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Biomedical subjects

J A Prada

Publications and source records attributed to J A Prada.

At least 19 recordsLinked to original sources

Pregnant adolescent and adult women have similarly low intakes of selected nutrients.

OBJECTIVE: To examine the dietary intake of pregnant adolescents during the second and third trimester of pregnancy, and to compare their nutrient intake with that of pregnant adults. DESIGN: Two 7-day food records (14 days) from subjects participating in a larger randomized clinical calcium trial: the first at 19 to 21 weeks and the second between 29 and 31 weeks gestation. Intake of energy and selected nutrients were calculated and compared with dietary standards. SUBJECTS/SETTING: Fifty-nine pregnant adolescents and 97 pregnant adults recruited from prenatal clinics at a metropolitan university hospital. STATISTICAL ANALYSES: Two sample t tests, equality of variances, and repeated measures (analysis of variance). RESULTS: There was no difference in mean nutrient intakes between the second and third trimesters. Using two 7-day food records, we found mean intakes for energy, iron, zinc, calcium, magnesium, folate, and vitamins D and E to be below recommended standards in both groups. Other nutrients examined met or exceeded reference values. Total daily intakes for energy and 11 nutrients were significantly higher in the adolescent compared to the adult diets (P < .05). These differences were not evident when nutrient values were corrected for energy, indicating that increased energy intake in the teen-aged population was contributed by nutrient-dense foods. APPLICATIONS: This study indicates the need for continued dietary monitoring of pregnant adolescents and pregnant adults, including nutrition guidance that stresses food sources of calcium, magnesium, zinc, iron, fiber, folate, and vitamins D and E, the nutrients found deficient in their diets.

Adolescent↗

Thyrotropin-like immunoreactivity in the developing chicken retina.

In this paper we analysed the presence and localisation of thyrotropin during retinal development in Gallus domesticus. Specific thyrotropin-like immunohistochemical staining was observed from the beginning of the second incubation week to one day post-hatching in chicken retina. Thyrotropin is a 28.3 KDa glycoprotein, synthesised by the anterior pituitary gland, and it is implicated in the stimulation of the synthesis and release of thyroid hormones. Until now, the action of thyrotropin has been established exclusively in hormonal terms. Recently, this glycoprotein has been localised in synaptic processes in the human retina by using a specific antiserum (Fdez-Trujillo et al., 1995). To the best of our knowledge this report is the first time that thyrotropin has been immunocytochemically demonstrated in the chicken retina. The pattern of thyrotropin-like immunoreactivity suggests that this glycoprotein could act as modulator of synaptic transmission, but it may also play a much broader role in regulating trophic functions.

Animals↗

The promoter of the C1 inhibitor gene contains a polypurine.polypyrimidine segment that enhances transcriptional activity.

The C1 inhibitor (C1INH) promoter is unusual in two respects: 1) It contains no TATA sequence, but instead contains a TdT-like initiator element (Inr) at nucleotides -3 to +5; 2) it contains a polypurine.polypyrimidine tract between nucleotides -17 and -45. Disruption of the Inr by the introduction of point mutations reduced promoter activity by 40%. A TATA element inserted at nucleotide -30 in the wild-type promoter and in promoter constructs containing the mutated Inr led to a 2-fold increase in basal promoter activity. Previous studies suggested that the potential hinged DNA-forming polypurine.polypyrimidine tract might be important in the regulation of C1INH promoter activity. The present studies indicate that this region is capable of such intramolecular triple helix formation. Disruption of the polypurine.polypyrimidine sequence by substitution of 5 of the 23 cytosine residues with adenine prevented triple helix formation. Site-directed mutagenesis experiments demonstrate that the regulation of promoter activity is independent of hinged DNA-forming capacity but requires an intact AC box (ACCCTNNNNNACCCT) or the overlapping PuF binding site (GGGTGGG). The C1INH gene also contains a number of potential regulatory elements, including an Sp-1 and an hepatocyte nuclear factor-1 binding site and a CAAT box. The role of these elements in regulation of the C1INH promoter was examined. Elimination of the hepatocyte nuclear factor-1 site at nucleotides -94 to -81 by truncation reduced the activity of the promoter by approximately 50%. Similarly, site-directed mutations that disrupt this site reduce promoter activity by 70%.

