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Biomedical subjects

I Lopez

Publications and source records attributed to I Lopez.

88 records · Page 5Linked to original sources

Differentiation of multiple neurokinin receptors in the guinea pig ileum.

We have studied the selectivity and competitiveness of three neurokinin antagonists and atropine against substance P, neurokinin A, and neurokinin B. DPDTNLE-NB, [D-Pro2, D-Trp6,8, Nle10]-neurokinin B is a competitive antagonist of neurokinin B (pA2 = 5.5), but not substance P or neurokinin A. DPDT-SP ([D-Pro2,Trp7,9]-substance P), competitively blocks substance P (pA2 = 6.9) and neurokinin B (pA2 = 6.8), but not neurokinin A. Spantide ([D-Arg1, D-Trp7,9, Leu11]-substance P) competitively blocks substance P (pA2 = 6.7) and at a log unit higher concentration blocks neurokinin A (pA2 = 5.8), but does not block neurokinin B. Atropine is a competitive antagonist of neurokinin B (pA2 = 9.0) at ten times the concentration needed to block acetylcholine (pA2 = 10.1), but does not inhibit the other neurokinins. These results support the hypothesis of multiple neurokinin receptors in the guinea pig ileum and indicate that the site of neurokinin B, but not substance P or neurokinin A is predominantly on intramural neurons. This indirect stimulation appears to be dependent on the release of acetylcholine. Neurokinin B also has activity on smooth muscle receptors since the contractile response could not be completely antagonized by atropine. There appear to be two smooth muscle neurokinin receptors on the basis of results obtained with DPDT-SP and spantide, one predominantly responsive to substance P and the other to neurokinin A. Only spantide appeared to have any effect on the neurokinin A receptor and that was at a much higher concentration than that needed to block substance P.

Animals↗

Effect of cytidine(5')diphosphocholine (CDP-choline) on the total urinary excretion of 3-methoxy-4-hydroxyphenylglycol (MHPG) by rats and humans.

We examined the effects of orally administered cytidine(5')-diphosphocholine (CDP-choline) on the total levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) in human and rat urine. Four subjects who had been on a low-choline diet (less than 1 gm/day) for 24 hours received three doses of CDP-choline (2 gm each) at 8 a.m., 10 a.m., and noon; urines were collected at two-hour intervals after each dose. Rats received water for three days; then CDP-choline (100 mg/kg) or equimolar doses of choline for five days; then water again for three more days. Twenty-four hour urine samples were collected on each day of the study. The levels of MHPG in human urine increased by 45-68% when subjects were receiving CDP-choline (p less than 0.01). CDP-choline, but not choline, also elevated urinary MHPG significantly in rats (p less than 0.01). These data suggest that CDP-choline enhances norepinephrine release, and that this action may be mediated by more than just its choline content.

Administration, Oral↗

Absorption of fortification iron from milk formulas in infants.

The bioavailability of iron added to different types of cows' milk formulas was studied using mono-isotopic and double-isotopic methods in 396 infants aged 5-18 mo. All the milk formulas were fortified with ferrous sulfate in concentrations varying between 10 and 19 mg elemental iron/liter. Iron absorption from low-fat milks and full-fat milks varied from 2.9 to 5.1%. A higher range of mean absorption, 5.9 to 11.3%, was observed in the same formulas with the addition of ascorbic acid at concentrations of 100 mg/l or higher (up to 800 mg/l), demonstrating its enhancing effect on iron absorption in fortified milks. The amount of milk fat, the addition of carbohydrates, or acidification did not seem to influence iron absorption.

Animals↗

Antisecretory activity of fenoctimine in rat and dog.

Fenoctimine (4-(diphenylmethyl)-1-[(octylimino)methyl]piperidine) sulfate was evaluated for gastric antisecretory activity in the acute gastric fistula rat and chronic gastric fistula dog. It showed potent gastric antisecretory activity of long duration in the rat, and was more potent on a mg/kg basis than cimetidine. In the dog, fenoctimine showed significant activity against gastrin tetrapeptide, histamine, and bethanechol. It was least potent against bethanechol, indicating a lack of significant anticholinergic activity in the dog at the doses tested. It had a long duration of action in the dog with doses of 6 mg/kg, showing significant activity even at 24 hr. Fenoctimine does not appear to fit the spectrum of activity associated with other known antisecretory agents and may have a unique mechanism of action related to effects directly on parietal cells.

