Growth of the two layers of the chick sclera is modulated reciprocally by visual conditions.

PURPOSE: Although visual deprivation causes increased ocular elongation and myopia in both birds and mammals, changes in sclera appear to be in opposite directions. Because avian sclera has a cartilaginous layer as well as the fibrous layer found in mammals, we examined whether the scleral responses to various visual manipulations differ between the two layers. METHODS: To produce increases in ocular elongation and myopia, monocular diffusers or negative lenses were fitted to eyes. Conversely, to produce decreases in ocular elongation, diffusers were removed (restoring normal vision) or monocular positive lenses were fitted. Scleral layers were then dissected apart, and incorporation of labeled precursors into glycosaminoglycans (GAGs), DNA, and protein was assessed. Tissue coculture experiments were used to assess humoral interactions between scleral layers and with the choroid. RESULTS: In the cartilaginous layers, the incorporation of label into proteoglycans and DNA was significantly higher in eyes elongating faster than normal because of wearing diffusers or negative lenses and significantly lower than normal in eyes elongating slower than normal because of removal of the diffuser or wearing positive lenses. In the fibrous layers, the reverse was the case. Coculturing cartilaginous sclera from normal eyes with fibrous sclera from myopic or recovering eyes produced the same increase or decrease in sulfate incorporation into GAGs in the cartilaginous layer as though the tissue measured was from the animal providing the conditioning tissue. Coculturing with choroid, especially from recovering eyes, also inhibited cartilaginous sclera. CONCLUSIONS: The fibrous layer of the avian sclera shows changes in sulfate incorporation into GAGs during deprivation and recovery from deprivation in the same direction as does the mammalian sclera, whereas the cartilaginous layer changes in the opposite direction. The responses of the cartilaginous layer may be controlled by the fibrous layer, although they are influenced by the choroid as well.

Differences in time course and visual requirements of ocular responses to lenses and diffusers.

PURPOSE: Myopia can be induced in chickens by having them wear either negative lenses (lens-compensation myopia [LCM]) or diffusers (form-deprivation myopia [FDM]), whereas positive lenses cause lens-compensation hyperopia (LCH). These three conditions were compared with respect to (i) their early time course and (ii) the effect of two manipulations of the lighting. METHODS: Longitudinal changes in ocular dimensions and refractive error were measured in chicks maintained under three different conditions: (i) wearing either -15 D lenses or diffusers in a normal light/dark cycle; (ii) wearing either +15 D lenses, -15 D lenses, or diffusers with brief periods of stroboscopic lights at the beginning and end of the dark period; (iii) wearing either +6 D lenses, -6 D lenses, or diffusers with the nights interrupted by brief periods of white light. In addition, scleral and choroidal proteoglycan synthesis was measured in eyes that wore positive lenses, negative lenses, or diffusers for 3 hours followed by different periods of darkness. RESULTS: (i) The time course of the changes in axial length over the first 72 hours was significantly faster in LCM than in FDM. Indeed, the diffusers did not begin to significantly affect the total length of the globe for 3 days, although the vitreous chamber had deepened after 9 hours, because the choroid thinned extremely rapidly (within 1 hour) with either diffusers or negative lenses. (ii) Scleral proteoglycan synthesis was higher in eyes with negative lenses than in those with diffusers at 11 hours, but the reverse was true at 27 hours. (iii) Brief periods of stroboscopic light attenuated FDM more than LCM. (iv) In contrast, interruption of the nights by brief periods of light attenuated LCM more than FDM. (v) Neither lighting manipulation affected LCH. (vi) Choroidal proteoglycan synthesis decreased similarly with 3 hours of wearing either diffusers or negative lenses. CONCLUSIONS: Although both negative lenses and diffusers cause similar increases in the rate of ocular elongation, the responses differ in time course and in the effect of manipulations of the daily lighting. The responses to positive lenses differ from both of these.

Muscarinic acetylcholine receptor antagonists inhibit chick scleral chondrocytes.