5' Untranslated Regions↗

Biological mechanisms of environmentally induced causes of IUGR.

The causes of intrauterine growth retardation (IUGR) are multiple, involving many different factors. Studies in humans and animals have shown that the maternal environment is the most important determinant of newborn weight, accounting for more similarity in birth weights of siblings than does genetic affinity. In addition to a direct relationship with the degree of maternal plasma volume expansion, many clinical factors are associated with IUGR. These factors include multiple gestation; fetal, genetic, and chromosomal anomalies (Down's syndrome and Turner's syndrome); infections such as TORCH syndrome (acronym for toxoplasmosis, rubella, cytomegalic disease, and herpes); and various maternal disorders including anemia, severe chronic asthma, chronic renal disease, heart disease and hypertension. Maternal stress factors, including narcotic addiction, cigarette smoking and chronic alcoholism, are associated with IUGR. Placental anomalies including hemangiomas, placental infarcts, single umbilical artery, and small placental size are also associated with intrauterine growth retardation. Poor nutritional status of the mother at conception and inadequate energy and protein intakes during pregnancy can also result in IUGR. Because IUGR children are not a homogeneous group, they have a broad spectrum of growth, health, and developmental outcomes. In general they have higher rates of subnormal growth, morbidity, and neurodevelopmental problems. The biomedical mechanisms reflected in nutritional, infection-related, hormonal, and metabolic parameters are not likely to be independent causative factors of IUGR, but important mediating factors of a pathologic process set in motion by other agents and insults. This paper focuses mainly on the possible negative effects that a deficient maternal diet might have on fetal development and growth.

Animals↗

Characterization of the IFN-gamma-responsive element in the 5' flanking region of the C1 inhibitor gene.

Treatment of a variety of cell lines with IFN-gamma leads to enhanced synthesis and secretion of C1 inhibitor (C1inh). The induction of C1inh synthesis by IFN-gamma is primarily regulated at the transcriptional level, and is controlled by elements in the 5' flanking region and the first intron of the C1inh gene. Hep3B cells transfected with reporter constructs containing truncated segments between -738 and -81 of the 5' flanking region and stimulated with IFN-gamma expressed increased levels of chloramphenicol acetyl transferase. These data as well as the data obtained from studies using constructs with mutated IFN-gamma-activated sequence (GAS) indicate that the most proximal GAS element (GAS 4) that mapped to nucleotides -126 to -118 is responsible for this IFN-gamma responsiveness. Electrophoretic mobility shift assays using GAS 4 yielded a single band that appeared within 5 min after stimulation with IFN-gamma. In competition experiments, both GAS 4 and consensus GAS probes, but not a mutated GAS probe, competed for the GAS binding protein present in Hep3B and U-937 cell extracts. The identity of the GAS binding protein was confirmed using anti-STAT-1alpha Abs in supershift assays. The results indicate that STAT-1alpha binds to GAS 4, which is the primary element in the 5' flanking region responsible for IFN-gamma induction of the C1inh gene.

Carcinoma, Hepatocellular↗

Hypocalcemia and pregnancy-induced hypertension produced by low-calcium diet.

Recent studies from our laboratory in fasting pregnant ewes with twin gestation have implicated low serum calcium concentration in the etiology of hypertension in pregnancy. We hypothesized that the reduction in serum calcium concentration produced by feeding of a calcium-deficient diet in twin gestation would lead to a significant increase in maternal arterial blood pressure, vascular resistance, and protein in the urine and decreased uterine blood flow. Twenty-five instrumented ewes were used in the present study. After surgery a calcium-deficient diet and deionized water (calcium ion free) were provided ad libitum to 19 animals. Blood pressure, cardiac output, heart rate, and uterine blood flow were monitored every other day. Six control animals were provided with standard Rumilab diet and tap water (group 1). Animals on a low-calcium diet (group 2) were subdivided according to the blood ionized calcium response to low dietary calcium intake. Non-hypocalcemic animals were assigned to group 2a (n = 10), and hypocalcemic animals (calcium concentration below two standard deviations from the control group) were assigned to group 2b (n = 9). In group 2b calcium concentration decreased from 1.03 +/- 0.04 mmol/L on day 110 of gestation to 0.77 +/- 0.03 mmol/L by day 125 of gestation. Arterial blood pressure increased significantly from 76 +/- 2 to 91 +/- 2 mm Hg, and uterine blood flow decreased from 950 +/- 53 to 579 +/- 48 mL/min. Urinary protein increased from 1.7 +/- 0.3 to 10.5 +/- 1.2 g/L.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Hypocalcemia and pregnancy-induced hypertension produced by maternal fasting.

