Punto domal cefálico en rinoplastía: una nueva alternativa en contornos de punta nasal / Cephalic dome suture in rhinoplasty: a new alternative in nasal tip contours

Introducción: El manejo de los contornos de la punta nasal requiere de un adecuado conocimiento de la composición anatómica y superficie estética para lograr resultados satisfactorios y naturales. Objetivo: Describir la técnica del punto domal cefálico, beneficios y sus resultados en una serie de pacientes sometidos a rinoseptoplastía. Material y método: Trabajo retrospectivo descriptivo, de los pacientes intervenidos quirúrgicamente por autor principal (FC) utilizando la técnica señalada. Resultado: La casuística consta de 31 pacientes sometidos a rinoseptoplastía, de los cuales el 71% corresponde al género femenino, siendo el promedio de edad de la muestra de 28 años. El tipo de abordaje fue vía delivery en 29 pacientes. No hubo complicaciones tanto intra como posoperatorias. Los resultados fueron exitosos en el 100% de los casos. Discusión y conclusión: El manejo de los contornos nasales es vital para obtener un resultado estético exitoso, idealmente sin estigmas quirúrgicos para lograr un aspecto natural de la nariz. El punto domal cefálico como nueva alternativa de manejo de los contornos nasales es una técnica efectiva y simple de realizar.

Introduction: The management of the contours of the nasal tip requires adequate knowledge of the anatomical composition and aesthetics to achieve satisfactory results and natural surface. Aim: To describe the technique of domal cephalic extent, benefits and results in a series of patients undergoin rhinoseptoplasty. Material and method: Retrospective descriptive labour patients operated on for primary author using the indicated technique. Results: The casuistry consists of 31 patients undergoing rhinoseptoplasty, of which 71% were female, the average age of the sample of 28 years. The type of approach was via delivery in 29 patients. There were no complications intra and post operative. We were successful in 100% of cases. Discussion and Conclusion: The management of nasal contours is vital for successful cosmetic result, ideally without surgical stigmas to achieve a natural appearance of the nose. The cephalic domal point as a new alternative management of nasal contours is an effective and simple technique.

Developing genomic resources for the common bottlenose dolphin (Tursiops truncatus): isolation and characterization of 153 single nucleotide polymorphisms and 53 genotyping assays.

Although single nucleotide polymorphisms (SNPs) are commonly used in human genetics, they have only recently been incorporated into genetic studies of non-model organisms, including cetaceans. SNPs have several advantages over other molecular markers for studies of population genetics: they are quicker and more straightforward to score, cross-laboratory comparisons of data are less complicated, and they can be used successfully with low-quality DNA. We screened portions of the genome of one of the most abundant cetaceans in U.S. waters, the common bottlenose dolphin (Tursiops truncatus), and identified 153 SNPs resulting in an overall average of one SNP every 463 base pairs. Custom TaqMan(®) Assays were designed for 53 of these SNPs, and their performance was tested by genotyping a set of bottlenose dolphin samples, including some with low-quality DNA. We found that in 19% of the loci examined, the minor allele frequency (MAF) estimated during initial SNP ascertainment using a DNA pool of 10 individuals differed significantly from the final MAF after genotyping over 100 individuals, suggesting caution when making inferences about MAF values based on small data sets. For two assays, we also characterized the basis for unusual clustering patterns to determine whether their data could still be utilized for further genetic studies. Overall results support the use of these SNPs for accurate analysis of both poor and good-quality DNA. We report the first SNP markers and genotyping assays for use in population and conservation genetic studies of bottlenose dolphins.

