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Biomedical subjects

S Visentin

Publications and source records attributed to S Visentin.

At least 19 recordsLinked to original sources

Hypertrophic obstructive cardiomyopathy and pregnancy: anesthesiological observations and clinical series.

Hypertrophic obstructive cardiomyopathy represents a genetic disorder characterized by hypertrophy, usually asymmetrical, of the ventricular musculature at the base of the septum in the left ventricular efflux tract. Patients suffering from this disorder can be extremely sensitive to small alterations in ventricular volumes, arterial pressure, cardiac frequency and rhythm. This disorder is found in pregnancy with an incidence of 0.1-0.5% and, because of its gravity, represents a contraindication which is often absolute to pregnancy. Hemodynamic variations such as those found in pregnancy, labor and delivery have complex influences on hypertrophic cardiomyopathy. Our clinical series includes 2 pregnant patients suffering from hypertrophic obstructive cardiomyopathy who both underwent caesarian section in general anesthesia, the first due to the gravity of cardiac obstruction and the second due to the emergent need to proceed after the beginning of labor. The small number of clinical cases in the literature, especially in the last few years, clearly underlines the difficulty of defining both the most correct method for delivery and the most appropriate anesthesiological techniques. In accordance with the literature and our clinical experience, we can conclude that a carefully managed pregnancy can proceed without complications in patients with moderate obstruction and that a regional anesthesiological approach is also possible with careful hemodynamic monitoring. General anesthesia, however, remains the safest method and has fewer risks for patients with serious obstruction or with worsening of their clinical condition during pregnancy.

Adult↗

Rat Schwann cells express M1-M4 muscarinic receptor subtypes.

The expression of different muscarinic receptor subtypes was analyzed in immature Schwann cells obtained from sciatic nerve of 2-day neonatal rats. By using RT-PCR analysis, we demonstrated the presence of M1, M2, M3, and M4 receptor subtypes in cultured Schwann cells, with M2 displaying the highest expression levels. Muscarinic subtypes were also quantified by immunoprecipitation and [3H]QNB binding. With this approach, we found the levels of receptor expression to be M2 > M3 > M1. M4 is expressed at very low levels, and M5 receptor was not detectable. Moreover, we also demonstrated that stimulation of the receptors by muscarinic agonists activates previously described signal transduction pathways, leading to a decrease of cAMP and an increase of IP3 levels not associated with an efficient intracellular Ca2+ release. The presence and activity of particular muscarinic receptors in immature Schwann cells suggest that ACh may play an important role in Schwann cell development.

Analysis of Variance↗

Metabotropic P2 receptor activation regulates oligodendrocyte progenitor migration and development.

To gain insights into the role of purinergic receptors in oligodendrocyte development, we characterized the expression and functional activity of P2 receptors in cultured rat oligodendrocyte progenitors and investigated the effects of ATP and its breakdown products on the migration and proliferation of this immature glial cell population. Using Western blot analysis, we show that oligodendrocyte progenitors express several P2X (P2X(1,2,3,4,7)) and P2Y (P2Y(1,2,4)) receptors. Intracellular Ca(2+) recording by Fura-2 video imaging allowed to determine the rank potency order of the P2 agonists tested: ADPbetaS = ADP = Benzoyl ATP > ATP > ATPgammaS > UTP, alpha,beta-meATP ineffective. Based on the above findings, on pharmacological inhibition by the antagonists oxATP and MRS2179, and on the absence of alpha,betameATP-induced inward current in whole-cell recording, P2X(7) and P2Y(1) were identified as the main ionotropic and metabotropic P2 receptors active in OPs. As a functional correlate of these findings, we show that ATP and, among metabotropic agonists, ADP and the P2Y(1)-specific agonist ADPbetaS, but not UTP, induce oligodendrocyte progenitor migration. Moreover, ATP and ADP inhibited the proliferation of oligodendrocyte progenitors induced by platelet-derived growth factor, both in purified cultures and in cerebellar tissue slices. The effects of ATP and ADP on cell migration and proliferation were prevented by the P2Y(1) antagonist MRS2179. By confocal laser scanning microscopy, P2Y(1) receptors were localized in NG2-labeled oligodendrocyte progenitors in the developing rat brain. These data indicate that ATP and ADP may regulate oligodendrocyte progenitor functions by a mechanism that involves mainly activation of P2Y(1) receptors.

