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1.
Neurologia ; 25(6): 349-56, 2010.
Article in Spanish | MEDLINE | ID: mdl-20738954

ABSTRACT

INTRODUCTION: Travelling, when searching for knowledge and emotion, can cause psychic discomfort that occasionally leads the traveller to seek medical attention. The psychiatrist Graziella Magherini described, in tourists visiting Florence, acute attacks including disorders of thought and affects, and even including, anxiety attack. She named it the Stendhal syndrome (SS) remembering the experience of the writer when visiting the Basilica of Santa Croce in Florence. METHODS: We attempt to investigate the incidence of SS or isolated symptoms related to it, in a homogeneous group of travellers. We review other artists who experienced emotion sickness during their trips throughout history. RESULTS: At the end of the III Neurohistory Meeting (Spanish Neurology Society, Italy, February, 2008) a questionnaire was handed out to the participant neurologists, in order to evaluate if during the practical workshops included in the meeting they had experienced symptoms as those described in SS. A total of 48 questionnaires were completed. The mean age was 50+/-9 years and the male/female ratio 1.7/1. Twenty-five percent of the subjects considered they had experienced a partial SS. No panic attacks or thought disorders were identified, but they did suffer artistic effects, mainly in pleasure (83%) and emotion (62%). CONCLUSIONS: No SS case was identified among neurologists attending this Neurohistory meeting, but most of them experienced mild disorders of affects and one out of four recognized they have had a partial form of the syndrome.


Subject(s)
Emotions , Neurology , Travel/psychology , Anxiety , Congresses as Topic , Female , Humans , Male , Middle Aged , Panic Disorder , Somatoform Disorders/physiopathology , Somatoform Disorders/psychology , Space-Time Clustering , Surveys and Questionnaires , Syndrome , Workforce
2.
Neurología (Barc., Ed. impr.) ; 25(6): 349-356, jul.-ago. 2010. tab, ilus
Article in Spanish | IBECS | ID: ibc-138740

ABSTRACT

Introducción: El viaje, en su búsqueda de conocimiento y emoción, puede causar malestar psíquico que ocasionalmente lleva al viajero a solicitar atención médica. La psiquiatra Graziella Magherini describió en turistas que visitaban Florencia un cuadro caracterizado por trastornos del pensamiento, los afectos e incluso crisis de pánico. Lo denominó síndrome de Stendhal (SS) en recuerdo de la experiencia del escritor cuando visitó la iglesia de la Santa Croce de Florencia. Métodos: Investigar la incidencia de SS o síntomas aislados en un grupo homogéneo de viajeros. Revisar las experiencias de creadores enfermos de emoción durante sus viajes a lo largo de la historia. Resultados: Al finalizar el III Curso de Neurohistoria de la Sociedad Española de Neurología (SEN) (Italia, febrero de 2008), se entregó a los neurólogos participantes una encuesta para evaluar si durante los talleres prácticos del curso habían experimentado síntomas compatibles con los descritos en el SS. Se cumplimentaron 48 encuestas. Media de edad, 50 ± 9 años. Proporción varones/mujeres, 1,7/1. El 25% de los encuestados consideró que había experimentado una forma parcial de SS. No se identificaron crisis de pánico ni alteraciones del pensamiento, pero fue frecuente la influencia del arte en los afectos, principalmente en el placer (83%) y la emoción (62%). Conclusiones: No hubo ningún caso de SS entre los neurólogos asistentes al III Curso de Neurohistoria de la SEN, pero un significativo número de ellos experimentó alteraciones parciales del afecto y uno de cada cuatro reconoció haber presentado una forma parcial del síndrome (AU)


Introduction: Travelling, when searching for knowledge and emotion, can cause psychic discomfort that occasionally leads the traveller to seek medical attention. The psychiatrist Graziella Magherini described, in tourists visiting Florence, acute attacks including disorders of thought and affects, and even including, anxiety attack. She named it the Stendhal syndrome (SS) remembering the experience of the writer when visiting the Basilica of Santa Croce in Florence. Methods: We attempt to investigate the incidence of SS or isolated symptoms related to it, in a homogeneous group of travellers. We review other artists who experienced emotion sickness during their trips throughout history. Results: At the end of the III Neurohistory Meeting (Spanish Neurology Society, Italy, February, 2008) a questionnaire was handed out to the participant neurologists, in order to evaluate if during the practical workshops included in the meeting they had experienced symptoms as those described in SS. A total of 48 questionnaires were completed. The mean age was 50 ± 9 years and the male/female ratio 1.7/1. Twenty-five percent of the subjects considered they had experienced a partial SS. No panic attacks or thought disorders were identified, but they did suffer artistic effects, mainly in pleasure (83%) and emotion (62%). Conclusions: No SS case was identified among neurologists attending this Neurohistory meeting, but most of them experienced mild disorders of affects and one out of four recognized they have had a partial form of the syndrome (AU)


