Anthropometry as a predictor of high speed performance.

To assess anthropometry as a predictor of high-speed performance, subjects performed four seated knee- and hip-extension workouts with their left leg on an inertial exercise trainer (Impulse Technologies, Newnan GA). Workouts, done exclusively in either the tonic or phasic contractile mode, entailed two one-minute sets separated by a 90-second rest period and yielded three performance variables: peak force, average force and work. Subjects provided the following anthropometric data: height, weight, body mass index, as well as total, upper and lower left leg lengths. Via multiple regression, anthropometry attempted to predict the variance per performance variable. Anthropometry explained a modest (R2=0.27-0.43) yet significant degree of variance from inertial exercise trainer workouts. Anthropometry was a better predictor of peak force variance from phasic workouts, while it accounted for a significant degree of average force and work variance solely from tonic workouts. Future research should identify variables that account for the unexplained variance from high-speed exercise performance.

Effects of insulin-like growth factor 1 on olfactory neurogenesis in vivo and in vitro.

The rate of neurogenesis in the peripheral olfactory neuroepithelium is regulated by unknown mechanisms. The members of the insulin-like growth factor (IGF) family can influence neuronal generation, survival and/or differentiation. Several members of this family, in particular IGF-1, are expressed at high levels in the olfactory bulb and epithelium, where they could influence the generation and/or survival of olfactory receptor neurons (ORNs). To explore the role of IGF-1 in the olfactory epithelium (OE), we asked which cells expressed IGF-1 receptors (IGF-1Rs), using olfactory cell cultures and cryostat-cut tissue sections of neonatal (postnatal day four) and adult rat OE. An antibody specific for the alpha subunit of the IGF-1R densely labeled a subset of ORNs but not other cell types in sections and cultures. These ORNs were primarily immature, as determined by double labeling with neuronal markers. The number of IGF-1R-labeled cells as well as the levels of IGF-1R protein (determined by immunoprecipitation and Western blotting) decreased with age, which is consistent with normal developmental changes. To study IGF-1 effects in the intact animal, we infused IGF-1 and related growth factors into the noses of newborn Sprague-Dawley rats, i.e., when the epithelium is still developing. Growth factors or carrier solution (0.9% NaCl with 0.25% bovine serum albumin to prevent nonspecific binding) were applied (10 microliters) to the left nostril once per day starting shortly after birth on postnatal day 1 (P1), P2 and P3, and the animals were sacrificed on P4 by decapitation. After paraformaldehyde immersion fixation, cryostat sections of the olfactory area of the nose were immunostained for the proliferating cell nuclear antigen (PCNA). Sections were position-matched by turbinate structure and then epithelial height and area of PCNA staining at the base of the epithelium (which represents division of primarily neuronal precursors) were measured by image analysis. Both were significantly increased by rat IGF-1 (20 ng/ml, 2.6 nM), but not insulin (20 ng/ml, 2.6 nM) or an IGF-1 derivative, LongR3 IGF-1 (200 ng/ml, 22 nM), that does not bind to the IGF-1 binding proteins (IGFBPs). Thus IGF-1 appears to influence the rate of olfactory neurogenesis, and its actions are not modified by the IGFBPs. These data suggest an important role for IGF-1 in the OE.

3-Methylindole alters both olfactory and trigeminal nasal mucosal potentials in rats.

Data from human studies imply that vanillin is an olfactory stimulant, whereas CO2 activates intranasal trigeminal nociceptors. We examined the effects of the olfactotoxin 3-methylindole (3-MI) on nasal mucosal potentials evoked by vanillin and CO2 in rats. A single i.p. administration of 300 mg/kg 3-MI altered both olfactory and trigeminal mucosal responses. Relative to amplitude values determined in non-3-MI-injected rats, the response to vanillin was reduced to 6%, 7%, and 43%, and the response to CO2, recorded in the same rats, decreased to 25%, 38%, and 51% at 4, 8 and 16 days post-3-MI, respectively. The results suggest that 3-MI affects both olfactory and trigeminal elements within the nasal mucosa.

Olfactory neurons in vitro show phenotypic orientation in epithelial spheres.

