Motility of rabbit proximal colon

To better define the physiologic relevance of the cholinergic muscarinic input to the rabbit colon and the role of different muscarinic receptor subtypes, we studied the effects of atropine, telenzepine (M₁ antagonist) and DF594 (M₃ antagonist) on colonic motility in eight conscious rabbits fitted with bipolar electrodes and strain gauges along the proximal colon. In some experiments, the chronotropic and mydriatic effect of the pharmacological agents were also assessed. Two main patterns of spike activity were identified: short spike bursts (SSBs), which were usually stationary, and long spike bursts (LSBs), which were usually propagated. Both myoelectrical patterns were dose-dependently inhibited by atropine (0.06–4 mol/kg). Atropine, at the doses of 2–4 mol/kg, abolished both myoelectrical and mechanical activity. Telenzepine (0.008–0.125 mol/kg) dose-dependently inhibited migrating LSBs without significant effect on SSBs. Higher doses (0.25–0.5 mol/kg) inhibited both LSBs and SSBs. DF594 (0.06–2 mol/kg) dose-dependently inhibited both migrating LSBs and SSBs. The three antimuscarinic agents, at doses that inhibited colonic spike activity by approximately 80% (equiactive doses), behaved as follows on heart rate and pupil diameter: atropine induced tachycardia and mydriasis, telenzepine had no effect, and DF594 induced slight mydriasis with no effect on heart rate. We conclude that spontaneous motility in the rabbit proximal colon depends on a muscarinic excitatory input. M₃ receptors are involved in the control of both LSBs and SSBs, while M₁ receptors play an important role in the regulation of LSBs. The development of selective antimuscarinic drugs, acting on a given motility pattern and with minimal side effects, may offer new perspectives in the treatment of functional bowel motor disorders.This work was supported in part by a grant from the Ministero dell'Università e della Ricerca Scientifica e Tecnologica.A preliminary report of this paper was presented at the Fifth European Symposium on Gastrointestinal Motility held in Augsburg, Germany, June 13–16, 1990, and appears in abstract form inJ Gastrointest Motil 2:156, 1990.     

Effect ob broad-spectrum antibiotics on in vitro synthesis of DNA in the rabbit colon

Rabbit colonic mucosa was cultured in vitro in the presence of broad-spectrum antibiotics. DNA synthesis, as determined by [3H]thymidine incorporation into DNA, was inhibited by clindamycin (32%) and tetracycline (28%). Penicillin G, ampicillin, and metronidazole had no effect. When bile acids were added to the incubation at a concentration of 10 mM, the more lipophilic drug, lincomycin, inhibited DNA synthesis by 38% (cholic acid) and by 23% (chenic acid). Bile acids alone did not alter thymidine incorporation. Inhibition by clindamycin demonstrated a gradual dose-response curve, with inhibition first noted at about 20 microgram of antibiotic/ml and maximal inhibition at 1,000 microgram/ml. The more biologically active metabolite of clindamycin, N-demethylclindamycin, inhibited DNA synthesis at concentrations of as low as 10 microgram/ml. The inhibition was reversible, and the drugs did not affect thymidine uptake, thymidine pool concentrations, or protein or mucopolysaccharide synthesis at concentrations of up to 300 microgram/ml. These data demonstrate a direct but reversible toxic action on mammalian colonic mucosa by certain antibiotics implicated in the production of pseudomembranous colitis and are consistent with the hypothesis that such a toxic action may be one factor in the pathogenesis of antibiotic-associated colitis.     

