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Biomedical subjects

M Botta

Publications and source records attributed to M Botta.

At least 73 records · Page 4Linked to original sources

[Lung cancer mortality in Casale Monferrato (Italy) and attributable risk to occupations in the asbestos-cement production].

The study presents mortality rates for lung cancer in the town of Casale Monferrato, where the largest Italian asbestos cement-plant was located. Cases of lung cancer dying in 1989-94 were exhaustively searched for in the register of deaths. Each case of lung cancer has been identified as ever or never employed in the factory with a linkage to the rosters of employees in the plant. Women were also identified as ever or never married to an asbestos-cement worker. The number of person-years at risk for asbestos cement workers and their wives was measured on the basis of the most recent follow-up. Mortality rates were computed separately for those exposed (workers and wives of workers) and for those with no evidence of exposure. Mortality rates for non-exposed were similar to rates in Piedmont (the region where Casale is located). The relative risk (ever exposed vs. never exposed) was 2.8 among men and 2.1 among women. Attributable risk among the exposed was 64.5% for men and 53.1% for women while among the general population it was 18.1% for men and 13.2% for women. The study confirms the dramatic effect of occupational asbestos exposure in Casale Monferrato but does not suggest an increase in lung cancer mortality among people with no occupational activity in the asbestos-cement production.

Adult↗

Novel hypotensive agents from Verbesina caracasana. 2. Synthesis and pharmacology of caracasanamide.

Caracasanamide, one of the hypotensive agents isolated from Verbesina caracasana, is a mixture of (Z)-1a and (E)-1b forms of 1-[(3,4-dimethoxycinnamoyl)amino]-4- [(3-methyl-2-butenyl)-guanidino]butane. The structure of (E)-caracasanamide (1b) was confirmed by high-yielding synthesis starting from N,N'-bis(tert-butoxycarbonyl)-S-methylisothiourea. The water-soluble Z-form of 1a, assayed by i.v. route in anesthetized rats at doses ranging from 50 to 1600 micrograms/kg body weight, was found to decrease blood pressure, to increase cardiac inotropism, respiratory frequency, and tidal volume, and to induce a very slight and not significant tachycardia. Higher doses determined respiratory depression and, in some cases, consequent cardiac arrest. The compound was shown to affect cardiovascular function by acting at the vascular level in inducing arterial vasodilation, by determining sympathetic hypotone through central neurogenic mechanisms, and by interacting with the cardiac beta 1-adrenoreceptors. The respiratory effects were independent of the cardiovascular ones. In lowering blood pressure, the compound was more potent than guanethidine and not less potent than reserpine and papaverine. (Z)-Caracasanamide may therefore be useful in the treatment of arterial hypertension of moderate degree.

Acylation↗

Gd(DOTP)5-outer-sphere relaxation enhancement promoted by nitrogen bases.

The relaxation properties of Gd(DOTP)5- (1, 4, 7, 10-tetra-azacyclododecane- N,N',N'',N'''-tetrakis(methylenephosphonic acid)) have been investigated as a function of pH, temperature, concentration, and magnetic field strength. We have found that the complex has one exchangeable water molecule in its inner coordination sphere, at a distance of 3.26 A from the metal ion, and it does not form oligomers in solution in the concentration range 0.2 to 10 mM. The possible presence of two species in solution with an average fractional hydration number is also taken into accounts. The NMRD profiles were recorded at 5 degrees C, 25 degrees C, and 35 degrees C and quantitatively analyzed in terms of the paramagnetic relaxation equations. Interestingly the addition to a solution of the Gd(III)-complex of nitrogen bases results in a marked relaxation enhancement, which shows a strong pH dependence with a maximum around pH = 9. The relaxivity gain has been shown to depend on outer-sphere effects originating from multiple electrostatic interactions between the anionic complex and the organic cations that bring the exchangeable protons of the substrate molecules in to close proximity with the paramagnetic center. High resolution NMR relaxation data for N-methyl-D(-)-glucamine suggest that the hydroxyl group on the beta-carbon plays a role in stabilizing the interaction, presumably through a hydrogen bond with an uncoordinated oxygen atom of the complex.

