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Biomedical subjects

X D Martin

Publications and source records attributed to X D Martin.

23 records · Page 2Linked to original sources

Type a syndrome of insulin resistance: anterior chamber anomalies of the eye and effects of insulin-like growth factor-I on the retina.

BACKGROUND: The purpose of this work was to describe the anterior chamber and iris anomalies as well as to evaluate the effects of recombinant human insulin-like growth factor-I (rhIGF-I) on the retinal vessels in 2 diabetic patients with type A syndrome of insulin resistance, a rare condition associated with acanthosis nigricans. METHODS: Ophthalmologic examinations, including photographs and fluorescein angiograms, were performed before, and 2 and 4 weeks after starting subcutaneous rhIGF-I treatment, and 3 months after withdrawal of rhIGF-I treatment. RESULTS: Both patients had goniodysgenesis with mild elevation of the intraocular pressure. Before and after 2 weeks of treatment with rhIGF-I, the fundus and the fluorescein angiograms were mainly normal. After 4 weeks of rhIGF-I treatment both patients' retinas revealed leakage of fluorescein. Three (case 1) and 4 months (case 2) after withdrawal of rhIGF-I, the fundus of all four eyes were again without leakage. CONCLUSIONS: The anterior chamber anomalies found in these patients may be part of the type A syndrome of insulin resistance and could alert clinicians that these patients might not have the usual type of diabetes. Moreover, the data show that exogenous rhIGF-I administration in patients with type A syndrome of insulin resistance alters the permeability of the superficial layer of retinal capillaries which is comparable to the earliest angiographic changes in childhood diabetic retinopathy. Whether this is a direct effect of rhIGF-I, as suggested by experiments in an animal model, or an indirect effect due to the near-normalization of the glucose levels by rhIGF-I warrants further investigations. Finally, this work points to an important caveat regarding the therapeutic use of rhIGF-I in this patient population.

Acanthosis Nigricans↗

The ciliary body--the third organ found to synthesize indoleamines in humans.

Indoleamines are associated with circadian rhythms in pineal gland and retina. Because the ciliary epithelium has an embryonic origin similar to that of pineal gland and retina, and intraocular pressure shows circadian variations, indoleamines were searched for in aqueous humor and ciliary body in humans. In aqueous humor, serotonin, 6-hydroxymelatonin, and melatonin were simultaneously detected and measured using high-performance liquid chromatography with electrochemical detection. The concentration was 48.7 +/- 10.9 ng/ml for serotonin, 0.47 +/- 0.8 ng/ml for melatonin, and 13.9 +/- 7.7 ng/ml for 6 hydroxymelatonin. In ciliary bodies from freshly enucleated human eyes, tryptophan, 5-hydroxytryptophan, serotonin, and 5-hydroxyindoleacetic acid were detected using high-performance liquid chromatography with simultaneous fluorescence- and electrochemical detection. Finally, the enzymatic activities of arylalkylamine N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT), enzymes indispensable in the synthesis of melatonin, were measured. The NAT activity was 273 +/- 25 pmol/mg protein/hour and that of HIOMT, 13520 +/- 50 pmol/mg protein/hour in ciliary body. Comparison of these activities (NAT versus HIOMT) permits the suggestion that NAT is a limiting enzyme in serotonin metabolism in this tissue. These findings indicate that a circadian rhythm of indoleamines exists in human aqueous humor and that the human ciliary body is the third organ, after the pineal gland and the retina, found to synthesize indoleamines in humans.

Acetylserotonin O-Methyltransferase↗

Dopamine and its metabolites in human tears.

Dopamine is known to stimulate ion transport in the corneal epithelium. Since epithelium is in contact with tears, we searched for dopamine and its metabolites in tears. Twenty normal subjects participated in this study. Twenty microliters of tears were collected in capillary tubes after trigeminal stimulation and immediately analyzed using high-performance liquid chromatography with electrochemical detection. Dopamine and two of its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), were identified and measured. The mean concentration of dopamine was 8.9 +/- 5.1 ng/ml; DOPAC, 2.2 +/- 1.6 ng/ml; and HVA, 0.55 +/- 0.4 ng/ml. These results permit us to suggest that dopamine is deaminated by monoamine oxidase, then methylated by catechol-O-methyltransferase and that catabolism occurs in the lacrimal gland and perhaps in corneal epithelium. Finally, part of the dopamine involved in ion transport may come from tears.

3,4-Dihydroxyphenylacetic Acid↗

Serotonin in human tears.

It has been postulated that serotonergic receptors are present in the corneal epithelium and that their activation by serotonin released from subepithelial corneal nerves raises the level of cyclic AMP, which in turn stimulates active CI-secretion by the corneal epithelium. We looked for serotonin in tears because these bathe the corneal epithelium. Twenty-two normal subjects, 14 women and 8 men between 25 and 60 years of age (average 36.5 +/- 9 years), participated in this study. Twenty microliters of tears were collected in capillary tubes after trigeminal stimulation (pepper in the nose) and were immediately analysed using high-performance liquid chromatography with electrochemical detection. Serotonin was identified and measured in every subject. Its mean concentration was 2.74 +/- 1.99 ng/ml. No difference was found between women and men. Emotionally evoked tears were obtained from two subjects. The amount of serotonin in these samples was much higher than in the samples obtained by trigeminal stimulation. These results demonstrate for the first time that serotonin is present in human tears. The possible role of this serotonin in chloride transport in the corneal epithelium and the probable difference between "emotional" and stimulated tears warrants further investigation.

Adolescent↗

3-hydroxykynurenine transamination leads to the formation of the fluorescent substances in human lenses.

The levels of alanine, aspartate and glutamine transaminase increase considerably in some diseases. We measured the activity of these enzymes and of the transaminase of 3-hydroxykynurenine, an aminoacid, which acts as a UV lens filter. Alanine and glutamine transaminases (carboxypeptidase) were not detected in normal and cataractous human lenses, and aspartate transaminase was found only in the cortex of normal lenses. 3-hydroxykynurenine transaminase was not found in lenses from persons below thirty years of age, but was found in lenses at about fifty years of age, and in cataractous lenses. Transamination of 3-hydroxykynurenine leads to the formation of xanthurenic acid and its derivatives. These substances appear to be responsible for the increase of lens fluorescence during cataract development.

Adult↗