes bound MAL II in duodenum, Con A in cecum, DBA, and Con A in distal colon of all rabbits, SNA in distal colon of coarse fed ones. Brunner's glands displayed high presence of acidic/sulfated mucins in fine fed rabbits, neutral glycoconjugates and reactivity with MAL II, SNA, PNA, KOH-sialidase-PNA, and Con A in all rabbits. Goblet cells exhibited: (i) in duodenum neutral and sulfomucins as well as MAL II and KOH-sialidase-PNA staining, than SNA and DBA in fine and coarse fed rabbits, respectively, (ii) in cecum sulfated glycans, MAL II, SNA, KOH-sialidase-PNA, DBA reactivity, and (iii) in distal colon acidic/sulfomucins, MAL II and SNA staining, and DBA reactivity in fine fed specimens. Crypt cells exhibited neutral and PNA reactive glycoconjugates in the cecum. In the distal colon also acidic/sulfated glycans, and MAL II, KOH-sialidase-PNA, DBA; SNA staining showed weaker reactivity in fine fed rabbits, which bound Con A.

Effects of Solanum glaucophyllum toxicity on cell proliferation and apoptosis in the small and large intestine of rabbits

Vitamin D regulates mineral homeostases and enterocyte proliferation and differentiation. Hypervitaminosis D generates changes in cell proliferation, differentiation and apoptosis in several organs. We analysed morphometric parameters and proliferative and apoptotic indices in the intestinal epithelium of rabbits with hypervitaminosis D induced by the chronic treatment with the calcinogenic plant Solanum glaucophyllum. Rabbits were treated for 15 or 30days. A group was treated for 15days and led to possible recovery for 30days. Another group was nutritionally restricted for 30days. Morphological, morphometric, proliferative and apoptotic changes were found in the treated animals. Mild atrophy and reduced proliferation was found in the jejunum and ileum. Apoptosis increased in the crypts of the ileum and in the superficial epithelium and crypts of the rectum. Most of the alterations were partially recovered. The possible involvement in these changes of the hypervitaminosis D-like state induced by S. glaucophyllum is discussed.

Polymer-Anchored Peroxo Compounds of Vanadium(V) and Molybdenum(VI): Synthesis, Stability, and Their Activities with Alkaline Phosphatase and Catalase

We generated a series of new polymer-bound peroxo complexes of vanadium(V) and molybdenum(VI) of the type [VO(O(2))(2)(sulfonate)]-PSS [PSS = poly(sodium 4-styrene sulfonate)] (PV(3)), [V(2)O(2)(O(2))(4)(carboxylate)VO(O(2))(2)(sulfonate)]-PSSM [PSSM = poly(sodium styrene sulfonate-co-maleate)] (PV(4)), [Mo(2)O(2)(O(2))(4)(carboxylate)]-PA [PA = poly(sodium acrylate)] (PMo(1)), [MoO(O(2))(2)(carboxylate)]-PMA [PMA = poly(sodium methacrylate)] (PMo(2)), and [MoO(O(2))(2)(amide)]-PAm [PAm = poly(acrylamide)] (PMo(3)) by reacting V(2)O(5) (for PV(3) and PV(4)) or H(2)MoO(4) (for PMo(1), PMo(2), and PMo(3)) with H(2)O(2) and the respective water-soluble macromolecular ligand at pH 5-6. The compounds were characterized by elemental analysis (CHN and energy-dispersive X-ray spectroscopy), spectral studies (UV-vis, IR, (13)C NMR, (51)V NMR, and (95) Mo NMR), thermal (TGA) as well as scanning electron micrographs (SEM), and EDX analysis. It has been demonstrated that compounds retain their structural integrity in solutions of a wide range of pH values and are approximately 100 times weaker as substrate to the enzyme catalase relative to H(2)O(2), its natural substrate. The effect of the title compounds, along with previously reported compounds [V(2)O(2)(O(2))(4)(carboxylate)]-PA (PV(1)) and [VO(O(2))(2)(carboxylate)]-PMA (PV(2)) on rabbit intestine alkaline phosphatase (ALP) has been investigated and compared with the effect induced by the free diperoxometallates viz. Na[VO(O(2))(2)(H(2)O)] (DPV), [MoO(O(2))(2)(glycine)(H(2)O)] (DMo(1)), and [MoO(O(2))(2)(asparagine)(H(2)O)] (DMo(2)). It has been observed that although all the compounds tested are potent inhibitors of the enzyme, the polymer-bound and neat complexes act via distinct mechanisms. Each of the macromolecular compounds is a classical noncompetitive inhibitor of ALP. In contrast, the action of neat pV and heteroligand pMo compounds on the enzyme function is consistent with a mixed type of inhibition.

