The role of cannabinoids in neurodevelopmental disorders of children and adolescents. / El papel de los cannabinoides en los trastornos del neurodesarrollo de niños y adolescentes.

INTRODUCTION: Neurodevelopmental disorders have a multifactorial etiology that results from the interaction between biological and environmental factors. The biological basis of many of these disorders is only partially understood, which makes therapeutic interventions, especially pharmacological ones, particularly difficult. The impact of medical cannabis on neurological and psychiatric disorders has been studied for a long time. This study aimed to review the currently available clinical and pre-clinical studies regarding the use of cannabinoids in pediatric neurodevelopmental disorders and to draw attention to the potential therapeutic role of cannabidiol in this field. DEVELOPMENT: Cannabidiol is an endocannabinoid system modulator and exerts its effects on both developing and mature brains through numerous mechanisms. Cannabidiol holds a relatively high toxicity limit and current literature suggests that it may have anxiolytic, antipsychotic, and neuroprotective properties. Clinical evidence suggests that early treatment with cannabidiol might be a promising therapy for neurodevelopmental disorders, including intellectual disability, autism spectrum disorders, tics, and attention/deficit hyperactivity disorder. CONCLUSIONS: This review hopefully draws attention to an emerging body of evidence concerning cannabidiol's significant potential to safely improve many of the common symptoms affecting children and adolescents with neurodevelopmental disorders, especially autism spectrum disorder.

TITLE: El papel de los cannabinoides en los trastornos del neurodesarrollo de niños y adolescentes.Introducción. Los trastornos del neurodesarrollo tienen una etiología multifactorial que resulta de la interacción entre factores biológicos y ambientales. La base biológica de muchos de estos trastornos se comprende sólo parcialmente, lo que hace que las intervenciones terapéuticas, especialmente las farmacológicas, sean particularmente difíciles. El impacto del cannabis medicinal en los trastornos neurológicos y psiquiátricos se ha estudiado durante mucho tiempo. Este estudio tuvo como objetivo revisar los estudios clínicos y preclínicos actualmente disponibles con respecto al uso de cannabinoides en trastornos del neurodesarrollo pediátrico y llamar la atención sobre el posible papel terapéutico del cannabidiol en este campo. Desarrollo. El cannabidiol es un modulador del sistema endocannabinoide y ejerce sus efectos tanto en cerebros en desarrollo como en cerebros maduros a través de numerosos mecanismos. El cannabidiol tiene un límite de toxicidad relativamente alto, y la bibliografía actual sugiere que puede tener propiedades ansiolíticas, antipsicóticas y neuroprotectoras. La evidencia clínica sugiere que el tratamiento temprano con cannabidiol podría ser una terapia prometedora para los trastornos del desarrollo neurológico, incluida la discapacidad intelectual, los trastornos del espectro autista, los tics y el trastorno por déficit de atención/hiperactividad. Conclusiones. Es de esperar que esta revisión llame la atención sobre un cuerpo emergente de evidencia sobre el potencial significativo del cannabidiol para mejorar de manera segura muchos de los síntomas comunes que afectan a niños y adolescentes con trastornos del neurodesarrollo, especialmente el trastorno del espectro autista.

Copper molybdate synthesized by sonochemistry route at room temperature as an efficient solid catalyst for esterification of oleic acid.

Copper molybdate nanoplates were synthesized by a sonochemical process at room temperature, which we report as a simple and cost-effective route. Structural analysis of the material by the Rietveld method of X-ray diffraction (XRD) data revealed lindgrenite Cu3(MoO4)2(OH)2 in a single-phase structure. All the vibrational modes characteristic of the space group were identified by Raman vibrational and near-infrared (NIR) spectroscopies. The profile obtained for N2 adsorption/desorption was type III hysteresis, characteristic of mesoporous materials, with a surface area of 70.77(1) m2 g-1. The micrographs of the material obtained by scanning electron microscopy showed nanoplates with nanometric sizes and an anisotropic growth aspect. The catalytic activity of lindgrenite was evaluated by esterifying oleic acid with methanol, showing high conversion rate to methyl oleate and good catalyst stability after seven recycling cycles. Above all, the best catalytic performance was reached when we optimized parameters such as oleic acid:methanol molar ratio of 1:5, 5% of catalyst dosage, and reaction time of 5 h, resulting in 98.38% of conversion at 413 K. Therefore, sonochemically synthesized lindgrenite proved to be a high potential material for biofuel production by oleic acid esterification.

