Alternativas terapéuticas de reciente desarrollo en la dermatitis atópica

La dermatitis atópica es una dermatopatía de gran importancia en la especie canina por la frecuencia de presentación. Una vez que debuta en el paciente, sabemos que le va a acompañar durante toda su vida en forma de proceso inflamatorio crónico con diferentes grados de prurito y lesiones cutáneas. El abordaje terapéutico es complejo ya que se deben tener en cuenta diferentes factores como la alimentación, el hábitat del animal, la estación del año, la edad y la raza del paciente, o la forma clínica. El éxito del control de la dermatitis atópica canina se considera un verdadero arte clínico porque será el resultado de una combinación de terapia tópica y sistémica muy adaptada a cada uno de los individuos y sus circunstancias ambientales. En los últimos años se ha investigado en el desarrollo de nuevas moléculas, como es el caso de oclacitinib, un inhibidor selectivo de las JAK o el lokivetmab que es un tratamiento monoclonal. Estas moléculas suponen una alternativa con muchas ventajas frente a los corticosteroides, que han sido las drogas base de la terapia para la mayoría de los pacientes hasta hace escasos años

Plan de mejora para la promoción de la donación de médula ósea

El trasplante de médula ósea es un recurso terapéutico empleado para sustituir la médula ósea dañada por células madre de médula ósea sana. Tan solo 1 de cada 4 pacientes que precisa un trasplante de progenitores hematopoyéticos dispone de un donante familiar compatible. Por ello el 70% de los pacientes necesitan recurrir a los donantes voluntarios inscritos en los registros internacionales de donantes. Las probabilidades de compatibilidad entre personas no emparentadas son muy bajas, aproximadamente 1 entre 4.000. Por esta razón se debe promover la donación de progenitores hematopoyéticos y para conseguirlo es imprescindible proporcionar información adecuada a la población.<br /

Reduced nicotinamide adenine dinucleotide phosphate‐diaphorase/nitric oxide synthase profiles in the human hippocampal formation and perirhinal cortex

Nicotinamide adenine dinucleotide phosphate‐diaphorase (NADPH‐d)‐stained profiles were evaluated throughout the human hippocampal formation (i. e., dentate gyrus, Ammon\u27s horn, subicular complex, entorhinal cortex) and perirhinal cortex. NADPH‐d staining revealed pleomorphic cells, fibers, and blood vessels. Within the entorhinal and the perirhinal cortices, darkly stained (type 1) NADPH‐d pyramidal, fusiform, bipolar, and multipolar neurons with extensive dendrites were scattered mainly within deep layers and subjacent white matter. Moderately stained (type 2) NADPH‐d round or oval neurons were seen mainly in layers II and III of the entorhinal and perirhinal cortices, in the dentate gyrus polymorphic layer, in the CA fields stratum pyramidal and radiatum, and in the subicular complex. The distribution of type 2 cells was more abundant in the perirhinal cortex compared to the hippocampal formation. Lightly stained (type 3) NADPH‐d pyramidal and oval neurons were distributed in CA4, the entorhinal cortex medial subfields, and the amygdalohippocampal transition area. Sections concurrently stained for NADPH‐d and nitric oxide synthase (NOS) revealed that all type 1 neurons coexpressed NOS, whereas types 2 and 3 were NOS immunonegative. NADPH‐d fibers were heterogeneously distributed within the different regions examined and were frequently in close apposition to reactive blood vessels. The greatest concentration of fibers was in layers III and V–VI of the entorhinal and perirhinal cortices, dentate gyrus polymorphic and molecular layers, and CA1 and CA4. A band of fibers coursing within CA1 divided into dorsal and ventral bundles to reach the presubiculum and entorhinal cortex, respectively. Although the distribution of NADPH‐d fibers was conserved across all ages examined (28–98 years), we observed an increase in the density of fiber staining in the aged cases. These results may be relevant to our understanding of selective vulnerability of neuronal systems within the human hippocampal formation in aging and in neurodegenerative diseases. © 1995 Wiley‐Liss, Inc. Copyright © 1995 Wiley‐Liss, Inc

Retrograde transport of brain-derived neurotrophic factor (BDNF) following infusion in neo- and limbic cortex in rat: Relationship to BDNF mRNA expressing neurons