Medición de nitratos y nitritos en agua y saliva de población rural precordillerana de la VIII región / Nitrate and nitrite in water and saliva of rural population in the Andes foothills of the VIII Region

Introducción: Un factor de riesgo para las neoplasias escamosas de faringe son las nitrosaminas, las que derivan de los nitratos salivales que provienen de la dieta y en especial del agua si los niveles están por sobre la norma. Objetivos: Conocer y comparar los niveles de nitratos y nitritos en agua y saliva de habitantes de la región precordillerana y en población urbana de Concepción. Material y método: Estudio prospectivo, tipo caso y control. Determinan niveles de nitratos y nitritos en agua de la zona precordillerana y en agua de Concepción y en saliva de habitantes de la zona rural y de grupo control de Concepción. Resultados: Se obtienen 10 muestras de agua del sector rural y 1 muestra de agua potable de Concepción. Nivel de nitratos en agua rural 23,29 mg/L, en agua urbana 3,6 mg/L (p <0,05). En saliva, grupo estudio (n =15) con nivel de nitritos de 9,58 mg/ml, grupo control (n =24) nivel de 3,8 mg/ml (p <0,05). Conclusión: En la zona rural hay niveles significativamente mayores de nitratos en el agua y nitritos en saliva. Los niveles en agua son superiores a normas nacionales e internacionales. Nuestros resultados resaltan la posible importancia de las nitrosaminas y sus precursores como elementos carcinogónicos en los carcinomas escamosos orofaríngeos.

Introduction: A risk factor for squamous carcinomas of the oropharynx are the nitrosamines, which are derived from salivary nitrate coming from diet and water, especially if the levels are above the allowed levels. Aim: To determine and compare the levels of nitrates and nitrites in drinking water and saliva of people at the foothills of our region and urban population of Concepcion. Material and method: A descriptive cross sectional study. Determination of levels of nitrates and nitrites in drinking water in the Andean foothills and Concepcion and in saliva of people from same locations. Results: We obtained 10 rural water samples and 1 from Concepcion drinking water. Nitrate levels in rural water were 23.29 mg/L and 3.6 mg/L (p <0.05) in urban water. In saliva, the study group (n =15) had 9.58 mg/ml nitrite in saliva, the control group (n =24) 3.8 mg/ml (p <0.05). Conclusion: In rural areas there are significantly higher levels of nitrates in drinking water and saliva. The water levels are higher than national and international standards. Our results confirm high amounts of nitrogen cycle products (nitrites and nitrates) in drinking water and in saliva so it could be considered as carcinogenic elements in oropharyngeal squamous cell carcinomas.

Restricted dispersal in a continuously distributed marine species: common bottlenose dolphins Tursiops truncatus in coastal waters of the western North Atlantic.

The marine environment provides an opportunity to examine population structure in species with high dispersal capabilities and often no obvious barriers to genetic exchange. In coastal waters of the western North Atlantic, common bottlenose dolphins, Tursiops truncatus, are a highly mobile species with a continuous distribution from New York to Florida. We examine if the highly mobile nature coupled with no obvious geographic barriers to movement in this region result in a large panmictic population. Mitochondrial control region sequences and 18 microsatellite loci indicate dolphins are partitioning the habitat both latitudinally and longitudinally. A minimum of five genetically differentiated populations were identified among 404 samples collected in the range of New Jersey to northern Florida using both genetic marker types, some inhabiting nearshore coastal waters and others utilizing inshore estuarine waters. The genetic results reject the hypothesis of a single stock of coastal bottlenose dolphins put forth after the 1987-1988 epizootic that caused a large-scale die-off of dolphins and suggest instead the disease vector was transferred from one population to the next as a result of seasonal migratory movements of some populations. These coastal Atlantic populations also differ significantly from bottlenose dolphin samples collected in coastal waters of the northern Gulf of Mexico, implying a long-term barrier to movement between the two basins.

Relación entre la frecuentación de los niños y la de sus padres en una consulta de atención primaria / Relationship between frequency of visits of children and their parents to a primary care office

