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Biomedical subjects

S Norton

Publications and source records attributed to S Norton.

At least 19 recordsLinked to original sources

Effects of hyperglycemia on mitochondrial morphology in the region of the anterior neuropore in the explanted rat embryo model: evidence for a modified Reid hypothesis as a mechanism for diabetic teratogenesis.

Congenital malformations are the leading cause of the increased perinatal mortality in the infants of insulin-dependent diabetic mothers. The mechanisms(s) of diabetic teratologic development has yet to be defined. Hyperglycemia is known to depress aerobic metabolism in many organisms and cell lines. Reid hypothesized that exposure to hyperglycemia could result in decreased mitochondrial biogenesis in embryonic cells. Should these cells suddenly be changed to an environment of lower glucose concentration, decreased energy capabilities would exist until sufficient numbers of mitochondria could be regenerated. Such cells may not be capable of meeting temporal-spatial requirements, thereby resulting in structural abnormalities. In our study the explanted rat embryo model demonstrated that in the head-fold region hyperglycemia produced morphologic alterations of mitochondria but no difference in the number of mitochondria per cell. Specifically, embryos cultured in euglycemia demonstrated orthodox mitochondrial configuration, whereas those cultured in hyperglycemia had mitochondria in a condensed configuration. These findings were reversible. A modification of Reid's original hypothesis may provide an explanation for the mechanism of diabetic teratologic development.

Abnormalities, Multiple

Pulsed ultrasound and the hyperbarically exposed mouse fetus.

To enhance the likelihood of cavitation, pregnant mice were subjected to hyperbaric conditions and quickly returned to atmospheric pressure. Following this treatment, they were exposed to spatial average, pulse average intensities of 100 W/cm2 (2.2-MHz, 20-microseconds pulses with a duty cycle of 1/1000 or a temporal average spatial average intensity of 0.1 W/cm2). Fetal weights, deaths and malformations were scored. No statistically significant effects were observed in the offspring.

Animals

Influence of rapeseed meal, whole rapeseed, and soybean meal on fatty acid composition and cholesterol content of muscle and adipose tissue from ram lambs.

Twenty-four Suffolk x Hampshire ram lambs (average 46 kg) were assigned to one of three diets containing rapeseed meal (RM), soybean meal (SBM), or whole rapeseed-soybean meal (RSSBM) as the protein source. Diets contained 75% roughage, 14% CP and 2.0 Mcal of ME/kg and lambs were allowed ad libitum access to diets for 35 d. Lipid composition of the longissimus, semimembranosus, and triceps brachii muscles and their corresponding s.c. adipose tissue was determined by gas-liquid chromatography (GLC). The total lipid content in either muscle or subcutaneous fat was not different (P greater than .01) by diet. In lean tissue, palmitic and palmitoleic acids were higher and stearic acid was lower (P less than .01) in rams fed RM than in rams fed RSSBM or SBM, regardless of anatomical location. In the s.c. adipose tissue, the amounts of myristoleic, pentadecylic, and palmitoleic acids were lower and the amount of stearic acid was higher (P less than .01) in rams fed RSSM than in those fed RM or SBM, regardless of anatomical location. The semimembranosus and triceps brachii muscles from all treatments contained 12 to 19% more polyunsaturated fatty acids (PUFA) than the longissimus muscle. The cholesterol content of the three muscles was highest in SBM-fed lambs, lowest in RM-fed lambs, and intermediate in RSSBM-fed lambs. These results demonstrate that dietary treatments of the types used in the present study elicit changes in fatty acid composition of both adipose and muscle tissue without affecting the quantity of total lipid.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue

Prenatal and postnatal consequences in the brain and behavior of rats exposed to ultrasound in utero.

As a result of a prior experiment demonstrating damage to the developing cortex of the fetal rat 24 hours after maternal exposure to ultrasound, postnatal consequences of similar exposure on rat behavior were examined. No decrease in postnatal weight or growth rate was found and no significant decrease in cortical thickness was present postnatally at 28 days. In two of four behavioral tests, rats exposed to ultrasound in utero resembled similarly treated controls. In one test, ultrasound-exposed rats showed slower performance, and in one, faster performance. These data provide no consistent evidence that ultrasound exposure resulted in deleterious postnatal effects.

Animals

Basic animal research.