Brain-derived neurotrophic factor (BDNF) was the second member of the nerve growth factor (NGF) family to be isolated. The ability of BDNF to be retrogradely transported following intraparenchymal infusion represents a unique neurobiological tool to determine the location of putative neuron- specific BDNF-responsive neuronal systems. In the present study, we infused recombinant human (rh) BDNF into the rodent neo- and limbic cortex and used a turkey anti-BDNF antibody to determine specific populations of neurons which retrogradely transport this neurotrophin. Frontal cortex infusion retrogradely labeled neurons within the ipsilateral and contralateral frontal cortex, basal forebrain, lateral hypothalamus, centrolateral, mediodorsal, ventrolateral, ventromedial, ventral posterior, rhomboid, reuniens, and medial geniculate thalamic nuclei, and locus coeruleus. Occipital cortex infusion retrogradely labeled neurons in the frontal, temporal, occipital, and perirhinal cortices as well as the claustrum, basal forebrain, thalamus, epithalamus, hypothalamus, and raphe nuclei. Dorsal hippocampal infusion retrogradely labeled neurons within the septal diagonal band, supramammillary nucleus, and entorhinal cortex and was also transported within various hippocampal subfields. Entorhinal cortex infusion retrogradely labeled neurons within the perirhinal cortex, endopiriform nucleus, piriform cortex, dentate gyrus, presubiculum, parasubiculum, CA1-CA4 fields, amygdaloid nuclei, basal forebrain, thalamus, hypothalamus, periaqueductal gray, raphe nuclei, and locus coeruleus. Amygdala infusion labeled neurons in the endopiriform nucleus, temporal cortex, piriform cortex, paralimbic cortex, hippocampus, subiculum, entorhinal cortex, amygdala, basal forebrain, thalamus, hypothalamus, substantia nigra, pars compacta, raphe, and pontine parabrachial nuclei. In situ hybridization experiments demonstrated that virtually all areas which retrogradely transport BDNF also express its message. Neuroanatomical distributional studies of BDNF will unravel specific central nervous system neurotrophic-responsive systems

Distribution and retrograde transport of trophic factors in the central nervous system: Functional implications for the treatment of neurodegenerative diseases

Neurotrophins play a crucial role in the maintenance, survival and selective vulnerability of various neuronal populations within the normal and diseased brain. Several families of growth promoting substances have been identified within the central nervous system (CNS) including the superfamily of nerve growth factor related neurotrophin factors, glial derived neurotrophic factor (GDNF) and ciliary neurotrophic factor (CNTF). In addition, other non-neuronal growth factors such as fibroblast growth factor (FGF) have also been identified. This article reviews the trophic anatomy of these factors within the CNS. Intraventricular and intraparenchymal injections of exogenous nerve growth factor result in retrograde labeling mainly within the cholinergic basal forebrain. Distribution of brain derived neurotrophic factor (BDNF) following intraventricular injection is minimal due to the binding to the trkB receptor along the ventricular wall. In contrast, intraparenchymal injections of BDNF results in widespread retrograde transport throughout the CNS. BDNF has also been shown to be transported anterogradely within the CNS. Infusion of GDNF into the CNS results in retrograde transport limited to the nigrostriatal pathway. Hippocampal injections of NT-3 retrogradely label mainly basal forebrain neurons. Retrograde transport of radiolabeled CNTF has only been observed in sensory neurons of the sciatic nerve. Following intraventricular and intraparenchymal infusion of radiolabeled bFGF, retrograde neuronal labeling was found in the telecephalon, diencephalon, mesencephalon and pons. In contrast retrograde labeling for aFGF was found only in the hypothalamus and midbrain. Since select neurotrophins traffic anterogradely and retrogradely within the nervous system, these proteins could be used to treat neurological diseases such as Alzheimer\u27s disease, Parkinson\u27s disease and amyotrophic lateral sclerosis

Apo E polymorphism associates with body fatness independently of plasma lipids in middle age men -the aragon workers health study

Background: The apolipoprotein E (APOE) gene is polymorphic, encoding one of 3 common alleles (e2, e3, e4) produced from combinations of 2 non-synonymous SNPs (rs429358 and rs7412). APOE plays an important role controlling plasma lipids but its association with adipocyte functionality and body fatness remains to be determined. Methods: We analyzed fasting plasma lipids and genotyped the two main APOE-SNPs (rs429358 and rs7412), both located in the fourth exon of the APOE, in 4660 Caucasian middle-aged men free of cardiovascular disease. Results: The rs7412 SNP, which determines the APOE2 isoform, was significantly associated with Body Mass Index (BMI) and Waist Girth (WG) in a multivariate model accounting for age, smoking status and plasma lipids. BMI and WG were highest in TT homozygotes and lowest in CC homozygotes. This effect was independent of the rs429358 SNP, which failed to show any association with the BMI and WG variables. The odds ratio of being obese (BMI.30) for individuals carrying the APOe2 allele, present in 14% of the cohort and defined by the rs7412 SNP, was also significant in this multivariate model, with an OR of 1.27 (95% CI: 1.01–1.59). Conclusions: This study provides an evidence of a lipid-independent association between the APOE SNP rs7412 and body fatness surrogates, BMI and WG, in a large cohort of middle-aged males