The Effect of Tramadol on the Peristaltic Movement Small Intestine in Rabbit

The Effect of Tramadol on the Peristaltic Movement Small Intestine in Rabbit

Pituitary Adenylate Cyclase‐Activating Peptide (PACAP) and Substance P (SP) induce the release of Brain‐Derived Neurotropic Factor (BDNF) from the longitudinal muscle layer of the intestine

BDNF has been implicated in neuronal development and plasticity. While BDNF is expressed in neural and non-neuronal cells, the expression and secretion of BDNF in gastrointestinal smooth muscle is not well defined. Aim To determine if BDNF is expressed and secreted from intestinal smooth muscle. Methods BDNF expression in intestinal segments was evaluated immunohistochemically. Longitudinal muscle cells were cultured for 24 to 48 hours in the absence or presence of SP or PACAP (10 to 100 nM); BDNF content in cells and secretion into media was measured by western blot and ELISA. Results Immunohistochemically, BDNF was identified primarily in the longitudinal rather than circular muscle layer of mouse and rabbit intestine. Western blot analysis of BDNF from longitudinal muscle cultures confirmed basal BDNF expression and demonstrated time- and concentration-dependent increase in BDNF content in response to both neuropeptides, with PACAP being more effective than SP. Similar results were obtained for release of BDNF into culture medium. Conclusion In the basal state, intestinal smooth muscle cells from the longitudinal layer express and secrete BDNF. Contractile and relaxant neuropeptides modulate this expression and secretion suggesting crosstalk between enteric neurons and smooth muscle via interplay between neuropeptide transmitters and neurotrophins. Supported by NIDDKD.

Motilin receptor expression in the interstitial cells of Cajal

To look for the evidences of motilin receptor expression on interstitial cells of Cajal (ICC) of the rabbit. Smooth muscle segments with ICC were isolated from the small intestine of 10-day old rabbits. The tissue segments equilibrated in Ca(2+)-free Hanks' solution were dispersed with an enzyme solution containing collagenase type II and then Ficoll density centrifugation was used to dissociate ICC. The cells were suspended and cultured in the M199 medium. The c-kit antibody was applied to distinguish the cultured ICC. The motilin receptor was identified by immunocytochemical assay with GPR38 antibody, c-kit antibody and hoechst 33342 combined to label ICC. Cells cultured for a few days were sorted for ICC with c-kit stained green fluorescent through flow cytometry. The total RNA and proteins extracted from the sorted ICC were respectively used to verify motilin receptor on the ICC by reverse-transcriptase polymerase chain reaction (RT-PCR) and Western blotting. We had successfully dissociated and cultured ICC of rabbit small intestine in vitro. Fluorescent staining with c-kit antibody confirmed that the culture ICC was successful. Triple-labeled immunofluorescent staining had detected the motilin receptor on membrane of ICC. Flow cytometry analysis showed that the ratio of c-kit positive cell in the cultured cells was 64.3%. The number of sorted ICC was 6.7 × 10(5) and 5.6 × 10(6). The results of RT-PCR and Western blot confirmed that the ICC had motilin receptor expression. Our study demonstrated presence of motilin receptor on ICC of the rabbit. The present results may suggest that ICC play an important role in gastrointestinal movement induced by motilin.

