[A protocol for the treatment of retinopathy of prematurity in Spain]. / Protocolo de tratamiento de la retinopatía del prematuro en España.

OBJECTIVE: To prepare a protocol for the treatment of retinopathy of prematurity (ROP) agreed by the majority of Spanish ophthalmologists dedicated to this topic. MATERIAL AND METHOD: A draft of the protocol was produced taking into account the experience of the participants and up to date publications. This draft was corrected by all the ophthalmologists participating in the project, and the final document was agreed by all of them. RESULTS: We present general guidelines as an aid for the treatment of ROP, including treatment criteria, treatment methods, a calendar of action, and follow-up. CONCLUSIONS: It is important to have a common working protocol for the treatment of ROP to improve care and to avoid mistakes. Although individual Hospitals may adapt the protocol to their daily activity, it is recommended that there is a minimal working protocol agreed by most of professionals dedicated to pediatric ophthalmology in Spain.

Screening program for retinopathy of prematurity in Spain.

OBJECTIVE: To prepare a retinopathy of prematurity (ROP) screening program as agreed by most of Spanish ophthalmologists dedicated to this topic. MATERIALS AND METHODS: A draft of the protocol was produced taking into account the experience of the participants and current publications. This draft was corrected by all the ophthalmologists participating in the project and the final document produced was agreed by all of them. RESULTS: We present general guidelines to help in the screening of ROP, including treatment criteria, treatment methods, and a calendar of action. CONCLUSIONS: It is important to have a common working protocol in the screening of ROP to improve the action and to avoid mistakes. Although individual Hospitals may adapt the protocol to their daily activity, it is recommended that there is a minimal working protocol agreed by most of professionals dedicated to pediatric ophthalmology in Spain.

The human area postrema and other nuclei related to the emetic reflex express cAMP phosphodiesterases 4B and 4D.

Phosphodiesterase 4 (PDE4) inhibitors, i.e. rolipram, are being extensively investigated as therapeutic agents in several diseases. Emesis is one of the most common side effects of PDE4 inhibitors. Given the fact that the area postrema is considered the chemoreceptor trigger zone for vomiting, the present study investigates the regional distribution and cellular localization of the four gene transcripts of the PDE4 subfamily (PDE4A, PDE4B, PDE4C and PDE4D) in human brainstem. In situ hybridization histochemistry was used to locate the mRNA distribution of the four PDE4 subfamilies in the area postrema and related nuclei of human postmortem brainstem. We have found that in the brainstem PDE4B and PDE4D mRNA expression is abundant and distributed not only in neuronal cells, but also in glial cells, and on blood vessels. The hybridization signals for PDE4B and PDE4D mRNAs in the area postrema were stronger than those in any other nuclei in the brainstem. They were also found in vomiting-related nuclei such as the nucleus of the solitary tract and the dorsal vagal motor nucleus. These findings suggest that cAMP signaling modification in the area postrema could mediate the emetic effects of PDE4 inhibitors in human brainstem.

Neuronal expression of cAMP-specific phosphodiesterase 7B mRNA in the rat brain.

cAMP plays an important role as second messenger molecule controlling multiple cellular processes in the brain. cAMP levels depend critically on the phosphodiesterases (PDE) activity, enzymes responsible for the clearance of intracellular cAMP. We have examined the regional distribution and cellular localization of mRNA coding for the cAMP-specific phosphodiesterase 7B (PDE7B) in rat brain by in situ hybridization histochemistry. PDE7B mRNA is specifically distributed in rat brain, preferentially in neuronal cell populations. The highest levels of hybridization are observed in olfactory tubercle, islands of Calleja, dentate gyrus, caudate-putamen and some thalamic nuclei. Positive hybridization signals are also detected in other areas, such as cerebral cortex, Purkinje cells of the cerebellum and area postrema. By double in situ hybridization histochemistry, we found that 74% and 79% of the cells expressing PDE7B mRNA in striatum and olfactory tubercle, respectively, were GABAergic cells (expressing glutamic acid decarboxylase mRNA), in contrast with the lack of expression in the few cholinergic cells (expressing choline acetyltransferase mRNA) present in those two areas (around 0.4% in olfactory tubercle). In the thalamic nuclei, a majority of cells containing PDE7B mRNA also expresses a glutamatergic marker (76.7% express vesicular glutamate transporter vGluT1 and 76% express vGluT2 mRNAs). Almost all PDE7B expressing cells in dentate gyrus (93%) were glutamatergic. These results offer a neuroanatomical and neurochemical base that will support the search for specific functions for cAMP dependent PDEs and for the development of specific PDE7 inhibitors.

[Surgical arteriovenous decompression (sheathotomy) in branch retinal vein occlusion: retrospective study]. / Descompresión venosa quirúrgica en las oclusiones de rama venosa retinianas: estudio retrospectivo.