Subject(s)
Female , Humans , Male , Middle Aged , Emotions , Neurology , Travel/psychology , Anxiety , Congresses as Topic , Panic Disorder , Surveys and Questionnaires , Somatoform Disorders/physiopathology , Somatoform Disorders/psychology , Space-Time Clustering
3.
Neuroscience ; 168(2): 514-22, 2010 Jun 30.
Article in English | MEDLINE | ID: mdl-20382206

ABSTRACT

Glioblastoma multiforme is the most commonly diagnosed malignant primary brain tumour in adults. Invasive behaviour is the pathological hallmark of malignant gliomas; consequently, its inhibition has been suggested as a therapeutic strategy. Tumour cell-derived gelatinases (matrix metalloproteinase-2, matrix metalloproteinase-9) can be considered prime factors in glioma invasiveness: their expression correlates with the progression and the degree of malignancy. Thus, broad spectrum matrix metalloproteinase inhibitors (MMP inhibitors) have been included in clinical trials. In the present study, the invasiveness, viability and progression of the human glioma cell line U87MG were investigated following treatment with N-O-isopropyl sulfonamido-based hydroxamates (compounds 1 and 2) as MMP-2 inhibitors used at nanomolar concentration. A standard broad spectrum MMP-inhibitor belonging to the classical tertiary sulfonamido-based hydroxamates family (CGS_27023A) was used too. The compounds 1 and 2 resulted in potent inhibition of cell invasiveness (P<0.0001) without affecting viability. In some clinical trials, the combined therapy of temozolomide (an alkylating agent used in glioma treatment) plus marimastat (a broad spectrum MMP inhibitor) has provided evidence of the importance of MMPs to tumor progression and invasiveness. On this basis, the effect on U87MG cells of a combined treatment with temozolomide, plus each of the two MMP inhibitors at nanomolar concentration, was investigated. The obtained data demonstrated the inhibition of cell invasiveness and viability after treatment. These results can help in developing clinical combined therapy using MMP inhibitors that, at low doses, increase the anticancer efficacy of chemotherapeutic drugs, probably without causing the side effects typical of broad-spectrum MMP inhibitors.


Subject(s)
Antineoplastic Agents/pharmacology , Brain Neoplasms/enzymology , Glioblastoma/enzymology , Hydroxamic Acids/pharmacology , Matrix Metalloproteinase Inhibitors , Sulfonamides/pharmacology , Brain Neoplasms/pathology , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Chemotaxis/drug effects , Dacarbazine/analogs & derivatives , Dacarbazine/pharmacology , Drug Interactions , Glioblastoma/pathology , Humans , Matrix Metalloproteinase 2/biosynthesis , Neoplasm Invasiveness , Temozolomide
4.
Rev. neurol. (Ed. impr.) ; 39(2): 142-145, 16 jul., 2004. ilus
Article in Es | IBECS | ID: ibc-34477

ABSTRACT

Introducción. La coexistencia de siringomielia no comunicante con tumores intradurales extramedulares en series quirúrgicas es extremadamente rara. Caso clínico. Se describe el caso de una mujer de 68 años, con paraparesia progresiva, asimétrica, de predominio proximal, sin afectación de los esfínteres, de cuatro meses de evolución, en la que la exploración clínica delimitaba una banda de hipoestesia térmica D7-D8. El estudio con resonancia magnética (RM), tras la administración de gadolinio, demostró la coexistencia de una lesión expansiva intradural extramedular, que por sus características sugería un meningioma, y de una siringomielia dorsal. La cavidad afectaba a dos segmentos medulares situados por encima del tumor y no había anomalías asociadas en la unión bulbomedular. Tras la resección completa del tumor, cuyo diagnóstico histológico fue de meningioma transicional con abundantes cuerpos de psamoma, la paciente ha recuperado la marcha independiente. Conclusiones. La RM con contraste es el mejor medio diagnóstico disponible para la detección y delimitación de los dos componentes de esta rara asociación, aunque su capacidad para detectar signos sugerentes de turbulencias en el líquido intracavitario, especialmente en cavidades pequeñas, se debe contrastar. La variabilidad de tamaño y de situación de la cavidad respecto al asiento del tumor, y la falta de controles evolutivos con RM en los casos publicados, no permiten identificar el mecanismo patogénico responsable de esta asociación, ni proponer el tipo de derivación de elección para prevenir una eventual ampliación de la cavidad siringomiélica (AU)


