Mesenchymal Stromal Cells from the Epidermis and Dermis of Psoriasis Patients: Morphology, Immunophenotype, Differentiation Patterns, and Regulation of T Cell Proliferation.

Psoriasis is a skin disease characterized by hyperproliferation of keratinocytes and chronic inflammation. Mesenchymal stem/stromal cells (MSCs) exhibit an immunoregulatory function that can be altered in the skin of these patients. However, to date, the presence and functional capacity of MSCs in the dermis and epidermis of patients with psoriasis have not been fully established. In the present study, we evaluated the presence of MSCs in the skin of patients by obtaining adherent cells from the dermis and epidermis of lesional and nonlesional areas and characterizing them in a comparative manner with corresponding cells obtained from the dermis (HD-MSCs) and epidermis (HE-MSCs) of healthy donors. We determined whether the adherent cells had immunophenotypic profiles and differentiation potentials that were characteristic of MSCs. In addition, we analyzed their immunosuppression function by evaluating their capacity to decrease T cell proliferation. Our results indicate the presence of MSCs in the dermis and epidermis of healthy donors and patients with psoriasis; adherent cells from all skin sources exhibited MSC characteristics, such as expression of CD73, CD90, and CD105 markers and a lack of hematopoietic and endothelial marker expression. However, the cell populations obtained showed differences in differentiation potential toward adipogenic, osteogenic, and chondrogenic lineages. In addition, we observed a low MSC obtention frequency in nonlesional epidermal samples (NLE-MSCs), which also showed alterations in morphology and proliferation rate. Interestingly, MSCs from both the nonlesional dermis (NLD-MSCs) and lesional dermis (LD-MSCs) showed higher HLA class I antigen (HLA-I) expression than HD-MSCs. Moreover, NLD-MSCs showed a low T cell proliferation suppression capacity. In summary, this study demonstrates the presence of MSCs in the epidermis and dermis of patients with psoriasis and suggests that such cells may favor the inflammatory process and thus psoriatic lesion development through high HLA-I expression and low immunosuppression capacity.

Human mesenchymal stromal cells from adult and neonatal sources: comparative analysis of their morphology, immunophenotype, differentiation patterns and neural protein expression.

BACKGROUND: Bone marrow (BM) has been recognized as the main source of mesenchymal stromal cells (MSC); however, MSC have also been detected in umbilical cord blood (UCB) and placenta (PL). In the present study, we obtained MSC from these three sources and characterized them in a comparative manner. METHODS: MSC were obtained from BM, UCB and PL samples and analyzed to determine their morphology, cell-surface antigen (Ag) expression and differentiation potential. Particular emphasis was placed on the expression of neural markers. RESULTS: MSC were detected in 9/9, 11/104 and 5/5 samples from BM, UCB and PL, respectively. MSC populations comprised several morphologically distinct cell types, including neural-like cells. MSC were positive for 'mesenchymal' Ag (CD105, CD73 and CD90), although CD90 expression was very heterogeneous. Interestingly, CD13 expression was high in all three sources. In all cases, MSC showed osteogenic and chondrogenic differentiation; however, UCB MSC showed no adipogenic potential. Furthermore, MSC from UCB produced a different type of cartilage compared with MSC from BM and PL. It is noteworthy that in all three sources we detected the expression of neural proteins without any neural differentiation stimuli. A significant increase in the proportion of neural marker-positive MSC was observed in the presence of neural inducers. DISCUSSION: Our results indicate that PL may prove to be a more appropriate source for obtaining MSC than UCB, and suggest the possibility that a subpopulation of MSC may possess neural potential, which is favored by neural inducers.

Copper complexes with heterocyclic sulfonamides: synthesis, spectroscopic characterization, microbiological and SOD-like activities: crystal structure of [Cu(sulfisoxazole)2(H2O)4] . 2H2O.