Therapeutic effectiveness of a Calendula officinalis extract in venous leg ulcer healing.

OBJECTIVE: Non-healing venous leg ulcers (VLUs) have a significant effect on patients' quality of life and substantially increase expenditures in health-care systems. The aim of this study was to evaluate the clinical efficacy of the Calendula officinalis extract, Plenusdermax, in the treatment of VLUs. METHOD: Patients treated with Calendula officinalis extract (n=38) and control patients (n=19) were evaluated every two weeks for 30 weeks or until their ulcers healed. Assessments included determination of the wound area by planimetry, infection control, and evaluation of the clinical aspects of the wounds. The percentage of healing velocity per week (%HVw), taking the initial area at baseline into account, was also determined. RESULTS: The proportion of the treatment patients achieving complete epithelialisation was 72 % and 32 % in the treatment and control groups, respectively. The average healing time was approximately 12 weeks in the treatment group and 25 % in control patients. Patients with ulcers treated with Calendula officinalis extract had a significant 4-fold increase in percentage healing velocity per week, 7.4 %, compared with 1.7 % in the control group. No adverse events were observed during the Calendula officinalis extract treatment. CONCLUSION: Our findings indicate that Calendula officinalis extract is an effective treatment for VLUs. DECLARATION OF INTEREST: The authors have no conflict of interest.

A policy analysis of teamwork as a proposal for healthcare humanization: implications for nursing.

AIM: To analyse the implications of the political devices of the Brazilian National Humanization Policy, Singular Therapeutic Project and Reference Team and Matrix Support, for nursing as a professional discipline. BACKGROUND: The Brazilian Unified Health System, SUS-Brazil, has as its principles regarding health care: universal access at all levels of care; equality and non-discrimination; integrality; community participation; and political and administrative decentralization, regionalization, and hierarchization. The National Humanization Policy is a public health policy that serves as the methodological apparatus for the application of the SUS-Brazil principles. Reference Teams refers to inter- and transdisciplinary/professional teams. These team approaches are associated with increased quality of care. METHODS: Qualitative lexical content policy analysis of the official documents for the Brazilian National Humanization Policy. FINDINGS: The Reference Team model that is used to carry out Singular Therapeutic Projects leads to discussion of disciplinary boundaries in the context of health care. CONCLUSION AND IMPLICATIONS FOR NURSING AND HEALTH POLICY: The Brazilian National Humanization Policy demands inclusion of various kinds of knowledge and networking. Research is needed to elucidate the nature of nursing care and its distinctive character in relation to the work objectives of other professional disciplines.

Localization of the gene for X-linked calvarial hyperostosis to chromosome Xq27.3-Xqter.

X-linked calvarial hyperostosis is a rare disorder characterized by isolated calvarial thickening. Symptoms are prominent frontoparietal bones, a flat nasal root and a short upturned nose, a high forehead with ridging of the metopic and sagittal sutures, and lateral frontal prominences. The mandible is normal, as are the clavicles, pelvis and long bones. The thickened bone in the skull appears to be softer than normal bone. Despite calvarial hyperostosis, increased intracranial pressure and cranial nerve entrapment do not occur. The major disability seems to be cosmetic. The disease segregates with an X-linked recessive mode of inheritance. Female carriers do not show any clinical symptoms. To date, only one family has been described with X-linked calvarial hyperostosis including three affected individuals. In order to localize the disease causing gene, 31 polymorphic microsatellite markers that spread across the X-chromosome were analyzed. Genotypes were combined in haplotypes to delineate the region. A chromosomal region spanning from Xq27.3 to Xqter cosegregates with the disorder. This region encompasses 23.53cM or 8.2Mb according to the deCODE map and contains 165 genes. CNV-analysis did not show small duplications or deletions in this region. Exome sequencing was performed on a male patient in this family. However, this did not reveal any putative mutation. These results indicate that a non-coding regulatory sequence might be involved in the pathogenesis of this disorder.

No conclusive evidence for association of polymorphisms in the adiponectin receptor 1 gene, AdipoR1, with common obesity.