Objetivo: Estimar la relación entre la frecuentación de los niños y la de sus padres en una consulta de pediatría en atención primaria. Material y métodos: Se analiza la frecuentación de 229 niños de 1, 2, 4, 6, 11 y 13 años, de 127 padres y 152 madres de estos niños. La frecuentación se obtuvo del programa de historia clínica del centro de salud OMI-AP Se calculó la correlación entrelas visitas de los niños y las de sus padres/madres, y se compararon las medias de visitas de los padres de niños normofrecuentadores y de padres de niños hiperfrecuentadores, considerando hiperfrecuentadoresa quellos niños que acuden a la consulta un número de veces superior a 2 desviaciones estándar respecto a la media de los niños de su edad. Resultados: No se encontró correlación entre la frecuentación de los niños pequeños y sus padres. En cuanto a los niños y niñas mayores (6 y 13 años), existe una relación lineal entre el número de sus consultas y las de sus madres, no encontrandoesta correlación con el número de consultas de los padres.No se establecieron diferencias significativas entre el númerode visitas al centro de salud de los padres de niños normo ehiperfrecuentadores.ConclusionesN: o encontramosr elación entre la frecuentaciónde los padres y las madres de niños pequeños c on la frecuentaciónde sus hijos. Los datos obtenidos nos permiten sugeriruna relación entre la frecuentación de las madres deniños/as mayores y la de sus hijos/as

Objective: To determine the relationship between the frequency of visits of children and the visits of their parents to apediatric primary care office. Material and methods: We analyzed the frequency of visits of 229 children aged 1, 2, 4. 6, 11 and 13 years and that of the visits of 127 fathers and 152 mothers of those children. The frequency of visits was obtained with the OMI-AP software package for health centers. The linear correlation between the children's visits and those of their fathers/mothers was studied,and the mean number of visits on the part of parents whobrought their children with a normal frequency was comparedwith the mea nnumber of visits of parents who brought their children with a higher than normal frequency (number of visits greater than 2 standard deviations with respect to the mean for children of the same age).Results: We found no correlation between the frequency of visits of fathers and mothers of little children. However, we observed a linear correlation between mothers of children aged 6 and mothers of children aged 13 and their sons/daughters,a correlation that did not exist with the fathers of the same children. There were no statistically significant differences between the numbers of visits on the part of the fathers ofchildrenw ho were broughtw ith a normalf requency when compared with those who were brought with a higher than normal frequency. Conclusions: We found no correlation between the frequency of visits of the fathers and mothers of small children and the frequency of visits of their sons/daughters. The data obtained suggests the existence of a correlation between the frequency of visits of the mothers of older children and that of their sons/daughters

Cerebrospinal fluid: postmortem biochemical study.

UNLABELLED: Postmortem phenomena can change and alter biochemical components in body fluids such as blood and as cerebrospinal fluid (CSF). AIMS OF THE STUDY WERE: (a) to analyse urea, glucose, potassium, chloride, protein, creatinine, calcium, alkaline phosphatase and cortisol in CSF fluid and (b) to compare results between two age groups, between groups with or without mental or degenerative neurological illness and between a group reported as dying from natural causes and a group that had a violent death. MATERIALS AND METHODS: The study was carried out in Hospitalet de Llobregat (Barcelona) of 55 corpses. Samples were obtained following section of the corpus callosus, through the lateral ventricles and frozen to -80 degrees C until processed. RESULTS: Significant differences were found in urea levels between the two age groups, in protein between natural and violent death groups and in alkaline phosphatase between the two age groups and between the natural and violent death group. Cortisol levels revealed significant difference between the two age groups and is those supplying natural and violent death. CONCLUSIONS: The study indicates to the need for further studies designed to include groups with defined diagnose of mental or degenerative disorders as well as different age groups.

Genetic differentiation among recently diverged delphinid taxa determined using AFLP markers.

In the mid-1990s, a new common dolphin species (Delphinus capensis) was defined in the northeast Pacific using morphological characters and mitochondrial DNA (mtDNA) sequences. This species is sympatric with a second species, Delphinus delphis; morphological differences between the two are slight and it is clear they are closely related. Does the phenotypic distinction result from only a few important genes or from large differences between their nuclear genomes? We used amplified fragment length polymorphism (AFLP) markers to broadly survey the nuclear genomes of these two species to examine the levels of nuclear divergence and genetic diversity between them. Furthermore, to create an evolutionary context in which to compare the level of interspecific divergence found between the two Delphinus taxa, we also examined two distinct morphotypes of the bottlenose dolphin (Tursiops truncatus). A nonmetric multidimensional scaling analysis clearly differentiated both Delphinus species, indicating that significant nuclear genetic differentiation has arisen between the species despite their morphological similarity. However, the AFLP data indicated that the two T. truncatus morphotypes exhibit greater divergence than D. capensis and D. delphis, suggesting that they too should be considered different species.