During pregnancy, maternal calcium needs increase as a result of increasing calcium requirements for fetal bone development. These needs have to be completely supplied by the mother via placental transfer. Several studies link low serum ionized calcium concentrations with the development of hypertension and pregnancy-induced hypertension. We hypothesized that maternal hypocalcemia would develop concomitantly with the development of hypertension in sheep that were fasted in late gestation. Sixteen instrumented ewes were used in the present study. After a 2-day baseline period, food was withdrawn from 10 animals in the experimental group (group 2) for 3 days, whereas the remaining six were allowed to eat and drink normally (group 1). Blood pressure, uteroplacental blood flow, and heart rate were monitored daily. Fasted animals were given deionized water (calcium free) to drink, whereas control animals were given tap water containing 32.9 mg/l calcium concentration. Based on the analysis of the ionized calcium concentration response to fasting, group 2 animals were placed in one of two groups: hypocalcemia did not develop in group 2a, whereas in group 2b the ionized calcium concentration decreased 27% (from 1.09 +/- 0.07 to 0.80 +/- 0.06 mM, p = 0.01) by the third day of fasting. Group 2b responded with a 16% elevation in maternal blood pressure (p = 0.01) and a 43% reduction in uteroplacental blood flow. Furthermore, a positive correlation was found between maternal and fetal blood ionized calcium concentrations (r = 0.860).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of atrial natriuretic peptide and other vasoactive compounds on the uterine vascular bed of the nonpregnant sheep.

It has been reported that atrial natriuretic peptide (ANP) concentrations are elevated in pregnancy and further elevated in pregnancy-induced hypertension. Atrial stretch and volume expansion appear to be important stimuli for ANP release. During normal pregnancy, a striking change in hemodynamics occurs that may increase plasma ANP concentrations. ANP has potent natriuretic, diuretic, and smooth muscle relaxant activities. The biological effects of ANP during pregnancy may play an important role in the physiology and pathophysiology of pregnancy. Because of possible interactions during pregnancy due to secondary effects of maternal cardiovascular changes and physiological adaptation, the present study sought to evaluate and characterize the local effects of atriopeptin II on the uterine vascular bed of the nonpregnant sheep. Ewes with catheters in the femoral artery, femoral vein, and uterine artery and electromagnetic flow probes on the middle uterine arteries were monitored for blood pressure (BP), heart rate (HR), and uterine blood flow before and after the administration into the uterine artery of bolus injections of 2, 4, 20, and 40 x 10(-9) M (5, 10, 50, and 100 micrograms) of the synthetic ANP (atriopeptin II). For comparison purposes, the effects of prostaglandin I2 in doses of 1.2, 2.5, 12, and 25 x 10(-8) M (5, 10, 50, and 100 micrograms), vasoactive intestinal polypeptide in doses of 3, 9, 30, 90, 300, and 900 x 10(-11) M (0.1, 0.3, 1, 3, 10, and 30 micrograms), and bradykinin in doses of 9.4, 28, 94, 280, 940, and 2800 x 10(-11) M (0.1, 0.3, 1, 3, 10, and 30 micrograms) were also tested. Appropriate vehicles were tested and found to be without effect. All four compounds were found to be vasodilators of the nonpregnant uterine vasculature. ANP administered into the uterine artery decreased BP (87 +/- 4 mm Hg to 79 +/- 4 mm Hg with 50 micrograms [20 x 10(-9) M]), increased HR (90 +/- 5 bpm to 105 +/- 4 bpm), and significantly increased uterine blood flow (from 14 +/- 3 to 37 +/- 4 ml/min with a dose of 100 micrograms [40 x 10(-8) M, P < 0.05]). Prostaglandin I2 failed to alter BP, but caused significant increases on HR (100 +/- 4 to 124 +/- 13 bpm, P < 0.05) and uterine blood flow (17 +/- 4 to 73 +/- 10 ml/min, P < 0.05). Vasoactive intestinal polypeptide caused a significant tachycardia (97 +/- 10 to 158 +/- 9 bpm, P < 0.05) at the highest dose.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Effects of adenosine analogs alone and in combination with caffeine in the squirrel monkey.