Introduction. The coexistence of non-communicating syringomyelia with extramedullary intradural tumours in surgical series is extremely rare. Case report. We report the case of a 68-year-old female who had been suffering from predominantly proximal asymmetrical progressive paraparesis, with no involvement of the sphincters; the clinical exploration revealed a band of thermal hypaesthesia D7-D8. Magnetic resonance imaging (MRI), following the administration of gadolinium, confirmed the coexistence of an extramedullary intradural expansive lesion, which had features suggesting it could be a meningioma, and a dorsal syringomyelia. The cavity involved two medullary segments situated above the tumour and there were no associated anomalies at the junction of the medulla and upper spinal cord. Following complete resection of the tumour, which was diagnosed histologically as being a transitional meningioma with abundant psammoma bodies, the patient recovered the ability to walk independently. Conclusions. MRI with contrast is the best diagnostic means available for the detection and delimitation of the two components in this rare association, although its capacity to detect signs suggesting turbulences in the intracavity fluid, especially in small cavities, has still to be confirmed. The variations in the size and situation of the cavity with respect to the seat of the tumour, and the fact that progress is seldom monitored with MRI in the cases published to date, do not allow us to identify the pathogenic mechanism responsible for this association or to suggest the best type of shunt to prevent a possible expansion of the syringomyelic cavity (AU)


Subject(s)
Female , Aged , Humans , Spinal Cord , Dura Mater , Syringomyelia , Cervical Vertebrae , Treatment Outcome , Comorbidity , Meningioma , Medulla Oblongata , Magnetic Resonance Imaging , Spinal Cord Neoplasms
5.
Rev Neurol ; 36(8): 771-80, 2003.
Article in Spanish | MEDLINE | ID: mdl-12717658

ABSTRACT

INTRODUCTION: Primary brain death (BD) is a clinical situation characterised by the total and irreversible absence of functioning in the brain as a consequence of its being destroyed, while heartbeat and breathing are maintained by artificial means. The Royal Decree 2070/1999, dated 30 December, lawfully regulates the diagnosis of BD and the activities concerning the donation of organs for transplant in Spain. METHOD: In certain patients who have suffered structural injury to the brain, serious intracranial hypertension occurs which blocks the blood flow throughout the brain, while breathing is maintained by mechanical means, together with heartbeat. The diagnosis of BD is eminently clinical and is based on the verification of three circumstances: the existence of a non reactive coma, the disappearance of brain stem reflexes and activity in its parasympathetic nuclei, and the absence of spontaneous breathing. The diagnosis can be reinforced with certain complementary tests, which in some cases are compulsory. In the paper we describe the explorations that are considered to be appropriate by current Spanish legislation. We also review the most important clinical and legal aspects of organ donation. CONCLUSIONS: BD is an iatrogenic state, known only since the development of reanimation and assisted ventilation techniques, which amounts to the death of the person. Obtaining organs for transplants is currently possible in Spain from donors in this situation, but also from those who have died from an initial cardiopulmonary arrest and from live donors.