Loss of the circadian variation of platelet [3H]imipramine binding in delusional compared with non-delusional endogenously depressed patients.

BACKGROUND: The circadian variations of the serotonin reuptake sites were studied in 16 patients meeting DSM-IV criteria for major depression with melancholia, either with (n=8) or without (n=8) psychotic symptomatology. METHOD: The [3H]imipramine binding sites were measured in platelet samples. RESULTS: While no statistically significant difference was found between the morning (09:00 h) and evening (21:00 h) [3H]imipramine B(max) values in the control group, both the non-delusional and delusional melancholic patients showed higher evening than morning B(max) values, which were only statistically significant in the former. When both diagnostic groups were compared, the delusional patients showed significantly lower [3H]imipramine binding values than the non-delusional patients both in the morning and evening samples. Within the non-delusional depressed patients, those individuals with mood circadian variation, assessed by the 18th item of the HDRS, showed significantly lower B(max) values than those without mood variation. Lowest morning and evening B(max) values were noted in the delusional depressed group without mood variations. CONCLUSIONS: These results suggest that delusional depressions might have a different neurobiological substrate with loss of chronobiological rhythms.

[Genetic dysfunction of the serotonin receptor 5-HT2A in psychiatric disorders]. / Disfunción genética del receptor de serotonina 5-HT2A en los trastornos psiquiátricos.

So far, there is increasing evidence of the active role of molecular biology in the psychiatric nosology as well as in the identification of psychiatric fenotypes. In this respect, the neurotransmitter serotonin (5-HT) has been involved in the etiopathogeny of multiple psychiatry conditions, such as affective disorder, schizophrenia, panic disorder, obsessive-compulsive disorder, alcoholism, eating disorder and personality disorder. The 5-HT2 receptor family includes the subtype 5-HT2A, a G protein coupled receptor whose activation leads to the stimulation of the enzyme phospholipase C and to the subsequent hydrolysis of the membrane located phosphoinositides, with the synthesis of the second messengers inositol triphosphate and diacylglicerol. This paper includes a review of the main findings concerning the polymorphism of the 5-HT2A in psychiatric disorders.

Water metabolism disturbances at different stages of primary thyroid failure.

The aim of the present study was to study salt and water metabolism in thyroid deficiency. We performed an oral water loading test (OWL) and a hypertonic 5% saline infusion test (HSI) in 16 patients with overt primary hypothyroidism before replacement treatment (PRE group) and after, in eight patients with subclinical hypothyroidism (SUB group) and in 16 normal individuals (CG group). In the PRE group, a lower free water clearance was detected in the OWL (P < 0.022), with lower plasma osmolality (OWL: P < 0.005; HSI: P < 0.001) and arginine vasopressin (AVP) (OWL: P < 0.001; HSI: P < 0.001) than the CG group, across both tests; they normalized with the replacement treatment. The same plasma abnormalities were detected in the SUB group with the HSI. Although the AVP and thirst thresholds did not differ between the groups, the lag between them was lower in the PRE (4.1+/-3.2 mOsm/kg) and SUB group (2.6+/-2.1 mOsm/kg) than in the CG group (13.3+/-9.2 mOsm/kg) (P < 0.05). There were no differences in atrial natriuretic hormone (ANH), plasma renin activity (PRA) and plasma aldosterone among the groups. These results indicate that plasma hypo-osmolality and low levels of AVP are present in primary hypothyroidism, and indeed are already present in the subclinical phase of the disease. An overlap between the thresholds of thirst and AVP seem to play a role in these abnormalities, but ANH, PRA and plasma aldosterone do not appear to contribute.