Chemical Phenomena↗

A cohort study on mortality among wives of workers in the asbestos cement industry in Casale Monferrato, Italy.

The study investigates mortality from cancer and other diseases in a cohort of wives of asbestos cement workers in Casale Monferrato (northwest Italy). After the exclusion of women with an occupational record in the asbestos cement industry, the cohort comprised 1964 women. Their domestic exposure was estimated according to their husbands' periods of employment in the plant: 1740 had a period of domestic exposure whereas the remaining 224 married an asbestos cement worker only after he definitely stopped his activity in the asbestos cement plant; these have, therefore, been considered as unexposed. The cohort of wives was constructed entirely through official records in the town offices and is both exhaustive and unaffected by recall bias. At the end of follow up (1988) 1669 women were alive, 270 were dead and 25 (1.2%) were untraced. Main mortality analyses were only up to age 79 to reduce the misclassification of causes of death. Expected mortality was based on local rates. Mortality analyses were limited to the period 1965-88 due to the availability of local rates: in that period 210 deaths occurred among women with domestic exposure v 229.1 expected. There were four deaths from pleural tumours (one diagnosed as mesothelioma at necropsis) and six from lung cancer v. 0.5 and 4.0 expected respectively. Two further cases of mesothelioma were diagnosed by histological examination after the end of follow up. None of the three wives with histologically diagnosed mesothelioma had been engaged in industrial activities. Corresponding information for the other three cases could not be traced.

Adult↗

Pyrrolobenzodiazepines and related systems. 2. Synthesis and biological properties of isonoraptazepine derivatives.

The synthesis of some derivatives and analogues of 12,13,14,14a-tetrahydro-9H,11H-pyrazino-[2,1-c]pyrrolo[1,2- a][1,4]benzodiazepine (isonoraptazepine) is reported. The new derivatives have been subjected to pharmacological tests for evaluation of antidepressant effects. Neurobehavioral assays were also carried out to acquire data on neurotoxicity and sedative action. Isonoraptazepine analogues and derivatives lacked the pharmacological activity of mianserin and aptazepine and showed properties similar to imipramine. Molecular modeling studies revealed structural similarities between isonoraptazepine derivatives and imipramine, thus explaining the similar pharmacological profile found in some of the tests employed. Based on pharmacological data the title compounds cannot be regarded as alpha 2 presynaptic adrenoceptors antagonists. In vitro studies for receptor binding gave support to this observation. The above studies lead us to conclude that isonoraptazepine derivatives are conformationally restricted analogues of imipramine, but their antidepressant activity cannot be correlated to inhibition of 5HT uptake. Among the derivatives tested, 7b and 8e show some affinity for the d-fenfluramine receptor site, a serotonin presynaptic site connected with anorectic activity.

Animals↗

Structure of (+)-(S)-1,3-dimethyl-6-oxiranyl-2,4-pyrimidinedione showing anti-ASFV activity.

C8H10N2O3, Mr = 182.18, monoclinic, P2(1), a = 6.6405 (7), b = 7.9493 (9), c = 8.3662 (9) A, beta = 103.07 (1) degrees, V = 430.18 (8) A3, Z = 2, Dx = 1.41 Mg m-3, lambda (Cu K alpha) = 1.54184 A, mu = 0.879 mm-1, F(000) = 192, T = 298 K, R = 0.037 for 1247 reflections with Fo greater than or equal to 4 sigma (Fo). The configuration at C7 is S. The pyrimidine-2,4-dione ring is nearly planar [r.m.s. deviation: 0.010 (8) A] and is antiperiplanar with respect to the epoxide ring. This arrangement is stabilized by intermolecular C-H ... O interactions.