Recent research with animal models of the fetal alcohol syndrome has resulted in advances in the areas of prenatal and postnatal growth retardation, facial dysmorphology, immune system deficiencies, endocrine dysfunction, and central nervous system alterations, including behavior. The rat is the most common species used in these studies, although similar experimental changes have been produced in a limited number of studies in other species. The specific deleterious effects of ethanol on the fetus are dose-related and dependent on the stage of gestation, as with other fetotoxic agents. However, the precise timing and dose-effect curves have yet to be established for most types of ethanol-induced damage. Various exposure regimens have been employed, including inhalation of ethanol vapor and intraperitoneal injection, as well as oral exposure by gavage, diet, or drinking water. In the early postnatal period, following gestational exposure, altered function is most marked, with recovery in some measurements with postnatal maturation. The present literature clearly defines developmental damage from gestational exposure to ethanol as well as areas for additional research.

Animals

Acute response of the fetal telencephalon to short-term maternal exposure to ethanol in the rat.

Pregnant rats were exposed to either ethanol (total dose 18 g/kg) on gestational days 14 and 15 or whole-body ionizing radiation (0.5 Gy) on gestational day 15. On gestational day 16, 24 h following the last dose of ethanol or exposure to ionizing radiation, the developing cerebral cortex of the fetus was examined histologically. Ionizing radiation caused extensive cell death within the fetal cerebral cortex whereas ethanol caused more subtle morphological changes such as cortical thinning and petechial intraventricular hemorrhages. These findings suggest that ethanol, unlike ionizing radiation, acts by some mechanism other than cell death to cause cortical thinning and cortical malformations. The pathogenesis of ethanol-induced cortical dysgenesis may include fetal hypoxia and inhibition of neuroblast proliferation within the developing cerebral cortex.

Animals

Acute response of fetal rat telencephalon to ultrasound exposure in utero.

Pregnant rats were exposed to ultrasound or microwaves from transducers located over one uterine horn. Ultrasound intensity (SPTA) was 0.78 W/cm2 for 30 min at a frequency of 2.5 MHz. Microwave exposure was used to reproduce approximately the rate of rise of uterine temperature of the rats exposed to ultrasound. The average peak temperature was 40.1 degrees C for ultrasound exposure and 42.2 degrees C for microwave exposure. On Gestational Day 16, 24 h after exposure, fetuses were removed and prepared for morphological examination of the developing cerebral cortical mantle. Morphometric measurements were made of nuclear area of subventricular zone cells, number of mitoses per mm in the ventricular zone, number of pyknotic cells in the mantle per mm, and number of ventricular macrophages per mm. Both exposures increased nuclear size and numbers of pyknotic cells and macrophages, and decreased the number of mitotic figures. The data from the four measurements were evidence of damage from ultrasound similar to the effects produced by microwave heating. The thermal effects of ultrasound, even at relatively low levels of rise in temperature, may have been the cause of the damage to the fetal cortex in these experiments or may have interacted with other effects of ultrasound energies to produce damage to developing neurons.

Animals

Pressure threshold for shock wave induced renal hemorrhage.

Studies were performed with an interest in determining a pressure threshold for extracorporeal shock wave induced renal damage. Histological evidence of intraparenchymal hemorrhage was used as an indicator of tissue trauma. Depilated C3H mice were anesthetized and placed on a special frame to enhance visualization and treatment of the kidneys in situ. A Wolf electrohydraulic generator and 9 French probe designed for endoscopic use were utilized to expose the kidneys to 10 double spherically divergent shock waves. Measurements of the shock waves revealed two positive pressure peaks of similar magnitude for each spark discharge. The kidneys were exposed to different peak pressures by choice of distance from the spark source and were removed immediately after treatment for histologic processing. A dose response was noted with severe corticomedullary damage apparent following 15 to 20 MPa shocks. Hemorrhage was more apparent in the medulla where evidence of damage could be seen following pressures as low as three to five MPa. When a latex membrane was interposed to prevent possible collapse of the initial bubble from the spark source against the skin surface, histological evaluation revealed substantial reduction of severe tissue damage associated with the highest pressures tested, 20 MPa. However, the threshold level for evidence of hemorrhage remained about three to five MPa. Hydrophonic measurements indicated that the membrane allowed transmission of the acoustic shock waves and suggested that collapse of the bubble generated by electrohydraulic probes may have local effects due to a cavitation-like mechanism.

Animals

Ultrasonic heating of the skull.

Comparatively simple analysis shows that diagnostic ultrasound devices, in some cases, may approach output levels that can produce significant heating of tissues, particularly if the propagation path includes bone. Experimental tests of these predictions using rodents show that temperature increments of the order of 3 degrees C/W/cm2 are produced in skull bone with sharply focused fields at medically relevant frequencies.

