Velázquez: farmacología básica y clínica

Prefacio, los directores. Prólogo a la primera edición (1930), Teófilo Hernando. Farmacología básica. Sistema nervioso periférico. Sistema nervioso central. Aparato cardiovascular. Autacoides, inflamación y respuesta inmunológica. Aparato digestivo. Sistema nervioso endocrino. Aparato respiratorio. Sangre. Quimioterapia antiinfecciosa y antitumoral. Miscelánea. Farmacología clínica. Variabilidad de la repsuesta farmacológica. Efectos no deseados de los medicamentos. Evaluación de los efectos de los medicamentos. Evaluación y mejora del uso de medicamentos. Nuevas perspectivas

Velázquez: farmacología básica y clínica

Prefacio, los directores. Prólogo a la primera edición (1930), Teófilo Hernando. Farmacología básica. Sistema nervioso periférico. Sistema nervioso central. Aparato cardiovascular. Autacoides, inflamación y respuesta inmunológica. Aparato digestivo. Sistema nervioso endocrino. Aparato respiratorio. Sangre. Quimioterapia antiinfecciosa y antitumoral. Miscelánea. Farmacología clínica. Variabilidad de la repsuesta farmacológica. Efectos no deseados de los medicamentos. Evaluación de los efectos de los medicamentos. Evaluación y mejora del uso de medicamentos. Nuevas perspectivas

An oligoarray for the detection of human papillomavirus type 16 variants.

On the basis of human papillomavirus (HPV) E6 gene mutations, there are more than five variants of HPV 16. We applied a sensitive and specific stacking hybridization assay using an oligoarray for the detection of Asian-American (AA) and European (E) (E350G) HPV 16 variants. A simple glass slide was coated with capture probes consisting of short oligonucleotide DNA sequences (7-9 mers) specific for AA and E variants. Two different regions of the E6 HPV 16 gene were amplified with a set of two primers, which were used as target DNA. These targets were preannealed with auxiliary labeled oligonucleotides and hybridized to the oligoarray in the presence of specific and complementary capture probes. Our designed array based on shorter capture probes successfully discriminated between HPV 16 AA and E variants. The present DNA oligoarray system could be useful as a reliable technique for HPV 16 detection and does not require specialized equipment; nevertheless, further intra- and interlaboratory studies are needed.

Differentially expressed genes between high-risk human papillomavirus types in human cervical cancer cells.

Cervical carcinoma (CC) is one of the most common cancers among women worldwide and the first cause of death among the Mexican female population. Human papillomavirus (HPV) infection is the most important etiologic factor for CC. Of the oncogenic types, HPV16 and HPV18 are found in 60-70% of invasive CCs worldwide. HPV18 appears to be associated with a more aggressive form of cervical neoplasia than HPV16 infection. At present, there are no studies on differentially expressed cellular genes between transformed cells harboring HPV16 and HPV18 sequences. Based on previous complementary DNA microarray data from our group, 13 genes were found to be differentially overexpressed between HPV16- and HPV18-transformed cells. These genes were as follows: E6BP, UBE4A, C20orf14, ATF7, ABCC8, SLC6A12, WASF3, SUV39H1, SPAG8, CCNC, E2FFE, BIRC5, and DEDD. Differential expression of six selected genes was confirmed by real-time reverse transcription-polymerase chain reaction (RT-PCR). All real-time RT-PCRs confirmed differential expression between HPV18 and HPV(-) samples. The present work identifies genes from signaling pathways triggered by HPV transformation that could be differentially deregulated between HPV16(+) and HPV18(+) samples.

Clinical epidemiology of childhood cancer in Central America and Caribbean countries.

BACKGROUND: Countries with scarce resources have the right to appropriate essential health care but very few reports discuss how this can be achieved. We assessed the survival of a large cohort of pediatric oncological patients to provide hard data on which to base realistic evaluation and planning schemes. PATIENTS AND METHODS: This multicenter retrospective survey covered consecutively diagnosed and treated patients admitted to eight national level hospitals in seven countries in Central America and the Caribbean. The research protocol was discussed extensively, so the data to be collected and the criteria for their evaluation were clearly pre-defined. We analysed 2214 patients diagnosed between 1996 and 1999 with various cancers, classified as hemato-oncological disorders (70%) and solid tumors (30%). RESULTS: Three-year overall survival was 48.4% [standard error (SE) 1.3]. Detailed analysis of acute lymphoblastic leukemia highlighted the wide intercountry variability: 3-year survival was 62.2% (SE 5.3) in Cuba, 74.2% (SE 3.3) in Costa Rica, 61.7% (SE 4.9) in Nicaragua, and lower in the other four countries. CONCLUSIONS: The yield of diagnostic-therapeutic protocols depends largely on the context of care in which they are applied. This paper documents the importance of including epidemiological research in interventions for cooperation in complex health areas such as pediatric oncology.