AdipoR1 is one of the adiponectin receptors which are important for adiponectin signaling. Because adiponectin is a candidate gene for common obesity, it is also hypothesized that variations in AdipoR1 may be involved in the development of complex obesity. Therefore, we designed an association study for the AdipoR1 gene. We performed a case-control association study including 1,021 obese subjects (mean age 42 ± 12 years; mean BMI 38.2 ± 6.2 kg/m²) and 226 lean, healthy individuals (mean age 36 ± 7 years; mean BMI 22.1 ± 1.7 kg/m²). Nine tagSNPs were selected to cover the entire AdipoR1 gene and surrounding 7 kb region (based on HapMap data). TagSNPs were genotyped using AcycloPrime-Fluorescence Polarization (FP) SNP Detection kits and TaqMan Pre-Designed SNP Genotyping assays according to manufacturer's protocols. We found that the rs1075399 non-reference allele decreases obesity risk by 45 % in men only [odds ratio (OR) = 0.55, 95 % CI 0.35-0.87, nominal P = 0.010]. However, after Bonferroni correction for multiple testing, this association is lost. None of the other tagSNPs were associated with obesity when studying the entire population, nor when looking at men and women separately. Quantitative analysis of the effect of each SNP on height, weight, and BMI revealed that none of the tagSNPs are associated with weight or BMI. We report here that we found no decisive evidence for association between AdipoR1 tagSNPs and complex obesity in our Belgian Caucasian population.

Polymorphisms in the endocannabinoid receptor 1 in relation to fat mass distribution.

OBJECTIVE: Both animal and human studies have associated the endocannabinoid system with obesity and markers of metabolic dysfunction. Blockade of the cannabinoid receptor 1 (CB1) caused weight loss and reduction in waist size in both obese and type II diabetics. Recent studies on common variants of the CB1 receptor gene (CNR1) and the link to obesity have been conflicting. The aim of the present study was to evaluate whether selected common variants of the CNR1 are associated with measures of obesity and fat distribution. DESIGN AND METHODS: The single nucleotide polymorphisms (SNPs) rs806381, rs10485179 and rs1049353 were genotyped, and body fat and fat distribution were assessed by the use of dual-energy X-ray absorptiometry and magnetic resonance imaging in a population-based study comprising of 783 Danish men, aged 20-29 years. RESULTS: The rs806381 polymorphism was significantly associated with visceral fat mass (FM) only, whereas the rs1049353 was significantly and directly associated with visceral and intermuscular FM. None of the SNPs analysed were associated with total body FM or subcutaneous FM. CONCLUSION: The results point towards a link between common variants of the CNR1 and fat distribution in young men.

Frecuencia de anticuerpos IgA e IgM anti Chlamydia trachomatis: en mujeres embarazadas procedentes de una consulta prenatal Cumaná, Estado Sucre, Venezuela, marzo-junio de 2006 / Frequency of IgA and IgM anti Chlamydia trachomatis antibodies: in pregnant women coming from a prenatal consult in Cumana, State of Sucre, Venezuela, march-june of 2006

Con el propósito de establecer la frecuencia de anticuerpos IgA e IgM anti-C-trachomatis en mujeres embarazadas se realizó un estudio en 84 mujeres con esa condición, en edades comprendidas entre 14 y 43 años, que acudieron a la consulta prenatal, del Servicio Autónomo Hospital Universitario “Antonio Patricio de Alcalá”, en Cumaná, estado Sucre, Venezuela, durante el período marzo-junio de 2006. Para ello se obtuvieron 84 muestras de suero para la determinación de anticuerpos IgA e IgM anti C-trachomatis a través del método de inmunoabsorción ligado a enzimas ELISA (Diagnostic Automation INC). Del total de muestras analizadas 16 (19,05 por ciento) y 55 (65,48 por ciento) resultaron positivas para la determinación de anticuerpos IgA e IgM anti C-trachomatis respectivamente. No se encontró asociación entre la presencia de estos anticuerpos con la edad de las pacientes, aunque el mayor número de pacientes positivas se ubicó en el intervalo de edades comprendidas entre 14 a 23 años. Asimismo al asociarse las manifestaciones clínicas genitales con la presencia de anticuerpos IgA e IgM anti C- trachomatis no se encontraron valores estadísticamente significativos. Por lo anteriormente expuesto se concluye que la infección genital por Chlamydia trachomatis en mujeres embarazadas es extremadamente frecuente, de manera especial en las edades comprendidas entre 24 a 33 años, y ocurre habitualmente en forma asintomática con las graves repercusiones que esto acarrea a la paciente, al feto y a su pareja.