Disfunción genética del receptor de serotonina 5-HT2A en los trastornos psiquiátricos / Genetic dysfunction of the serotonin receptor 5-HT2A in psychiatric disorders

Estudios realizados hasta el momento han demostrado la participación de la genética molecular en muchos de los síndromes definidos por la nosología psiquiátrica, así como su utilidad en la clasificación de los trastornos psiquiátricos y en la identificación de determinados fenotipos. La serotonina (5-HT) constituye uno de los más importantes neuromediadores desde el punto de vista filogenético y ontogénico, y ha sido implicada en la etiopatogenia de múltiples trastornos psiquiátricos como los trastornos a fectivos, la esquizofrenia, el trastorno de pánico, el trastorno obsesivo-compulsivo, la dependencia de alcohol, los trastornos del control de impulsos y los trastornos alimenticios. La familia del receptor 5-HT2 incluye el receptor 5-HT2A, un receptor acoplado a las proteínas G y cuya activación produce la estimulación de la fosfolipasa C y la hidrólisis de los fosfoinosítidos de membrana, con la formación de los segundos mensajeros inositol trifosfato y diacilglicerol. En este artículo se revisarán los principales resultados publicados hasta el momento sobre la posible alteración genética del receptor 5-HT2A en diversos trastornos psiquiátricos (AU)

Altered 5-HT(2A) binding sites and second messenger inositol trisphosphate (IP(3)) levels in hippocampus but not in frontal cortex from depressed suicide victims.

The binding parameters of 5-HT(2A) and levels of its second messenger, 1,4,5-trisphosphate (IP(3)), were simultaneously studied in frontal cortex and hippocampus from the brains of 18 control subjects and 18 depressed suicide victims. All suicides met DSM-III-R criteria for depressive symptoms, suffered a violent death and had not taken any antidepressant drugs for at least 6 months prior to death. A significant decrease in the number of 5-HT(2A) binding sites (154+/-22 vs. 254+/-36 fmol/mg), together with a significantly lower apparent affinity constant (1.02+/- 0.08 vs. 1. 36+/-0.09 nM), was detected in hippocampus but not in frontal cortex from the depressed suicides compared to the control subjects. Furthermore, IP(3) concentrations were significantly increased in hippocampus (3.2+/-0.3 vs. 2.1+/-0.3 pmol/g) but not in frontal cortex (1.3+/-0.3 vs. 2.7+/-0.5 pmol/g) from the suicide victims. The reported results may indicate a significant hypersensitivity of the 5-HT(2A) postsynaptic receptor located in the hippocampus from depressed suicide victims, giving rise to an enhancement of its intracellular signaling system with higher IP(3) production.

Weak androgen levels, glucocorticoid therapy, and bone mineral density in postmenopausal women with rheumatoid arthritis.

OBJECTIVE: To study dehydroepiandrosterone sulfate (DHEAS) and androstenedione (AND) status in postmenopausal women with rheumatoid arthritis (RA), the effects of glucocorticoid therapy on DHEAS and AND levels, and their relationship with bone mineral density (BMD). METHODS: Forty-six postmenopausal women with RA were separated into two groups based on whether they had a negative history for glucocorticoid therapy (n = 24) or were currently on glucocorticoid therapy (n = 22). The control group was composed of 39 postmenopausal women who had never received hormone replacement therapy. Serum DHEAS and AND levels were measured using a radioimmunoassay. BMD was determined at the lumbar spine (L2-L4) and femoral neck using a DEXA Hologic QDR-1000 densitometer. Results. RA patients and controls were similar in age, weight, body mass index, and years since menopause. DHEAS and AND levels were lower in the glucocorticoid-treated RA group than in the other two groups. The glucocorticoid-treated RA group also had a significantly lower femoral BMD value than the nonglucocorticoid-treated RA group. Lumbar BMD was similar in the two RA groups and in the controls. CONCLUSION: Decreases in DHEAS and AND levels in postmenopausal women with RA are probably related to glucocorticoid therapy rather than to the disease itself.

Constitutive and regulated secretion of epidermal growth factor and transforming growth factor-beta1 in MDA-MB-231 breast cancer cell line in 11-day cultures.

