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Biomedical subjects

F Capasso

Publications and source records attributed to F Capasso.

At least 37 records · Page 2Linked to original sources

Intracoronary shunt prevents left ventricular function impairment during beating heart coronary revascularization.

OBJECTIVE: Beating heart coronary revascularization is becoming increasingly popular world-wide. Temporary occlusion of the coronary artery is often required in order to perform the anastomosis. An alternative method to maintain perfusion is to use an intracoronary shunt. In this study, we monitored global left ventricular function and regional wall motion in the presence or absence of a shunt using transesophageal echocardiography (TEE). METHOD: Left ventricular wall motion score index (WMSI), wall motion score (WMS) in the left anterior descending (LAD) coronary artery territory, and ejection fraction (EF%) were measured by multiplane TEE during construction of the left internal mammary artery (LIMA)-LAD coronary artery anastomosis in 40 patients undergoing revascularization with or without the use of a shunt. WMSI was assessed preoperatively, 1, 3 and 6 min during the construction of the anastomosis and after 5 min of reperfusion. WMS was assessed at 6 min during anastomosis and after 5 min of reperfusion. EF% was calculated preoperatively, 5 min into the construction of the anastomosis, and 5 min after reperfusion. RESULTS: During construction of the anastomosis, when the shunt was used, there were no changes in WMSI, WMS in the LAD territory or EF%. A significant decline in these parameters was seen in the group in which the shunt was not used, although on reperfusion all the values returned to baseline control. CONCLUSION: (i) occlusion of the LAD to perform the anastomosis results in temporary impairment in left ventricular function with complete recovery on reperfusion; (ii) the use of an intracoronary shunt presumably by maintaining myocardial perfusion prevents deterioration in ventricular function; (iii) from this data it seems therefore advisable to use an intracoronary shunt in patients with unstable angina, poor left ventricular function, or in cases in which a longer time to perform the anastomosis is anticipated.

Aged↗

Does senna extract promote growth of aberrant crypt foci and malignant tumors in rat colon?

Current evidence suggests that aberrant crypt foci (ACF) can be used to evaluate agents for their potential colon carcinogenic activity. The aim of the present study was to determine whether senna pod extract (SE) itself induces ACF and tumors in the rat colon or increases the development of ACF and tumors induced by azoxymethane (AOM). A daily administration of SE 10 mg/kg by mouth for 13-28 weeks produced a weak laxative effect but did not itself cause the appearance of ACF or tumors. The numbers of ACF and tumors induced by AOM were, however, increased by a dose of SE (100 mg/kg) able to induce chronic diarrhea over three months. These results suggest that SE does not cause the appearance of ACF or tumors in the rat colon nor does it have a promoting effect when given to rats at a dose that produces laxation (10 mg/kg), whereas a diarrhogenic dose (100 mg/kg) increases the appearance of tumors induced by AOM.

Animals↗

High-power directional emission from microlasers with chaotic resonators

High-power and highly directional semiconductor microcylinder lasers based on an optical resonator with deformed cross section are reported. In the favorable directions of the far-field, a power increase of up to three orders of magnitude over the conventional circularly symmetric lasers was obtained. A "bow-tie"-shaped resonance is responsible for the improved performance of the lasers in the higher range of deformations, in contrast to "whispering-gallery"-type modes of circular and weakly deformed lasers. This resonator design, although demonstrated here in midinfrared quantum-cascade lasers, should be applicable to any laser based on semiconductors or other high-refractive index materials.

Journal Article↗

Effect of selective phosphodiesterase inhibitors on synaptic transmission in the guinea-pig ileum.