Administration, Oral↗

Fragile X screening program in a Spanish region.

In a Spanish region with a population of one million, we screened 371 mentally retarded males, who had no previous diagnosis for fragile X [fra(X))] syndrome. Fifty-three of the 371 males were fra(X) positive. Of these 44 of 362 or 12.1% were unrelated. Family studies identified a large number of obligate carriers and women at risk for being carriers who were given genetic counseling including prenatal diagnostic information. Considering the age of the carriers and the fertility rate, 23 affected males could be born to these women. The prevention potential of this program suggests that it is highly cost-effective.

Adolescent↗

Ethanol accelerates acrosomal loss in human spermatozoa.

The effects of ethanol on the loss of the human sperm acrosome, as determined by the chlortetracycline fluorescence assay and by indirect immunofluorescence assay, were assessed over 6 hours during incubation at 37 C in BWW medium containing 0 to 250 mM ethanol. Both assays gave the same results. At the end of 6 hours, 48 +/- 6% acrosomal loss was found in samples in 250 mM ethanol compared with 4 +/- 1% in the absence of ethanol. After 0.25 hour, the first time point chosen for sampling, the spermatozoa in 250 mM ethanol showed 23 +/- 3% loss of acrosomes compared with less than 1% in the absence of ethanol. Ultrastructural studies revealed that the ethanol-treated spermatozoa showed complete acrosomal loss as well as loss of the equatorial segment. No examples of the vesiculation characteristic of the physiologic acrosome reaction were found in the 150 cells examined. Calcium is required for the ethanol-mediated acrosomal loss: omission of Ca2+, addition of 2 mM EGTA, or 0.2 mM verapamil blocked the effect. Ethanol induced a dose-dependent efflux of cholesterol from human spermatozoa, but the ethanol-induced acceleration of acrosomal loss occurred to the same extent in the presence of cholesterol microdispersions that prevented this efflux. The loss of the equatorial segment, which is necessary for egg penetration, during ethanol-induced acrosomal loss would explain the known effect of ethanol in inhibiting, rather than enhancing, the penetration of zona-free hamster eggs by human spermatozoa.

Acetaldehyde↗

Age-related change of the neuronal number in the human medial vestibular nucleus: a stereological investigation.

An unbiased stereological method was used to assess the effect of aging on the number of neurons in the human medial vestibular nucleus. We studied 13 normal brainstem specimens (age at death from 40 to 93 years) that were part of a prior study that counted neuronal profiles and used a correction factor to estimate the number of neurons in the human vestibular nucleus. On average, we found 151.10(3) (CV = 0.15) neurons in the medial vestibular nucleus, which is 18% more than that in the prior study. Regression analysis showed a significant decrease in the number of neurons with aging. This age-related neuronal loss in the vestibular nucleus could have important functional implications regarding the well-known deterioration in balance that occurs with aging.

Adult↗

Aging and the human vestibular nucleus.

Degenerative changes during aging have been identified in the inner ear and in the vestibular nerve, but not in the human vestibular nuclear complex (VNC). Therefore, the purpose of this study was to document quantitative morphometric changes within the VNC in humans as a function of age. The VNC of normal human subjects was examined for age-related changes using computer-based microscopy. Neuronal counts, nuclear volume, neuronal density, and nuclear length of the 4 vestibular nuclei were determined in 15 normal people, age 40 to 93 years. Based on a linear model, there was approximately a 3% neuronal loss per decade from age forty to ninety. VNC volume and neuronal density also decreased significantly with age, although to a lesser degree than did the number of neurons. Neuronal loss as a percentage of the total number of neurons was greatest in the superior vestibular nucleus and least in the medial vestibular nucleus. Despite the overall loss of neurons, the number of giant neurons (> 500 microns2) increased in older people. This increase in giant neurons could be traced to the accumulation of lipofuscin deposits in the cell somata. The overall rate of neuronal loss with aging in the VNC is comparable to that previously observed in hair cells, primary vestibular neurons, and cerebellar Purkinje cells, but is in contrast to prior reports of no age-related loss of neurons in other brain stem nuclei.

Adult↗