The synthesis, characterization and comparative biological study of a series of antibacterial copper complexes with heterocyclic sulfonamides were reported. Two kinds of complexes were obtained with the stoichiometries [Cu(L)2] . H2O and [Cu(L)2(H2O)4] . nH2O. They were characterized by infrared and electronic spectroscopies and the crystal structure of [Cu(sulfisoxazole)2(H2O)4] . 2H2O was determined by single crystal X-ray diffraction. It crystallized in the C2/c with Z = 8 monoclinic space group C2/c with Z = 8. The Cu(II) is in a slightly tetragonal distorted octahedron formed by four oxygen atoms from water molecules and two nitrogen atoms from two isoxazole rings. The antimicrobial activity was evaluated for all the synthesized complexes and ligands using the agar dilution test. The results showed that the complexes with five-membered heterocyclic rings were more active than the free sulfonamides while the pyrimidine, pyridine and pyridazine complexes had similar or less activity than the free ligands. In order to find an explanation for this behavior lipophilicity and superoxide dismutase-like activity were tested, showing that the [Cu(sulfamethoxazol)2(H2O)4] . 3H2O presented the highest antimicrobial potency and a superoxide dismutase-like activity comparable with pharmacological active compounds.

Validación de la prueba nacional de pesquisa de trastornos de desarrollo psicomotor en niños menores de 6 años / Validation for screening test of detecting psychomotor development problems in children under six

Introducción. El uso de una prueba de pesquisa en los primeros años de vida permite la detección temprana de retrasos en el desarrollo psicomotor y su tratamiento oportuno. En la Argentina contamos con una Prueba Nacional de Pesquisa preparada en base a un estudio nacional. El objetivo del trabajo fue validar la prueba, comparando sus resultados con evaluaciones diagnósticas, realizadas en forma simultánea por varios servicios del Hospital Garrahan. Pacientes y métodos. Se seleccionó una muestra de 106 niños de 0 a 5,99 años que concurrían al área de bajo riesgo del Hospital. Se realizaron los siguientes estudios diagnósticos: evaluación del desarrollo psicomotor (Bayley II), examen neurológico, salud mental, coeficiente intelectual (Wechsler, Terman), conducta adaptativa (Vineland), lenguaje (prueba de Gardner receptiva y expresiva, ITPA), audición (emisiones otoacústicas, audiometría tonal, PEAT), examen visual. Se utilizó el DSM-IV como referencia de trastornos del desarrollo. Se evaluó la sensibilidad y especificidad obtenidas según la aplicación de diferentes puntos de corte (número de ítems fracasados). Resultados. El mejor punto de corte se estableció en un ítem tipo A o 2 tipo B, con una sensibilidad del 80%, especificidad: 93%, valor predictivo positivo: 94%, valor predictivo negativo: 77%, porcentaje de coincidencia: 85%. Fue inesperada la elevada prevalencia de problemas de desarrollo encontrada en la muestra: 57%. La prueba es capaz de detectar problemas en las cuatro áreas del desarrollo, incluidos trastornos del lenguaje. Conclusión. Los resultados confirman a la Prueba Nacional de Pesquisa como un instrumento válido para ser usado en el primer nivel de atención para el reconocimiento de niños con sospecha de sufrir trastornos del desarrollo. Asimismo, el trabajo de información permite establecer diferentes puntos de corte y constituye un instrumento útil para su aplicación en la práctica pediátrica.