Procedimientos diagnósticos neurofisiológicos en epilepsia refractaria / Neurophysiologic diagnostic procedures in intractable epilepsy

A pesar del desarrollo de nuevas drogas antiepilépticas, la prevalencia de epilepsia refractaria es de al menos un 20 por ciento. Este grupo de pacientes tiene un alto índice de morbilidad directa y mortalidad asociada a epilepsia. La evaluación sistemática con protocolos específicos permite discriminar un subgrupo que se se beneficia con tratamiento quirúrgico. La adecuada selección y clasificación sindromática de los candidatos quirúrgicos permite la obtención de mayores índices de remisión postquirúrgica. El protocolo de evaluación de epilepsia refractaria de nuestro Centro de Epilepsia se basa en una serie de procedimientos diagnósticos neurofisiológicos. Sobre los mismos se discutirán sus indicaciones, alcances e impacto en definir conductas terapéuticas

Procedimientos diagnósticos neurofisiológicos en epilepsia refractaria / Neurophysiologic diagnostic procedures in intractable epilepsy

A pesar del desarrollo de nuevas drogas antiepilépticas, la prevalencia de epilepsia refractaria es de al menos un 20 por ciento. Este grupo de pacientes tiene un alto índice de morbilidad directa y mortalidad asociada a epilepsia. La evaluación sistemática con protocolos específicos permite discriminar un subgrupo que se se beneficia con tratamiento quirúrgico. La adecuada selección y clasificación sindromática de los candidatos quirúrgicos permite la obtención de mayores índices de remisión postquirúrgica. El protocolo de evaluación de epilepsia refractaria de nuestro Centro de Epilepsia se basa en una serie de procedimientos diagnósticos neurofisiológicos. Sobre los mismos se discutirán sus indicaciones, alcances e impacto en definir conductas terapéuticas

Pilot study of the relationship between the hardness and abrasion resistance of two base metal alloys used for metal-ceramic restorations.

STATEMENT OF PROBLEM: Base metal alloys present high values of strength and hardness, which have been associated with the greater abrasion resistance and polishing of metal-ceramic restorations. However, surface hardness has been shown to be a poor indicator of abrasion resistance. PURPOSE: The study aimed to compare the hardness and abrasion resistance of Ni-Cr alloys and determine whether there is a correlation between these 2 properties. MATERIAL AND METHODS: Two Ni-Cr alloys for metal-ceramic restorations with different hardness values were subjected to the following procedures: (1) initial measurement of Vickers hardness, (2) a series of abrasion cycles, (3) measurement of mass loss after each cycle, and (4) Vickers hardness measurements after each cycle. RESULTS: For each alloy, linear regression revealed a negative correlation between hardness and reduction in mass. The higher hardness of alloy A was associated with higher mass loss during abrasion when compared with alloy B. CONCLUSION: There was no significant correlation between hardness and mass loss for either alloy.

Possible participation of nitric oxide in the increase of norepinephrine release caused by angiotensin peptides in rat atria.

In rat atria isolated with their cardioaccelerans nerves and labeled with [3H]norepinephrine, exposure to 1 x 10(-7) mol/L angiotensin II (Ang II) and 1 x 10(-7) mol/L Ang-(1-7) increased the release of radioactivity elicited by nerve stimulation (0.5-millisecond-long square-wave pulses at 2 Hz during 2 minutes) by 90% and 60%, respectively. The facilitatory effect on noradrenergic neurotransmission caused by both peptides was stereospecifically prevented by N omega-nitro-L-arginine methyl ester (1 x 10(-4) mol/L), an inhibitor of nitric oxide synthase that catalyzes the conversion of L-arginine to nitric oxide, as well as by 1 x 10(-5) mol/L methylene blue, a substance that inhibits the guanylate cyclase considered as the final target of nitric oxide action. On the other hand, the precursor of nitric oxide synthesis. L-arginine (1 x 10(-3) mol/L), reversed the prevention produced by N omega-nitro-L-arginine methyl ester on the increased release of norepinephrine caused by Ang II and Ang-(1-7). The present results suggest that nitric oxide could be involved in the neuromodulatory function elicited by both Ang II and Ang-(1-7) in rat atria. The physiological role of this observation is still under study.