Mechanisms mediating CCK-8S-induced contraction of proximal colon in guinea pigs

AIM:To investigate the effects of sulfated cholecystokinin octapeptide (CCK-8S) on the contractile activity of guinea-pig proximal colon.METHODS:Proximal colonic smooth muscle (PCSM) strips were obtained from adult female guinea pigs and contractile response of PCSM strips was recorded using a polyphysiograph.PCSM cells were isolated by enzymatic digestion.Resting potential (RP),action potential (AP),large conductance potassium channel currents (IBKCa) and L-type calcium currents (ICa-L) were recorded by patch-clamp techniques.RESULTS:(1) CCK-8S (10-7 mol/L) enhanced the mean contractile amplitude of colonic circular muscle and longitudinal muscle (LM) strips by 56.53% ± 11.92%(P=0.038) and 65.93% ± 12.98% (P=0.019),respectively,as well as the mean frequency of LM by 31.69% ± 13.58% (P=0.023),which were significantly attenuated by pretreating strips with devazepide,nifedipine,iberiotoxin,thapsigargin (TG) and BAPTA-AM (BA) respectively;(2) CCK-8S (10-7 mol/L) increased the AP amplitude by 38.6% ± 3.2% (P=0.015),decreased AP duration by 36.9% ± 8.7% (P=0.026),and depolarized the RP from-61.3 ± 2.7 mV to-29.8 ± 5.9 mV (P=0.032);and (3) Compared with the normal control group,CCK-8S (10-7 mol/L) enhanced the peak current of IBKCa by 18.7% ± 2.1% (from 916 ± 183 pA to 1088 ± 226 pA;at +60 mV;P=0.029),which was inhibited by respective pretreatment with iberiotoxin and devazepide.Additionally,CCK-8S (10-7 mol/L) intensif ied the peak current of ICa-L by 40% (from 60 ± 8 pA to 84 ± 11 pA;at +10 mV;P=0.012),compared to the normal control group,which was apparently suppressed by respective pretreatment with nifedipine,devazepide,TG and BA.In the respective presence of heparin and staurosporine,CCK-8S did not signif icantly enhance IBKCa and ICa-L.CONCLUSION:The results suggest that CCK-8S promotes guinea-pig proximal colon contraction by CCK1 receptors,following activation of the inositol triphosphate-protein kinase C signal transduction pathway.     

Perinatal changes in bombesin-stimulated muscle contraction in rabbit stomach and colon

Bombesin and its mammalian homologue, gastrin-releasing peptide, stimulate smooth muscle contraction and may promote the growth of gastrointestinal tissues. Isometric contraction of strips from circular muscle of the gastric fundus and longitudinal muscle of the distal colon were used to compare changes in the response to bombesin in newborn and weanling rabbits. There was an age-related qualitative change in gastric muscle from biphasic contractions including phasic and tonic components in the newborn to phasic contractions alone in the weanling. The colon contractions were tonic at both ages. In both tissues there was an age-related fivefold increase in stress in response to maximally effective concentrations of bethanechol (P less than 0.05). In contrast, in the stomach age-related decreases in the response to maximally effective concentrations of bombesin were observed, from 2930 +/- 179 mN/cm2 (98% of the maximal response to bethanechol) in the newborn to 565 +/- 81 mN/cm2 (4% of the maximal response to bethanechol) in the weanling (P less than 0.005). In the colon, a twofold increase in response to bombesin was observed, from 446 +/- 59 mN/cm2 (82% of the response to bethanechol) in the newborn to 862 +/- 11 mN/cm2 (29% of the response to bethanechol) in the weanling (P less than 0.05). No age-related changes were observed in the potency of bombesin in either tissue. Neither atropine nor tetrodotoxin altered the contractions in either tissue, suggesting that bombesin interacted directly with myocytes. There was three times as much bombesinlike immunoreactivity in the stomach compared with the colon, but no age-related changes in either tissue. In summary, by the age of weanling the stomach lost the tonic component of contraction and 80% of the efficacy of bombesin-stimulated phasic contraction that had been present in the newborn. The loss of efficacy, absolute in the stomach and relative to bethanechol in the colon, suggest that bombesin may be most important in stimulating motility in the neonatal period.     

