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The behavioural and electrocorticographic (ECoG) convulsant effects of several xanthine derivatives injected intraperitoneally (i.p.) were studied in genetically-epilepsy prone rats. The aim of the study was to evaluate the relationship among convulsant potency, molecular structure and lipophilicity of some xanthines. Animals were injected i.p. with various doses (250-1000 micromol/kg) and a different convulsant potency was observed among the various xanthines tested. IBMX (3-isobutyl-1-methylxanthine), theophylline (1,3-dimethylxanthine) and caffeine (1,3,7-trimethylxanthine) induced an epileptogenic pattern that consisted in an initial phase characterized by wet-dog shakes followed by head tremor, nodding, clonic convulsion and they appeared to be the most potent xanthines among those studied. During seizures, the electrocortical activity was usually characterized by single or multiple sharp- or spike-wave episodes followed by polyspike discharges. After the highest doses of IBMX, theophylline and caffeine, the animals react with falling down, transient tonic clonic seizures, escape response and generalized seizures followed by post-ictal period. Equimolar doses of 8-chlorotheophylline and theobromine (3,7-dimethylxanthine) produced less evident epileptic responses in comparison to previous compounds, whereas no epileptic signs were observed following the administration of enprofylline (3-propylxanthine), etofylline [7-(2-hydroxyethyl)theophylline], diprophylline [7-(2,3-dihydroxy-propyl)theophylline] and doxofylline [7-(1,3-dioxolan-2-ylmethyl) theophylline]. Lipophylicity of the compounds was determined, but no convincing correlations were found between the rank order of lipophilicities and the convulsant potencies of the compounds studied. On the other hand, structure-activity relationship was also investigated. We suggest that the substitution pattern on the xanthine nucleus may explain, in part, the different convulsant potency of the compounds studied. Furthermore, a selective antagonism of adenosine subtype receptors should be considered.

In 1964, Pfeiffer described a syndrome consisting of craniosynostosis, broad thumbs, broad great toes, and partial soft tissue syndactyly of the hands and feet. It belongs to acrocephalosyndactyly syndromes. We describe a male baby product of an eighth full-term uncomplicated uncontrolled pregnancy, mother and father normal and unrelated, 32 and 50 years old, respectively. He had all diagnostic and prognostic criteria of Subtype 2 Pfeiffer's Syndrome. The clinical, radiological, tomographic, and genetic aspects are discussed.

The behavioral and convulsant effects of pefloxacin (PEFLO), a quinolone derivative, were studied after intraperitoneal (i.p.) administration to Dilute Brown Agouti DBA/2J (DBA/2) mice, a strain genetically susceptible to sound-induced seizures. The anticonvulsant effects of some excitatory amino acid (EAA) antagonists acting at N-methyl-D-aspartate (NMDA) or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate (KA) receptors and of some compounds enhancing gamma-aminobutyric acid (GABA)-ergic transmission against seizures induced by PEFLO were also evaluated. The present study demonstrated that both groups of compounds administered i.p. or intracerebroventricularly were able to protect against seizures induced by PEFLO. However, ifenprodil and (+/-)-alpha-(chlorophenyl)-4-[(4-fluorophenyl)methyl]-1-piperidine-ethan ol (SL 82.0715), two compounds acting on the polyamine site of the NMDA receptor complex, were unable to provide any protection. The relationship between the different sites of action and the anticonvulsant activities of these derivatives were discussed. Although the main mechanisms of PEFLO-induced seizures cannot be easily determined, potential interactions with the receptors of EAA exist. In fact, antagonists of EAA, and in particular, those acting at NMDA receptors, were able to increase the threshold for the seizures or to prevent the seizures induced by PEFLO, while compounds acting at the polyamine site did not provide any protection. The AMPA-KA receptor antagonists were also able to exert anticonvulsant activity, but with minor potency in comparison to those of NMDA antagonists. In addition, the fact that compounds enhancing GABA-ergic neurotransmission were also able to protect the mice against seizures induced by PEFLO suggests an involvement of GABA system.