Epidermal growth factor (EGF) and transforming growth factor type beta1 (TGF-beta1) exert opposite effects in most cells. A potential regulation between the two factors has been studied at a transcriptional level, but never at a protein level. MDA-MB-231 is a breast carcinoma cell line which possesses large quantities of membrane receptors and expresses high activities for both factors. In this study, conditioned mediums (CM) of 11-day cultures of these cells were collected to measure EGF and TGF-beta1 by immunochemical assays. Four types of cultures were tested: (1) controls; (2) after treatment with 17-beta-estradiol; (3) treated with EGF; and (4) treated with TGF-beta1. These cells secreted constitutively quantifiable concentrations of both factors to the CM. EGF treatment inhibited TGF-beta1 levels in CM throughout the study period (P = 0.002), while EGF levels diminished after TGF-beta1 treatment (P = 0.05). This finding suggests a dual regulation between EGF and TGF-beta1, at a protein level, in this cell line.

Platelet serotonergic binding sites in alcohol-dependent patients.

The serotonin (5-hydroxytryptamine, 5-HT) uptake sites assessed with both [3H]imipramine and [3H]paroxetine, and the 5-HT2A receptors were simultaneously measured in platelets from 24 male subjects meeting the American Psychiatric Association's DSM-IV criteria for alcohol dependence and admitted for inpatient detoxification. Blood samples from alcoholic patients were collected during acute alcohol intoxication (day 0), during withdrawal (day 1), and after 2 weeks of abstinence (day 14). All patients met the criteria for type II alcoholism. Alcohol misuse was found to be associated with an increased number and a lower affinity of [3H]paroxetine binding in comparison to the control values. Abstinence from alcohol for 2 weeks (day 14) resulted in a decrease in the number of 5-HT uptake sites labelled with [3H]paroxetine compared to normal values, together with a significant decrease in the number of 5-HT2A binding sites. The present data indicate that altered serotonergic function existing in alcoholic patients is a reversible phenomenon that normalizes after detoxification and withdrawal.

Altered [3H]imipramine and 5-HT2 but not [3H]paroxetine binding sites in platelets from depressed patients.

BACKGROUND: Serotonergic system alterations were studied in 51 depressed patients classified according to DSM-III-R criteria for major depression with melancholia compared to 31 healthy controls. METHOD: [3H]Imipramine and [3H]paroxetine binding sites and the 5HT2 receptor were simultaneously determined in blood platelet membranes. RESULTS: A significantly lower maximum binding in [3H]imipramine binding was observed in depressed patients compared to controls (1134+/-74 vs. 1712+/-106 fmol/mg protein, P<0.0001) without changes in the equilibrium dissociation constant (1.10+0.05 vs. 1.25-/+0.09 nM). [3H]Paroxetine binding did not differ between the two groups (Bmax, 1441+/-55 vs. 1280+/-81 fmol/mg protein; Kd, 0.060+/-0.002 vs. 0.062+/-0.002 nM). The K(d) value of 5HT2 binding was lower in depressed patients than controls (0.95+/-0.04 vs. 1.15+/-0.09 nM, P<0.039) without changes in maximum binding (140+/-11 vs. 127+/-14 fmol/mg protein). CONCLUSIONS: Taken together, these results suggest that [3H]imipramine and 5HT2 receptors may be good biological markers for serotonergic dysfunction in depressive disorders.

Secretion and dual regulation between epidermal growth factor and transforming growth factor-beta1 in MDA-MB-231 cell line in 42-hour-long cultures.

MDA-MB-231 is a breast cancer cell line which possesses large quantities of epidermal growth factor (EGF) receptors and specific high-affinity transforming growth factor-beta1 (TGF-beta1) receptors. We have established that these cells secrete constitutively measurable levels of EGF and TGF-beta1 in conditioned medium. The constitutive secretion of EGF decreased over time in culture (42 h), while the constitutive secretion of TGF-beta1 remained constant. TGF-beta1 secretion in EGF-treated cells was lower than in controls (P < 0.0001), but EGF concentrations were not modified after TGF-beta1 supplement. We postulate that in MDA-MB-231 cell line there is a dual regulation between both growth factors.

Genetic structure of harbour porpoise Phocoena phocoena populations in the northwest Atlantic based on mitochondrial and nuclear markers.