Macromolecular transport across the rabbit proximal and distal colon

Background—Although many studieshave investigated macromolecular uptake in the stomach and smallintestine, little is known about macromolecular uptake in the colon.
Aims—To investigate the mechanismsinvolved in the transport of large antigenically intact macromoleculesacross the proximal and distal colonic epithelium in the rabbit.
Methods—The mucosal to serosalmovement of bovine serum albumin (BSA) was examined in modified Ussingchambers under short circuited conditions. The mucosal surface wasexposed to varying concentrations of BSA, and after a 50 minuteequilibration period, the mucosal to serosal flux of immunologicallyintact BSA was determined by ELISA. Total BSA flux was determined by the transport of radiolabelled ¹²⁵I-BSA.
Results—Intact BSA transport inproximal and distal colonic tissue showed saturable kinetics. IntactBSA transport in the proximal and distal segment was 7% and 2% of thetotal ¹²⁵I-BSA flux respectively. Immunologically intactBSA transport in the distal segment was significantly less than that inthe proximal segment. Intact BSA transport in the proximal colon was significantly reduced following treatment with sodium fluoride, colchicine, and tetrodotoxin. Cholinergic blockade had no effect on theuptake of intact BSA.
Conclusion—The findings indicatethat the transport of intact macromolecules across the proximal anddistal large intestine is a saturable process. Further, intact BSAtransport in the proximal colon is an energy dependent process thatutilises microtubules and is regulated by the enteric nervous system.

     

Short-chain fatty acid absorption in rabbit colon in vitro

Short-chain fatty acids are the predominant luminal anion in the colon and are generally absorbed rapidly in vivo. However, the mechanisms of in vitro transport of short-chain fatty acids have not been fully delineated. Therefore, we examined [14C]propionate fluxes in rabbit proximal colon under short-circuit conditions. There was minimal metabolism of propionate (less than 10%), permitting accurate flux measurements using a radioisotopic tracer. In a 20 mmol/L propionate Ringer's solution at pH 7.4, there was a significant rate of propionate secretion (-0.58 +/- 0.08 microEq.cm-2.h-1). Decreasing pH to 6.8 by decreasing bicarbonate concentration in the bathing medium resulted in increases in unidirectional fluxes but no change in net transport. Reversal of propionate secretion to propionate absorption was elicited by HEPES substitution for bicarbonate at pH 6.8 or by serosal addition of epinephrine, which increases apical Na(+)-H+ exchange in this epithelium. Propionate absorption was blocked by both amiloride, an Na(+)-H+ exchange inhibitor, and ouabain. Under basal conditions, there was a concentration-dependent increase in basal unidirectional propionate fluxes with no change in net transport as the concentration of propionate increased from 10 to 60 mmol/L. In contrast, a concentration-dependent saturation of epinephrine-stimulated propionate absorption was apparent. Transepithelial propionate gradients did not yield a significant diffusion potential. These results suggest that, in rabbit proximal colon, (a) there is bidirectional diffusion of propionate, most probably in the protonated rather than the ionized form; (b) a component of propionate transport is active and linked to electroneutral Na+ absorption through apical Na(+)-H+ exchange; and (c) changes in composition of the fluid bathing the proximal colon in vitro may significantly alter both rates and direction of short-chain fatty acid transport. Regulation of transcellular active transport may play an important role in colonic short-chain fatty acid conservation.     

Sources of calcium in agonist-induced contraction of rat distal colon smooth muscle in vitro

AIM： To study the origin of calcium necessary for agonist-induced contraction of the distal colon in rats.METHODS： The change in intracellular calcium concentration （[Ca^2＋]i） evoked by elevating external Ca^2＋ was detected by fura 2/AM fluorescence. Contractile activity was measured with a force displacement transducer. Tension was continuously monitored and recorded using a Powerlab 4/25T data acquisition system with an ML110 bridge bioelectric physiographic amplifier.RESULTS： Store depletion induced Ca^2＋ influx had an effect on [Ca^2＋]i. In nominally Ca^2＋-free medium, the sarco-endoplasmic reticulum Ca^2＋-ATPase inhibitor thapsigargin （1 μmol/L） increased [Ca^2＋]i from 68 to 241 nmol/L, and to 458 （P 〈 0.01） and 1006 nmol/L （P 〈 0.01）, respectively, when 1.5 mmol/L and 3.0 mmol/L extracellular Ca^2＋ was reintroduced. Furthermore, the change in [Ca^2＋]i was observed with verapamil （5 μmol/L）, La3＋ （1 mmol/L） or KCl （40 mmol/L） in the bathing solution. These channels were sensitive to La3＋ （P 〈 0.01）, insensitive to verapamil, and voltage independent. In isolated distal colons we found that in normal Krebs solution, contraction induced by acetylcholine （ACh） was partially inhibited by verapamil, and the inhibitory rate was 41% （P 〈 0.05）. On the other hand, in Ca^2＋-free Krebs solution, ACh induced transient contraction due to Ca^2＋ release from the intracellular stores. The transient contraction lasted until the Ca^2＋ store was depleted. Restoration of extracellular Ca^2＋ in the presence of atropine produced contraction, mainly due to Ca^2＋ influx. Such contraction was not inhibited by verapamil, but was decreased by La3＋ （50 μmol/L） from 0.96 to 0.72 g （P 〈 0.01）. CONCLUSION： The predominant source of activator Ca^2＋ for the contractile response to agonist is extracellular Ca^2＋, and intracellular Ca^2＋ has little role to play in mediating excitation-contraction coupling by agonists in rat distal colo     