Subject(s)
Brain Death/legislation & jurisprudence , Tissue and Organ Procurement/legislation & jurisprudence , Humans , Organ Transplantation/legislation & jurisprudence , Spain
6.
Rev. neurol. (Ed. impr.) ; 36(8): 771-780, 16 abr., 2003. tab
Article in Es | IBECS | ID: ibc-27585

ABSTRACT

Introducción. La muerte encefálica (ME) primaria es una situación clínica caracterizada por la ausencia total e irreversible de las funciones del encéfalo como consecuencia de la destrucción del mismo, al tiempo que se conservan el latido cardíaco y la respiración por medios artificiales. El Real Decreto 2070/1999, de 30 de diciembre, regula en España el diagnóstico de la ME y las actividades relacionadas con la donación de órganos para trasplantes. Desarrollo. En determinados pacientes que han sufrido una lesión en el encéfalo de naturaleza estructural se desarrolla una hipertensión intracraneal grave que bloquea el flujo sanguíneo encefálico, mientras se conserva la respiración por medios mecánicos y el latido cardíaco. El diagnóstico de la ME es eminentemente clínico y se basa en la constatación de tres circunstancias: existencia de un coma arreactivo, desaparición de los reflejos del troncoencéfalo y de la actividad de sus núcleos parasimpáticos y ausencia de respiración espontánea. El diagnóstico puede reforzarse con ciertas pruebas complementarias, que en algunos casos son obligatorias. Se describen las exploraciones consideradas apropiadas por la legislación española actual. Se revisan, además, los aspectos clínicos y legales más importantes de la donación de órganos. Conclusiones. La ME es un estado yatrógeno, conocido a partir del desarrollo de las técnicas de reanimación y de ventilación asistida, que equivale a la muerte de la persona. La obtención de órganos para trasplantes es posible en la actualidad en España a partir de donantes en esta situación, pero también de fallecidos por un paro cardiorrespiratorio inicial y de donantes vivos (AU)


Introduction. Primary brain death (BD) is a clinical situation characterised by the total and irreversible absence of functioning in the brain as a consequence of its being destroyed, while heartbeat and breathing are maintained by artificial means. The Royal Decree 2070/1999, dated 30 December, lawfully regulates the diagnosis of BD and the activities concerning the donation of organs for transplant in Spain. Method. In certain patients who have suffered structural injury to the brain, serious intracranial hypertension occurs which blocks the blood flow throughout the brain, while breathing is maintained by mechanical means, together with heartbeat. The diagnosis of BD is eminently clinical and is based on the verification of three circumstances: the existence of a non-reactive coma, the disappearance of brain stem reflexes and activity in its parasympathetic nuclei, and the absence of spontaneous breathing. The diagnosis can be reinforced with certain complementary tests, which in some cases are compulsory. In the paper we describe the explorations that are considered to be appropriate by current Spanish legislation. We also review the most important clinical and legal aspects of organ donation. Conclusions. BD is an iatrogenic state, known only since the development of reanimation and assisted ventilation techniques, which amounts to the death of the person. Obtaining organs for transplants is currently possible in Spain from donors in this situation, but also from those who have died from an initial cardiopulmonary arrest and from live donors (AU)


Subject(s)
Humans , Spain , Organ Transplantation , Brain Death
7.
Eur J Med Chem ; 36(10): 799-807, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11738487

ABSTRACT

Some optically active 3-(arylmethylidene)aminoxy- (3a-g, 4a-g) and fluorenylideneaminoxy-2-methylpropionic acids (5, 6), were prepared as analogues of the antiinflammatory arylpropionic acids of type B, in which the aromatic group is substituted by an MAOM moiety. Some of the new compounds, tested in vivo for their antiinflammatory properties by means of the carrageenan-induced paw edema method in rats, exhibited activity indices similar to that shown in the same test by ibuprofen. Compounds 3a,b and 4a,b, for which at least one of the two enantiomers had shown an inhibition value higher than 40% in the in vivo test, were assayed for their in vitro enzymatic inhibitory activity, showing percentage inhibition values between 40 and 50% at a concentration of 10 microM against COX-2; at the same concentration, they appeared to be devoid of any activity towards COX-1. Compounds 3a,b and 4a,b also proved to possess a similar toxicity. The lack of enantioselectivity shown by compounds 3-6 was tentatively explained in terms of a conformational freedom of the enantiomers which allows their quasi-superimposition.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Propionates/chemical synthesis , Propionates/pharmacology , Animals , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Carrageenan , Cell Line , Cyclooxygenase 2 , Disease Models, Animal , Edema/chemically induced , Edema/drug therapy , Female , Isoenzymes/antagonists & inhibitors , Macrophages/drug effects , Macrophages/enzymology , Mice , Phenylpropionates/chemical synthesis , Phenylpropionates/pharmacology , Phenylpropionates/therapeutic use , Prostaglandin-Endoperoxide Synthases , Rats , Rats, Wistar , Stereoisomerism
8.
Eur J Med Chem ; 36(2): 185-93, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11311749