The effect of selective phosphodiesterase (PDE) inhibitors was studied on neural transmission within the enteric nervous system employing a two-compartment bath (containing the oral and the anal end of a segment of guinea-pig ileum, respectively). Ascending excitatory enteric nerve pathways were activated by electrical field stimulation (10 Hz for 2 s, 45 mA, 0.5 pulse duration) in the anal compartment and the resulting contraction of the intestinal circular muscle in the oral compartment was recorded. The partitioned bath enables PDE inhibitors and other drugs to be applied to enteric nerve pathways (in the anal compartment) without interfering with the recording of the smooth muscle contraction in the oral compartment. The PDE 4 inhibitors rolipram (0.01-10 microM) and Ro-20-1724 (0.01-10 microM) significantly (P<0.01) inhibited (10-91% and 9-83%, respectively) the nerve-mediated contractions. When both rolipram and Ro-20-1724 were tested after phentolamine (1 microM) or yohimbine (0.1 microM), they were significantly (P<0.01) less effective. By contrast prazosin (1 microM) was ineffective. Vinpocetine (50 microM), milrinone (30 microM) and zaprinast (100 microM), which inhibit PDE 1, 3 and 5, respectively, did not modify the nerve-mediated contractions. 8-Bromoadenosine 3',5'-cyclic monophosphate (8-Br-cyclic AMP) or N6,2'-O-dibutyryladenosine 3',5' cyclic monophosphate (dibutyryl cyclic AMP), two analogues of cyclic AMP, at lower concentrations (0.1-1 microM) significantly (P<0.01) inhibited (15-73% and 5-49%, respectively) the nerve-mediated contractions, while at higher concentrations (10-100 microM) they caused a significant (P<0.01) potentiating (48-68% and 77-78%, respectively) effect. These results indicate that inhibition of PDE 4 (but not PDE 1, PDE 3 or PDE 5) produces a depression of neural transmission within the enteric nervous system, possibly by releasing noradrenaline acting at alpha2-adrenoceptors on enteric neurons.

4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗

Recent findings on the mode of action of laxatives: the role of platelet activating factor and nitric oxide.

Platelet activating factor (PAF) is a phospholipid mediator of inflammation and stimulates anion secretion in animals and in isolated preparations of human colon. Nitric oxide (NO), synthesized from the amino acid L-arginine, is an important enteric inhibitory neurotransmitter. In addition, NO-donating compounds stimulate anion secretion in rat and guinea-pig colon. In this article, Angelo A. Izzo and colleagues review the key pharmacological features of the involvement of NO and PAF in the action of laxatives and propose that the classification of laxatives should take into account the important implications of these endogenous mediators.

Animals↗

Nitric oxide as a modulator of intestinal water and electrolyte transport.

The role of nitric oxide in intestinal fluid and electrolyte secretion depends upon whether the conditions under study are physiological or pathophysiological. In physiological conditions, endogenous nitric oxide seems to be a proabsorptive molecule, based on the findings that nitric oxide synthase inhibitors reverse net fluid absorption to net secretion in mice, rats, guinea pigs, rabbits, and dogs. This proabsorptive mode involves the enteric nervous system, the suppression of prostaglandin formation, and the opening of basolateral K+ channels. However, in some pathophysiological states nitric oxide synthase may be produced at higher concentrations that are capable of evoking net secretion. Thus nitric oxide synthase contributes to the diarrheal response in trinitrobenzene sulfonic acid-induced ileitis in guinea pigs and is the mediator of the laxative action of several intestinal secretagogues including castor oil, phenolphthalein, bisacodyl, magnesium sulfate, bile salts, senna, and cascara in the rat. Corresponding with the in vivo results, nitric oxide-donating compounds or nitric oxide itself stimulate chloride secretion in the guinea pig and rat intestine in vitro. Exceptions are the diarrhea produced by bacterial enterotoxins in the rat, in which nitric oxide seems to have a proabsorptive role, and the mouse ileum in vitro, in which nitric oxide-donating compounds produce a net proabsorptive effect on basal ion transport. Several endogenous secretagogues (substance P, 5-hydroxytryptamine, interleukin-1beta), which are important mediators of the inflammatory bowel diseases, act, at least in part, through the liberation of nitric oxide. Clinical studies have shown that nitric oxide is elevated in several inflammatory bowel diseases and other secretory conditions including ulcerative colitis, Crohn's disease, toxic megacolon, diverticulitis, infectious gastroenteritis, and infantile methemoglobinemia. However, the determination of nitric oxide in secretory diarrhea per se does not give conclusive information on the nitric oxide contribution to clinical secretory diarrhea.