Animals

Early effects of low doses of ionizing radiation on the fetal cerebral cortex in rats.

Pregnant rats were exposed to gamma radiation from a 137Cs irradiator on gestational Day 15. Fetuses that received 0.25, 0.5, 0.75, or 1.0 Gy were examined 24 h after irradiation for changes in the cells of the cerebral mantle of the developing brain. The extent of changes following 0.5 Gy was studied at 3, 6, 12, or 24 h after exposure. Cortical thickness of the cerebral mantle was not significantly altered. The number of pyknotic cells, number of macrophages, nuclear area, and number of mitotic cells were altered in a dose-related way. The number of pyknotic cells was significantly increased at all doses. A positive correlation between the number of pyknotic cells and the number of macrophages developed with time. At 3 h after irradiation about 60% of pyknotic cells were found in the subventricular zone and about 25% in the intermediate zone and cortical plate. The number of such cells in the upper layers of the cortex steadily increased up to 24 h, at which time about 70% of pyknotic cells were in these two layers. The relationship of the movement of pyknotic cells to migration of postmitotic neuroblasts is discussed.

Animals

Morphometric analysis of developing rat cerebral cortex following acute prenatal ethanol exposure.

Morphologic alterations of fetal rat cerebral cortex were quantified by morphometric analysis following acute ethanol exposure on Gestational Day 14, a critical period of development of cerebral cortex. Pregnant rats were intubated with a total dose of 9 g/kg of ethanol on Gestational Day 14. Maternal blood ethanol levels ranged from 51 to 202 mg% during the period of ethanol exposure. Fetal brains were examined on Gestational Day 15, 24 h after the last dose of ethanol. The acute morphologic changes associated with ethanol exposure include enlargement of subventricular zone nuclei, cortical swelling, and dilation of pial blood vessels over the affected cortex. In some fetuses, cortical swelling was accompanied by the protrusion into the lateral ventricles of cytoplasmic blebs of ventricular zone cells. It is concluded that maternal ethanol exposure during a critical period of brain development produces measurable morphologic changes in fetal rat cerebral cortex within 24 h after ethanol exposure.

Animals

Improved pulmonary function in chronic quadriplegics after pulmonary therapy and arm ergometry.

Quadriplegics suffer from restrictive lung disease due to neural damage, spasticity, and prolonged immobilisation. These studies were undertaken to see whether respiratory therapy can improve expiratory capacity in quadriplegics. Fifteen patients with chronic quadriplegia participated in a programme of pulmonary therapy and resistance exercise for 7 to 12 weeks. Pulmonary therapy consisted of incentive spirometry for 15 minutes a day 3 to 5 days per week. Resistance exercise consisted of pedalling an arm ergometer up to 30 minutes three times a week. Forced vital capacity was measured with the subject in a wheelchair wearing a nose clip. The volume of expired air (max Ve) was as determined with a paramagnetic analyser during arm ergometry. The volume of expired air was divided by the number of breaths, giving the volume of expired air per breath (Ve). The results indicated that a combination of incentive spirometry and arm ergometry improves vital capacity and increased the maximum volume of expired air during exercise. These methods are non-invasive, and such modalities should constitute part of the rehabilitation of patients with neuromuscular disease.

Adolescent

Cerebral cortical morphology and behavior in rats following acute prenatal ethanol exposure.

Cerebral cortical morphology and early motor development were evaluated in offspring from ethanol-exposed mothers, pairfed control mothers and ad libitum control rats. Ethanol-exposed rats received a total dose of 18 g/kg of ethanol by intubation on gestational Days 14 and 15, a critical period of development of the cerebral cortex. Pairfed control mothers received isocaloric sucrose on gestational Days 14 and 15 and were pairfed to ethanol-exposed animals from gestational Day 12 through gestational Day 20. Ethanol-exposed offspring weighed significantly less than control offspring from postnatal Day 7 through postnatal Day 28. Ethanol-exposed offspring also showed significant delays in reflex suspension (time an animal maintained its grip on a crossbar) and continuous corridor (number of turns in 5 min). The thickness of the cerebral cortex of ethanol-exposed offspring was significantly different from ad libitum and pairfed control offspring on postnatal Day 1. However, only Layer V and total cortical thickness were affected in ethanol-exposed offspring on postnatal Day 28. The results of this study indicate that ethanol exposure during a critical period of development causes alterations in central nervous system development and developmental delays.

Animals

Correlation of cerebral cortical morphology with behavior.