ABSTRACT

Some new cephem derivatives of types 4 and 5, viewed as analogues of type I esters in which the atomic sequence of the C-2 ester group is formally inverted, were synthesised and tested in vitro for their inhibitory activity towards human leukocyte elastase and porcine pancreatic elastase. An examination of the inhibition data obtained for the new type 4 and 5 derivatives, while exhibiting a considerable reduction in their activity against porcine pancreatic elastase, indicated that these compounds still maintain an appreciable inhibitory activity against human leukocyte elastase. On this basis the new type of C-2 substitution appears to contribute to the research of new, potentially interesting, cephalosporinic human leukocyte elastase inhibitors.


Subject(s)
Cephalosporins/pharmacology , Lactams/pharmacology , Leukocytes/enzymology , Pancreatic Elastase/antagonists & inhibitors , Animals , Cephalosporins/chemical synthesis , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/pharmacology , Humans , Kinetics , Lactams/chemical synthesis , Pancreas/enzymology , Structure-Activity Relationship , Swine
9.
Eur J Med Chem ; 35(1): 53-67, 2000 Jan.
Article in English | MEDLINE | ID: mdl-10733603

ABSTRACT

Some monocyclic beta-lactam derivatives of type 3 (MAOAs) in which the leaving group (LG) on the C(4) is a methyleneaminoxy moiety, were synthesised and tested in vitro and in vivo for their inhibitory activity towards human leukocyte elastase (HLE). Some compounds showed an appreciable in vitro inhibitory activity against this enzyme. Effects on the anti-HLE activity due to the nature of the substituents R and R(1) present on their LG were observed and rationalised by means of molecular modelling techniques. The results of in vivo pharmacological tests indicated that MAOAs, while showing an inhibitory activity on the haemorrhage induced by HLE, did not exhibit any effects due to the R and R(1) substituents.


Subject(s)
Azetidines/chemistry , Enzyme Inhibitors/chemical synthesis , Lactams/chemical synthesis , Leukocyte Elastase/antagonists & inhibitors , Models, Molecular , Animals , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/therapeutic use , Hemorrhage/chemically induced , Hemorrhage/drug therapy , Humans , Lactams/pharmacology , Lung Diseases/chemically induced , Lung Diseases/drug therapy , Mice , Phenylacetates/pharmacology
10.
Farmaco ; 54(4): 224-31, 1999 Apr 30.
Article in English | MEDLINE | ID: mdl-10384715

ABSTRACT

Some 7-aminocephalosporanic acid (7-ACA) derivatives substituted on the C(7) nitrogen with 2-(arylmethyloxyimino)propionyl (3a-f), 2-(arylmethyloxyamino)propionyl (4a-d) and (arylmethyloxyamino)acetyl (2a-d) moieties were synthesized by reaction of the appropriate acylating agents with 7-ACA protected as a t-butyl ester, followed by removal of the t-butyl protecting group. The new compounds, tested in vitro for their antimicrobial activity against Gram-positive and Gram-negative bacteria, proved to possess a modest activity directed only against Gram-positive microorganisms.


Subject(s)
Cephalosporins/chemical synthesis , Cephalosporins/pharmacology , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Magnetic Resonance Spectroscopy , Microbial Sensitivity Tests
11.
Farmaco ; 54(4): 242-7, 1999 Apr 30.
Article in English | MEDLINE | ID: mdl-10384718

ABSTRACT

Some new tetrahydrobenzoquinazolinediones 2a-4a, tetrahydrobenzocycloheptenuracils 5a, 6a and their thioxo analogues 2b-6b were synthesized within a project aimed at obtaining new HIV-1 tricyclic inhibitors whose scaffold includes a pyrimidine and a phenyl ring, which are present in various HIV-1 non-nucleoside inhibitors. Among the tetrahydrobenzoquinazolinediones 2a-4a, compounds 3a and 4a, in which the tricyclic system is respectively in an angular or linear arrangement, proved to possess a HIV-1 inhibitory activity which was in the micromolar range, while compound 2a, in which the tricyclic system is in the angular arrangement opposite to that of 3a, was found to be completely inactive. As regards the tetrahydrobenzocycloheptenuracil derivatives (5a and 6a), only 5a showed an inhibitory activity similar to that of 3a and 4a. Furthermore, all thioxo analogues 2b-6b were found to be devoid of any activity.