In order to establish the frequency of IgA and IgM anti-C. Trachomatis antibodies in expectant women, a study was made of 84 women between the ages of 14 and 43, who attended prenatal consults in the Autonomous Service at the University Hospital “Antonio Patricio of Alcalá,” Cumaná, State of Sucre, during the March-June period, 2006. 84 serum samples were obtained to determine IgA and IgM anti-C. trachomatis antibodies using the immunoabsorption method connected to ELISA enzymes (Diagnostic Automation INC). Of the total samples studied, 16 (19.05 percent) and 55 (65.48 percent) resulted positive for the IgA and IgM anti-C. trachomatis antibodies, respectively. No association was found between the presence of these antibodies and the age of the patients, although the greater number of positive patients was in the 14 to 23 year age interval. Likewise, no statistically significant values were found between the association of clinical genital manifestations and the presence of IgA and IgM anti C- trachomatis antibodies; therefore, it was shown that Chlamydia trachomatis is presented asymptomatically in most cases. Conclusions were that genital infection by Chlamydia trachomatis in pregnant women is extremely frequent, especially for ages between 24 and 33 years, and it occurs habitually in an asymptomatic form with the serious repercussions that this produces on the patient, the fetus and the partner.

Prevalencia de enfermedades infecciosas de transmisión sanguínea en donantes que asisten al banco de sangre del Hospital Universitario “Antonio Patricio de AlcalᔠCumaná estado Sucre / Prevalence of blood-transmitted infectious diseases in donors at the University Hospital “Antonio Patricio de Alcalᔠblood bank in Cumaná state of Sucre

Se evaluaron 356 muestras de sangre de individuos aparentemente sanos, que acudieron en calidad de donantes al Banco de Sangre del Hospital Universitario “Antonio Patricio de AlcalᔠCumaná, estado Sucre para la prevalencia de varias enfermedades de trasmisión sanguínea. Se determinó la presencia de anticuerpos por ELISA contra el core (anti-HBc) y antígeno de superficie (HBsAg) del virus de la hepatitis B, contra el virus de la hepatitis C (VHC), contra el virus de la inmunodeficiencia humana (VIH) y contra Trypanosoma cruzi. Además, se efectuó la prueba de anticuerpos no treponémicos contra la sífilis y antígenos de Plasmodium falciparum y Plasmodium vivax. Del total de pacientes, 84 (23,6 por ciento) presentaron positividad para uno o más marcadores, siendo la distribución: 41(11,52 por ciento) reactivas para el Anti-HBc, 9 (2,53 por ciento) para HBsAg, 2 (0,56 por ciento) para VHC, 1 (0,28 por ciento) para T. cruzi y 31 (8,71 por ciento) para VDRL. Para VIH y Plasmodium no se encontraron casos positivos. Estos resultados demuestran que la población estudiada puede estar dentro del grupo clasificado como de alto riesgo para transmitir el VHB, sin excluir a las otras patologías que no deja de ser importante su despistaje para evitar así el riesgo de propagación de infecciones.

Identification and molecular characterization of a novel splice-site mutation (G1205C) in the SQSTM1 gene causing Paget's disease of bone in an extended American family.