Production and differentiation of olfactory neurons occur in spherical, multi-neuronal aggregates that form in cultures where dissociated newborn rat nasal cells are plated on to CNS glial cells. We show here that neuronal cell bodies were primarily located in the peripheral layers of the spheres, and almost every neuronal sphere contained one or several non-cellular central cavities. The dendrite-like processes of the olfactory neurons, immunostained for neuron-specific tubulin or the olfactory marker protein, were aligned and directed towards the central cavities. Olfactory neurons in the intact animal show a similar relationship with the nasal lumen. Non-neuronal cells formed multiple layers centrally, bordering the cavities. This degree of phenotypic re-creation is unusual in a dissociated monolayer culture system.

Microvillar cells of the olfactory epithelium: morphology and regeneration following exposure to toxic compounds.

In recent years microvillar cells (MVC) have been identified in the olfactory epithelium of numerous species, including rodents, canines, and primates. However, there is no consensus on the morphologic or histochemical features of this cell, nor is the function of these cells currently known. Previous studies have examined MVC during development and in the mature olfactory epithelium, but not after toxic insult. A microvillar cell, defined by specific morphologic criteria, was studied in adult male Long-Evans rats exposed via inhalation to either 200 ppm methyl bromide for 4 h/day, 4 days/week for 2 weeks, or to 635 micrograms/m3 nickel for 6 h/day for 16 consecutive days, and sacrificed serially over several months. The pattern of recovery for MVC differed according to the severity and specificity of the insult to the olfactory epithelium. With methyl bromide, all cell types were completely depleted from olfactory epithelium immediately after injury, including MVC. MVC were slow to repopulate the epithelium, and appeared only when olfactory epithelium was complete in other respects. With nickel exposure, where the major effect was a gradual decrease in sustentacular cells with a thinning of the apical cytoplasm thickness, MVC showed a decline during exposure, but reappeared during recovery. In both cases, there was no difference in olfactory function, even when MVC were absent from the olfactory epithelium. A mature olfactory epithelium appears to be necessary to support the presence of this MVC, suggesting that it is not crucial to the regeneration processes or recovery of olfactory function, but perhaps plays some role, as yet undefined, in the unperturbed olfactory epithelium.

Chronic dexamethasone treatment potentiates insult to olfactory receptor cells produced by 3-methylindole.

The effect of chronic dexamethasone treatment on damage to olfactory receptor cells produced by 3-methylindole (3-MI) was examined. Twelve rats were injected, every other day, with dexamethasone (1.5 mg/kg, i.p.), and 12 rats with saline alone. Injections began 1 week before and continued, in different rats, from 1 to 4 weeks after a single intraperitoneal administration of 150 mg/kg 3-MI. One, two, three, and four weeks after exposure to 3-MI, different groups of rats, three specimens per each treatment condition, received bilateral application of horseradish peroxidase to the olfactory mucosa and were subsequently sacrificed. Anterograde labeling of primary afferents, i.e., an inverse correlate of the degree of cellular damage, was quantitatively determined by measuring the mean optical density (MOD) of staining in sections of the olfactory bulb. In saline-injected rats, the MOD values were 27.0, 46.6, 87.1, and 104.7 for one, two, three, and four post-3-MI weeks, respectively. The corresponding values in the dexamethasone-treated rats were 15.7, 29.7, 87.5, and 110.5. The MOD values of the dexamethasone-injected rats were significantly lower than those of the saline-injected rats for post-3-MI weeks 1 and 2, indicative of stronger damage to olfactory receptor cells in the rats treated with the glucocorticoid. The data suggest that dexamethasone potentiates the 3-MI olfactotoxicity during the first 2 weeks after insult. This effect, at least partly, may be due to the inducing action of dexamethasone on the cytochrome P450 responsible for metabolic bioactivation of 3-MI.

Olfactory primary neurons as a route of entry for toxic agents into the CNS.

Reports in the literature suggest that the primary sensory neurons of the olfactory system may provide a direct route of entry for agents into the central nervous system (CNS). To investigate whether cadmium, a heavy metal which is normally excluded from the CNS by the blood-brain barrier, can enter the CNS via the olfactory system, rats were exposed either intranasally (unilaterally) or ip to 109Cd (1 mumol Cd labeled with 1 microCi 109Cd). Rats were allowed to survive 7 days, at which point they were euthanized and the kidneys, livers, right and left forebrains, right and left olfactory bulbs, and right and left olfactory epithelia were removed. Tissues were placed in scintillation vials and radioactivity counted. In rats exposed by intranasal instillation, Cd levels were significantly elevated in the kidney, liver and ipsilateral olfactory bulb and epithelium, but not in the contralateral bulb and epithelium or forebrain areas. With the ip exposure, Cd levels were only elevated in the kidney and liver. In a second study the protocol was repeated (without ip exposure), but the olfactory bulbs and epithelium were washed in EDTA before counting. Cd was still present in the bulbs after washing, suggesting that the metal was internal and not bound to the external membrane. In the final experiment, both time course and dose effect of this phenomenon were explored. Rats were exposed either intransally to 1 mumol Cd labeled with 109Cd (1 microCi) and then sacrificed after 1, 3, 7, or 14 days or were exposed to 0.01, 0.1, or 1.0 mumol Cd labeled with 1 microCi 109Cd and sacrificed after 7 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Self-deprivation: a test of the reward hypothesis.