Adenosine Diphosphate↗

ATP regulates oligodendrocyte progenitor migration, proliferation, and differentiation: involvement of metabotropic P2 receptors.

Extracellular nucleotides act as potent signaling molecules in the neuron-glia and glia-glia communication, via the activation of specific ligand-gated P2X and G-protein-coupled metabotropic P2Y receptors. Most of the data available about the effects of P2 receptor activation in the CNS concern astrocytes, microglia, and neurons. To gain insights into the role of purinergic receptors in oligodendrocyte development, we characterized the expression and functional activity of P2 receptors in rat oligodendrocyte progenitors (OPs) and investigated the effects of ATP and its breakdown products on their functions. We describe here that rat OPs express different types of P2 receptors and that nucleotide-induced Ca(2+) raises in these progenitor cells are mainly due to the activation of P2X(7) ionotropic and ADP-sensitive P2Y(1) metabotropic receptors. We also show that ATP and ADP stimulate OP migration, inhibit the mitogenic response of OPs to PDGF and promote oligodendrocyte differentiation. The pharmacological profile of the nucleotide-induced effects demonstrates the important regulatory role of P2Y(1) receptor signaling in OP functions. These findings suggest that ATP, which is released in high amounts under inflammatory conditions and following cell death, might regulate remyelination processes in inflammatory demyelinating diseases of the CNS, like multiple sclerosis.

Adenosine Triphosphate↗

Periportal fibrosis and other liver ultrasonography findings in vinyl chloride workers.

AIMS: To investigate the presence of liver lesions and their relation with vinyl chloride monomer (VCM) exposure or other personal risk factors, in workers involved in the production of VCM and polyvinyl chloride (PVC). METHODS: A liver ultrasonography examination was conducted in 757 workers, some of whom had long standing service in the production of VCM and PVC. The study involved: assessment of individual past and present VCM exposure of each worker; collection of past personal health history, lifestyle and personal data; routine liver function tests; and liver ultrasonography. RESULTS: No cases of liver malignancies were detected. Angiomas and liver cysts were found with a frequency of occurrence within the expected range of the general population. The main findings consisted of hepatomegaly (34.7%), steatosis (31.8%), and periportal fibrosis (16.0%). A logistic regression analysis indicated that hepatomegaly and steatosis were associated with obesity and lipid metabolism disturbances and not with VCM exposure. Periportal fibrosis, in addition to constitutional or dietary factors, was shown to be associated with VCM exposure, but only when maximum exposure in the subject's history had been at least 200 ppm as a yearly average; no effects were observed at 50 ppm or below. CONCLUSIONS: Workers exposed to 200 ppm VCM for at least one year have a fourfold increased risk of developing periportal liver fibrosis. Liver ultrasonography is a suitable and important diagnostic test for the medical surveillance of vinyl chloride workers.

Adult↗

Ethylenethiourea in urine as an indicator of exposure to mancozeb in vineyard workers.

In the present study, the personal exposure to mancozeb and/or ethilenethiourea (ETU) in 13 Italian vineyard workers and in 13 subjects without occupational exposure to pesticides was investigated. With this aim, the level of ETU in urine and the dermal exposure to mancozeb were determined. Baseline urinary ETU results were lower than the analytical limit of detection for all controls (<0.5 microg/g creatinine) and for ten workers (median <0.5, range <0.5-3.4 microg/g creatinine). In workers, urinary ETU was significantly increased at the end of shift (2.5, <0.5-95.2 microg/g creatinine) compared with baseline levels. End-shift urinary ETU was higher in operators using open tractors (n=7) than in those using closed tractors (n=5) (16.2 vs. 2.4 microg/g creatinine), but the difference was not significant (P=0.073). End-shift urinary ETU was positively correlated with dermal exposure to mancozeb determined both over the clothes and on the skin (Spearman's rho=0.770 and 0.702, P=0.009 and 0.024, respectively). Wine consumption positively influenced the excretion of ETU.