African Swine Fever Virus↗

Paramagnetic water proton relaxation enhancement: from contrast agents in MRI to reagents for quantitative "in vitro" assays.

The use of stable complexes of paramagnetic metal ions as probes in analytical applications of the NMR technique is discussed. Two examples are given that involve the determination of the total Fe3+ content of human serum transferrin (Tf) and the extent of glycation of human serum albumin (HSA). The method is based on the measurement of the longitudinal water proton relaxation times, conveniently altered following a selective chemical interaction between the substrate and the paramagnetic probe.

Contrast Media↗

Cardiac surgery in HIV-positive intravenous drug addicts: influence of cardiopulmonary bypass on the progression to AIDS.

In the last years the number of HIV-positive patients needing cardiac surgery has greatly increased. Cardiopulmonary bypass is suspected to have a role in the progression of HIV-infection to acquired immunodeficiency syndrome (AIDS). From October 1988 to December 1990, 6 intravenous drug addicts underwent cardiac surgery for infective endocarditis at our Department. Preoperative and postoperative absolute lymphocyte T-helper (CD4) and T-suppressor (CD8) counts did not show a close association between the temporary lymphopenia induced by cardiopulmonary bypass and progression to AIDS.

Acquired Immunodeficiency Syndrome↗

Inhibition of adenosine 3',5'-cyclic monophosphate phosphodiesterase by flavonoids from licorice roots and 4-arylcoumarins.

Isoliquiritigenin, glabridin, licoarylcoumarin and licoricidin were identified as strong inhibitors of adenosine 3',5'-cyclic monophosphate (cAMP) phosphodiesterase in waste materials which were obtained during the industrial extraction of glycyrrhizin from licorice roots. The structure-activity relationships of 12 flavonoids from licorice roots and 34 4-arylcoumarins were studied. In 4-arylcoumarins, 5,7-dihydroxy derivatives were generally highly inhibitory towards cAMP phosphodiesterase.

3',5'-Cyclic-AMP Phosphodiesterases↗

Mortality from respiratory and digestive cancers among asbestos cement workers in Italy.

A cohort study is presented on the mortality of blue-collar workers in an asbestos-cement production plant that has been operating since 1907. Use of both crocidolite and chrysotile is reported. The cohort includes 2608 men and 759 women who were employed in the plant on Jan. 1, 1950 and those who started to work between 1950 and 1980. Follow-up was terminated on April 15, 1986 with 97.9% traced. Expected deaths were estimated from the age- and sex-specific regional mortality rates for the years 1969 to 1981. The data have been analyzed for the period 1964 to 1986 based on person-years at risk: 43,000 for men and 14,494 for women. A statistically significant increase was found in both sexes for mortality from all causes. From 1964 to 1986, 728 men died from all causes (608 expected), 275 with cancer at any site (158 expected) 110 with lung cancer (41 expected), 28 with pleural tumors (1 expected) and 85 with asbestosis (less than 1 expected). Corresponding figures for women were--all causes: 136 deaths versus 102 expected; all cancers: 79 verses 32 expected; lung cancer: 7 versus 2 expected; pleural tumor: 15 versus 0 expected and asbestosis: 4 versus 0 expected. Deaths from digestive tract cancer were in excess only among women (18 observed versus 10 expected, p less than 0.01). No excess was found for deaths from laryngeal cancer. Standardized mortality rates (SMR) for lung cancer among males showed a clear increase in direct relationship with length of follow-up. SMR according to length of employment were 234 for length 10 to 19 years, 363 for 20 to 29 years, and 256 for 30 years or longer (p less than 0.05 and lower).

Adult↗

Gastroepiploic artery free graft for coronary bypass.