Cholinergic innervation in the human hippocampal formation including the entorhinal cortex

The cholinergic innervation of the hippocampal formation is thought to play an important role in memory processes, but its organization in humans has not been described in detail. We studied the cholinergic innervation of the human hippocampal formation by means of immunohistochemistry with polyclonal antisera directed against acetyleholinesterase (AChE), choline acetyltransferase (ChAT), and the low‐affinity (p75) nerve growth factor receptor (NGFR). The density of ChAT‐like immunoreactive (ChAT‐li) fibers differed substantially among the various regions, in general paralleling the pattern of AChE‐li staining. One notable exception was the presence of AChE‐li cell bodies. In contrast, ChAT immunoreactivity was associated only with fibers and terminals. NGFR‐li staining corresponded closely to the ChAT‐li fiber pattern. ChAT‐li fibers in the CA fields diffusely filled the stratum pyramidale and extended into the stratum oriens and radiatum as well. The highest density was consistently observed in CA4 and CA3 subfields. Staining decreased from CA4 to CA1 and was substantially less dense in the subicular complex. In the entorhinal cortex, the ChAT‐ and NGFR‐li fiber innervation displayed a laminar pattern, most intense over the nests of cells in layer II. There was a trend towards an age‐related reduction in the density of ChAT‐ and AChE‐li fibers and terminals. Nonetheless, we also found a surprisingly conserved NGFR‐li innervation and the presence of occasional NGFR‐li pyramidal cells, providing evidence of a plastic response in the brains of the elderly patients.© 1994 Wiley‐Liss, Inc. Copyright © 1994 Wiley‐Liss, Inc

TrkA‐immunoreactive profiles in the central nervous system: Colocalization with neurons containing p75 nerve growth factor receptor, choline acetyltransferase, and serotonin

The present investigation used an antibody directed against the extracellular domain of the signal transducing nerve growth factor recepto, trkA, to reveal immunoreactive perikarya or fibers within the olfactory bulb and tubercle, cingulate cortex, nucleus accumbens, striatum, endopiriform nucleus, septal/diagonal band complex, nucleus basalis, hippocampal complex, thalamic paraventricular and reuniens nuclei, periventricular hypothalamus, interpeduncular nucleus, mesencephalic nucleus of the fifth nerve, dorsal nucleus of the lateral lemniscus, prepositus hypoglossal nucleus, ventral cochlear nucleus, ventral lateral tegmentum, medial vestibular nucleus, spinal trigeminal nucleus oralis, nucleus of the solitary tract, raphe nuclei, and spinal cord. Colocalization experiments revealed that virtually all striatal trk‐Aimmunoreactive neurons (\u3e 99%) coexpressed choline acetyltransferase (ChAT) but not p75 nerve growth factor receptor (NGFR). Within the septal/diagonal band complex virtually all trkA neurons (\u3e 95%) coexpressed both ChAT and p75 NGFR. More caudally, dual stained sections revealed numerous trkA/ChAT (\u3e 80%) and trkA/p75 NGFR (\u3e 95%) immunoreactive neurons within the nucleus basalis. In the brainstem, raphe serotonergic neurons (45%) coexpressed trkA. Sections stained with a pan‐trk antibody that recognizes primarily trkA, as well as trkB and trkC, labeled neurons within all of these regions as well as within the hypothalamic arcuate, supramammilary, and supraoptic nuclei, hippocampus, inferior and superior colliculus, substantia nigra, ventral tegmental area of T\u27sai, and cerebellar Purkinje cells. Virtually all of these other regions with the exception of the cerebellum also expressed pan‐trk immunoreactivity in the monkey. The widespread expression of trkA throughout the central neural axis suggests that this receptor may play a role in signal transduction mechanisms linked to NGF‐related substances in cholinergic basal forebrain and noncholinergic systems. These findings suggest that pharmacological use of ligands for trkA could have beneficial effects on the multiple neuronal systems that are affected in such disorders as Alzheimer\u27s disease. © 1994 Wiley‐Liss, Inc. Copyright © 1994 Wiley‐Liss, Inc

The Aragon Workers Health Study (AWHS) baseline characteristics.

<p>The Aragon Workers Health Study (AWHS) baseline characteristics.</p

Association between individual APOE SNPs, rs429358 and rs7412, with body fatness.

<p>Means and standard error of the means (SEM) of Body Mass Index (BMI) and waist girth values, adjusted for age, smoking status and lipid values.</p><p>Association between individual APOE SNPs, rs429358 and rs7412, with body fatness.</p