Contractile effect of tachykinins on rabbit small intestine

To study the role of the tachykinin receptors in spontaneous contractions of longitudinal and circular smooth muscle from rabbit small intestine and to determine the mechanism of action of Substance P (SP). Rabbit duodenum, jejunum and ileum segments were prepared. The spontaneous contractions of longitudinal and circular smooth muscle were recorded using a computer via an isometric force transducer. The specific agonists and antagonists of tachykinin receptors were added into the organ bath. The agonists of tachykinin NK1 receptor (SP and [Sar9] SP), NK2 receptor (NKA and (β-Ala8)-NKA), and NK3 receptor (NKB and Senktide) all induced contractions in the small intestine. The contractions were diminished by NK1 receptor antagonist L-733,060, NK2 receptor antagonist GR-94800, and NK3 receptor antagonist SB 218795. Contractions caused by SP were also reduced by atropine, verapamil, PKC inhibitor staurosporine, and PLC inhibitor U73122. Ttachykinin NK1, NK2, and NK3 receptors mediate the contractions of the smooth muscle in rabbit intestine. Furthermore, SP acts directly on smooth muscle cells through the tachykinin NK1 receptor.

Sesquiterpene lactones: antispasmodic principles of the freshwater algae Hydrodictyon reticulatum

Hydrodictyon reticulatum is used in traditional medicine in Mexico to decrease gastrointestinal disorders suggesting that some of its chemical components have properties that relax smooth muscle. The hexane extract showed the most promising biological effects, with IC50 of 49.34 μg/ml in the spontaneous contraction of ileum. A detailed phytochemical analysis of the hexane extract led to the isolation of the known sesquiterpenes: β-Cayophyllene-4,5-α-oxide (1) and two new sesquiterpene lactones, 3α,4α,8α-trihydroxy-10α-methoxy-1α,5α,7α,11βH-guaia,6α,12-olide (2) and 4α,8α-dihydroxy-10α-methoxy-1α,5α,7α,11-βH-guaia,6α,12- olide (3). The identification and characterization of these compounds were determined using 1-D and 2-D-NMR (through interpretation of NMR data). The antispasmodic activity of sesquiterpenes of H. reticulatum was studied on isolated tissue preparations from rabbit and rat intestine. The compounds at 1.79 at 3.44 × 10−8 M doses reduced acetylcholine (Ach), histamine, and barium chloride-induced contractions on isolated rat ileum. Therefore, possess similar relaxant mechanism of action, in view of the fact that sesquiterpenes inhibit K+-induced contraction and act through serotoninic, muscarinic, and histaminic receptors. So these data support that extract may interfere with calcium mobilization from intracellular stores or with calcium interaction with regular proteins or in the other steps in the calcium-signaling pathway.

The Effect of Amlodipine Alone and in Combination with Atenolol on Bowel Habit in Patients with Hypertension: An Observation

The prevalence of hypertension increases with advancing age. The management of hypertension especially in the elderly has its own limitations. Verapamil is not recommended in the elderly on account of high incidences of troublesome constipation. Amlodipine has become very popular with the cardiologists and general physicians. Survey of literature has not yielded any citation where the troublesome effect of amlodipine on the gastrointestinal tract has been reported. In an experimental study on isolated rabbit intestine we have demonstrated that amlodipine dose-dependently inhibit the spontaneous activity of the intestinal tract. With this background the present observational study was planned. A total of 100 hypertensive patients were included in the present study. Fifty patients were on amlodipine alone and 50 patients on combination of amlodipine and atenolol. The main parameter analyzed was the frequency and consistency of stool before and after intake of drug. The relative risk (RR) of developing constipation was 4.00 with 95% CI 0.8930 to 17.917 in amlodipine alone group. From this study it can be concluded that the relative risk of developing constipation is 4 times more in patients who are taking amlodipine alone as compared to those patients who are on combination of amlodipine and atenolol.