Complete Androgen Insensitivity Syndrome (CAIS) is a type of Male Pseudohermaphroditism due to a defect in the androgen receptor which is a DNA-binding, transcription-regulating protein whose properties are induced on androgen binding. This defect is caused by mutations of a gene localized in Xq11-12. The objective of this study is the description of the clinical and pathological features of patients with female phenotype, karyotype 46, XY and diagnosis of CAIS. They were referred to Medical Genetic Unit of University of Zulia, Maracaibo, Venezuela, between 1971-1995. The diagnostic criteria and clinical and pathological findings are reviewed. Twenty-three patients fulfilled the diagnostic criteria. Most of patients were 13 years old or older (postpuberal). The main reasons for consultation were: primary amenorrhea, inguinal hernia, familial history of CAIS and fusion of labia minora. Seventeen patients from 5 families were diagnosed with CAIS and only one per family in 6 families. All patients showed a female general phenotype with unambiguously female external genitalia. Gonadal localization (right/left) was as follows: abdominal/abdominal: 65%; abdominal/inguinal: 26%; inguinal/abdominal: 9%. Histologic features of gonads were similar to those in cryptorchid testes of otherwise normal males. There was no evidence of development of gonadal neoplasia. The patients reported here provide a remarkable opportunity to study the molecular genetic characterization that can serve as a primary tool for diagnosis and subsequent therapy.

Injection of zymosan-activated plasma into the rat paw induced oedema formation. Subplantar injection of the non isoform- selective inhibitors of nitric oxide (NO) synthase, N(G)-nitro-L-Arginine methyl ester and N(G)-methyl-L-Arginine, and of a scavenger of NO, haemoglobin, inhibited the early phase of oedema development. Inhibition of cyclooxygenase activity by indomethacin reduced the late increase in paw volume after the injection of zymosan-activated plasma. Methylene blue, an inhibitor of the soluble guanylate cyclase, had no effect. Our results suggest that in paw oedema induced by zymosan-activated plasma, the inflammatory response is dependent on NO (for the early phase) and prostaglandins (for the late phase). The effect of NO is likely to be mediated by a pathway which does not involve cyclic GMP.

Asthma results from a complex interaction between genetics and environmental factors. Authors have demonstrated the role play by these, however a greatest number of family and asthmatic patients not identify the sources of pollution into their home. A sampling of 369 patients finds that males were predominant mainly affecting before five years of age. 67.2% have factors of risk in their microenvironment (RR = 4.06; OR = 11.38; RA = 53.21; P = .001). Tobacco predominant with 129 patients (RR = 3.12; OR = 3.76; RA = 37.08; P = 0.04). Carpets in 32.29% (RR = 2.81; OR = 4.52; RA = 31.44; P = .007). Animals 19.24% (RR = 1.64; OR = 1.90; RA = 11.27; P = .051). Patients with a great number of broncoespasm acute description have been hospitalized rely on factors risk in their home. Data demonstrate the necessity to design projects of education to limit the family injury.

Lamotrigine [0.5-10 mg/kg, intraperitoneally (i.p.)] was able to antagonize the audiogenic seizures in DBA/2 mice in a dose-dependent manner. Lamotrigine at doses of 0.5 and 1.25 mg/kg i.p., which per se did not significantly affect the occurrence of audiogenic seizures in DBA/2 mice, markedly potentiated the anticonvulsant activity of carbamazepine, diazepam, phenytoin, phenobarbital and valproate against sound induced seizures in DBA/2 mice. The degree of potentiation by lamotrigine was greatest for diazepam and valproate, lower for phenobarbital, and least for phenytoin and carbamazepine. The increase in anticonvulsant activity was associated with a comparable increase in motor impairment. However, the therapeutic index of combined treatment of diazepam + lamotrigine or valproate + lamotrigine was more favourable than the diazepam + saline or valproate + saline treatment. Since lamotrigine did not significantly influence the plasma levels of the anticonvulsant drugs studied we might suggest that pharmacokinetic interactions, in terms of total plasma levels, are not probable. However, the possibility that lamotrigine alters protein binding and increases the relative free vs protein bound ratio may not be excluded. Lamotrigine did not significantly affect the hypothermic effects of the anticonvulsant compounds studied. Lamotrigine showed an additive effect when administered in combination with some classical anticonvulsants, most notably valproate and diazepam.