Effects of the adenosine analogs R-N6-phenylisopropyl-adenosine (R-PIA) and 5'-N-ethylcarboxamidoadenosine (NECA), alone and in combination with caffeine, were studied in squirrel monkeys trained to respond under multiple fixed-interval fixed-ratio schedules of reinforcement. Both drugs produced dose-related decreases in rates of responding, with little difference between effects in the two components. NECA was about ten times more potent than R-PIA in producing these effects, the order of potency suggests that these effects may be mediated by actions at A2-adenosine receptors. Effects of either drug were antagonized by caffeine. Caffeine when administered alone increased rates of responding. The increases in response rates produced by caffeine were altered by R-PIA only at doses of R-PIA that alone decreased response rates. Effects of caffeine were either enhanced or attenuated by doses of NECA that were inactive when administered alone. These results do not support the notion that increases in rates of behavior, e.g., psychomotor-stimulant effects, produced by caffeine are due to its antagonist actions at adenosine receptors.

Adenosine↗

Stereoselective behavioral effects of N6-phenylisopropyl-adenosine and antagonism by caffeine.

Effects of the (-)- and (+)-isomers of N6-(phenylisopropyl)-adenosine (PIA) were studied in rats trained to respond under fixed-interval and fixed-ratio schedules of food reinforcement. Both isomers of PIA decreased response rates; however, the (-)-isomer decreased response rates at doses as low as 0.1 microM/kg and was 100-300 times more potent than the (+)-isomer. The potency differences suggest that the effects observed were due to actions at A1-adenosine receptors. Caffeine, an adenosine-receptor antagonist, when administered alone in doses of 10-154 microM/kg, increased response rates under the fixed-interval schedule and did not affect rates of responding under the fixed-ratio schedule. Higher doses decreased response rates under both schedules. Caffeine shifted the (-)-PIA dose-effect curve to the right. At a low dose of caffeine (25.7 microM/kg), which alone modestly increased response rates under the 5-min fixed-interval schedule, the disruptions in rates and patterns of responding produced by (-)-PIA were restored to resemble control performances. The higher dose of caffeine (77.2 microM/kg), which alone produced larger increases in rates of responding under the fixed-interval schedule, restored overall response rates to control levels when administered in combination with (-)-PIA. However, patterns of responding after the combination of doses remained disrupted. These effects suggest that some of the behavioral effects of caffeine are a result of mechanisms other than adenosine-receptor blockade.

Adenosine↗

Effects of nicotine, cocaine and some of their metabolites on schedule-controlled responding by beagle dogs and squirrel monkeys.

The behavioral effects of nicotine were compared with those of its metabolites, nornicotine and cotinine, in beagle dogs and squirrel monkeys. Subjects responded under a multiple fixed-interval (FI) 300-sec, fixed-ratio (FR) 30 response schedule of food presentation. Nicotine (0.01-1.0 mg/kg i.m.) and nornicotine (0.03-3.0 mg/kg i.m.) produced qualitatively similar effects in both dogs and monkeys. Nicotine produced dose-related increases, then decreases in rates of responding during FI components; rates of responding during FR components were only decreased. Nornicotine produced only dose-dependent decreases in responding during both FI and FR components. In the dogs, cotinine (0.01-10.0 mg/kg i.m.) produced only dose-dependent decreases in rates of responding during both FI and FR components. In the squirrel monkeys, however, cotinine (0.1-3.0 mg/kg i.m.) increased responding during FI components; a high dose of 30.0 mg/kg decreased responding during both FI and FR components. The behavioral effects of cocaine (0.03-3.0 mg/kg i.m.) and its metabolite norcocaine (0.01-1.0 mg/kg i.m.) were compared in the dogs. FI rates of responding first increased and then decreased with increasing doses of each drug, whereas FR rates of responding only decreased in a dose-related manner. Norcocaine was slightly more potent than cocaine in producing these effects on schedule-controlled responding in dogs. These experiments indicate the metabolites of nicotine and cocaine are behaviorally active and may contribute to the pharmacological profile of the parent compounds.