Subject(s)
Anti-HIV Agents/chemical synthesis , HIV-1/drug effects , Quinazolines/chemical synthesis , Uracil/analogs & derivatives , Uracil/chemical synthesis , Anti-HIV Agents/pharmacology , Cells, Cultured , Humans , Quinazolines/pharmacology , Uracil/pharmacology
12.
Bioorg Med Chem Lett ; 9(7): 1035-40, 1999 Apr 05.
Article in English | MEDLINE | ID: mdl-10230635

ABSTRACT

The synthesis and the antimicrobial properties of a new series of cephalosporinic beta-lactam antibiotics is described. The data reported in the present paper show the potential of this type of substituted cephalosporins as new anti Gram-positive antibiotic drugs. In fact, all compounds tested showed a good in vitro antibacterial activity against the most relevant Gram-positive pathogens including resistant species that currently represent unmet medical need. On the contrary, the new synthesized compounds were found to be completely devoid of any activity on Gram-negative bacteria up to a concentration of the single agent of 128 microg/ml.


Subject(s)
Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Cephalosporins/chemistry , Cephalosporins/pharmacology , Streptococcus pneumoniae/drug effects , Anti-Bacterial Agents/chemical synthesis , Cephalosporins/chemical synthesis , Microbial Sensitivity Tests , Staphylococcus aureus/drug effects , Streptococcus pyogenes/drug effects , Structure-Activity Relationship
13.
Bioorg Med Chem ; 6(11): 2151-60, 1998 Nov.
Article in English | MEDLINE | ID: mdl-9881105

ABSTRACT

The N-isopropyl- (3a-g) and N-tert-butyl-substituted (4a-g) (Z)-N-(3-(amino)-2-hydroxypropylidene)-(arylmethyloxy)amines were synthesized in order to compare their beta 1- and beta 2-adrenergic properties with those of their previously studied corresponding analogues with the E configuration (1a-g and 2a-g). Compounds 3 and 4 were tested for their affinity for beta 1-a and beta 2-adrenoceptors by radioligand binding experiments, and the compounds with the highest affinity were also assayed for their activity towards the same types of beta-adrenoceptors by functional tests on isolated preparations. The Z-methyloxyiminomethyl (Z-MOIM) compounds 3 and 4 proved to possess, on the whole, affinity (Ki) and activity (PIC50) indices similar to those of the E isomers 1 and 2, thus indicating that for the MOIM-type beta-adrenergic antagonists 1-4, the type of configuration around the MOIM double bond does not have any appreciable effect either on the affinity or on the activity towards beta-adrenoceptors. These results are rationalized on the basis of the steric and electronic analogies existing between the MOIM groups of 1-4 in the two types of configurations (E and Z).


Subject(s)
Adrenergic beta-Antagonists/chemical synthesis , Amines/chemistry , Amines/chemical synthesis , Receptors, Adrenergic, beta-1/physiology , Receptors, Adrenergic, beta-2/physiology , Adrenergic beta-Antagonists/chemistry , Adrenergic beta-Antagonists/pharmacology , Amines/pharmacology , Animals , Brain/metabolism , Cattle , Drug Design , Guinea Pigs , Ileum , In Vitro Techniques , Indicators and Reagents , Kinetics , Lung/metabolism , Male , Models, Molecular , Molecular Conformation , Molecular Structure , Muscle Contraction/drug effects , Muscle, Smooth/drug effects , Muscle, Smooth/physiology , Rats , Receptors, Adrenergic, beta-1/drug effects , Receptors, Adrenergic, beta-2/drug effects , Static Electricity , Structure-Activity Relationship , Trachea
14.
Farmaco ; 51(4): 283-6, 1996 Apr.
Article in English | MEDLINE | ID: mdl-8645417

ABSTRACT

Some 7-amino cephalosporanic acid derivatives substituted on the C(7) nitrogen with (S)-and (R)-3-(methyleneaminoxy)-2-methylpropionyl groups were synthesised and tested in vitro for their antimicrobial activity against Gram-positive and Gram-negative bacteria. Some of the new compounds showed a modest activity directed only against Gram-positive microorganisms.