Animals↗

Effect of sodium rhein on electrically-evoked and agonist-induced contractions of the guinea-pig isolated ileal circular muscle.

1. This study examined the effects of sodium rhein (0.03-30 microM) on the contractions of the isolated circular muscle of guinea-pig ileum induced by acetylcholine (100 nM), substance P (3 nM) and electrical stimulation (10 Hz for 0.3 s, 100 mA, 0.5 ms pulse duration). The effect of sodium rhein was also evaluated on the ascending excitatory reflex using a partitioned bath (oral and anal compartments). Ascending excitatory enteric nerve pathways were activated by electrical field stimulation (10 Hz for 2 s, 20 mA, 0.5 pulse duration) in the anal compartment and the resulting contraction of the guinea-pig intestinal circular muscle in the oral compartment was recorded. 2. Sodium rhein (0.3, 3 and 30 microM) significantly potentiated (52+/-11% at 30 microM) acetylcholine-induced contractions. In the presence of tetrodotoxin (0.6 microM) or omega-conotoxin GVIA (10 nM) sodium rhein (3 and 30 microM) did not enhance, but significantly reduced (49+/-10% and 44+/-8%, respectively, at 30 microM) acetylcholine-induced contractions. 3. Sodium rhein (0.3, 3 and 30 microM) significantly increased (65+/-11% at 30 microM) substance P-induced contractions. In the presence of tetrodotoxin (0.6 microM), omega-conotoxin GVIA (10 nM) or atropine (0.1 microM), sodium rhein (3 and 30 microM) significantly reduced (50+/-10%, 55+/-8% and 46+/-10%, respectively, at 30 microM) substance P-induced contractions. 4. NG-nitro-L-arginine methyl ester (L-NAME, 100 microM) abolished the potentiating effect of sodium rhein on acetylcholine and substance P-induced contractions. At the highest concentration (30 microM), sodium rhein, in presence of L-NAME, reduced the acetylcholine (30+/-6%)- or substance P (36+/-6%)-induced contractions. 5. Sodium rhein (30 microM) significantly potentiated (29+/-9%) the electrically-evoked contractions. L-NAME (100 microM), but not phentolamine, enhanced the effect of sodium rhein. Sodium rhein (30 microM) significantly increased (32+/-9%) the ascending excitatory reflex when applied in the oral, but not in the anal compartment. 6. These results indicate that sodium rhein (i) activates excitatory cholinergic nerves on circular smooth muscle presumably through a facilitation of Ca2+ entry through the N-type Ca2+ channel, (ii) has a direct inhibitory effect on circular smooth muscle and (iii) does not affect enteric ascending neuroneural transmission. Nitric oxide could have a modulatory excitatory role on sodium rhein-induced changes of agonist-induced contractions and an inhibitory modulator role on sodium rhein-induced changes of electrically-induced contractions.

Acetylcholine↗

Excitatory transmission to the circular muscle of the guinea-pig ileum: evidence for the involvement of cannabinoid CB1 receptors.

1. The effect of cannabinoid drugs has been investigated on cholinergic and non-adrenergic non-cholinergic (NANC) contractile responses to the circular smooth muscle of guinea-pig ileum elicited by electrical field stimulation (EFS). 2. The cannabinoid receptor agonist WIN 55,212-2 (1-1000 nM) and the putative endogenous ligand anandamide (0.1-100 microM) both produced a concentration-dependent inhibition of the cholinergic (9-57% and 1-51% inhibition) and NANC (9 55% and 2-57% inhibition) contractile responses. WIN 55,212-2 and anandamide did not modify the contractions produced by exogenous acetylcholine or substance P. 3. Apamin (30 nM), a blocker of Ca2+-activated K+ channels, reduced the inhibitory effect of WIN 55,212-2 on cholinergic, but not NANC, contractile response. NG-nitro-L-arginine methyl ester (100 microM), an inhibitor of nitric oxide synthase, or naloxone (1 microM), an opioid receptors antagonist, did not modify the inhibitory effect of WIN 55,212-2 on both cholinergic and NANC contractions. 4. The inhibitory effects of WIN 55,212-2 and anandamide on both cholinergic and NANC contractile response was competitively antagonized by the cannabinoid CB1 receptor antagonist SR 141716A (10-1000 nM). 5. In absence of other drugs, SR 141716A (1-1000 nM) enhanced cholinergic (1-45% increase) and NANC (2-38% increase) contractile responses elicited by electrical stimulation, but did not modify the contractions produced by acetylcholine or substance P. 6. It is concluded that activation of prejunctional cannabinoid CB1 receptors produces inhibition of cholinergic and NANC excitatory responses in the guinea-pig circular muscle. The inhibition of cholinergic (but not NANC) transmission involves activation of apamin-sensitive K+ channels. In addition, an endogenous cannabinoid ligand could inhibit cholinergic and NANC transmission in the guinea-pig ileal circular muscle.