Self-deprivation refers to the observation that despite severe levels of water and food deprivation some rats dramatically reduce food and water intake when brain stimulation reward and the alternative reward are placed in competition. In order to determine if the rewarding properties of brain stimulation are responsible for self-deprivation, rats were implanted bilaterally with stimulating electrodes and subsequently tested for self-deprivation and preferences among various electrode locus/stimulation current combinations. According to the reward hypothesis, the relative degree of self-deprivation observed for each electrode/current pair should predict the order of preference for each combination when different electrode/current pairs are placed in competition. Likewise, across all combinations of electrodes and intensities, increasing preferences should be associated with increasing self-deprivation. The findings of the study provide support for the reward hypothesis of self-deprivation. The correlation between the self-deprivation and the preference measure was r = 0.62 (p less than 0.001), which rose to r = 0.80 (p less than 0.001) when floor and ceiling effects were taken into account. It was concluded that the rewarding aspects of brain stimulation are responsible for the self-deprivation phenomenon.

Behavioral effects of low level neonatal lead exposure.

Rats exposed to lead via maternal milk were tested at various stages of development on a number of behavioral tasks. Beginning at paturition, the dams were given either tap water, 0.02%, or 0.10% lead acetate in the drinking water. Pups from all three groups were weaned to normal chow and tap water at 21 days of age. The mean lead concentration of the dam's blood and of neonatal (20 days of age) brain and blood were all below 50 microgram/100 ml. No significant differences were found between the high lead-exposed group and controls in general as measured by wheel running over a 21 day period beginning at 30 days of age. However, there was a significant difference in wheel running behavior during the first three hr of testing. Both lead-exposed groups were found to display significantly less aggressive behavior as measured by the shock-elicited aggression test. Low level lead exposure had no discernable effect on the acquisition and subsequent reversal of a successive brightness discrimination task. Lead exposure under these conditions appears to affect some aspects of emotional behavior, while having little effect on general activity or cognitive function.

Sensory neurotoxicology: use of the olfactory system in the assessment of toxicity.

Although many compounds are purported to cause olfactory dysfunction, little experimental research has been done in this area. The nasal epithelium, being one of the first "wet tissues" to come into contact with airborne compounds, should be a good indicator of toxic insult. The same general procedures used to measure visual or auditory function can be applied to the olfactory system, although olfactory stimuli are much more difficult to generate and control. Cadmium exposure, which is frequently cited as causing olfactory dysfunction in humans, did not produce anosmia (loss of smell) in rats, even though there was a large increase in cadmium levels in their olfactory bulbs. Rats exposed to methyl bromide showed a severe disruption in olfactory function as well as in morphology and neurochemical indices. However, functional recovery occurred even in the presence of continuing morphological and neurochemical evidence of damage. A nonsensory function of the olfactory system, transneuronal transport via the primary sensory neurons, may represent a mechanism of entry into the central nervous system for compounds that are normally excluded by the blood-brain barrier.

Effects of inhalation of cadmium on the rat olfactory system: behavior and morphology.

To investigate the effects of cadmium on olfaction, two separate studies were conducted in which male adult rats were exposed to CdO, via inhalation, for 5 h per day, 5 days a week for 20 weeks. Target exposure values of 250 and 500 micrograms/m3 were measured at 200 and 325 micrograms/m3 for the low concentration in two experiments, and 550 and 660 micrograms/m3 for the high concentration. Prior to exposure, olfactory thresholds were obtained using a conditioned suppression technique. After 20 weeks of cadmium exposure, there was no evidence of anosmia in any of the rats nor were there any significant changes observed in olfactory thresholds. Although olfaction was not impaired, cadmium levels in the olfactory bulbs of exposed rats were significantly elevated compared to controls. Cardiac and respiratory histopathology were observed at all exposure levels, but there was no evidence of nasal pathology related to exposure to cadmium. Failure of cadmium to produce olfactory dysfunction may be due to the protective effects of metallothionein and/or to the highly resilient nature of the rodent olfactory system.