Adult↗

Gallstone disease and related risk factors in patients with Crohn disease: analysis of 330 consecutive cases.

BACKGROUND: The reported prevalence of gallstone disease (GD), defined as current gallstones or previous cholecystectomy for gallstones, in patients with Crohn disease ranges from 13% to 34%. The aim of this study was to characterize the still undefined risk factors of this complication. METHODS: A total of 330 consecutive patients with Crohn disease (189 males and 141 females aged 17-82 years, mean +/- SD age, 41 +/- 14 years) underwent liver ultrasonography. RESULTS: A diagnosis of GD was made in 78 patients (24%), 54 with current gallstones and 24 who had undergone previous cholecystectomy. Its frequency was comparable in males and females (23% vs 25%), but was significantly associated with age (P =.001), being 13%, 36%, and 51% in patients aged 44 years and younger, 45 to 59 years, and 60 years and older, respectively (P =.001). Its prevalence significantly differed according to the site of the disease at diagnosis (P =.02) and was unrelated to disease duration. Gallstone disease was more frequent in patients who had undergone surgery (34% vs 14%; P =.001) and was significantly associated with the number (P =.001) and site of bowel resections (P =.001), increasing from 28% in the patients who had undergone 1 resection to 53% in those having had 2 or more resections (P =.005) and being significantly higher in patients with a resection involving the ileocecal region. Multivariate analysis showed that age; site of disease at diagnosis; and the presence, number, and site of bowel resections were significantly related to GD. CONCLUSIONS: In patients with Crohn disease, the frequency of GD is significantly higher than that reported in the general population with comparable characteristics (z = 5.04, P<.001). Age; site of disease at diagnosis; and the history, number, and site of bowel resections are independently associated with GD.

Adolescent↗

What is the quality of drug therapy clinical practice guidelines in Canada?

BACKGROUND: The Canadian Medical Association maintains a national online database of clinical practice guidelines developed, endorsed or reviewed by Canadian organizations within 5 years of the current date. This study was designed to identify and describe guidelines in the database that make recommendations related to the use of drug therapy, and to assess their quality using a standardized guideline appraisal instrument. METHODS: Drug therapy guidelines in the database were identified with the use of search terms and hand searching. Descriptive information about the developers, endorsement by other organizations, publication status, disease and drug focus was abstracted. Each guideline was independently assessed by 3 appraisers (a physician, a pharmacist and a methodologist) with the use of the Appraisal Instrument for Clinical Guidelines. Conditions were classified according to the tenth revision of the International Statistical Classification of Diseases and Related Health Problems. RESULTS: We identified 217 drug therapy guidelines produced or reviewed from 1994 to 1998. Guideline developers included national organizations (47.0%), paragovernment organizations (39.6%) and professional associations (30.9%); 31.3% of the guidelines were published, and 10.6% stated drug company sponsorship. The most common conditions addressed by the guidelines were infections and parasitic diseases (39.6%), neoplasms (11.5%) and diseases of the circulatory system (11.5%). Drugs most commonly cited were anti-infective agents (42.9%), antiviral agents (15.2%) and cardiovascular drugs (16.1%). Eleven organizations produced 176 (81.1%) of the guidelines. In all, 14.7% of the guidelines met half or more of the 20 items assessing rigour of guideline development on the appraisal instrument (mean quality score 30.0% [95% confidence interval (CI) 27.5%-32.6%]), 61.8% met half or more of the 12 items assessing guideline context and content (mean score 57.0% [95% CI 54.6%-59.3%]), and none met half or more of the 5 items assessing guideline application (mean score 5.6% [95% CI 4.7%-6.5%]). Overall, 64.6% of the guidelines were recommended with modification by at least 2 of the 3 appraisers, 9.2% were recommended without change, and 26.3% were not recommended. The quality of the guidelines assessed varied significantly by developer, publication status and drug company sponsorship. No substantial improvement in guideline quality was observed over the 5-year study period. INTERPRETATION: Developers of Canadian drug therapy guidelines are producing guidelines that are often perceived to be clinically useful to physicians and pharmacists, although the methods (or the description of the methods) by which they are developed need to be more rigorous and thorough.