Paget's disease of bone (PDB) is a common late-onset bone disorder characterized by focal areas of abnormal bone remodeling. Positional cloning efforts resulted in the identification of seven genetic loci (PDB1-7) with putative involvement in the pathogenesis of PDB. Meanwhile, the PDB-causing gene from the PDB3 region on chromosome 5q35 has been identified as the SQSTM1 gene. All mutations identified in this gene so far are located in or close to the ubiquitin-associated (UBA) domain of the protein. In 2001, we reported genotyping results of genetic markers located in the PDB3 region in an extended American family, indicating the involvement of the PDB3 locus. Here, we report the identification of a novel mutation (G1205C) in the SQSTM1 gene in this family. The G1205C mutation is located in the splice donor site of intron 7 and reverse-transcription polymerase chain reaction experiments showed that the presence of the C allele results in the production of two abnormal mRNA transcripts. Translation of the first transcript would result in a protein that lacks amino acids 351-388, including 26 amino acids of the second PEST domain in addition to two amino acids of the UBA domain. The second mutant mRNA transcript could result in a truncated protein (390X) that lacks almost the complete UBA domain. PDB mutations that disrupt the function of the PEST domain of SQSTM1 have not been reported before, so probably the pathogenic effect of both transcripts resides in the disruption of the ubiquitin-binding properties of the protein.

An intermediate form of juvenile Paget's disease caused by a truncating TNFRSF11B mutation.

Juvenile Paget's disease (JPD) is a rare condition with an autosomal recessive mode of inheritance. Typically presenting in infancy or early childhood, the disorder is characterized by a generalized widening of the long bones and thickening of the skull combined with sustained elevation of serum alkaline phosphatase levels. The extremely rapid bone turnover results in osteopenia, fractures, and progressive skeletal deformity. In 2002, mutations in TNFRSF11B, the gene encoding osteoprotegerin, were described as underlying JPD. We evaluated a patient with JPD at the clinical, biochemical, radiological, and molecular level. Mutation analysis of TNFRSF11B revealed a homozygous insertion/deletion in exon 5, predicted to result in truncation of the protein at amino acid 325. The residual activity of the mutated protein product was investigated by Western blotting and ELISA upon transient overexpression. Absence of the C-terminal domain abolished homodimerization and was shown to lead to a decreased capacity of the mutant protein to bind its ligand RANKL. We conclude that truncation of the C-terminal part of osteoprotegerin negatively affects functional activity. As a consequence, osteoclast formation and function are up-regulated, causing the increased bone turnover seen in this patient.

Characterization and cytochemical localization of an ATP diphosphohydrolase from Leishmania amazonensis promastigotes.

An ATP diphosphohydrolase was identified in the plasma membranes isolated from promastigote forms of Leishmania amazonensis. Both ATP and ADP were hydrolysed at similar rates by the enzyme. Other nucleotides such as UTP, GTP and CTP were also degraded, revealing a broad substrate specificity. Adding ATP and ADP simultaneously, the amount of hydrolysis achieved was compatible with the presence of a single enzyme. ATPase activity was not affected by addition of vanadate, ouabain, thapsigargin, dicyclohexylcarbodiimide, oligomycin and bafilomycin A, thus excluding involvement of P-, F- and V-type ATPases. The effects of pH in the range 6.5-8.5 were examined using ATP or p-NPP as substrate. At pH 7.4, the phosphatase activity decreased, and did not show a significant contribution to ATP hydrolysis. In addition, the enzyme was not inhibited by levamisole and ammonium molybdate, excluding alkaline phosphatase and nucleotidase activities, respectively. Sodium azide (5-10 mM) caused inhibition of the ATP and ADP hydrolysis in a dose-dependent manner. Calcium was the best activating metal ion for both ATPase and ADPase activities. Ultrastructural cytochemical microscopy showed ATP diphosphohydrolase on the surface and flagellar pocket of the parasite. We have proposed that L. amazonensis ATP diphosphohydrolase may participate in the salvage pathway of nucleosides.

Inotropic stimulation induces cardiac dysfunction in transgenic mice expressing a troponin T (I79N) mutation linked to familial hypertrophic cardiomyopathy.