Effects of 2-methoxyethanol on fetal development, postnatal behavior, and embryonic intracellular pH of rats.

The industrial solvent 2-methoxyethanol (2ME) is a reproductive and developmental toxicant when administered by inhalation, gavage, and IP injection. The present research established that this solvent can produce teratogenicity in rats when administered in liquid diet. Groups of 10 Sprague-Dawley rats were given various percentages of 2ME in liquid diet on gestation days 7-18. Day 20 fetuses were examined for visceral or skeletal malformations. Concentrations above 0.025% 2ME (approximately 73 mg/kg/day) produced total embryo-mortality. Cardiovascular malformations were produced at lower levels. The teratogenic no-effect level was 0.006% 2ME (16 mg/kg). In a second experiment, groups of 12 Sprague-Dawley rats were given 0, 0.006 and 0.012% of 2ME as above. Litters were culled to 8 pups, and tested for auditory and tactile startle and conditioned lick suppression, and for performance in figure-8 activity and the Cincinnati water maze on postnatal days 48-65. The high dose of 2ME produced approximately 50% mortality in the offspring and increased the number of errors in the Cincinnati maze. No other behavioral effects were observed at either dose. An interaction study was conducted to determine if simultaneous exposure to 2ME and ethanol would reduce the teratogenicity of 2ME, but no reduction was observed. The hypothesis that 2ME acts by altering embryonic intracellular pH was tested by injecting 0.33 ml/kg of 2ME into rats on gestation day 13, and determining embryonic intracellular pH at 2, 4, 8, and 24 hours thereafter. There was an increase in pH at 4 hours, but not at later time points. Another group of rats was given 2ME along with amiloride, which blocks the sodium/hydrogen antiporter. The combined 2ME-amiloride exposure produced an incidence of cardiovascular malformations in fetuses twice that of 2ME alone. These studies confirmed the structural teratogenicity of 2ME even when given in liquid diet, as it was given for the first time in the present study. At nonteratogenic doses, developmental toxicity (e.g., postnatal deaths) persisted, but only limited evidence of behavioral teratogenicity was observed. The pH data are consistent with the concept that 2ME may alter embryonic intracellular pH at critical stages of organogenesis.

A study testing the routine use of ultrasound measurements when selecting the electron energy for breast boost radiotherapy.

The determination of the depth of the tumour bed within the breast requiring an electron therapy boost dose is generally judged clinically and can be inconsistent between individual radiotherapists. High frequency ultrasound provides a reproducible, safe and quick method of measuring this depth. In order to improve current working practice at the Royal Marsden NHS Trust the routine use of ultrasound when planning breast boost radiotherapy was established. Fifty-three early stage postoperative breast cancer patients had both clinical and ultrasound assessments of boost depth performed. These measurements were converted into electron energy and compared. Measurements ranged from 0.8 cm to 4.9 cm and electron energy from 4 MeV to 15 MeV. As a direct result of the ultrasound measurements taken, 60% of patients had their electron energy changed from that chosen by the clinically assessed measurement. Overall, the energy was as likely to be increased as decreased. Breast size did not influence the need for change but patients with small breasts never required an increase in the energy from that chosen clinically. It was concluded that the use of ultrasound, once integrated into the planning process, can improve accuracy when selecting electron energy for patients receiving breast boost irradiation.

Relationships between the nuclear membrane, nuclear pore complexes, and organelles in the type II pneumocyte.

Functional relationships among organelles of the type II cell are suggested based upon the proximity of organelles to specialized areas of the plasma- and nuclear membranes. In a two-dimensional morphometric analysis of the profiles of organelles in type II cells of the ferret and rat (and beagle dog), lamellar bodies were more likely to be located near the nuclear membrane than at the alveolar space (where exocytosis occurs). The size of lamellar body profiles was not correlated with distance from the nuclear membrane; however, large profiles were nearer the apical membrane, and smaller ones nearer the basement membrane. Profiles of highly branched mitochondria were 10 times more frequently associated with nuclear pore complexes than with the inter-pore nuclear membrane. Forty percent of all mitochondrial profiles were within 0.25 microns of the nucleus, 5% were within 0.02 microns and half of these appeared to touch the filaments of the nuclear pore complexes. The size of mitochondrial profiles was not correlated with distribution. In the ferret and rat, 8.6% and 2.5% respectively, of the nuclear pore complexes were associated with mitochondria. Sebaceous cells, from control mice, demonstrated a spatial distribution of granules which was size dependent but unrelated to the nuclear membrane.