氟在体外对兔成骨细胞增殖行为的影响

目的通过体外培养幼兔成骨细胞,观察不同浓度的氟对成骨细胞增殖行为的影响.方法用幼兔肋骨培养成骨细胞,纯化、鉴定.用不同浓度的氟化钠处理(20、160、240、400μmol/L),MTT法测定氟对成骨细胞增殖的影响;嗜银蛋白(AgNoRs)分析计数细胞核内AgNORs颗粒数.结果低浓度的氟(20μmol/L)在体外可促进成骨细胞增殖,而高浓度的氟(160、240、400 μmol/L)则抑制成骨细胞的增殖.低浓度氟处理组(20μmol/L)细胞核内AgNORs颗粒数显著多于对照组(P＜0.01);而高浓度氟处理组(240、400μmol/L)胞核内AgNORs颗粒数显著减少(P＜0.05).结论低浓度的氟可以促进成骨细胞的增殖,高浓度的氟抑制成骨细胞的增殖,氟对成骨细胞的作用具有双向性.     

Effect of disodium azodisalicylate on electrolyte transport in rabbit ileum and colon in vitro. Comparison with sulfasalazine and 5-aminosalicylic acid

Azodisalicylate, used to treat ulcerative colitis, causes diarrhea in up to 12.5% of patients. We compared the in vitro effects of azodisalicylate, sulfasalazine, and 5-aminosalicylic acid on rabbit intestinal electrolyte transport. Distal ileal mucosae mounted in Ussing chambers were exposed to varying concentrations of the drugs. Mucosal addition of azodisalicylate (greater than 5 mM) caused the greatest anion-dependent increase in short-circuit current of 83 microA/cm2 (ED50 = 0.3 mM). Isotope flux measurements suggest that azodisalicylate may stimulate predominantly electrogenic HCO3 secretion and induces net NaCl secretion. In contrast, serosal addition of azodisalicylate and sulfasalazine (greater than 5 mM) decreased short-circuit current, and 5-aminosalicylic acid had no effect. Azodisalicylate had no effect on ion transport in distal colon. The effects of azodisalicylate in ileum were not inhibited with piroxicam (an inhibitor of cyclooxygenase). Mucosal cyclic adenosine monophosphate and cyclic guanosine monophosphate levels were unchanged after ileal exposure to azodisalicylate. Azodisalicylate appears to be a mechanistically unusual secretagogue, possibly explaining the increased incidence of diarrhea seen in patients taking the drug.     

Effect of genistein on voltage-gated potassium channels in guinea pig proximal colon smooth muscle cells

AIM:To investigate the action of genistein(GST),abroad spectrum tyrosine kinase inhibitor,on voltage-gated potassium channels in guinea pig proximal colonsmooth muscle cells.METHODS:Smooth muscle cells in guinea pig proximalcolon were enzymatically isolated.Nystatin-perforatedwhole cell patch clamp technique was used to recordpotassium currents including fast transient outwardcurrent(I_(Kto))and delayed rectifier current(I_(Kdr)),two ofwhich were isolated pharmacologically with 10 mmol/Ltetraethylammonium or 5 mmol/L 4-aminopyridine.Contamination of calcium-dependent potassium currentswas minimized with no calcium and 0.2 mmol/L CdCl_2 inan external solution.RESULTS:GST(10-100μmol/L)reversibly and dose-dependently reduced the peak amplitude of I_(Kto)with anICso value of 22.0 6.9μmol/L.To a lesser extent,I_(Kdr)wasalso inhibited in both peak current and sustained current.GST could not totally block the outward potassiumcurrent as a fraction of the outWard potassium current,which was insensitive to GST.GST had no effect on thesteady-state activation(n=6)and inactivation kinetics(n=6)of I_(Kto).Sodium orthovanadate(1 mmol/L),apotent inhibitor of tyrosine phosphatase,significantlyinhibited GST-induced inhibition(P<0.05).CONCLUSION:GST can dose-dependently andreversibly block voltage-gated potassium channels inguinea pig proximal colon smooth muscle cells.     