The use of a screening test in the first years of life allows the early detection of delays of psychomotor development and its treatment, thus contributing to improve the prognosis of the child with special needs. In Argentina, a screening test for detecting developmental problems in children under 6, made with local children and data is available (PRUNAPE). A validation procedure for this test was carried out on 106 children attending at low risk outpatient clinic in Hospital Garrahan. The test was administered to the children together with a battery of diagnostic examinations and studies, performed by experienced specialists from different Hospital services: psychomotor development, neurology examination, mental health, intellectual quotient (Wechsler, Terman), adaptive behaviour (Vineland), language (Gardner expressive and receptive, ITPA), hearing (otoacustic emissions, audiometry, BERA), vision. The DSM ­IV was used as a reference for developmental problems. Using as a failure criterion to the PRUNAPE, the failure of performing correctly one type A item or two type B item, sensitivity of the test was 80%, specificity, 93%; positive predictive value, 95%; negative predictive value, 77%; overall agreement, 85%. A very high prevalence of developmental problems was found: 57%. PRUNAPE was found to be capable of detecting a wide range of problems. These results confirm PRUNAPE as a valuable instrument for early detection of developmental problems in paediatric practice at the primary care level.

Prevalence of erectile dysfunction in Colombia, Ecuador, and Venezuela: a population-based study (DENSA).

The purpose of this study was to estimate the prevalence of erectile dysfunction (ED) in Colombia, Ecuador, and Venezuela. A 49-item questionnaire was completed by 1946 men aged 40 years and older. The age-adjusted combined prevalence of minimal, moderate, and complete ED for all three countries was 53.4%, with 19.8% of all men reporting moderate to complete ED. Age was the variable most strongly linked to ED; the prevalence of complete ED increased markedly in men older than 79 y of age (31.9%) and 70-79 y (17.2%) compared with men aged 40-49 y (<3%). Several medical conditions, such as hypertension, benign prostatic hyperplasia, and diabetes, and the use of medications to treat these conditions were correlated with the prevalence of ED. This study corroborates earlier studies demonstrating that ED is very common, increases dramatically with age, and has multiple correlates, including some that are also risk factors for cardiovascular disease.

[High altitude anemia: validity of definition criteria]. / Anémie en altitude: validité du critère de définition.

The effect of iron and folate supplementation on the hemoglobin response and iron status was studied in male and female equatorian medical students: 66 in Quito (2,800 m altitude) and 40 in Guayaquil (sea level). At the end of the supplementation, there was a nearly complete disappearance of biochemical evidence of iron deficiency in the two groups of students. In Quito, 30% of the men and 26% of the women increased their hemoglobin concentration by more than 1 g/dl after one month of supplementation and could be considered as true anemics, compared to 31% of the men and 29% of the women in Guayaquil. This study shows that at sea level, cut-off points defined by WHO for hemoglobin, taking as reference the impact of a supplementation trial, have a specificity of 100% but poor sensitivity (58%). For people living at high altitudes, cut-off limits adjusted for altitude seem unsuitable: the specificity is 98% but the sensitivity is 0%. Studies taking into account all the factors impacting on the hemoglobin level could be useful for defining cut-off points for high-altitude anemia better than those currently recommended.

Evaluación de la deficiencia de hierro y anemia ferropriva en poblacion de alto Riesgo

La evaluación de la deficiencia de hierro en población de alto riesgo puede lograrse a través de la selección cuidadosa de diversos indicadores bioquímicos, y hematológicos, que traduzcan adecuadamente los diferentes estadíos de su evolución: 1) deficiencia de las reservas corporales o IDS a travéz de la ferritina sérica 2) aporte medular de hierro deficiente o IDE mediante la dosificación de protoporfirina eritrocitaria, porcentaje de saturación de la trasnferina y receptores de la transferrina, y 3) anemia ferropriva, estimada por la cuantificación de la hemoglobina o el hematocrito. El objetivo que se proponga en la evaluación, permitirá seleccionar adecuadamente el o los indicadores para estimar el status de hierro de la población blanco. La sensibilidad y especificidad de estos es un aspecto importante a considerar, al igual que la magnitud de la carencia marcial y la concurrencia simultánea de otros factores de confusión como; hemoglobinopatías, malaria, infección, etc.

