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Biomedical subjects

M C Brennan

Publications and source records attributed to M C Brennan.

7 recordsLinked to original sources
PubMed1991

Sorbitol, myo-inositol, and rod outer segment phagocytosis in cultured hRPE cells exposed to glucose. In vitro model of myo-inositol depletion hypothesis of diabetic complications.

The "myo-inositol depletion hypothesis" remains a leading but still controversial contender among proposed pathogenetic mechanisms for the chronic complications of diabetes. The multifaceted interrelationships among altered tissue myo-inositol content and metabolism and tissue function have been difficult to elucidate in diabetic animal models due in part to the complex, heterogeneous nature of tissues prone to diabetic complications. The retinal pigment epithelium consists of a homogenous cell monolayer that exhibits related alterations in myo-inositol metabolism and function in diabetic animals. Nontransformed human retinal pigment epithelial (hRPE) cells, which retain their general phenotypic and morphological characteristics during monolayer culture in vitro, were examined for parallel alterations in myoinositol metabolism and cell function when grown under carefully controlled conditions in medium containing hyperglycemic concentrations of glucose. Exposure of hRPE cells to 20-40 mM glucose produced time- and dose-dependent increases in sorbitol content and decreases in myo-inositol content that were partially blocked by the aldose reductase inhibitor sorbinil. myo-Inositol was taken up by two Na-dependent transport systems, at least one of which was competitively inhibited by glucose. Exposure to 20 mM glucose impaired the ability of hRPE cells to take up human retinal rod outer segments, an important physiological function of these cells. The impairment of rod outer segment uptake by high glucose levels was prevented by an aldose reductase inhibitor or elevated medium myo-inositol that corrected the fall in myo-inositol content. Thus, hRPE cells provide a new in vitro model in which to examine the biochemical-functional interrelationships of the myo-inositol depletion hypothesis.

Adult↗
PubMed1988

Serotonin in human aqueous humor.

Circadian rhythms in serotonin metabolism have been observed in the pineal gland and retina, and there is evidence that the levels of serotonin and melatonin in these tissues may mediate events in the brain's sleep-wake cycle and the retina's cycle of disc shedding. Because the ciliary epithelium, which produces aqueous humor, has an embryonic origin similar to that of the retina and the pineal gland, the authors believe that serotonin metabolism might play an analogous role in the regulation of the diurnal cycle of aqueous secretion. As a first step in investigating this hypothesis, they measured serotonin concentrations in the aqueous humor of 34 cataract patients. Using high-performance liquid chromatography (HPLC) with electrochemical detection, a mean serotonin concentration of 52 +/- 11 ng/ml was found. This high concentration implies that serotonin has one or more functions: (1) perhaps it acts as a neurotransmitter and precursor of melatonin; (2) conceivably it is related to aqueous humor dynamics; and (3) in particular, perhaps it affects the circadian rhythm of intraocular pressure.

Adult↗
PubMed1983

A prospective study of lower limb amputations.

Most leg amputations are performed for vascular disease. A mortality of 30% was associated with above-knee amputations in this study. Healing by primary intention took place in 59% of patients, 31% had delayed healing and 10% required a revision. Only 10% of above-knee amputees used a prosthesis and 48% required total bed care. Below-knee amputations in which a rigid dressing was used had slightly better healing than when soft dressings were used but the difference was not significant. The overall reamputation rate was 15%, the mortality was 7.2% and 57% were fully ambulatory with a prosthesis. Amputation at either the transmetatarsal or digital level was carried out in 25% and 80% healed. The mortality was 11%. Clinical observation is still the best determinant of the level of amputation; below-knee amputation should be strived for in every patient who is a candidate for rehabilitation. Use of a rigid dressing is recommended.

Aged↗
PubMedDate not supplied

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↗
PubMedDate not supplied

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↗
PubMedDate not supplied

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↗