[Video-assisted thoracoscopic treatment for two ports for idiopathic palmar and axillary hyperhidrosis in children]. / Tratamiento videotoracoscópico por dos puertos para la hiperhidrosis palmar y axilar idiopática en el niño.

JUSTIFICATION: Primary hyperhidrosis is a benign disease that consists in the excessive production of sweat, mainly in the hands, axillas and feet. It may to interfere with the social and work life of the sufferer. It affects up to 3% of the population. In Cuba there are no epidemiological studies on its prevalence. One of the treatment modalities is videothoracoscopic sympathicotomy. OBJECTIVES: To describe the results of the videothoracoscopic sympathicotomy technique for two ports using apneic oxygenation to achieve lung collapse. METHOD: Descriptive, retrospective study of 27 cases operated by primary hyperhidrosis in the period from May 2015 to June 2018. Demographic and clinical characteristics of operated patients, results of the endoscopic surgical technique, postoperative complications and satisfaction were described. RESULTS: The 27 patients were adolescents with ages ranging from 11 to 19 years old, it was more frequent in the female sex. All patients had total solution of the symptoms in the intraoperative period, demonstrated by the cessation of sweat in the palms or axillas and by the verification of the increase of the palmar temperature in the monitor. No patient had intraoperative complications. Compensatory sweating occurred in four patients and one had intercostal neuritis. 100% of the patients were satisfied with the result at 30 days of treatment. CONCLUSIONS: It is a safe technique, with few complications, high satisfaction with the results and feasible to perform in pediatric hospitals with basic resources of minimal access surgery.

FUNDAMENTACION: La hiperhidrosis primaria es una enfermedad benigna que consiste en la excesiva producción de sudor, principalmente en manos, axilas y pies, y por ello puede llegar a condicionar la vida social y laboral de quien la padece. Afecta hasta el 3% de la población. En Cuba no hay estudios epidemiológicos sobre su prevalencia. Una de las modalidades de tratamiento es la simpaticotomía videotoracoscópica. OBJETIVOS: Describir los resultados de la técnica de simpaticotomía videotoracoscópica por dos puertos usando oxigenación apneica para lograr el colapso pulmonar. METODO: Estudio descriptivo, retrospectivo, de una serie de 27 casos operados por hiperhidrosis primaria en el periodo de mayo de 2015 a junio de 2018. Se describen características demográficas y clínicas de pacientes operados, resultados de la técnica quirúrgica endoscópica, complicaciones postoperatorias y satisfacción. RESULTADOS: Los 27 pacientes eran adolescentes con edades comprendidas entre 11 y 19 años, siendo más frecuente en el sexo femenino. Todos los pacientes tuvieron solución total de los síntomas en el periodo intraoperatorio, demostrados por el cese del sudor en palmas o axilas y por la comprobación del aumento de la temperatura palmar en el monitor. Ningún paciente tuvo complicaciones intraoperatorias. El sudor compensatorio se presentó en cuatro pacientes y un paciente tuvo neuritis intercostal. El 100% de los pacientes estuvieron satisfechos con el resultado a los 30 días del tratamiento. CONCLUSIONES: Es una técnica segura, con pocas complicaciones, elevada satisfacción con los resultados y factible de realizar en hospitales pediátricos con recursos básicos de cirugía de mínimo acceso.

The Alzheimer-related gene presenilin-1 facilitates sonic hedgehog expression in Xenopus primary neurogenesis.

We analyzed the influence of presenilins on the genetic cascades that control neuronal differentiation in Xenopus embryos. Resembling sonic hedgehog (shh) overexpression, presenilin mRNA injection reduced the number of N-tubulin+ primary neurons and modulated Gli3 and Zic2 according to their roles in activating and repressing primary neurogenesis, respectively. Presenilin increased shh expression within its normal domain, mainly in the floor plate, whereas an antisense X-presenilin-alpha morpholino oligonucleotide reduced shh expression. Both shh and presenilin promoted cell proliferation and apoptosis, but the effects of shh were widely distributed, while those resulting from presenilin injection coincided with the range of shh signaling. We suggest that presenilin may modulate primary neurogenesis, proliferation, and apoptosis in the neural plate, through the enhancement of shh signaling.