Estimación de la frecuencia de anemias nutricionales mediante un ensayo de suplementa con hierro y folatos en sujetos adultos que viven en adulto (2.800 m)

El efecto de la suplementación con una asociación de hierro y folatos sobre el estdo hematoyético y el status en hierro fue estudiado en 66 estudiantes de los dos sexos residentes en Quito (2800 m. de altitud y 40 estudiantes de la ciudad de Guayaquil (a nivel del mar). Después de un mes de suplementación, se observó la desaparición casi completa de los estigmas bioquímicos de la carencia en hierro en los estudientes de las dos ciudades. La anemia definida en función del incremento de la tasa de hemoglobina superior a 1 g/dl se observó en el 30% de los varones y en el 26% de las mujeres residentes en Quito y en el 31% y 29% respectivamente de los residentes en Guayaquil. Este estudio pone en evidencia que los límites de referencia de la hemoglobina propuestos por la O,M.S. para poblaciones asentadas a nivel del mar, tienen una buena especificidad, pero carecen de sensibilidad: 12.5% de los sujetos estudiados fueron considerados como normales siendo realmente anémicos, como lo demuestra el efecto de a suplementación. Para los sujetos que viven en altitud, los límites de referncia ajustados para la altitud correspondiente son totalmente inadecuados: todos los individuos anémicos fueron mal clasificados

Nuevo indicador de la carencia de hierro: relación hemoglobina y protoporfirina eritrocitaria

La protoporfirna es metabolismo indispensable en al síntesis del HEM, pues su presencia hace posible que el hierro en estado ferroso se incorpore en su interior mediante la acción catalítica de una enzima mitrocondrial denominada ferroquetalasa o hem sintetasa y finalmente formarse el Hem. Este hecho puede alterarse ya sea, por un estado deficitário en hierro en forma crónica o por acumulación anormal de plomo. El estudio se realiza en 199 personas de la zona rural de Sto. Domingo de los Colorados, integrado por 87 hombres (43.72%) y 112 mujeres (56.28%). Los resultados nos permiten inferir la existencia de un estado deficitario de este mineral son: niños en crecimiento rápido (lactantes, preescolares y escolares), mujeres en edad fértil y mujeres embarazadas (no consideradas en este trabajo). En este presente estudio aproximadamente el 90% de las personas pertencientes a estos grupos señalados presentan algún trastorno relacionado con el metabolismo del hierro, definido por una disminución en la concentración sanguínea de hemoglobina y un aumento en la concentración de protoporfirina eritrocitaria. Con el presente estudio pretendemos insistir en el uso de indicadores adecuados y técnicas de laboratório fáciles y fiables para determinar el estado de hierro en el organismo

Iron status in Ecuadorian pregnant women living at 2,800 m altitude: relationship with infant iron status.

An evaluation of iron status was performed in 84 pregnant women at delivery (and in cord blood from their newborn) and in a control group of 32 menstruating women living in Quito (2800 m altitude). Anemia as defined according to the WHO references adjusted to altitude was observed in 46% of pregnant women. Iron deficiency was defined as the combination of a low serum ferritin level (12 micrograms/l or less) and a low transferrin saturation percentage (less than 16%). A moderate elevation in the serum ferritin concentration (between 13 and 50 micrograms/l) associated with low transferrin saturation indicated iron deficiency in an inflammatory context. Iron deficiency was present in 46% of pregnant women. Anemia was associated with iron deficiency in 59% of cases. A correlation between maternal and cord blood hemoglobin was found and some iron parameters in cord blood were related to maternal iron status, and especially to maternal iron stores assessed by serum ferritin concentration.

[Neurohumoral control of the pineal gland. A model for the study of neuroendocrine integrative processes]. / Control neurohumoral de la glándula pineal. Un modelo para el estudio de procesos integrativos neuroendócrinos.