Involvement of monoamine oxidase and noradrenaline uptake in the positive chronotropic effects of apigenin in rat atria.

In rat isolated atria spontaneously beating and labelled with [3H]noradrenaline, exposure to the flavonoid apigenin increased the atrial rate in a concentration-dependent manner (0.01-30 microM). This increase was accompanied by a reduction of 60% in the uptake of [3H]noradrenaline as well as by a modification in the pattern of [3H]noradrenaline and metabolites spontaneously released. Sixty minutes after exposure to 30 microM apigenin, the proportion of unmetabolized [3H]noradrenaline increased from 11% to 45% of the total products collected in the organ bath whereas the tritiated O-methylated deaminated metabolites decreased from 33% to 14% of the total efflux. A small but significant decrease in the outflow of [3H]3,4-dihydroxymandelic acid as well as a tendency to a decrease in the efflux of [3H]3,4-dihydroxyphenylglycol was also observed. Furthermore, apigenin inhibited in a concentration-dependent manner the activity of monoamine oxidase in the rat atrial homogenates. The calculated IC50 (7.7 microM) was within the range that produced 50% of the maximal increase in atrial rate. It is concluded that apigenin possesses the property to increase the atrial rate, probably as a result of a reduction in noradrenaline uptake as well as in monoamine oxidase activity.

Effects of the in vitro treatment with gangliosides on the release of endogenous amino acids from rat hypoxic atria.

1. In the rat isolated atria the in vitro exposure to 60 min of hypoxia in the absence of glucose followed by 30 min of reoxygenation increased the release of the amino acids glutamate (Glu) and taurine (Tau). The efflux of the remaining amino acids assayed (aspartate, glycine and alanine) did not change throughout the period studied. 2. The increase in Tau release started 45 min after the onset of the hypoxic period whereas that of Glu started during the reoxygenation phase. These increases were not observed when glucose was present during the hypoxic period. 3. The in vitro pretreatment for 2 h with 50 microM bovine brain gangliosides (BBG) prevented the increases in the release of Tau and Glu induced by the hypoxia reoxygenation. 4. These results constitute a further example where BBG appears to exert a protective role in cardiac tissues submitted to injuries.

Prostanoid production in hypoxic rat isolated atria: influence of acute diabetes.

The effects of hypoxia on prostanoid production were studied in atria from normal, acute diabetic and insulin-treated diabetic rats. Diabetes was induced by intravenous administration of 65 mg/kg of streptozotocin, the rats were killed 5 days later. Hypoxia was performed by incubation of the atria during 60 min in nitrogen-equilibrated glucose free Krebs' solution followed by 15 min of reoxygenation. The prostanoids 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha) and thromboxane B2 (TXB2), stable metabolites of prostacyclin and TXA2, respectively, as well as PGF2, were measured by reversed phase HPLC-UV. In control atria, the production of 6-keto PGF1 alpha was equivalent to that of PGE2, whereas TXB2 was released in a much smaller amount. In diabetic atria, 6-keto PGF1 alpha production was reduced by 65%, whereas TXB2 release was increased by 158% compared to the controls. When the normal atria were exposed to 60 min of hypoxia, the release of 6-keto PGF1 alpha increased by 142% compared to basal values and remained elevated after 15 min of reoxygenation whereas in diabetic and insulin-treated diabetic tissues the 6-keto PGF1 alpha production was not modified by the hypoxia-reoxygenation period. The release of TXB2 was increased after 60 min hypoxia in normal as well as in diabetic and insulin-treated diabetic tissues and remained elevated during the reoxygenation. The PGE2 output increased only after the onset of the reoxygenation in the three groups studied.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of L-glutamate on the responses to nerve stimulation in rat isolated atria.