PURPOSE: Muscarinic acetylcholine receptors (mAChRs) have been implicated in the control of myopia in humans and in animal models. This study was conducted to determine whether mAChRs influence the growth of the chick sclera and, if so, which mAChR subtypes are involved. METHODS: Sclera and scleral chondrocytes from normal and form-deprived eyes of 10- to 14-day-old chicks were treated with a total of seven ligands: two agonists, carbachol (nonselective) and McN-A-343 (selective for the M1 mAChR subtype); and five antagonists, atropine (nonselective), pirenzepine and telenzepine (M1), gallamine (M2), and 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP; M1 and M3). Incorporation of sulfate into glycosaminoglycans and of thymidine into DNA were quantified and normalized to sample DNA content. Possible toxicity of ligands at high doses was examined by analysis of cell number (by cell counting), viability (by trypan blue exclusion), and cellular metabolic activity (by dehydrogenase activity). RESULTS: Cellular proliferation and extracellular matrix production were inhibited by atropine in whole sclera and in its cartilaginous layer. Sulfate incorporation by chondrocytes from normal and form-deprived eyes was inhibited by mAChR antagonists with a rank order of potency (atropine > pirenzepine = 4-DAMP >> gallamine) consistent with regulation by M1, rather than M3 or M2 mAChR subtypes. Pirenzepine inhibited sulfate incorporation by chondrocytes from form-deprived eyes more effectively than those from normal eyes. Chondrocyte cultures were not viable when grown in high doses of any of the ligands used except gallamine. CONCLUSIONS: In chick scleral chondrocytes, synthesis of DNA and glycosaminoglycans was inhibited by mAChR antagonists. This inhibition was probably mediated by the M1 subtype mAChR. Therefore in vivo the sclera may be a site of action for the mAChR antagonists previously used to influence myopia. Although at high concentrations mAChR antagonists tested seemed to be toxic to chondrocytes, at lower doses inhibition occurred without toxic effects.

Difficult hGH treatment in a patient with type III glycogen storage disease.

The case of a boy affected by type III glycogen storage disease and total GH deficiency is reported. Substitutive treatment with hGH caused an extreme elevation of blood lipids. His lipid profile returned near to basal values 1 month after treatment was discontinued. The association of growth hormone and amylo-1-6-glucosidase deficiencies is unusual and difficult to treat; however growth hormone deficiency should be considered in patients with hepatic glycogenoses and severe growth retardation.

[Chronic HB virus hepatitis in children. A study of 29 cases]. / L'hépatite chronique à virus HB de l'enfant. Une étude de ving-neuf observations.

Clinical, biochemical and histological features of chronic hepatitis type B were studied in 29 children aged 8 months to 13 years. On entry into the study, all were known to have had hepatitis B surface antigen (HBsAg) with elevated serum transaminase levels for at least six months. A possible source of infection was found in 15 children. When they entered the study, all patients were anicteric and all but one asymptomatic. Hepatomegaly was detected in 15 patients and was associated with splenomegaly in two. Hypergammaglobulinemia was present in 4 children. Serological evaluation of hepatitis B virus markers showed evidence of complete viral replication (HBeAg positivity) in 24 cases and incomplete replication (anti-HBeAg positivity) in 5. Liver histology showed chronic persistent hepatitis (CPH) in 18 children, and chronic aggressive hepatitis (CAH) in 10 (3 moderately active and 7 with major signs of aggressivity ) associated with cirrhosis in 5. One patient had only minimal histological changes. Evaluation of clinical, biochemical and virological parameters did not strictly parallel the histological diagnosis in terms of "activity" of the disease. Follow-up for a mean period of 13 months showed good clinical tolerance to the disease in both CPH and CAH patients. Only 2 children with CAH were given corticosteroids and/or azathioprine for a short period. During follow-up no children with active disease developed liver insufficiency or evidence of portal hypertension. No significant difference in the percentage of children who had seroconversion to antiHBe was found between CPH and CAH groups. Only one child with CAH became HBsAg negative.(ABSTRACT TRUNCATED AT 250 WORDS)