This article discusses the experimental evidence which suggests that the pineal gland and its innervating neurons are useful paradigms for the study of neuroendocrine integrative processes. The obtained results can be summarized as follows: 1) existence of putative receptors for various hormones (estradiol, testosterone, 5 alpha-dihydrotestosterone, progesterone, prolactin) in the mammalian pineal gland; (2) steroid metabolic pattern in the pineal gland resembling other brain areas involved in gonadotrophic regulation; (3) control of pineal estrophilic and androphilic receptors by adrenergic transmitter through beta-adrenergic receptors and at a translational level; (4) denervation supersensitivity of hormone receptors to neurotransmitter; (5) modification of neuronal activity by hormone treatment at ganglionic and preganglionic sites of action; (6) estrophilic binding sites in ganglia; (7) correlation of pineal responsiveness to hormones with activity of sympathetic nerves; (8) modification by hormones of pineal beta-adrenergic mechanisms; (9) dissociation of hormone effects on the pineal gland in those mediated or modulated by changes in afferent neuronal activity and those relatively unaffected by denervation. Collectively these data indicate that neuroendocrine, endocrine-neural and endocrine-endocrine transducing processes occur in the pinealocytes and superior cervical ganglia.

Control neurohumoral de la glándula pineal. Un modelo para el estudio de procesos integrativos neuroendócrinos. / [Neurohumoral control of the pineal gland. A model for the study of neuroendocrine integrative processes]

This article discusses the experimental evidence which suggests that the pineal gland and its innervating neurons are useful paradigms for the study of neuroendocrine integrative processes. The obtained results can be summarized as follows: 1) existence of putative receptors for various hormones (estradiol, testosterone, 5 alpha-dihydrotestosterone, progesterone, prolactin) in the mammalian pineal gland; (2) steroid metabolic pattern in the pineal gland resembling other brain areas involved in gonadotrophic regulation; (3) control of pineal estrophilic and androphilic receptors by adrenergic transmitter through beta-adrenergic receptors and at a translational level; (4) denervation supersensitivity of hormone receptors to neurotransmitter; (5) modification of neuronal activity by hormone treatment at ganglionic and preganglionic sites of action; (6) estrophilic binding sites in ganglia; (7) correlation of pineal responsiveness to hormones with activity of sympathetic nerves; (8) modification by hormones of pineal beta-adrenergic mechanisms; (9) dissociation of hormone effects on the pineal gland in those mediated or modulated by changes in afferent neuronal activity and those relatively unaffected by denervation. Collectively these data indicate that neuroendocrine, endocrine-neural and endocrine-endocrine transducing processes occur in the pinealocytes and superior cervical ganglia.

Control neurohumoral de la glándula pineal. Un modelo para el estudio de procesos integrativos neuroendócrinos / [Neurohumoral control of the pineal gland. A model for the study of neuroendocrine integrative processes]

This article discusses the experimental evidence which suggests that the pineal gland and its innervating neurons are useful paradigms for the study of neuroendocrine integrative processes. The obtained results can be summarized as follows: 1) existence of putative receptors for various hormones (estradiol, testosterone, 5 alpha-dihydrotestosterone, progesterone, prolactin) in the mammalian pineal gland; (2) steroid metabolic pattern in the pineal gland resembling other brain areas involved in gonadotrophic regulation; (3) control of pineal estrophilic and androphilic receptors by adrenergic transmitter through beta-adrenergic receptors and at a translational level; (4) denervation supersensitivity of hormone receptors to neurotransmitter; (5) modification of neuronal activity by hormone treatment at ganglionic and preganglionic sites of action; (6) estrophilic binding sites in ganglia; (7) correlation of pineal responsiveness to hormones with activity of sympathetic nerves; (8) modification by hormones of pineal beta-adrenergic mechanisms; (9) dissociation of hormone effects on the pineal gland in those mediated or modulated by changes in afferent neuronal activity and those relatively unaffected by denervation. Collectively these data indicate that neuroendocrine, endocrine-neural and endocrine-endocrine transducing processes occur in the pinealocytes and superior cervical ganglia.