Animals↗

The role of histamine H1, H2 and H3 receptors on enteric ascending synaptic transmission in the guinea pig ileum.

The role of histamine H1-, H2- and H3-receptors was studied on neural transmission in ascending excitatory pathways of the guinea pig ileum. A two-compartment (oral and anal compartments) bath was used: ascending neural pathways were activated by electrical stimulation in the anal compartment and the resulting contraction of the circular muscle in the oral compartment was recorded. Drugs were applied in the anal compartment and each agonist was evaluated in the presence of the antagonists of the other two receptors. In the presence of cimetidine (10 microM) and thioperamide (1 microM), histamine (0.03-3 microM) depressed the nerve-mediated contractions (5-70% inhibition, P <.05-.01). The inhibitory effect of histamine was antagonized by mepyramine. At the higher concentrations (10 and 30 microM), histamine elicited contractions of the circular muscle in the oral compartment, and these were abolished by mepyramine (1 microM) and tetrodotoxin (0.6 microM). The H2 agonists dimaprit (30 and 100 microM) and amphamine (0.1-300 microM) produced small contractions of the circular muscle in the oral compartment. These contractile responses were abolished by tetrodotoxin (0.6 microM) and cimetidine (10 microM). The H3 agonist R-alpha-methylhistamine (0.001-1 microM) inhibited (2-58%, P <.05) the nerve-mediated contractions. This inhibitory effect was antagonized by the H3 antagonist thioperamide. These results indicate that 1) histamine, acting at H1 receptors, at lower concentrations depresses synaptic transmission, although at higher concentrations activates the enteric excitatory ascending pathway; 2) activation of H2 receptors by H2 agonists stimulates the enteric excitatory ascending pathways and 3) activation of H3 receptors inhibits synaptic transmission.

Animals↗

High-Power Infrared (8-Micrometer Wavelength) Superlattice Lasers

A quantum-cascade long-wavelength infrared laser based on superlattice active regions has been demonstrated. In this source, electrons injected by tunneling emit photons corresponding to the energy gap (minigap) between two superlattice conduction bands (minibands). A distinctive design feature is the high oscillator strength of the optical transition. Pulsed operation at a wavelength of about 8 micrometers with peak powers ranging from approximately 0.80 watt at 80 kelvin to 0.2 watt at 200 kelvin has been demonstrated in a superlattice with 1-nanometer-thick AlInAs barriers and 4.3-nanometer-thick GaInAs quantum wells grown by molecular beam epitaxy. These results demonstrate the potential of strongly coupled superlattices as infrared laser materials for high-power sources in which the wavelength can be tailored by design.

Journal Article↗

The role of constitutive and inducible nitric oxide synthase in senna- and cascara-induced diarrhoea in the rat.

The role of constitutive and inducible nitric oxide (NO) synthase in rats treated with senna and cascara was studied. Senna (60 mg/kg p.o.) and cascara (800 mg/kg p.o.) ex vivo significantly increased Ca(2+)-dependent constitutive NO synthase activity in the rat colon. Induction of NO synthase (12% of the total NO synthase) was associated with cascara, but not senna, administration. Dexamethasone (0.03-0.3 mg/kg i.p.), which inhibits the expression of inducible NO synthase, significantly and dose-dependently reduced cascara-(but not senna-) induced diarrhoea and colonic fluid secretion. These findings suggest that senna probably exerts its laxative effect through stimulation of the constitutive isoform of NO synthase, while the inducible isoform of NO synthase also seems to be involved in the laxative effect of cascara.