Canada↗

Altered outward-rectifying K(+) current reveals microglial activation induced by HIV-1 Tat protein.

Microglial cells are believed to be one of the key elements in the development of the HIV-related neuropathology. Not only can microglial cells be productively infected by the virus, but they are also sensitive to viral proteins. Among them, the HIV-1 regulatory protein Tat, which was shown to have neurotoxic activity, is able to promote some proinflammatory functions of microglia. Considering that microglial activation goes along with a change of ion channel profile, we aimed to study whether Tat could influence microglial electrophysiology. When microglial cultures obtained from neonatal rats were treated with Tat (> or = 100 ng/ml), whole-cell recording showed the appearance of a large outwardly rectifying current (OR) virtually absent in untreated control cells. According to voltage dependence of the kinetic variables, K(+) permeability, and pharmacological sensitivity, the Tat-induced current was due to the presence of functional Kv1.3 channels. The effect of Tat was abolished by specific anti-Tat polyclonal antibody and by heat denaturation of Tat protein, confirming that the OR enhancement was due to the viral protein. Interestingly, the OR current induced by Tat was largely prevented by two inhibitors of the transcription factor NF-kappaB, TPCK and SN50, which suggests an involvement of NF-kappaB in the effect of the viral protein. The relatively high dose of Tat needed to observe an effect (> or = 100 ng/ml) might indicate that the action of Tat required entrance of the protein into the cell, rather than being mediated by a membrane receptor. In conclusion, the HIV-1 protein Tat is able to enhance OR K(+) current in rat microglia through a mechanism involving the activation of NF-kappaB. We propose that such effect of Tat could be part of the process of microglial activation known to take place in the brain of persons with neuro-AIDS.

Animals↗

Nitroanilines are the reduction products of benzofuroxan system by oxyhemoglobin (HbO2 2+).

Benzofuroxans are interesting compounds which display several biochemical and pharmacological properties. Recent studies from our laboratory demonstrate that they are reduced by ferrous salts at room temperature and that the principal reaction products are o-nitroanilines. This paper shows that simple benzofuroxan derivatives are also able to oxidise HbO2 2+ to methemoglobin (MetHb3+) (UV detection) and to form o-nitroanilines (HPLC detection). From a toxicological point of view this reaction is interesting, since it indicates that the blood is a site for metabolism of these compounds with consequent methemoglobinemia and formation of toxic compounds.

Aniline Compounds↗

"Hepatitic flare", asthenia, peripheral polyneuropathy and diffuse liver steatosis in a hepatitis C virus asymptomatic chronic carrier.

In July 2000, a 62-year-old female, with a ten-year history of chronic hepatitis C virus infection and persistently normal aspartate amino-transferase and alanine aminotransferase levels, presented with asthenia, weight loss, peripheral polyneuropathy and increased levels of aspartate aminotransferase (8 times upper normal limit), alanine aminotransferase (10 times upper normal limit) and gamma glutamyl-transferase (6 times upper normal limit). The ultrasound findings were consistent with massive liver steatosis. The patient had been previously diagnosed elsewhere as having hepatitis C virus-related "hepatitic flare" with neurological involvement related to concomitant mixed type-III cryoglobulinaemia. However intense exposure to trichloroethylene since April 2000 was revealed and liver histology was fully consistent with non-alcoholic steatohepatitis. The pathogenetic role of the solvent was definitely supported by the complete clinical and biochemical remission within six months of trichloroethylene withdrawal.