NO对小鼠结肠平滑肌自主收缩活动的影响及其机制

目的:观察一氧化氮(NO)供体左旋精氨酸(L-arginine,L-Arg)对小鼠离体结肠自主收缩活动的影响及其机制.方法:用张力换能器记录肌标本自主收缩的方法,以离体结肠肌条收缩张力的变化为指标,观察NO的作用及一氧化氮合酶(nitricoxide synthase,NOS)抑制剂L-NNA、可溶性鸟苷酸环化酶(soluble guanylyl cyclase, sGC)抑制剂ODQ、磷酸二酯酶抑制剂氨茶碱(aminophylline)、M-受体的阻断剂阿托品(atropine)和激动剂乙酰胆碱(acetylcholine, ACh)对NO作用的影响.结果:NO抑制小鼠结肠平滑肌自主收缩活动,抑制效应呈浓度依赖性,1 × 10-3和1× 10-5的L-Arg抑制百分率分别为55.7%±4.4%和38.0%±4.2%.1× 10-8mol/L时对结肠自主收缩幅度的影响无显著性.L-NNA(1× 10-5mol/L)明显减弱L-Arg的抑制效应.ODQ(1× 10-6mol/L)减弱L-Arg的抑制效应.aminophylline(1× 10-6mol/L)使L-Arg的效应明显增强.atropine(1×10-3mol/L)明显增L-Arg的抑制效应.ACh(1×10-7mol/L)减弱L-Arg的效应.结论:L-Arg由NOS催化生成NO后经cGMP途径发挥对小鼠结肠自主收缩的抑制作用.M-受体途径也部分参与了NO的作用过程.     

Effects of alverine on the spontaneous electrical activity and nervous control of the proximal colon of the rabbit.

To analyse the mechanisms of the antispasmodic action of alverine, the effects of this drug on the spontaneous motility and nervous control of the proximal colon of the rabbit were studied in vivo. The electrical activity of the colonic smooth muscle was recorded using extracellular electrodes. The parasympathetic efferents were activated by electrical stimulation of distal ends of the vagus nerves. Alverine given intravenously inhibits spike potentials without modifying the slow waves. Excitatory and inhibitory responses induced by parasympathetic efferent stimulations, as well as the hyperpolarization due to intraluminal distension, were also blocked after drug injection. Our results show that alverine is able to block the spontaneous contractions and the nervous control of rabbit proximal colon, indicating that this drug has powerful antispasmodic effects.     

Effect of gut-associated lymphoid tissue on cellular proliferation in proximal and distal colon of the rat

In previous studies, chemically induced colonic carcinomas were found to originate preferentially from crypts adjacent to lymphoid tissue. Proliferative parameters and mucosecretion were analyzed in proximal and distal rat colon in relation to the proximity of lymphoid patches. Animals received an intraperitoneal pulse of bromodeoxyuridine 1-hr before death. In both proximal and distal colon, crypts located at the immediate proximity of the lymphoid formations contained fewer mucous cells (P<0.001), but a higher percentage of proliferative epithelial cells (P<0.001) than the crypts far from lymphoid formations. The labeling index was higher in crypts adjacent to lymphoid patches compared to crypts distant from lymphoid patches only in the lower third of the crypts. The association of an increased proliferative activity and a decrease in differentiated mucosecreting cells in colonic crypts adjacent to lymphoid patches could be related to the particular sensitivity of these crypts cells to the effects of mutagens and carcinogens.     

