ABSTRACT
Aim of the study was to assess cardiovascular effects in the farmers exposed to noise. We assessed two samples of 143 farmers using tactor (mean age 51.0 +/- 10.5 years, length of service 33.0 +/- 10.5 years) and 193 farmers not exposed to noise (controls) (mean age 48.3 +/- 13.7 years, length of service 30.6 +/- 14.7 years). After the phonometric measurements all farmers were undergone to a medical examination, measurements of blood pressure, a audiometric test and a electrocardiogram. The collected data show an increased prevalence of hypertension and electrocardiographic anomalies in farmers exposed to noise (systolic hypertension n. 53, 37.1%; diastolic hypertension n. 60, 42.0%; electrocardiographic anomalies n. 44; 30.8%) compared to the control group (systolic hypertension n. 23, 16.1%; diastolic hypertension n. 26, 18.2%; electrocardiographic anomalies n. 5; 3.5%) (systolic hypertension p = 0.002; diastolic hypertension p = 0.003; electrocardiographic anomalies p = 0.030). Our results could be taken to mean that there are effects of chronic exposure to noise on cardiovascular apparatus; this would stimulate the screening programmes for farmers.
Subject(s)
Agriculture , Cardiovascular Diseases/etiology , Noise, Occupational/adverse effects , Occupational Exposure/adverse effects , Humans , Male , Middle AgedABSTRACT
A series of 5-phenyl-3-ureidobenzodiazepine-2,4-diones was synthesized and evaluated as cholecystokinin-B (CCK-B) receptor antagonists. Structure-activity relationship (SAR) studies revealed the importance of the N-1 substituent for potent and selective CCK-B affinity. Addition of substituents at the urea side chain provided in some cases more potent compounds. Moreover the introduction of bulky substituents such as adamantylmethyl at N-1 and resolution of the racemic ureas resulted in our lead compound GV150013.
Subject(s)
Anti-Anxiety Agents/chemical synthesis , Benzodiazepines/chemical synthesis , Receptors, Cholecystokinin/antagonists & inhibitors , Animals , Anti-Anxiety Agents/chemistry , Anti-Anxiety Agents/pharmacology , Benzodiazepines/chemistry , Benzodiazepines/pharmacology , Callithrix , Cerebral Cortex/metabolism , Crystallography, X-Ray , Guinea Pigs , HeLa Cells , Humans , In Vitro Techniques , Membranes , Mice , Models, Molecular , Pancreas/metabolism , Radioligand Assay , Rats , Receptor, Cholecystokinin A , Receptor, Cholecystokinin B , Receptors, Cholecystokinin/metabolism , Stereoisomerism , Structure-Activity RelationshipABSTRACT
A preliminary exploration of analogues of 4,5-bis(3,5-dichlorophenyl)-2-trifluoromethyl-1H-imidazole, 1, as novel antibacterial agents was carried out to determine the basic features of the structure responsible for the observed biological activity. The presence of two aryl rings, the imidazole NH and either a good electron withdrawing group or an aldehyde or amino group at C-2 were required for good levels of activity against methicillin resistant Staphylococcus aureus (MRSA).
Subject(s)
Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Bacillus subtilis/drug effects , Imidazoles/chemistry , Imidazoles/pharmacology , Staphylococcus aureus/drug effects , Escherichia coli/drug effects , Methicillin Resistance , Microbial Sensitivity Tests , Structure-Activity RelationshipABSTRACT
The presence of a chain bearing a stereogenic centre at the N-5 position of 1-(1-adamantylmethyl)-3-arylureido-2,4-dioxo-1,5-benzodiazep ines induces optical resolution. The synthesis of these compounds and their potency as potential CCK-B receptor antagonists is discussed briefly here.
Subject(s)
Benzodiazepines/chemical synthesis , Receptors, Cholecystokinin/antagonists & inhibitors , Benzodiazepines/chemistry , Benzodiazepines/pharmacology , Receptor, Cholecystokinin B , Stereoisomerism , Structure-Activity RelationshipABSTRACT
The synthesis and biological evaluation of 3-ureido and 3-carbamate derivatives of 1,5-benzodiazepines bearing bridged cycloalkyl substituents at N-1 are reported. Their activity as CCK-B receptor ligands is briefly discussed.
Subject(s)
Benzodiazepines/chemical synthesis , Receptors, Cholecystokinin/antagonists & inhibitors , Animals , Benzodiazepines/pharmacology , Guinea Pigs , In Vitro Techniques , Ligands , Receptor, Cholecystokinin BABSTRACT
Imidazolidine-2,4-diones and 1,5-diphenyl tetramic acid derivatives were selected in order to evaluate some 5-membered heterocyclic ring compounds as potential templates for the synthesis of CCK receptor ligands. All the compounds were evaluated in vitro towards both CCK-B and CCK-A receptors.
Subject(s)
Imidazoles/chemical synthesis , Ligands , Pyrrolidinones/chemical synthesis , Receptors, Cholecystokinin/drug effects , Cells, Cultured , Imidazoles/pharmacology , Membranes/metabolism , Models, Molecular , Pyrrolidinones/pharmacology , Radioligand AssaySubject(s)
Benzodiazepines/chemical synthesis , Benzodiazepines/metabolism , Hydrocarbons, Halogenated/chemical synthesis , Hydrocarbons, Halogenated/metabolism , Receptors, Cholecystokinin/metabolism , Animals , Benzodiazepines/pharmacology , Guinea Pigs , Hydrocarbons, Halogenated/pharmacology , Kinetics , Ligands , Receptor, Cholecystokinin B , Stereoisomerism , Structure-Activity RelationshipABSTRACT
The synthesis of two "dipeptoids" structurally related to the CCK-B antagonist CI-988 (PD134308) is described. The 2- and 1-indolyl derivatives 4a, b were prepared in order to define the role of the tryptophan moiety in this series of "dipeptoids". They were evaluated as competitors in the binding of [3H]-CCK8S on guinea pig brain CCK-B receptors.