Nitric oxide mediates the inhibitory effect of tumor necrosis factor-alpha on prolactin release.

Tumor necrosis factor-alpha (TNF-alpha) is a pleiotropic cytokine that markedly affects neuroendocrine functions. This cytokine is expressed in the anterior pituitary where its receptors are also present. Nitric oxide (NO) is synthesized in gonadotropes and folliculo-stellate cells of the anterior pituitary. Since NO directly inhibits prolactin secretion, we investigated the involvement of NO in the inhibitory effect of TNF-alpha on prolactin release from anterior pituitary cells of female rats. The presence of L-NAME (1 mM), an inhibitor of NO synthase (NOS), in the incubation medium significantly blunted the inhibition of prolactin release produced by TNF-alpha (50 ng/ml). TNF-alpha increased nitrite release to the incubation medium. The activity of NOS as measured by [(14)C]citrulline production was significantly enhanced when anterior pituitary cells were incubated with TNF-alpha for 8 h or more. Also, TNF-alpha induced iNOS gene expression in anterior pituitary cells as assessed by reverse transcriptase-polymerase chain reaction. The current results indicate that NO is involved in the inhibitory effect of TNF-alpha on prolactin secretion and that TNF-alpha induces iNOS transcription and stimulates NO synthesis in anterior pituitary cells.

Functional association of retinoic acid and hedgehog signaling in Xenopus primary neurogenesis.

Previous work has shown that the posteriorising agent retinoic acid can accelerate anterior neuronal differentiation in Xenopus laevis embryos (Papalopulu, N. and Kintner, C. (1996) Development 122, 3409-3418). To elucidate the role of retinoic acid in the primary neurogenesis cascade, we investigated whether retinoic acid treatment of whole embryos could change the spatial expression of a set of genes known to be involved in neurogenesis. We show that retinoic acid expands the N-tubulin, X-ngnr-1, X-MyT1, X-&Dgr;-1 and Gli3 domains and inhibits the expression of Zic2 and sonic hedgehog in the neural ectoderm, whereas a retinoid antagonist produces opposite changes. In contrast, sonic and banded hedgehog overexpression reduced the N-tubulin stripes, enlarged the neural plate at the expense of the neural crest, downregulated Gli3 and upregulated Zic2. Thus, retinoic acid and hedgehog signaling have opposite effects on the prepattern genes Gli3 and Zic2 and on other genes acting downstream in the neurogenesis cascade. In addition, retinoic acid cannot rescue the inhibitory effect of Notch(ICD), Zic2 or sonic hedgehog on primary neurogenesis. Our results suggest that retinoic acid acts very early, upstream of sonic hedgehog, and we propose a model for regulation of differentiation and proliferation in the neural plate, showing that retinoic acid might be activating primary neurogenesis by repressing sonic hedgehog expression.

Differential effects of retinoic acid and a retinoid antagonist on the spatial distribution of the homeoprotein Hoxb-7 in vertebrate embryos.