Administration, Oral↗

Pharmacological investigation of Cassia italica.

In the present study, the ethanolic extract of the whole plant parts (root, stem leaves and pods) of Cassia italica (Mill.) Lam. ex F.W. Ander (Leguminosae) was investigated for bioactivities: namely anti-inflammatory, antipyretic, analgesic and prostaglandin (PG) release by rat peritoneal leucocytes, antineoplastic and antiviral. In rats, the extracts reduced carrageenin-induced paw swelling (100 mg/kg bw-31%) and fever (100 mg/kg bw-37%). The extract showed weak effect on writhing induced by acetic acid. A dose-dependent inhibition of PG release effect was observed using rat peritoneal leucocytes.

Animals↗

Effect of papaverine on synaptic transmission in the guinea-pig ileum.

1. The effect of papaverine, a well known smooth muscle relaxant, was investigated on neural transmission within the enteric nervous system. Segments of guinea-pig ileum were placed in a partitioned bath to enable drugs, including papaverine, to be applied to enteric nerve pathways without interfering with the recording of the smooth muscle contraction. Ascending excitatory enteric nerve pathways were activated by electrical field stimulation in the anal compartment (10 Hz for 2 s, 45 mA, 0.5 ms pulse duration) and the resulting contraction of the intestinal circular muscle in the oral compartment was recorded isotonically. 2. Tetrodotoxin (0.6 microM) and hexamethonium (100 microM) both abolished, or greatly reduced, the contractions when applied to either compartment indicating that nicotinic synapses are involved in this pathway. 3. Papaverine (0.3-30 microM) applied independently to each compartment depressed in a concentration-dependent manner, the nerve-mediated contractions. The IC50 of this inhibitory effect was 3.53 microM for the oral and 4.76 microM for the anal compartments, respectively. Two other phosphodiesterase (PDE) inhibitors, 3-isobutyl-1-methylxanthine (IBMX 10-300 microM) and theophylline (30-1000 microM) added to the anal compartment also inhibited the nerve mediated contractions. Papaverine applied to the anal bath, after IBMX 100 microM (or theophylline 300 microM) further inhibited the nerve-mediated contractions, but was less effective than when applied alone. 4. Phentolamine (1 microM), an alpha-adrenoceptor antagonist, reduced the inhibitory effect of papaverine, but not that of IBMX (100 microM) or theophylline (300 microM). A combination of phentolamine and IBMX (or theophylline) prevented the inhibitory effect of papaverine. 5. Tetrodotoxin, but not papaverine or hexamethonium, inhibited the contraction elicited by electrical stimulation just anal to the partition indicating that papaverine did not affect the generation or conduction of nerve action potentials. 6. Verapamil (1 microM) and nifedipine (1 microM), two smooth muscle relaxants which act by blocking L-type calcium channels, only inhibited the contractions when applied directly to the recording (oral) compartment. This indicates that L-type Ca2+ channels are probably not involved in synaptic transmission in these ascending pathways and thus that the PDE inhibitors do not inhibit synaptic transmission by acting on these channels. omega-Conotoxin GVIA (10 nM), a potent inhibitor of the N-type Ca2+ channels, blocked the nerve-mediated contractions applied to either compartment. Whether the PDE inhibitors exert their inhibitory actions via these channels remains to be established. 7. The results indicate that the PDE inhibitors, papaverine, IBMX and theophylline inhibit excitatory enteric neural pathways by depressing synaptic transmission. The inhibitory effect of papaverine (but not IMBX or theophylline) involves, at least in part, the release of noradrenaline from sympathetic nerves acting on alpha-adrenoceptors on enteric neurones.

1-Methyl-3-isobutylxanthine↗

Synthesis and pharmacological activity of 2-(substituted phenyl)-3-[2 or 3-[(4-substituted phenyl-4-hydroxy)piperidino]ethyl or propyl]-1,3-thiazolidin-4-ones.