The behavioural and convulsant effects of imipenem (Imi), a carbapenem derivative, were studied after intraperitoneal (i.p.) or intracerebroventricular (i.c.v.) administration in DBA/2 mice, a strain genetically susceptible to sound-induced seizures. The anticonvulsant effects of some excitatory amino acid antagonists and muscimol (Msc), a GABAA agonist, against seizures induced by i.p. or i.c.v. administration of Imi were also evaluated. The present study demonstrated that the order of anticonvulsant activity in our epileptic model, after i.p. administration, was (+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)-cyclohepten-5,10-imine maleate (MK-801) > (+/-)(E)-2-amino-4-methyl-5-phosphono-3-pentenoate ethyl ester (CGP 39551) > 3-((+/-)-2-carboxypiperazin-4-yl)propenyl-1-phosphonic acid (CPPene) > 3-((+/-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CCP) > 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(F)-quinoxaline (NBQX). Ifenprodil, a compound acting on the polyamine site of NMDA receptor complex was unable to protect against seizures induced by Imi, suggesting that the poliamine site did not exert a principal role in the genesis of seizures induced by Imi. In addition, the order of anticonvulsant potency in our epileptic model, after i.c.v. administration, was CPPene > MK-801 > Msc > (-)-2-amino-7-phosphonic acid (AP7) > gamma-D-glutamylaminomethylsulphonate (gamma-D-GAMS) > NBQX > kynurenic acid (KYNA) > 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX). The relationship between the different site of action and the anticonvulsant activity of these derivatives was discussed. Although the main mechanism of Imi induced seizures cannot be easily determined, potential interactions with the receptors of the excitatory amino acid neurotransmitters exists. In fact, antagonists of excitatory amino acids are able to increase the threshold for the seizures or to prevent the seizures induced by Imi. In addition, Imi acts on the central nervous system by inhibition of GABA neurotransmission and Msc, a selective GABAA agonist, was able to protect against seizures induced by Imi.

The anticonvulsant activity of 3-((+/-)-2-carboxypiperazin-4-yl)-1-propenyl-1-phosphonic acid (CPPene) and 2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo(F)quinoxoline (NBQX), two excitatory amino acid antagonists, was studied against audiogenic seizures in DBA/2 mice, following intraperitoneal (i.p.) or intracerebroventricular (i.c.v.) administration. Maximal anticonvulsant protection was observed 15-30 min following NBQX and 45-180 min after CPPene. Coadministration with fenbufen (20 mg kg-1, i.p.), a non-steroidal anti-inflammatory agent, enhanced and prolonged the anticonvulsant actions of CPPene and NBQX and also potentiated and prolonged the impairment of rotarod performance. The enhancement of the anticonvulsant activity and the prolonged impairment of rotarod performance suggests that fenbufen may have some pharmacokinetic interactions with CPPene and NBQX and that fenbufen is able to increase the brain levels of these excitatory amino acid antagonists. In particular, fenbufen was able to exert a major degree of potentiation of effects of NBQX rather than those of CPPene, suggesting that the chemical structures of these excitatory amino acid antagonists are responsible for the different degree of interactions between CPPene or NBQX and fenbufen. NBQX appears to have a notable similarity with quinolones whilst CPPene does not. Additionally fenbufen may displace CPPene and NBQX from plasma binding sites or inhibit the renal excretion. The present data are also consistent with previous studies showing pharmacokinetic interactions between fenbufen and quinolones.