In rat atria isolated with their sympathetic fibres the chronotropic responses to nerve stimulation with pulses of 2 ms duration were reduced in a concentration-dependent manner by 10 microM to 1 mM L-glutamate (Glu) and by 0.01 to 1.00 microM (R,S)-3-hydroxy-5-methoxyloxasole-4-propionic acid (AMPA), whereas they were unaffected by other agonists of Glu receptors such as 1 microM to 1 mM N-methyl-D-aspartic acid (NMDA), 10 microM to 1 mM kainate and 1 to 100 microM (+/-)-2-amino-4-phosphonobutyric acid (AP4). The reductions in the atrial responses to nerve stimulation caused by Glu were not accompanied by alterations in either the basal efflux of [3H]noradrenaline or its overflow in response to the stimulation. The sensitivity of the atria to exogenous noradrenaline was not modified by either Glu or AMPA. The decreases in the chronotropic responses caused by Glu and by AMPA were prevented by both the non-selective Glu receptor antagonist, 100 microM kynurenic acid, and the selective AMPA receptor antagonist, 10 to 50 microM 6,7-dinitroquinoxaline-2,3-dione (DNQX). In addition, the adenosine receptor antagonist, 8-phenyltheophylline (10 microM), as well as the muscarinic acetylcholine receptor antagonist, atropine (3 microM), prevented the inhibitory effects of both Glu and AMPA on the chronotropic responses of rat isolated atria. Since both adenosine and acetylcholine are known to exert negative inotropic and chronotropic effects in cardiac tissues, it is proposed that Glu could contribute, through the interaction with receptors of the AMPA type, to facilitate the release of adenosine and acetylcholine from the atria.(ABSTRACT TRUNCATED AT 250 WORDS)

Gangliosides prevent the dimethyl sulphoxide-induced increases in [3H]-noradrenaline release from rat isolated atria.

1. In the rat isolated atria labelled with [3H]-noradrenaline ([3H]-NA), the exposure to 1-4% v/v dimethyl sulphoxide (DMSO) during 15 min caused a concentration-dependent increase in the spontaneous outflow of tritiated products, which reached up to 50% with 2% DMSO and up to 100% with 4% DMSO. These effects were entirely prevented by a 2 h in vitro pretreatment with 50 microM bovine brain gangliosides mixture (BBG). 2. The pattern of the spontaneous release of tritiated products was 17.5 +/- 1.9% of [3H]-NA; 38.7 +/- 2.1% of [3H]-3,4-dihydroxyphenylglycol ([3H]-DOPEG); 36.1 +/- 2.4% of [3H]-O-methylated deaminated metabolites ([3H]-OMDA); 4.7 +/- 0.9% of [3H]-3,4-dihydroxymandelic acid ([3H]-DOMA) and 2.9 +/- 0.2% of [3H]-NMN. After 10 min exposure to 2% DMSO, the increase in basal outflow by this agent consisted of 7.4 +/- 2.5% [3H]-NA and 89.0 +/- 3.6% [3H]-DOPEG. The 2 h preincubation with 50 microM BBG protected from the increase of total radioactivity and also from the metabolic alterations caused by DMSO. The BBG per se did not modify either the basal efflux or the metabolic fate of the [3H]-transmitter. 3. In addition to enhancing the spontaneous outflow of radioactivity, the exposure to 2% v/v DMSO increased by 400% the overflow of the [3H]-transmitter elicited by nerve stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Relaxant effects of beta-carbolines on rat aortic rings.

The effects of two beta-carbolines, methyl 6,7-dimethoxy-4-ethyl-beta- carboline-3-carboxylate (DMCM) and ethyl beta-carboline-3-carboxylate (beta CCE) were assayed on rat aortic rings precontracted with different agonists. The beta-carbolines tested induced a concentration-dependent (2-200 microM) relaxation of aortic rings precontracted with 30 mM KCl. This relaxation was not modified by the removal of the rat aortic endothelium. Contractions elicited by the activation of either voltage-gated calcium channels (0.05 microM BAY K 8644) or receptor-operated calcium channels (0.1 microM norepinephrine), as well as contractions produced by the entry of calcium as a lipid-soluble complex (10 microM A23187), were also reduced by DMCM and by beta CCE. In addition, whereas DMCM did not modify calmodulin activity, both beta-carbolines inhibited in a concentration-dependent manner (0.6-200 microM) the rat aortic cyclic nucleotide phosphodiesterase activity. Moreover, DMCM as well as beta CCE potentiated the relaxation of K(+)-contracted aortic rings induced by the stimulation of either adenylyl cyclase with forskolin (0.1-1 microM) or guanylyl cyclase with sodium nitroprusside (0.1-100 nM). The intracellular rat aortic levels of cyclic AMP measured in the presence of 0.1 microM forskolin were increased by 100% in the presence of DMCM. On the other hand, 6 microM DMCM potentiated the relaxation induced by nifedipine in K(+)-contracted aortic rings, whereas the K+ channel blocker 10 mM tetraethylammonium did not modify the relaxation elicited by DMCM in the norepinephrine-contracted preparation.(ABSTRACT TRUNCATED AT 250 WORDS)