An antibody raised against the recombinant Xenopus laevis Hoxb-7 protein (López and Carrasco [1992] Mech. Dev. 36:153-164) recognizes the 30 kDa translation product of the Hoxb-7 gene in X. laevis and the cognate nuclear protein in chicken embryos. The X. laevis Hoxb-7 protein was expressed maternally and zygotically. Treatment of X. laevis and chicken embryos with either all-trans retinoic acid (RA) or the retinoid antagonist Ro 41-5253 (Ro; Apfel et al. [1992] Proc. Natl. Acad. Sci. U.S.A. 89:7129-7133) during early development induced malformations of the neural tube and complementary changes in the expression domain of the homeoprotein Hoxb-7. Treatment of X. laevis embryos with retinoic acid during gastrulation induced an anterior shift of the Hoxb-7 expression domain and was correlated with an enlargement of rhombomere r7. In addition to a reduction in rhombomere numbers and of forebrain size, various malformations involving all three germ layers were observed. Treatment of X. laevis embryos with the antagonist Ro before or during gastrulation caused a progressive reduction of the Hoxb-7 domain and also dose-dependent malformations of all three germ layers. RA or Ro treatment of chicken embryos from the beginning of gastrulation caused changes of the Hoxb-7 expression domain very similar to those observed in X. laevis. In particular, either a dose-dependent loss of the Hoxb-7 protein in the neural tube or an ectopic expression in the forebrain region was observed. The results of this study indicate that endogenous retinoids regulate the spatial expression of homeobox-containing genes in vertebrates.

The puzzle of Hox genes.

During the last few years, the regionalization of the rostral-caudal axis has been extensively studied through treatments with RA and genetic manipulations of Hox-C genes. RA shifts several Hox expression boundaries rostrally, deletes anterior rhombomeres but expands the caudal ones, and induces homeotic transformations in the vertebral column. These phenotypes indicate that retinoids may act in a graded fashion in the A-P axis, with maximum activity caudally. This excludes forebrain and midbrain, which apparently depend on neither Hox-C genes nor RA modulations, at least during early development. The phenotypes resulting from ectopic overexpression and loss of function of Hox genes described so far show homeotic transformations in paraxial mesoderm derivatives but not in the neurectoderm. An explanation for this discrepancy implies that the paraxial mesoderm may be already segmented in molecular terms at the time of Hox activation. Conversely, the activation of a distinct Hox-code without a previous "molecular segmentation" may specify rhombomeres with their own boundaries. This would explain why RA expands but does not duplicate the postotic rhombomeres. Finally, the atavistic transformations obtained by overexpressing Hox genes in the wrong place suggest that evolution might be introducing modifications within Hox regulatory regions. Thus, changes in their expression domains could sustain phylogenetic requirements.

Retinoic acid induces changes in the localization of homeobox proteins in the antero-posterior axis of Xenopus laevis embryos.

We have studied the localization of the proteins of Xeb1 and Xeb2, two homeobox (hbx)-containing genes that are expressed during the early development of Xenopus laevis. Both proteins are expressed in juxtaposed and partially overlapping domains along the antero-posterior axis of Xenopus laevis embryos, with clearly defined anterior boundaries. Xeb2 is predominantly expressed in the caudal region of the hindbrain, whereas the Xeb1 protein is located in the most rostral region of the spinal cord. Furthermore, both proteins are expressed in single cells dispersed in the lateral flanks of the embryo in positions that correlate with the expression domains in the neural tube. We suggest that these cells are migratory neural crest cells that have acquired positional information in the neural tube prior to migration. The Xeb2 protein was also detected in the most posterior branchial arches and the pronephros. In stage 45 embryos, nuclei of the IX-X cranial ganglia, the lung buds and cells spreading into the forelimb rudiment express the Xeb2 antigen. The Xeb1 protein was also detected in the lung buds and the forelimb rudiment. To examine the effect of retinoic acid on expression, gastrula embryos were treated with all-trans retinoic acid (RA). Increasing concentrations of RA caused progressive truncation of anterior structures. The most severely affected embryos lacked eyes, nasal pits, forebrain, midbrain and otic vesicles, and the anterior boundary of the hindbrain seemed to be displaced rostrally. This alteration correlates with a progressive displacement of the anterior boundary of the expression domain of Xeb2. On the other hand, 10(-6) M RA induces an ectopic site of Xeb1 expression at the anterior end of the central nervous system, located just anterior to the extended domain of Xeb2 whereas expression in the spinal cord remains unaffected.