Asthenia↗

Searching for balanced hybrid NO-donor 1,4-dihydropyridines with basic properties.

PURPOSE: Model compounds containing NO-donor furoxan moieties at the 3-positioned basic lateral chain of 1, a 1,4-dihydropyridine related to nicardipine, were synthesized in order to study their vasodilating activity as well as their basic and lipophilic behaviour. METHODS: All the compounds were obtained by a modified Hantzsch approach. Potentiometry was used to determine pKa and lipophilicity descriptors. The furoxan 4-aryl-1,4-dihydropyridines were assessed for their ability to release nitrite, in the presence of a large excess of cysteine, by the Griess reaction. Vasodilating activity of the products in the absence and in the presence of ODQ, a well-known guanylate cyclase inhibitor, was evaluated on rat thoracic aorta. RESULTS: The compounds display low basicity values and for this reason their log Ds at physiological pH are identical to the log Ps of the neutral forms. Products 2, 3 display vasodilating action principally dependent on their Ca2+-antagonist properties, whereas 4 behaves as a well-balanced hybrid with mixed Ca2+-channel blocker and NO-dependent vasodilator activities. CONCLUSIONS. Nitrogen containing lateral chain at the 3-position of 1 is a suitable molecular region to be modified in order to obtain well-balanced furoxan NO-donor 1,4-DHPs. This manipulation produces a decrease in the basicity. General analysis of pKa and lipophilicity descriptors of these new DHPs suggest that molecular flexibility could influence both their basicity and log PI.

Animals↗

Studies on agents with mixed NO-dependent and calcium channel antagonistic vasodilating activities.

PURPOSE: To obtain new cardiovascular agents with mixed Ca2+-channel antagonistic and NO-donor properties, a series of "hybrid" 1,4-dihydropyridines (1,4-DHPs), bearing NO-donating furoxan moieties on the 3-positioned lateral ester chain were synthesized and pharmacologically characterized. Furazan analogues were also prepared and investigated for control purposes, because they are unable to release NO. METHODS: Synthesis of the models was achieved by a modified Hantzsch approach. All of the final furoxan 1,4-DHPs were assessed for their ability to produce nitrite in the presence of a large excess of cysteine by the Griess reaction. Vasodilating activity was evaluated on rat aorta and expressed as EC50 and EC50MB values, obtained in the absence and in the presence of methylene blue (MB) respectively, a well-known guanylate cyclase inhibitor. Affinities to 1,4-DHP receptor on Ca2+-channels, expressed as IC50 values, were determined through displacement experiments of [3H]-nitrendipine on rat cortex homogenates. RESULTS: Some hybrid compounds (derivatives 15a, 15b, 16a, and 16b) displayed vasodilating activity depending predominantly on their Ca2+-channel blocker properties. By contrast, some others (derivatives 17a, 17b, and 21) behaved as well-balanced hybrids with mixed Ca2+-channel blocking and NO-dependent vasodilating activities. CONCLUSION: This work demonstrates the possibility of obtaining well-balanced hybrids endowed with mixed NO-donor and Ca2+-channel blocker properties using appropriate 1,4-DHP and furoxan moieties. A procedure for the individual evaluation of the NO-dependent vasodilator component and that due to Ca2+-channel blocking is proposed.

Animals↗

Renovascular impedance and esophageal varices in patients with Child-Pugh class A cirrhosis.