A series of aryl-hydroxy-piperidinoalkyl-thiazolidinones was synthesized and evaluated to inhibit castor oil-induced diarrhea in mice. The dose dependent antidiarrheal activity of the most active compound 2-(p-nitrophenyl)-3-¿2-[(4-(p-chlorophenyl)-4-hydroxy)piperidino]ethyl]- 1, 3-thiazolidin-4-one (6) was counteracted by naloxone, resulting comparable with that of loperamide, a mu opiate agonist.

Animals↗

NG-nitro-L-arginine methyl ester reduces senna- and cascara-induced diarrhoea and fluid secretion in the rat.

Senna (60 mg/kg orally) and cascara (800 mg/kg orally)-induced diarrhoea and net fluid secretion were studied in rats for a time period of 1-8 h. NG-Nitro-L-arginine methyl ester (L-NAME) (2.5-25 mg/kg i.p. twice, 15 min before and 4 h after laxative administration), an inhibitor of nitric oxide synthase, reduced the diarrhoeal response. This effect was counteracted by L-arginine (600 and 1500 mg/kg i.p. 15 min before laxative administration), the precursor of nitric oxide (NO). The senna- and cascara-stimulated fluid secretion was reduced by NG-nitro-L-arginine methyl ester 25 mg/kg i.p. (twice, 15 min before and 4 h after laxative administration), while the stereoisomer NG-nitro-D-arginine methyl ester (D-NAME) 25 mg/kg i.p. was without effect. These results suggest a possible involvement of NO in senna- and cascara-induced diarrhoea and fluid secretion.

Animals↗

Relationship between nitric oxide and platelet-activating factor in castor-oil induced mucosal injury in the rat duodenum.

The modulation of platelet activating factor (PAF) formation in duodenal tissue by nitric oxide (NO) released in response to castor oil was studied in rats pretreated with NG-nitro-L-arginine methyl ester (L-NAME, 6.25-25 mg/kg, i.p.), an inhibitor of NO synthase, NG-nitro-D-arginine methyl ester (D-NAME, 25 mg/kg, i.p.), the inactive enantiomer of L-NAME or isosorbide-5-mononitrate (IMN, 30-90 mg/kg, p.o.), a NO donating compound. Castor oil (2 ml/rat orally) increased PAF production in the rat duodenum 3 h after challenge. L-NAME, but not D-NAME, enhanced the amount of PAF formed by duodenal tissue, while IMN (30-90 mg/kg) counteracted the effects of L-NAME (12.5 mg/kg) and also reduced PAF release in the tissue of rats treated with castor oil. L-NAME 12.5 mg/kg, but not D-NAME, enhanced both macroscopic damage and acid phosphatase release induced by castor oil. These effects were reduced by a PAF antagonist BN 52021 (3-t-Butyl-hexahydro-4, 7b, 11-trihydroxy-8-methyl-9H-1, 7a-epoxymethano-1H, 6aH-cyclopenta [c] furo [2, 3b] furo [3'2':3,4] cyclopenta [1.2-d]furan-5,9,12(4H)trione) 10 and 20 mg/kg i.p. Such findings suggest that endogenous nitric oxide could reduce PAF biosynthesis in castor oil-treated rats.

Acid Phosphatase↗

Antidiarrhoeal activity of new thiazolidinones related to loperamide.

A series of thiazolidinones related to loperamide was synthesized and evaluated for antidiarrhoeal activity in mice, using the castor oil test. Of five compounds tested, antidiarrhoeal activity was found only for 2-(p-nitrophenyl)-3-¿3-[(4-(p-chlorophenyl)-4-hydroxy)piperidino]ethyl¿- 1,3-thiazolidin-4-one. The compound was less active than loperamide (ED50 values = 48.7 (24.8-95.6) and 0.91 (0.24-3.40) mg kg-1 respectively), but was also less toxic (LD50 values = 745.9 (545.2-929.8) and 108.9 (85.5-138.7) mg kg-1, respectively). Its antidiarrhoeal activity was counteracted by naloxone. Our results support the hypothesis that this compound, like loperamide, is an opiate-receptor agonist.

Animals↗