Subject(s)
Bacteria/drug effects , Cephalosporins/chemical synthesis , Cephalosporins/pharmacology , Microbial Sensitivity Tests , Structure-Activity Relationship
15.
Farmaco ; 51(1): 33-9, 1996 Jan.
Article in English | MEDLINE | ID: mdl-8721759

ABSTRACT

Some type C (E)-(methyloxyimino)acetamides were synthesised as analogues of type A neuroleptic and antipsychotic benzamides, in which the aromatic group is substituted by a methyloxyiminomethyl moiety with the E configuration (CH2ON = CH, E-MOIMM). Type C compounds were tested for their D2-dopaminergic binding affinity in order to obtain an indication of their potential neuroleptic and antipsychotic properties. Biological results showed that only a few aryl-substituted E-MOIM derivatives possess a certain affinity for the D2-dopaminergic receptor, at least one order of magnitude lower than that of metoclopramide and sulpiride.


Subject(s)
Acetamides/chemical synthesis , Antipsychotic Agents/chemistry , Oximes/chemical synthesis , Receptors, Dopamine D2/metabolism , Acetamides/metabolism , Animals , Crystallography, X-Ray , Dopamine Antagonists/pharmacology , In Vitro Techniques , Metoclopramide/pharmacology , Neostriatum/drug effects , Neostriatum/metabolism , Oximes/metabolism , Radioligand Assay , Receptors, Dopamine D2/drug effects , Sulpiride/pharmacology , Swine
16.
Farmaco ; 51(1): 75-8, 1996 Jan.
Article in English | MEDLINE | ID: mdl-8721766

ABSTRACT

A certain number of benzodihydrocarbazoles and benzotetrahydrocycloheptindoles were synthesized and tested for their antimicrobial activity. Compounds substituted on the nitrogen of the tetracyclic systems with a dimethylaminopropyl chain showed an antibacterial activity directed almost exclusively towards Gram-positive bacteria, while their N-unsubstituted analogs were completely inactive.


Subject(s)
Anti-Bacterial Agents/chemical synthesis , Carbazoles/chemical synthesis , Indoles/chemical synthesis , Anti-Bacterial Agents/pharmacology , Carbazoles/pharmacology , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Indoles/pharmacology , Microbial Sensitivity Tests , Structure-Activity Relationship
17.
Farmaco ; 50(10): 713-8, 1995 Oct.
Article in English | MEDLINE | ID: mdl-8590579

ABSTRACT

Some cephalosporanic acid derivatives substituted on the C(7) amino nitrogen with (arylmethyloxyimino)acetyl moieties were synthesized and tested in vitro for their antimicrobial activity against Gram positive and Gram negative bacteria. The new compounds showed a modest activity directed only against Gram positive microorganisms.


Subject(s)
Bacteria/drug effects , Cephalosporins/chemical synthesis , Cephalosporins/chemistry , Cephalosporins/pharmacology , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Magnetic Resonance Spectroscopy , Microbial Sensitivity Tests
18.
Farmaco ; 50(10): 719-24, 1995 Oct.
Article in English | MEDLINE | ID: mdl-8590580

ABSTRACT

Some type B (E)-(arylmethyleneaminoxy)acetamides were synthesised as analogues of type A neuroleptic and antipsychotic benzamides, in which the aromatic group is substituted by a (methyleneaminoxy)methyl moiety (C = NOCH2, MAOMM). Theoretical studies were performed in order to verify whether conformational analogies could exist between type A and type B compounds. Type B compounds were tested for their D2-dopaminergic binding affinity which represents a valid indication of their potential neuroleptic and antipsychotic properties. Biological results indicate that the MAOMM is not able to substitute the aromatic group effectively in the field of neuroleptic benzamides. The results are discussed in the light of the structural analogies and the differences between the MAOMM and the aryl.