The harbour porpoise, Phocoena phocoena, experiences high levels of nonnatural mortality owing to interactions with commercial fisheries throughout its range. To accurately evaluate the significance of this bycatch, information on population structure is required. We have examined the population structure of this species in the northwest Atlantic Ocean using mitochondrial DNA (mtDNA) sequence and nuclear microsatellite data. Samples from four previously proposed summer breeding populations--the Gulf of Maine, eastern Newfoundland, the Gulf of St Lawrence and West Greenland--were analysed. Control-region sequences revealed a significant partitioning of genetic variation among most of these summer populations, indicating that northwest Atlantic harbour porpoises should not be considered one panmictic population. Analysis of females alone yielded the highest levels of population subdivision, suggesting that females are more philopatric than males. At least three management units may be defined for harbour porpoises in the northwest Atlantic based on these data. Analysis of six microsatellite loci failed to detect significant population subdivision. Male-mediated gene flow may maintain homogeneity among nuclear loci, while female philopatry is sufficient to produce a signal of population subdivision in the maternally inherited mtDNA genome. mtDNA analyses also indicate that winter aggregations of harbour porpoises along the US mid-Atlantic states comprise animals from more than one summer breeding population.

Characterization of the 5-HT4 binding site in human brain.

In this study, drug inhibition and saturation experiments on the binding of the highly selective 5-HT4 antagonist [3H]GR 113808 were performed in human brain membranes so as to better characterize this binding site. Drug competition studies were carried out by incubating 0.2 nM [3H]GR 113808 in the presence of increasing concentrations of six different drugs, i.e. 5-HT, 5-CT, ondansetron, tropisetron, BIMU 1 and BIMU 8 (mixed 5-HT3 and 5-HT4 agonists). The binding displaced by 5-HT showed a drug inhibition constant (Ki) value of 197nM. The use of 5-CT or ondansetron also showed the existence of single-site models albeit with Ki values in the micromolar range (11,5 microM). Tropisetron, BIMU 1 and BIMU 8 displaced bound [3H]GR 113808 according to a two-site binding model, with the high affinity component in the nanomolar range and the low affinity site in the micro or milimolar range. Saturation experiments revealed high binding densities in basal ganglia (187 fmol/mg in putamen, and 149 fmol/mg in caudate nucleus), while lower densities were observed in cortical regions (49 fmol/mg in temporal cortex, 45 fmol/mg in parietal cortex and 71 fmol/mg in cingulate cortex). The apparent affinity (Kd) was similar in the brain regions studied, ranging from 0.13 to 0.34 nmol/l. Despite the enrichment of 5-HT receptors in human brain, their functional correlate in brain diseases remains to be clarified.

Variations in [3H]imipramine and 5-HT2A but not [3H]paroxetine binding sites in suicide brains.

Both the [3H]imipramine and [3H]paroxetine binding sites and the 5-HT2A receptor were simultaneously determined in frontal cortex, cingulate cortex, hippocampus and amygdala from 17 control subjects and 17 depressed suicide victims. A significant decrease in the maximum binding (Bmax) of [3H]imipramine was observed in the hippocampus of suicide victims as compared to control subjects (160 +/- 25 vs. 328 +/- 52 fmol/mg protein; P = 0.007) without changes in the apparent affinity constant (Kd). Furthermore, a significant decrease in the number of 5-HT2A binding sites, together with a significantly lower Kd, was also observed in the hippocampus of suicides as compared to control subjects (129 +/- 18 vs. 225 +/- 32 fmol/mg protein; P = 0.02 and 0.91 +/- 0.07 vs. 1.38 +/- 0.08 nM, respectively; P = 0.006). [3H]Paroxetine binding did not display modifications between the two groups in either Bmax or Kd from any of the brain regions studied. When all four brain regions were taken together, a down-regulation was noted between presynaptic [3H]imipramine binding and the postsynaptic 5-HT2A receptor (r = -0.40; P = 0.0013) in the control group. This correlation did not appear in the suicide group. No correlation was observed between [3H]paroxetine binding and the 5-HT2A receptor in either control subjects or suicides. Taken together, these results suggest that the 5-HT uptake site measured with [3H]imipramine and the 5-HT2A receptors are reliable markers of serotonergic dysfunction.