Biomedical Sciences

We studied the innervation of the cat testis using a panel of antisera against the following neuronal markers: protein gene product 9.5 (PGP), neuropeptide Y, C-terminal peptide of neuropeptide Y, galanin, vasoactive intestinal peptide (VIP), calcitonin gene-related peptide, and substance P. Immunoreactivity against PGP, a general neuronal label, demonstrated the arrangement of fibers from the superior spermatic nerve (SSN) in the testicular pedicle and the cephalic testicular pole, and those of the inferior spermatic nerve (ISN) along the vas deferens and the inferior testicular ligament. The testicular parenchyma exhibited a very rich innervation, mainly distributed to blood vessels and Leydig cell nests, but also in close association with seminiferous tubules. Numerous peptidergic fibers were present in the SSN and ISN, albeit in different proportions. Thus, VIP-immunoreactive fibers were almost absent in the SSN, but were the most abundant subpopulation of the ISN. The testicula...

A proliferative vitreoretinopathy-like condition induced by intravitreal dispase injection in C57BL/6J mice was studied using ophthalmoscopic and histochemical procedures. The frequency of intravitreal hemorrhage, intravitreal spots, retinal folds and epiretinal membranes was scored by ophthalmoscopic examination at 1, 2, 4, 6 and 8 weeks after the injection. Intravitreal spots corresponded to free cells exhibiting F4/80 immunoreactivity, a macrophage/microglial marker. Retinal folds always appeared before an epiretinal membrane could be observed. Dispase-injected eyes always showed a much higher frequency of folds and membranes than saline-injected eyes. Folds and membranes appeared earlier and were more extensive in the presence of intravitreal hemorrhage than in its absence. Mu È ller retinal cells exhibited signi®cant changes in glial ®brillary acidic protein-immunoreactivity. This was absent in normal Mu È ller cells but, in dispase-injected animals, it was expressed in radial processes at the site of retinal folds, later extending to the whole retina. Both epi-and subretinal membranes contained cells probably derived from Mu È ller cells, since they exhibited co-localization of glial ®brillary acidic protein-and glutamine synthase immunoreactivities. F4/80 was also present in numerous cells within the retina, epi-and subretinal membranes. By contrast, the retinal pigment epithelium cell marker RPE65 was restricted to subretinal membranes. It can be concluded that dispase induced a proliferative vitreoretinopathy-like condition in mice, with a strong contribution of macrophage-and glial-derived cells.

The Y1 receptor of neuropeptide Y (NPY) has been demonstrated in glial cells of astrocytic lineage in vitro. We have studied the immunohistochemical expression of Y1 receptors in the glia of the diseased human retina, in tissue samples obtained after surgery for proliferative vitreoretinopathy. In this condition, glia and other cell types migrate and form epi-or subretinal membranes. Both diseased retinas (n ϭ 8) and PVR membranes (n ϭ 43) contained numerous Y1-immunoreactive cells. In the diseased retina, the Y1 antiserum labeled cells with the morphological radial pattern characteristic of Mü ller cells, whereas in the membranes, label appeared in a large population of elongate cells, measuring up to 250 m. In both retina and membranes, double labeling demonstrated that the vast majority of Y1-immunoreactive cells were also labeled by a glial fibrillary acidic protein (GFAP) antibody, indicating their glial origin. Retinal regions devoid of GFAP immunoreactivity also lacked the Y1 label. None of these markers was detected in Mü ller cells of normal retina. Y1 immunoreactivity did not co-localize with smooth muscle actin immunoreactivity, a marker of myofibroblasts. Expression of Y1 receptors would characterize reactive and proliferating glial cells of the diseased retina and could perhaps be involved in the proliferation of injured glial cells causing regrowth of PVR membranes and the consequent secondary retinal detachments. GLIA 39: 320 -324, 2002.

Endothelin participates in a variety of conditions that cause pain. Local injection of ET-1 produces pain which is independent of its vasoactive properties. Pain due to inflammation, nerve injury and cancer has been studied extensively. Most of the studies indicate that ETA receptor antagonists decrease nociception; and some studies indicate that ETB receptor stimulation may be antinociceptive; while others indicate that ETB receptor antagonism may be antinociceptive. However, the idea of ETB receptor stimulation having antinociceptive effect is gaining ground. It was demonstrated that methylation of ETB receptors which results in transcription silencing is present in painful cancerous tissues and not in normal tissues from the same patients. Preclinical studies with ETA receptor antagonists demonstrated potential for reducing pain, and some clinical phase II studies also showed the benefit of using ETA receptor antagonists in reducing cancer pain. In experiments carried out in mice, with deletion of ETA receptors selectively in nociceptive sensory neurons, while preserving expression in non-neuronal cells and the CNS, it was found that ETA receptors are important in the modulation of cancer pain and act independent of ETA receptor function in tumor cells. However, human phase III studies have failed to demonstrate any benefit in reducing pain of cancer patients. It has been found that ETA receptor antagonism predominantly mediates its antinociceptive action through endogenous opiates. Secretion of beta-endorphin and leu-enkephalin is increased by ETA receptor antagonists. ETA receptor antagonists potentiate morphine and oxycodone antinociception in rats and mice; and tolerance to opioid agonists was reversed by treatment with ETA receptor antagonists. Moreover, ETA receptor antagonists enhanced G-protein coupling to opioid receptors and restored morphine analgesia in tolerant animals. This creates the possibility of combination therapies with opioids and ETA receptor antagonists to manage pain in cancer patients with lower doses of opiates and reduced probability of tolerance development.

Several cytokines have been involved in the regulation of Sertoli cell function. Further investigations are required to elucidate the role of interleukin-1beta (IL1beta) in Sertoli cell physiology. Twenty-day-old rat Sertoli cell cultures were used to investigate a possible role of IL1beta in the regulation of gamma-glutamyl transpeptidase (gammaGTP) and to elucidate the signaling pathway utilized by this cytokine. GammaGTP is a membrane-bound enzyme that has been involved in amino acid transport across the plasma membrane and in protection from oxidative stress through its importance in the regulation of glutathione levels. Previous studies suggested that IL1beta stimulates NO biosynthesis in other cell types. Therefore, we investigated whether IL1beta modified the level of nitrite, a stable metabolite of NO, in Sertoli cells. Dose-response curves to IL1beta for gammaGTP activity and nitrite production were observed. The increments observed in gammaGTP activity and nitrite producti...

We studied behavior in a group of children with specific language impairment in its 2 subtypes (expressive and mixed receptive/ expressive). After exclusion of other psychiatric conditions, we evaluated 114 children of ages 2 to 7 years using language developmental tests and behavioral screening scales. Behavior problems appeared in 54% of the children. Withdrawn was the most frequently found syndrome in preschool children, whereas anxious/depressed and social problems were the most frequent in older children. The high frequency of behavioral syndromes in children with specific language impairment is remarkable and requires the awareness of primary attendants and specialists. Anxiety, depression, social isolation, and aggressive and rulebreaking behavior can obscure identification of the language impairment. Taking into account this relationship would improve the chances of a timely and appropriate intervention.

The course of Age-related Macular Degeneration (AMD) is described as the effect of light (400–580 nm) on various molecular targets in photoreceptors and the retinal pigment epithelium (RPE). Photo-damage is followed by inflammation, increasing oxidative stress and, probably, unveiling new photosensitive molecules.