The internal mammary artery (IMA) is the graft of choice for CABG but has a limited number and length. For multivessel coronary disease, saphenous vein grafts have to be added but they show poorer long-term patency. Investigation to provide adjunctive reliable grafts has recently focussed on the right gastroepiploic artery (GEA) and encouraging results have been reported employing this vessel as a pedicled graft to bypass distal coronary vessels. From December 1988 to February 1989, to achieve complete myocardial revascularization with only arterial grafts we used a GEA free graft in combination with the two IMAs in 20 consecutive patients under 70 years of age undergoing elective surgery. Before starting, histological studies were carried out and a significant similarity between IMA and GEA was found. In the 20 patients, 76 coronary anastomoses were performed (3.8 bypasses/patient), the GEA graft revascularized the right coronary artery in 9 patients, the circumflex in 8 patients and the anterior descending and/or diagonal in 3 patients; in 7 patients the GEA graft was used for sequential anastomoses. No perioperative deaths, no myocardial infarctions and no gastroenterological complications occurred. Coronary angiographic postoperative control showed 20/20 patent GEA grafts. After follow-up ranging from 7 to 9 months, all patients are free from angina. The GEA free graft is not difficult to harvest, is easier than the pedicled GEA graft to handle in the pericardium and is suitable for sequential anastomoses. The use of GEA graft however increases the complexity of bypass operations.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Artery Bypass↗

5-HT and benzodiazepine receptor ligands. III. Synthesis and receptor affinities of 1,2,4-triazolo[4',3':1,6]pyridazino[4,5-b]quinoline and 2,3-dihydro-9-phenyl-1H-pyrrolo[3,4-b]quinoline-1-one derivatives.

The syntheses as well as 5-HT and Benzodiazepine receptor binding studies of some 1,2,4-Triazolo[4',3':1,6]piridazino[4,5-b]quinoline and 2,3-Dihydro-9-phenyl-1H-pyrrolo[3,4-b]quinoline-1-one derivatives are reported. While the triazole-containing heterocycles are devoid of any biological activity, 2-benzyl-2,3-dihydro-9-phenyl-1H-pyrrolo[3,4-b]quinoline-1-one shows some affinity for the central type of benzodiazepine receptors.

Animals↗

Research on antibacterial and antifungal agents. XIII. Synthesis and antimicrobial activity of 1-arylmethyl-4-aryl-1H-pyrrole-3-carboxylic acids.

Several 1-arylmethyl-4-aryl-1H-pyrrole-3-carboxylic acid derivatives have been synthetized and tested as antifungal and antibacterial agents. Reaction between tosylmethylisocyanide (TosMIC) and beta-arylacrylic esters under basic conditions furnished 4-aryl-1H-pyrrole-3-carboxylic esters, which were then benzylated at 1 position. Alkaline hydrolysis of ethyl 1-arylmethyl-4-aryl-1H-pyrrole-3-carboxylates afforded the title compounds. All tested derivatives were found to be inactive as antifungal agents. Some of them showed appreciable antibacterial activities against Staphylococcus spp.

Anti-Bacterial Agents↗

NMR studies of L-dopa melanin-manganese(II) complex in water solution.

The study of water relaxation rates of solutions of melanins with paramagnetic metal ions provides a powerful tool for investigating the binding sites and for obtaining useful structural and dynamic information. The measure of 1H- and 2H-longitudinal and transverse relaxation rates at a single, high-magnetic field for H2O/D2O (80:20) solutions allows the determination of tau c, tau R, tau e, tau M, r, q, and Z (the outer sphere contribution to the overall relaxation rate) for Mn(II)-L-Dopa melanin system.

Binding Sites↗

Cerebral complications of coronary by-pass surgery. A prospective study.

A prospective study was undertaken of cerebral complications in 91 patients undergoing coronary by-pass surgery. Patients showing clinically relevant neurological complications had longer pump-times but did not differ in pre-operative variables. Worsening of neurological state correlated with duration of pump-time but not with pre-operative variables. Duration of pump-time appears to be the main predictor of neurological complications after coronary by-pass surgery.

Adult↗