The cardiac troponin T (TnT) I79N mutation has been linked to familial hypertrophic cardiomyopathy and a high incidence of sudden death, despite causing little or no cardiac hypertrophy. In skinned fibers, I79N increased myofilamental calcium sensitivity (Miller, T., Szczesna, D., Housmans, P. R., Zhao, J., deFreitas, F., Gomes, A. V., Culbreath, L., McCue, J., Wang, Y., Xu, Y., Kerrick, W. G., and Potter, J. D. (2001) J. Biol. Chem. 276, 3743-3755). To further study the functional consequences of this mutation, we compared the cardiac performance of transgenic mice expressing either human TnT-I79N or human wild-type TnT. In isolated hearts, cardiac function was different depending on the Ca(2+) concentration of the perfusate; systolic function was significantly increased in Tg-I79N hearts at 0.5 and 1 mmol/liter. At higher Ca(2+) concentrations, systolic function was not different, but diastolic dysfunction became manifest as increased end-diastolic pressure and time to 90% relaxation. In vivo measurements by echocardiography and Doppler confirmed that base-line systolic function was significantly higher in Tg-I79N mice without evidence for diastolic dysfunction. Inotropic stimulation with isoproterenol resulted only in a modest contractile response but caused significant mortality in Tg-I79N mice. Doppler studies ruled out aortic outflow obstruction and were consistent with increased chamber stiffness. We conclude that in vivo, the increased myofilament Ca(2+) sensitivity due to the I79N mutation enhances base-line contractility but leads to cardiac dysfunction during inotropic stimulation.

Abnormal contractile function in transgenic mice expressing a familial hypertrophic cardiomyopathy-linked troponin T (I79N) mutation.

This study characterizes a transgenic animal model for the troponin T (TnT) mutation (I79N) associated with familial hypertrophic cardiomyopathy. To study the functional consequences of this mutation, we examined a wild type and two I79N-transgenic mouse lines of human cardiac TnT driven by a murine alpha-myosin heavy chain promoter. Extensive characterization of the transgenic I79N lines compared with wild type and/or nontransgenic mice demonstrated: 1) normal survival and no cardiac hypertrophy even with chronic exercise; 2) large increases in Ca(2+) sensitivity of ATPase activity and force in skinned fibers; 3) a substantial increase in the rate of force activation and an increase in the rate of force relaxation; 4) lower maximal force/cross-sectional area and ATPase activity; 5) loss of sensitivity to pH-induced shifts in the Ca(2+) dependence of force; and 6) computer simulations that reproduced experimental observations and suggested that the I79N mutation decreases the apparent off rate of Ca(2+) from troponin C and increases cross-bridge detachment rate g. Simulations for intact living fibers predict a higher basal contractility, a faster rate of force development, slower relaxation, and increased resting tension in transgenic I79N myocardium compared with transgenic wild type. These mechanisms may contribute to mortality in humans, especially in stimulated contractile states.

Identification of the Gbeta5-RGS7 protein complex in the retina.

The G protein beta subunit G beta 5 deviates significantly from the four other members of the G beta family in amino acid sequence, unique expression pattern (only in the CNS), and cytosolic localization. To identify the members of the G beta 5-mediated signaling pathway, we purified the native protein complex containing G beta 5 from the cytosolic fraction of bovine retina. Analysis of the isolated complex revealed that G beta 5 is tightly associated with RGS7, a member of the superfamily of negative regulators of G protein signaling. This finding, for the first time, demonstrates an interaction between a G beta subunit and an RGS protein. G beta 5 was not detected in the outer segments of photoreceptor cells, suggesting that the cytosolic G beta 5-RGS7 complex is not directly involved in phototransduction.

Prevalence of high blood pressure in children and adolescents. Influence of obesity.

Obesity is associated with high blood pressure BP, mainly in adults. It has been suggested that body fat patterning plays a role in the etiology of hypertension. This relationship also exists in children, however it is less well known. The aim of this study was to evaluate the prevalence of high blood pressure (HBP) in children and adolescents, and the influence of obesity on this population, as well as the presence of familial aggregation for these factors. Eight hundred and eighty-nine children (389 boys and 500 girls aged 5-18 years) and their parents, from the North of Portugal were studied. Systolic blood pressure, diastolic blood pressure, weight, height, triceps skinfold, body mass index and sexual maturation were measured. The criterion of high blood pressure was defined as the BP being higher than the 90th percentile. All variables were converted to age and sex in specific "Z-scores". A SPSS package was used. We found 47 (5.2%) people of both sexes to have high blood pressure. The children of this group were compared with the normotensive group. These children were heavier (p < 0.005) and more obese (p < 0.0001) than the others. No difference was found for sexual maturation or height. The parents of the group with high blood pressure were heavier (p < 0.001) and more obese (p < 0.01) than the parents of the normotensive group. In conclusion, obesity is an important factor in children with higher values. Children with HBP are more likely to come from families with history of obesity. The identification of these risk factors in children is an important contribution to the prevention of cardiovascular disease in adulthood.