PURPOSE: To evaluate the frequency of increased renovascular impedance and its relationship with the presence of esophageal varices in patients with Child-Pugh class A cirrhosis without ascites. MATERIALS AND METHODS: The intraparenchymal renal resistive index (RI) (reference value, <0.7) and portal congestive index (ie, the ratio between the portal cross-sectional area and mean flow velocity; reference value, <0.07) were measured by using duplex Doppler ultrasonography in 50 consecutive patients. The frequency of varices was assessed endoscopically. The data were analyzed with the Fisher exact test. RESULTS: The renal RI was consistent with increased impedance (ie, >0.7) in 18 (36%) patients and was normal in 32 (64%). The proportion of patients with varices was significantly higher in the former group: 14 (78%) versus 10 (31%) (P =.002). In detection of the presence of varices, the renal RI was uniformly better than the portal congestive index in terms of sensitivity (58% vs. 48%), specificity (84% vs 54%), and positive (3.60 vs 1.04) and negative (0.50 vs. 0.96) likelihood ratios. RI determination improved the ability to exclude the presence of varices from a basal pretest probability of 52% (26 of 50 patients) to a final one of 69% (22 of 32 patients) and that of predicting the presence of varices from 48% (24 of 50 patients) to 78% (14 of 18 patients). CONCLUSION: A substantial proportion of patients with Child-Pugh class A cirrhosis without ascites have increased renovascular impedance; this significantly correlates with the presence of varices.

Esophageal and Gastric Varices↗

Two different ionotropic receptors are activated by ATP in rat microglia.

1. Our aim was to assess whether ATP-induced inward currents in microglia are due to a single or more than one purinergic receptor. The ATP dose-response curve showed two components, whose presence might be due to the activation of high and low affinity receptors. 2. The P2Z/P2X7 specific receptor agonist benzoylbenzoyl-ATP (Bz-ATP) and some P2 receptor agonists were tested. The rank order of potency was Bz-ATP >> ATP = 2-methylthio-ATP (2-MeSATP) > alpha, beta-methylene ATP (alpha,beta-meATP) >= ADP. beta, gamma-MethyleneATP (beta,gamma-meATP), UTP and adenosine were ineffective. 3. The non-specific P2 receptor antagonist suramin antagonized by 92 +/- 2 % the inward current induced by 100 microM ATP, and by 51 +/- 8 and 68 +/- 6 % those induced by 3 mM ATP and 100 microM Bz-ATP, respectively. The P2Z/P2X7 antagonist oxidized ATP (oATP) almost abolished the inward current induced by 3 mM ATP or Bz-ATP, but was ineffective against 100 microM ATP. 4. Inward currents induced by low ATP concentrations (<= 100 microM) were generally followed by an almost complete and irreversible desensitization, while those elicited by ATP >= 1 mM showed only a partial decline. Interestingly, the inward current induced by 100 microM 2-MeSATP showed a large desensitization, while that induced by Bz-ATP did not. 5. In voltage-ramp experiments, the 100 microM ATP-induced current exhibited a slight inward rectification more visible at negative potentials, while the 3 mM ATP-induced current did not. 6. ATP induced a fast and large increase in [Ca2+] that promptly recovered in the continuous presence of low ATP doses, but did not recover in high ATP doses. As with desensitization, the response to Bz-ATP mimicked that of high doses of ATP. 7. When Ca2+ mobilization due to P2Y receptors was blocked by thapsigargin-induced Ca2+ depletion or by pertussis toxin treatment, 10 microM ATP was still able to induce a Ca2+ transient, which represented the contribution of the Ca2+ influx induced by P2X receptors 8. In conclusion, the inward currents and a fraction of the Ca2+ transients induced by ATP in microglia are due to at least two ATP-sensitive receptor channel types, whose different properties and sensitivity to ATP may be associated with different functional roles.

Adenosine Triphosphate↗

Synthesis and voltage-clamp studies of methyl 1,4-dihydro-2, 6-dimethyl-5-nitro-4-(benzofurazanyl)pyridine-3-carboxylate racemates and enantiomers and of their benzofuroxanyl analogues.