With the help of an structures observation we detect that 98% of the confined patients come from the emergency service. As a consequence of this, we proceed to go through some of the factors that bore upon the quality of the attention in that level. The medical staff non specialized subject to a survey reflect a diagnostic conviction only with the presence of sibilances. Review important fact its examine the management of the patient with a stay of some hours in the observation area in the emergency service.

Asthma is a chronic disease, that require familiar education and advisement in order to get control. The records of 71 asthmatics children were studied, the ages ranged from 6 months to 16 years, both sexes were included. All of them came up to the allergologic outpatient section at IMSS regional hospital located in Ciudad Madero, Tamaulipas. All cases reviewed in 1992. Males were predominant, mainly affecting school age, symptoms appeared in 56.6% before two years of age and 21.6% had less than one year of evolution, in 54.9% have received specialist medical treatment, only 18.3% know elementary information about the disease. As a result it improved control in 80% of cases, by means of a scheme that includes a specificity response to an integral diagnosis through the path that modify favorable risk factors in a six months period.

There is a need to know the epidemiology behavior of health problem, with the purpose of creating the supporting basis for all action to its concern. In the cities Tampico, Madero and Altamira, a systematic exploration of the prevalent situation of allergic disorders did not exist: now, there is a study of 730 people selected at random, by means of questionnaire including 55 items applied to the population as a whole that live in the different zones of this area. It has been found that 54% show an allergic illness, it must be observed that in 66% of them a familial allergic history existed, whereas 45% has seasoning crisis environmental-related.

Urticaria and angioedema are skins disorders more frequently in allergy sections of clinics. They are a serious health problem because in 90% of the cases, the causes are not determined and in a similar percentage, the results of treatment are not satisfactory either to the patient or the consulting physician. To find out some characteristics of chronic urticaria in our area, we studied 45 patients who sought consultation at the General Regional and Zone Hospital No. 6 of the IMSS in Ciudad Madero, Tamps., in a given time span. Persons of both sexes and all ages were included. All were given a complete allergy medical history and a complete series of laboratory exams to try to determine the diagnosis. Etiology the treatment was done separating the patients into two groups with four types of antihistaminics considered within the basic medicinal chart of the IMSS. The study shows that the skin rash and angioedema together had a frequency rate of 81.25% with a greater frequency in females (81.25%) between the ages of 20 and 40. The etiology could be determined in only 37.77% of the cases with a high emphasis on parasite. It is notable that in 56.25% of the cases there was an earlier history of some type of respiratory allergy not diagnosed. We observed that there were better results if two antihistamines H1 were combined to provide specific treatment of immunotherapy with good results.

Mice were rendered physically dependent by repeated administration of morphine, 25 mg/kg s.c., 5 times daily for 4 days, and on the 5th day, 2 h after the last morphine dose, they were challenged with a s.c. injection of either naloxone, 25 mg/kg, or the peripherally selective opioid antagonist SR 58002 C (N-methyl levallorphan mesilate), 75 mg/kg. Naloxone provoked jumping and diarrhea in all the animals; mice challenged with SR 58002 C presented no significant jumping but a high frequency of withdrawal diarrhea. When naloxone, 12 mg/kg, or SR 58002 C, 50 mg/kg, were given s.c. in combination with repeated morphine as above, mice which had received naloxone with morphine presented virtually no diarrhea or jumping upon naloxone challenge; those repeatedly treated with morphine plus SR 58002 C were substantially protected from naloxone-precipitated diarrhea, but not jumping. These results further support the remarkable selectivity for peripheral opioid receptors of SR 58002 C, even after repeated high-dose treatment, and are strongly consistent with the primary role of a local intestinal mechanism in the development and expression of opioid withdrawal diarrhea in mice. The in vivo dissociation of central and peripheral components of dependence on morphine is illustrated, apparently for the first time.