Effect of beta-blocker on metabolism and contraction of doxorubicin-induced cardiotoxicity in the isolated perfused rabbit heart

The effect of beta-blocker (propranolol) on the metabolism and contraction of doxorubicin-induced cardiomyopathy during pacing or ischemia was examined by the phosphorus 31-nuclear magnetic resonance (31 P-NMR) in Langendorff hearts of chronically treated rabbits after cumulative doses of 16 mg doxorubicin/kg. After 8 weeks of doxorubicin treatment, beta-blocker (propranolol) was given orally over a period of 2 weeks for a cumulative dose of 1.4 mg/kg. Isolated hearts were paced at higher heart rates, or hearts were perfused on low flow. Adenosine triphosphate (ATP), creatine phosphate (PCr), inorganic phosphate (Pi), pH, left ventricular systolic developed pressure (LVDev P), and coronary flow were measured. The hearts were divided into three experimental groups: Group I consisted of controls, Group II consisted of doxorubicin treatment, and Group III consisted of doxorubicin treatment with propranolol. Group II showed a significant decrease of ATP during pacing (48 +/- 2%) and during low flow (61 +/- 6%) compared with Group I (86 +/- 9% at pacing, 94 +/- 6% on low flow). But Group III showed a significantly marked improvement of ATP during pacing (95 +/- 10%) and during low flow (83 +/- 3%) compared with Group II. Furthermore, Group II showed a significant decrease of LVDev P during pacing (69 +/- 6 mm Hg) and during low flow (63 +/- 3 mm Hg) compared with Group I (101 +/- 5 mm Hg at pacing, 95 +/- 9 mm Hg on low flow). But Group III showed a significantly marked improvement of LVDev P during pacing (93 +/- 5 mm Hg) and during low flow (83 +/- 14 mm Hg) compared with Group II. In conclusion, propranolol had a significant beneficial effect on metabolism and contraction during high-energy demand and during low oxygen supply of doxorubicin cardiomyopathy.     

Tetraethylammonium-induced contraction of rabbit coronary artery

Summary The vasoactive effect of tetraethylammonium (TEA), a well-known K channel blocker, was tested on helical strips excised from the large epicardial coronary arteries of rabbit hearts. TEA (10 mM) induced transient tetanic contraction of greater amplitude as a result of summation of twitch responses. Occasionally, spontaneous periodic contractions occurred during prolonged exposure to 10 mM TEA. This TEA-induced contraction was abolished in Ca-free solution and suppressed by Ca-entry blockers: nitroglycerin, nicorandil, and isoproterenol, but not by phentolamine or atropine. In strips in which TEA did not induce remarkable contraction, subsequent addition of a subthreshold concentration of ergonovine, serotonin, acetylcholine, ouabain, K-rich solution, or alkalinization of the solution provoked remarkable contraction. These results are consistent with previous reports that TEA induced tetanic contraction as a result of summation of twitch responses due to spontaneous discharge of Ca-spikes in some arterial and tracheal smooth muscle. The results also support the idea that TEA-induced contraction of the rabbit coronary artery is mediated by the same mechanism, i.e., spontaneous Ca-spike discharge.     

Opposing effects of estradiol and progesterone on oxytocin receptors in rabbit uterus

Estradiol-17beta administration to young (10- to 12-week-old) rabbits to produce the "estrogen-dominated" uterus increased the uterine contractile response to both oxytocin and methacholine in vitro. In "progesterone-dominated" uteri, obtained from rabbits that received progesterone for 4 days after estrogen pretreatment, the contractile response to oxytocin in vitro was selectively abolished; the response to methacholine was unaffected. Parallel changes were observed in the concentration (but not affinity) of specific sites in uterine microsomal membranes that bind [(3)H]oxytocin with selectivity features expected for oxytocin receptors. Thus, estrogen-dominated uteri have an increased number of specific [(3)H]oxytocin binding sites per mg of membrane protein relative to untreated controls, whereas specific oxytocin binding sites are reduced to barely detectable levels in the progesterone-dominated uterus. Similar results are obtained when binding sites are measured in membranes from the myometrium of estrogen- or progesterone-dominated uteri. Short-term (24-hr) progesterone administration to estrogen-pretreated rabbits decreased, but did not abolish, specific [(3)H]oxytocin binding; the concentration of specific [(3)H]oxytocin binding sites was reduced without influence on the affinity of these sites. A sublethal dose of actinomycin D, administered over a 24-hr period to rabbits pretreated with estradiol for 4 days, likewise reduced specific oxytocin binding; additive effects were not observed when progesterone and actinomycin D were administered together. These results suggest that the regulatory effects of estrogens and progesterone upon the rabbit uterine contractile response to oxytocin are achieved, at least in part, by the opposing actions of these steroids in regulating the number of oxytocin receptors in smooth muscle cells. Estradiol increased the concentration of uterine oxytocin receptors; the maintenance of high receptor levels appears to depend upon the continuous de novo synthesis of oxytocin receptors. In contrast, progesterone, like actinomycin D, appears to act at the nuclear locus to repress synthesis of oxytocin receptors.     