Racemic methyl 1,4-dihydro-2, 6-dimethyl-5-nitro-4-(benzofurazanyl)pyridine-3-carboxylates (+/-)-10 and (+/-)-11 and their benzofuroxanyl analogues (+/-)-12 and (+/-)-13 were prepared using a modified Hantzsch reaction that involved the condensation of nitroacetone with methyl 3-aminocrotonate and the appropriate aldehydes. The racemic mixtures were resolved into the corresponding enantiomers. Whole-cell voltage-clamp studies on L-type Ca2+ channels expressed in a rat insulinoma cell line (RINm5F) showed that all the dextrorotatory antipodes were effective agonists of L-type Ca2+ currents, while the levorotatory ones were weak Ca2+ entry blockers. The (+)-enantiomer of benzofurazan-5'-yl derivative 11 demonstrated unusual activity in that, in addition to producing a potentiation of L-type currents, it interfered with the voltage-dependent gating of L-type channels by producing a net delay of their activation at low voltages. This compound represents an interesting tool to probe L-type Ca2+ channel structure and function.

Animals↗

Resolution of some 4-benzofurazanyl and 4-benzofuroxanyl 1, 4-dihydropyridine derivatives by chiral HPLC on whelk-o1 and some polysaccharide chiral stationary phases

The chromatographic chiral resolution of racemic methyl 1, 4-dihydro-2,6-dimethyl-5-nitro-4-benzofurazanyl-3-carboxylates 1 and 2 and their benzofuroxanyl analogues 3 and 4 were studied on Whelk-O1, Chiralcel OD-H, Chiralcel OJ, and Chiralpak AD and AS. These CSPs were selected on the basis of the results of structural searches in Chirbase. Examination of the data and cluster analysis pointed out the influence of benzofurazane-benzofuroxane change versus alpha-beta connection change on retention and enantioselectivity, respectively. The major contribution to the retention change arose from the type of heterocycle, whereas the major contribution to the enantioselectivity change came from the mode of connection (alpha or beta) almost irrespective of the nature of the heterocycle. It resulted in a similarity of behaviour between 1 and 2 on one hand and 3 and 4 on the other as far as capacity factors were concerned, and in a similarity of behaviour between 1 and 3 on the one hand and 2 and 4 on the other as far as enantioselectivities were concerned. Chiralpak AS was selected for semipreparative resolution of the enantiomers. The study of several CSPs allowed us to obtain correlations of structure with retention and enantioselectivity as well as the choice of a semipreparative support to provide the quantities for biological tests. Copyright 1999 Wiley-Liss, Inc.

Journal Article↗

NO donor and biological properties of different benzofuroxans.

PURPOSE: To investigate the effect of benzofusion on NO donor properties and related biological activities of the furoxan system. The biological properties considered were the ability to increase the cytosolic levels of cGMP in C6 cells and vasodilation. METHODS: NO donor properties were investigated either in the presence or the absence of cysteine by using the Griess reaction, chemiluminescence, and gas chromatography. Increase of cytosolic cGMP levels were evaluated by radioimmunoassay. Vasodilating activity was assessed on rat aorta strips precontracted with noradrenaline, in the presence and the absence of oxyhemoglobin (HbO2) and methylene blue (MB), respectively. RESULTS: Benzofuroxan and its methyl and cyano derivatives were unable to release NO under the experimental conditions. Generally these compounds displayed feeble vasodilating properties and were able to weakly stimulate soluble guanylate cyclase (sGC). By contrast, benzodifuroxan and benzotrifuroxan were able to produce both NO* and its reduced form NO- , the nitroxyl anion. They displayed potent vasodilating properties and were able to increase cytosolic levels of cGMP in a concentration-dependent manner. CONCLUSIONS: The simple benzofuroxans considered here are devoid of the capability to release NO, they weakly stimulate sGC as well as manifest feeble vasodilating properties by a mechanism that does not involve a thiol-induced NO production. By contrast, benzodifuroxan and benzotrifuroxan behave as typical NO donor furoxans.

Animals↗