Animals↗

Characteristics of chronic self-administration of morphine by dogs.

Each of five dogs that had been trained to chronically self-administer IV morphine was tested with changes in the morphine dose from the baseline dose (1 mg/kg/infusion) to 0.125, 0.5, or 2 mg/kg/infusion, and with passive administration of the usual daily morphine intake while either continuing the morphine self-administration at the baseline dose or changing the self-administered solution to saline. Each treatment lasted 5 weeks. Results indicated that there is a significant negative regression of response on dose, and chronic self-administration of morphine is not entirely accounted for by a need to avoid abstinence or to obtain a direct drug effect. A third element, which may be an acquired need to obtain a response-contingent drug effect, is necessary to account for the chronic self-administration of morphine by the dog.

Animals↗

Generalization of drug-seeking behavior in dogs.

Drug-naive dogs which do not spontaneously initiate morphine self-administration were given one of three treatments and tested for subsequent morphine self-administration. Neither the dogs given the treatment of response-contingent drinking water nor those given d-amphetamine by passive infusions subsequently showed significant self-administration of morphine. However, the third group which self-administered d-amphetamine did subsequently self-administer morphine. The data suggest that self-administration of one reinforcing psychoactive drug may increase the probability of subsequently self-administering another.

Animals↗

Effects of methadone and morphine maintenance on drug-seeking behavior in the dog.

The effects of methadone and morphine maintenance on morphine self-administration were studied in the dog. Methadone was given passively for 2 weeks by continuous i.v. infusion. The amount of methadone administered daily was the same in mg/kg as the mean daily mg/kg of morphine the dogs had self-administered during the premaintenance control week. Morphine self-administration was markedly reduced initially but returned to normal levels within 2 weeks of methadone administration. Following the methadone maintenance period, morphine self-administration was increased over the premaintenance period for 2 weeks. A result similar to that with methadone was obtained in a second experiment when morphine was used as the maintenance drug in an amount that was three times the amount the dogs had been self-administering during the premaintenance control week.

Animals↗

Drug-seeking behavior in the dog: lack of effect of prior passive dependence on morphine.

Twelve dogs were made dependent on morphine (20 mg/kg per 24 hours) by intravenous passive administration of the drug. Six were gradually withdrawn and six were withdrawn abruptly. Subsequent tests for self-administration of morphine began within 8 to 18 weeks after morphine was last administered passively. Morphine was available for self-administration at several unit dose levels for 8 weeks. In comparison with control dogs administered with saline, there was no evidence that prior dependence on morphine influences subsequent self-administration of morphine, or that morphine is a primary reinforcer for dogs. Possible implications of these and related observations are discussed.

Animals↗

A method for bioassay of physical dependence on sedative drugs in dog.

A method for an economical bioassay of physical dependence on sedatives is presented. Dogs maintained on sodium pentobarbital (200 mg/kg/24 h i.v.) were given periodic graded reductions in maintenance dose, and subscales for measuring signs of abstinence were developed. Using these subscales the relative potencies compared with sodium pentobarbital were determined for sodium secobarbital (RP = 0.85) and methaqualone (RP = 0.14). Sodium thiopental and methaqualone were assayed and found to be equipotent (RP = 0.96) in reducing the signs of abstinence from sodium pentobarbital. The occurrence of convulsions, during periods of complete reduction of the maintenance drug, became less frequent the longer the dogs had been maintained on a constant dose of sodium pentobarbital.

Animals↗

Effects of morphine, chlorpromazine and chlordiazepoxide on shock-induced changes in basal skin conductance.

Chlorpromazine (12.5 and 25 mg/70 kg, i.m.) and chlordiazepoxide (25 and 50 mg/70 kg, i.m.) were compared with morphine (15 and 30 mg/70 kg, i.m.) and placebo in their effects on electric shock-induced increases in basal skin conductance. Morphine and chlorpromazine attenuated the increase compared with placebo, while chlordiazepoxide did not. None of the treatments produced reliable effects on the phasic responses to the stimuli.

Adult↗