Subject(s)
Acetamides/chemical synthesis , Antipsychotic Agents/chemical synthesis , Oximes/chemical synthesis , Receptors, Dopamine D2/metabolism , Acetamides/pharmacokinetics , Acetamides/pharmacology , Animals , Antipsychotic Agents/metabolism , Antipsychotic Agents/pharmacology , Binding, Competitive/drug effects , Dopamine Antagonists/pharmacology , In Vitro Techniques , Metoclopramide/pharmacology , Molecular Conformation , Neostriatum/drug effects , Neostriatum/metabolism , Oximes/pharmacokinetics , Oximes/pharmacology , Radioligand Assay , Receptors, Dopamine D2/drug effects , Swine
19.
Farmaco ; 50(4): 239-43, 1995 Apr.
Article in English | MEDLINE | ID: mdl-7669168

ABSTRACT

The N-isopropyl- and N-t-butyl-substituted 1-[o-(3-amino-2-hydroxypropoxy)benzylideneaminoxy]-3-amino-2-propa nols (7a,b) and their meta (8a,b) and para (9a,b) isomers, in which a single aromatic ring is substituted both by the oxypropanolaminic chain of (aryloxy)propanolaminic beta-adrenergic antagonists (AOPAs) and the [(methyleneamino)oxy]propanolaminic chain of [(methyleneamino)oxy]-propanolaminic beta-blocking drugs (MAOPAs), were synthesized and assayed for their beta-adrenergic activity by functional tests on isolated preparations. Compounds 7-9 represent a new type of molecular duplication of beta-adrenergic drugs, formally deriving from the sharing of the aromatic portions of two different pharmacophoric subunits, namely the (aryloxy)propanolaminic portion of AOPAs and the [(benzylideneamino)oxy]propanolaminic portion of aryl-substituted MAOPAs. The pharmacological results showed that the beta-blocking activity of compounds 7-9 is closely related to the way in which the two subunits are linked by the aromatic nucleus: the activity decreases on passing from the ortho-compounds (7a,b) to the meta (8a,b) and then to the para (9a,b) isomers. A comparison of this activity trend with those found for series of both beta-blocking AOPAs and aryl-substituted MAOPAs seems to indicate that compounds 7-9 can be considered more as AOPAs substituted on the phenyl ring by a [(methyleneamino)oxy]propanolaminic chain rather than as aromatic MAOPAs substituted on the same phenyl moiety by an oxypropanolaminic portion.


Subject(s)
Adrenergic beta-Antagonists/chemical synthesis , Propanolamines/chemistry , Adrenergic beta-Antagonists/pharmacology , Animals , Guinea Pigs , Heart Atria , Male , Molecular Conformation , Myocardial Contraction/drug effects , Propanolamines/pharmacology , Trachea
20.
Farmaco ; 50(2): 83-90, 1995 Feb.
Article in English | MEDLINE | ID: mdl-7766280

ABSTRACT

A series of beta-aminoxypropionic acids (AOPAs) had previously been designed and synthesised as analogues of antiinflammatory arylacetic acids (ArAAs) in which the Ar portion is substituted by the (methyleneaminoxy) methyl moiety (C = NOCH2, MAOMM). Most of these AOPAs had exhibited a significant antiinflammatory and antiaggregating activity. This paper reports the synthesis of a new series of beta-aminoxypropionic acids (SAOPAs) which include the saturated (methylaminoxy)methyl moiety (CHNH-OCH2, SMAOMM) in the place of the MAOMM present in AOPAs. The antiinflammatory activity of SAOPAs was evaluated by the carrageenan-induced paw edema method and the antiaggregating activity was evaluated by means of tests using arachidonic acid (AA) and adenosine diphosphate (ADP) as the aggregating agents. Two SAOPAs were evaluated for their capacity to inhibit the cyclooxygenase enzyme by measuring the malondialdehyde (MDA) produced by incubation of sodium arachidonate with platelet-rich plasma (PRP). The pharmacological results showed that the saturation of the iminic double bond led to a reduction or even the disappearance of the antiaggreganting activity, whereas it did not induce any evident changes in the antiinflammatory activity. Theoretical studies were carried out in order to compare the conformation and the molecular reactivity of SAOPAs with those of AOPAs.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Platelet Aggregation Inhibitors/chemical synthesis , Propionates/chemical synthesis , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Carrageenan/antagonists & inhibitors , Edema/drug therapy , Female , Platelet Aggregation Inhibitors/chemistry , Platelet Aggregation Inhibitors/pharmacology , Propionates/chemistry , Propionates/pharmacology , Rabbits , Rats , Rats, Wistar , Structure-Activity Relationship
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