[Arterial hypertension in a patient with cardiac tamponade]. / Hipertensão arterial num doente com tamponamento cardíaco.

An elevated arterial pressure in cardiac tamponade, although not unusual might postpone the diagnosis of pericardial disease. We reported a case of cardiac tamponade, due to neoplastic infiltration of the pericardium, in which the diagnosis was first suspected by the presence of pulsus paradoxus. The patient presented cardiac tamponade and arterial hypertension simultaneously.

Structural characterization and promoter activity analysis of the gamma-kafirin gene from sorghum.

A genomic clone encoding the gamma-kafirin gene from sorghum was isolated and sequenced. A 2938 bp sequenced fragment includes an intronless open reading frame of 636 nucleotides encoding a putative polypeptide of 212 amino acids. Comparison of the deduced amino acid sequence of gamma-kafirin with the published sequences of gamma-prolamins of maize, and Coix revealed highly conserved domains. The N-terminal region of these proteins contains the conserved hexapeptide PPPVHL, which is repeated eight times in gamma-zein, four times in gamma-kafirin and three times in gamma-coixin. The number of PPPVHL repeats accounts predominantly for the differences in the molecular weights of gamma-prolamins. Several putative regulatory sequences common to the gamma-kafirin and gamma-zein genes were identified in both the 5' and the 3' flanking regions. Putative GCN4-like regulatory sequences were found at positions -192 and -476 in the 5' flanking region of gamma-kafirin. In the 3' noncoding region, three putative polyadenylation signals, two AATAAT and one AATGAA, were found at positions +658, +716, and +785, respectively. In order to investigate the role of the putative GCN4-like motifs and other possible cis-acting element(s) of the gamma-kafirin promoter, a series of deleted and chimeric promoter constructs were introduced into maize, Coix and sorghum tissues by particle bombardment. Histochemical analysis of beta-glucuronidase (GUS) activity in different tissues indicated that the element(s) responsible for tissue specificity is probably located in the 285-bp proximal region of the promoter, while the remaining promoter sequence seems to carry the element(s) responsible for the quantitative response.

[Refractory heart failure in a 26-year-old woman with idiopathic hemochromatosis]. / Insuficiência cardíaca refractária numa mulher de 26 anos com hemocromatose idiopática.

Idiopathic hemochromatosis, the most frequent inherited disease in Caucasians, is frequently undiagnosed. In this disorder, characterized by a continued inappropriated absorption of dietary iron, the clinical manifestations result from damage to those organ systems in which iron has been pathologically deposited, namely, the heart and the liver. Typically, hemochromatosis becomes clinically manifest in later life and in men more frequently than in women. This has been attributed to the extra loss of iron in women through menstruation and pregnancies. Removal of the excess iron by phlebotomy will prevent all of the complications of hemochromatosis of when begun early. In this paper, we report a case of a young woman with a eight years evolution of amenorrhea, cardiac failure, diabetes mellitus and increased pigmentation of the skin, associated with biochemical markers of iron overload. It is emphasized that hemochromatosis most be excluded in all patients with a unexplained cardiac failure.

Heart rate variability in 24-hour Holter recordings. Comparative study between short- and long-term time- and frequency-domain analyses.

Mean hourly parameters obtained from all beats (long series) were compared with those obtained from a sample of 512 beats extracted each hour (short series) in nine presumably normal subjects. For both the short and long series, the spectral components, very low frequency, (VLF), low frequency (LF), and high frequency (HF), and time-domain indices (such as the Ewing statistic [PNN50] and RR standard deviation [SD-RR]), have been estimated. The spectral components LF and HF, estimated from the short and long series, were not significantly different, whereas significant differences were found between VLF, SD--RR, and PNN50. In both the short and long series, a strong correlation was found between LF and SD-RR and between HF and PNN50. The results suggest that, over a period of 24 hours, hourly LF and HF spectral components can be obtained using a single series of 512 beats every hour, with a great advantage over the evaluation of the mean hourly parameters. This method would be particularly useful in the study of circadian heart rate spectral analysis in Holter recordings with multiple artifacts or ectopic beats, and in general, when analysis of the entire 24-hour series is not feasible.