Association between functional damage and damage to the central nervous system from toxic agents can be used to determine the value of behavioral tests as predictors of damage to the nervous system. Variability in data from behavioral tests may be caused, in part, by varying levels of structural differences in the nervous system. Stepwise multiple regression is one method for analyzing the relationship between variability in data resulting from linkage between functional and morphological or other parameters of the structure of the nervous system. As an example, the predictive value of four behavioral tests is assessed in detecting thinning of the cerebral cortex following gestational exposure of rats to ionizing radiation. In this analysis, there were seven independent variables for predicting cortical thickness. The sequence of number of times each variable was used in prediction, from most frequent to least frequent, was: angle of stride greater than negative geotaxis greater than continuous corridor greater than body weight greater than width of stride greater than length of stride greater than reflex suspension. The data support the concept that there are varying degrees of predictive associations between these functional and cortical parameters.

Animals

Randomised trial of prophylactic daily aspirin in British male doctors.

A six year randomised trial was conducted among 5139 apparently healthy male doctors to see whether 500 mg aspirin daily would reduce the incidence of and mortality from stroke, myocardial infarction, or other vascular conditions. Though total mortality was 10% lower in the treated than control group, this difference was not statistically significant and chiefly involved diseases other than stroke or myocardial infarction. Likewise, there was no significant difference in the incidence of non-fatal myocardial infarction or stroke--indeed, disabling strokes were somewhat commoner among those allocated aspirin. The lower confidence limit for the effect of aspirin on non-fatal stroke or myocardial infarction, however, was a substantial 25% reduction. Migraine and certain types of musculoskeletal pain were reported significantly less often in the treated than control group, but as the control group was not given a placebo the relevance of these findings was difficult to assess. There was no apparent reduction in the incidence of cataract in the treated group. The lack of any apparent reduction in disabling stroke or vascular death contrasts with the established value of antiplatelet treatment after occlusive vascular disease.

Aspirin

Behavioral changes and structural defects in rats irradiated in utero.

Pregnant rats were irradiated with whole-body doses (0.25-1.25 Gy) of Cs-137 gamma-rays on gestational day 15, or with 1.0 Gy on gestational days 11, 13, 15, or 17. Postnatal growth (body weight) and several preweaning behaviors (righting reflex, negative geotaxis, reflex suspension, modified open field activity, spatial maze exploration, continuous corridor activity, and gait) of the offspring were monitored prior to sacrifice on post-parturition day 28. Brain (sensorimotor cortex) and pituitary tissues were processed for histological evaluation and morphometric analysis. For most behavioral endpoints, there were dose-dependent changes produced by irradiation on gestational day 15, with one endpoint (continuous corridor activity) demonstrating changes after 0.25 Gy that were significantly different from control values. The data indicate that the most sensitive organ showing radiation-induced alterations changes from the pituitary at gestational day 11 to the primitive cortex of the brain at days 13 to 17 with a peak of sensitivity at day 15. These results demonstrate that a spectrum of related functional and morphological deficits can be produced by even low-dose in utero irradiation, with the specific endpoint showing the greatest change being determined by the specific day of gestation on which irradiation occurs. Extrapolating from these experimental data with rats to the human situation, it is recommended that care be taken, when possible, to avoid exposure of the fetus, even after the early stages of organogenesis.

Animals

Early motor development and cerebral cortical morphology in rats exposed perinatally to alcohol.

Specific tests of early motor development and cerebral cortical morphology were studied in rats born from alcohol-fed mothers, pair-fed mothers, and ad libitum controls (either liquid or pellet diets). Liquid Bio-Serv diets were used. Alcohol feeding began on day 5 of pregnancy and ended on day 10 postpartum. The weight gain of the pups after birth was drastically reduced compared with pair-fed and other control groups; however, removal of the alcohol on day 10 postpartum resulted in an upswing of the growth curve that paralleled control groups. Between days 2 and 21 (postnatal) three behavioral tests of motor function were performed. Righting reflex (time for an animal to return to all four feet after being placed on its dorsum) was slightly delayed but the delay was not significant. Negative geotaxis (time for an animal to rotate 180 degrees from a head-down position on an inclined plane), and reflex suspension (time an animal maintained its grip on a crossbar) were significantly delayed (approximately 2 days) in offspring from alcohol-fed mothers. In the frontal cortex the offspring of alcohol-treated mothers, a marked decrease (approximately 25%) in thickness of Lamina VI was found while the other Lamina (I-V) were less altered. These results indicate that the effect of alcohol on the frontal cortex is related to a significant delay in motor development of reflex suspension and negative geotaxis since both of these require frontal integration.

Animals