PURPOSE: To evaluate best-corrected visual acuity (BCVA), incidence of neovascularization and angiographic changes in patients with branch retinal vein occlusion (BRVO) treated with surgical decompression by sheathotomy. METHODS: Retrospective study including 17 cases of temporal BRVO with macular edema treated with surgical decompression. Results of BCVA, incidence of neovascularization and vitreous hemorrhage 6 months following surgery are included. Angiographic changes in the first 8 cases a month after decompression are also evaluated. RESULTS: The mean postoperatory BCVA was 0.40 with a mean improvement of 0.26. Seventy one percent of patients (12/17) improved 2 or more visual acuity lines and 53% of patients (9/17) improved 4 or more lines. Only in one case the vision worsened. There was no evidence of retinal neovascularization or rubeosis iridis six months after surgery. CONCLUSIONS: Surgical decompression is a therapeutical option for those patients suffering BRVO with macular edema. Our initial results are encouraging, not only regarding visual acuity improvement, but also because of a decreased risk of neovascularization. No patient included in our study developed neovascularization.

Alterations on phosphodiesterase type 7 and 8 isozyme mRNA expression in Alzheimer's disease brains examined by in situ hybridization.

Phosphodiesterases (PDEs) play a central role in signal transduction by regulating intracellular levels of cyclic AMP (cAMP) and cGMP. It has been suggested that cAMP pathways could be upregulated in Alzheimer's disease. By in situ hybridization histochemistry we have determined the expression pattern of two newly described cAMP-specific phosphodiesterases families, PDE7 and PDE8, in several brain areas in control subjects. The hybridization levels of PDE8A mRNA were very low in all brain areas examined. High PDE7B and PDE8B mRNA signal intensities were found in the hippocampal formation. PDE7A was found to be present in both neuronal and non-neuronal cell populations. When the expression of these isozymes in control brains was compared with that in Alzheimer's disease brains staged according to Braak and Braak (Acta Neuropathol. (Berl.) 82 (1991), 239), we found that PDE8B was the only isozyme showing a significant increase, in cortical areas and parts of the hippocampal formation, at Braak stages III-VI. Our results show that the expression of specific cAMP PDE isoforms is selectively regulated in Alzheimer's disease and associated with the stages of the disease. The availability of animal models of Alzheimer's disease and of new pharmacological tools such as selective PDE inhibitors will allow study of the therapeutic potential of the control of cAMP levels in AD.

Differential distribution of cAMP-specific phosphodiesterase 7A mRNA in rat brain and peripheral organs.

We investigated the regional distribution and cellular localization of mRNA coding for the cAMP-specific phosphodiesterase 7A (PDE7A) in rat brain and several peripheral organs by in situ hybridization histochemistry. The regional expression of two splice variants, PDE7A1 and PDE7A2, was examined by RT-PCR using RNA extracted from several brain regions. PDE7A mRNA was found to be widely distributed in rat brain in both neuronal and nonneuronal cell populations. The highest levels of hybridization were observed in the olfactory bulb, olfactory tubercle, hippocampus, cerebellum, medial habenula nucleus, pineal gland, area postrema, and choroid plexus. Positive hybridization signals were also detected in other areas, such as raphe nuclei, temporal and entorhinal cortex, pontine nuclei, and some cranial nerve motor nuclei. Both mRNA splice forms were differentially distributed in several areas of the brain with the striatum expressing only PDE7A1 and the olfactory bulb and spinal cord expressing PDE7A2 exclusively. In peripheral organs the highest levels of PDE7A hybridization were seen in kidney medulla, although testis, liver, adrenal glands, thymus, and spleen also presented high hybridization signal. These results are consistent with PDE7A being involved in the regulation of cAMP signaling in many brain functions. The consistent colocalization with PDE4 mRNAs suggests that PDE7A could have an effect on memory, depression, and emesis. The results offer clear anatomical and functional systems in which to investigate future specific PDE7 inhibitors.

Phosphodiesterase type 4 isozymes expression in human brain examined by in situ hybridization histochemistry and[3H]rolipram binding autoradiography. Comparison with monkey and rat brain.

We have examined the distribution of four different cyclic AMP-specific phosphodiesterase isozyme (PDE4A, PDE4B, PDE4C and PDE4D) mRNAs in the brain of different species by in situ hybridization histochemistry and by autoradiography with [3H]rolipram. We have compared the localization of each isozyme in human brain with that in rat and monkey brain. We have found that the four PDE4 isoforms display a differential expression pattern at both regional and cellular level in the three species. PDE4A, PDE4B and PDE4D are widely distributed in human brain, with the two latter appearing more abundant. In contrast, PDE4C in human brain, presents a more restricted distribution, limited to cortex, some thalamic nuclei and cerebellum. This is at variance with the distribution of PDE4C in rat brain, where it is found exclusively in olfactory bulb. In monkey brain, the highest expression for this isoform is found in the claustrum, and at lower levels in cortical areas and cerebellum. PDE4B presented a broad distribution, being expressed in both neuronal and non neuronal cell populations. In general, the distribution of binding sites visualized with [3H]rolipram correlated well with the expression of each PDE4 isozyme.