Adsorption of 222Rn by open-faced and diffusion-barrier canisters at different conditions of temperature and humidity.

Open-faced and diffusion-barrier charcoal canisters were individually exposed to a fixed temperature, humidity, and radon concentration in a chamber for a period of 7 d. The radon progeny activity in the canister under study was measured every 3 h. A total of 15 runs were made for the open-faced canisters and nine runs for the barrier canisters with temperatures and absolute humidities ranging from 15-30 degrees C and 0-15 g m-3, respectively. In addition, several runs were made with the radon, temperature, and humidity changing during the 7 d. Results show that open-faced canisters adsorb radon up to 60% more efficiently at 15 degrees C than at 30 degrees C while the barrier canisters show little temperature dependence. The barrier canisters are much less sensitive to humidity effects than the open-faced canister. When used to measure the radon concentration in air, the open-faced canister integrates over a period of only approximately 48 h while the barrier canister integrates over a period of approximately 96 h. The short integration time and the interference of water adsorption by open-faced canisters indicate that the open-faced canisters should be used for exposure times of 48 h and no longer.

Prenatal or postnatal indomethacin exposure and neonatal gut injury associated with isolated intestinal perforation and necrotizing enterocolitis.

OBJECTIVE: To examine the role of indomethacin in neonatal gut injury. STUDY DESIGN: Infants born at gestational age 23 weeks and with birth weights 400-1200 g were included in this prospective prevalence study of neonatal gut injury. Infants with isolated intestinal perforation (IIP) confirmed at laparotomy or at autopsy or with necrotizing enterocolitis (NEC) were identified. Data were abstracted bi-weekly. RESULT: Among 992 study infants, 58 infants exposed solely to prenatal indomethacin did not show an increased rate of neonatal gut injury. Any postnatal indomethacin exposure (n=611) increased the odds of IIP (OR 4.17, CI, 1.24-14.08, P=0.02) but decreased the odds of NEC (OR 0.65, CI 0.43-0.97, P=0.04). There was a negative association between the timing of indomethacin-exposure and the odds of developing IIP (OR 0.30, CI 0.11-0.83, P=0.02). Compared with NEC, IIP occurred at an earlier age (P<0.05) and was more common (P<0.05) among infants who received early indomethacin (first dose at <12 h of age) to prevent intraventricular hemorrhage than among infants who were treated with late indomethacin for closure of a patent ductus arteriosus (PDA). Unlike the classic hemorrhagic ischemic lesions of NEC in which large areas of tissue were inflamed or necrotic, the IIP lesions were small and discrete. CONCLUSION: Early (<12 h) postnatal indomethacin exposure was associated with an increased odds of IIP in very low birth weight infants whereas its later use for closure of a PDA appeared to provide protection against NEC. The paradoxical effect of the timing of indomethacin on IIP versus on NEC may be related to the different pathogeneses of the two diseases. Our findings also suggest that PDA may contribute to NEC.

Accumulation of Cd(II) in the CNS depending on the route of administration: intraperitoneal, intratracheal, or intranasal.

The uptake and subsequent neuronal transport of certain heavy metals in the olfactory mucosa may be a major means by which these compounds gain access to the CNS. To contrast olfactory versus blood-borne routes of exposure, three groups (n = 4) of adult Long-Evans rats were exposed to solutions of radiolabeled CdCl2. Exposure was by one of three routes: unilateral intranasal instillation (IN), intratracheal lavage (IT), or intraperitoneal injection (ip). The dose level for the intranasal route was 30 microliters of 1 microM CdCl2 labeled with 1 microCi 109Cd. For IT and ip, the dose was 30 microliters of 1 microM CdCl2 diluted to 300 microliters in saline and labeled with 1 microCi 109Cd. Rats were euthanized 24 hr after exposure, tissue samples were taken, and radioactivity was counted. Cd levels were low in the olfactory bulbs of rats exposed either intratracheally or intraperitoneally. However, in rats intranasally exposed, Cd levels were nearly 40 x higher in olfactory bulbs ipsilateral to the exposed side than in those on the contralateral side. With all routes of exposure, Cd levels in brain samples were only slightly elevated. These results suggest that for certain airborne toxicants, especially those that are excluded from the CNS by the blood-brain barrier, the olfactory system may provide a direct route of entry into the CNS.