Impact of proximal colon retroflexion on adenoma miss rates

BACKGROUND: Small adenomas are commonly missed during routine colonoscopy. The aim of this study was to determine whether routine retroflexion in the proximal colon would improve adenoma detection rates. METHODS: One hundred patients underwent colonoscopy from the cecum to the splenic flexure by a gastroenterology fellow, with the removal of all visualized polyps. The cecum was then reintubated and patients were randomized to a second exam of the proximal colon by an experienced staff physician in either the forward view or a retroflexed view. RESULTS: Two patients were excluded due to a difficult initial cecal intubation. Forty-eight patients were randomized to forward view and 50 patients were randomized to a retroflexed view. Retroflexion was successful in the cecum in 60%, the ascending colon 100%, and the transverse colon 98%. The success in retroflexion was determined in part by the type of colonoscope used. If any portion of the retroflexed examination could not be performed, that reexamination was performed in the forward view. The calculated miss rates for all polyps and adenomas among patients randomized to second examination in the forward view was 36.8% and 33.3%, respectively. The calculated miss rate for all polyps and for adenomas among patients randomized to a second examination in the retroflexed view was 38.1% and 23.7%, respectively. There was no difference in miss rates for all polyps or for adenomas (p= 0.31) when the second examination was performed in the forward view versus retroflexed view. CONCLUSIONS: A second examination by retroflexion in the proximal colon did not increase the calculated miss rate relative to that performed by a forward view examination. These results do not support the addition of routine right colon retroflexion to colonoscopy.     

Influence of pyruvate on economy of contraction in isolated rabbit myocardium

BACKGROUND: Treatment of acute heart failure frequently requires positive-inotropic stimulation. However, there is still no inotropic agent available, which combines a favourable haemodynamic profile with low expenditure for energy metabolism. Pyruvate exhibits positive inotropic effects in vitro and in patients with heart failure. The effect on myocardial energy metabolism however remains unclear, but is meaningful in light of a clinical application. AIMS AND METHODS: We investigated the influence of pyruvate on contractility and oxygen consumption in isolated isometric contracting rabbit myocardium compared to beta-adrenergic stimulation with isoproterenol. RESULTS: Pyruvate (30 mM) increased developed force from 18.7+/-4.1 to 50.8+/-12.1 mN/mm2 (n=10, p<0.01). Force-time integral (FTI) increased by 329%, oxygen consumption assessed by diffusion-microelectrode technique increased from 2.86+/-0.30 mlO2/min*100 g to 6.28+/-1.28 mlO2/min*100 g (n=7, p<0.05). Economy of myocardial contraction calculated as the ratio of total FTI to oxygen consumption remained unchanged. In contrast, while isoproterenol (10 microM) produced a comparable increase in developed force from 21.4+/-8.3 to 67.3+/-15 mN/mm2 (n=7, p<0.01), FTI increased only by 260% and MVO2 increased from 2.96+/-0.43 to 6.12+/-1.01 mlO2/min*100 g (n=7, p<0.01); thus, economy decreased by 23% (n=7, p<0.05). CONCLUSION: Pyruvate does not impair economy of myocardial contraction while isoproterenol decreases economy. Regarding energy expenditure, pyruvate appears superior to isoproterenol for the purpose of positive inotropic stimulation.