Arthralgias and cryoglobulinemia during protease inhibitor therapy in a patient infected with human immunodeficiency virus and hepatitis C virus

The effect of pre- and postnatal maternal dietary fatty acid composition on neurodevelopment in rat pups was studied. Timed pregnant dams were fed, beginning on d 2 of gestation and throughout lactation, either nonpurified diet (reference) or a purified diet whose fat source (22% of energy) was either corn oil or menhaden fish oil. On postnatal d 3, pups were randomly cross-fostered among dams of the same diet group and culled to 10 pups per dam. Milk was removed from stomachs of culled pups for fatty acid analyses. From postnatal d 4 to 30, pups were assessed daily for the appearance of neurodevelopmental reflexes. Auditory brainstem conduction times were measured on postnatal d 23 and 29. Pups were killed on postnatal d 30, and cerebrums were removed for fatty acid analyses. The fatty acid composition of maternal milk and pup cerebrums reflected maternal diet with higher levels of (n-3) and (n-6) fatty acids in the fish oil and corn oil groups, respectively. The time of appearance of auditory startle was significantly delayed (P = 0.004), and auditory brainstem conduction times on postnatal d 23 and 29 were significantly longer in pups of the fish oil- than corn oil-fed dams (P 相似文献   

Effect of zinc deficiency induced before and during pregnancy on the survival of female rats and their pups

The objective of the present study was to determine the consequences of Zn2+ deficiency on the gestational process. The study was conducted on adult Wistar virgin female rats fed isocaloric diets containing 16% protein and different Zn2+ concentrations, i.e., 2 ppm (severe restriction), 6 ppm (moderate restriction), and 20 ppm (control). Rats received the diets and water ad libitum for 7, 14 or 21 days before mating and throughout pregnancy. Survival of dams and pups decreased with increasing Zn2+ restriction and with time of exposure to the deficient diet. Mean survival rate for control dams and pups was 100%, whereas severe restriction (2 ppm for 21 days premating and during pregnancy) resulted in survival rates of 25% and 0 for dams and pups, respectively. Dam and pup survival rates for moderate restriction (6 ppm) for the same period were 83% and 72%, respectively. These results indicate the importance of Zn2+ before and during pregnancy and show that Zn2+ deficiency causes metabolic alterations which impair normal reproductive processes.     

Spaceflight and development of immune responses

The NIH.R1 Space Shuttle experiment was designed to study the effects of spaceflight on rodent development. Pregnant rats were flown on the Space Shuttle for 11 days, and pregnant control rats were maintained in animal enclosure modules in a ground-based chamber under conditions approximating those in flight. Additional controls were in standard housing. The effects of the flight on immunological parameters of dams, fetuses, and pups were determined. Blastogenesis of spleen cells in response to mitogen was inhibited in flown dams but was not inhibited in cells from their pups. Interferon-gamma production by spleen cells showed a trend toward inhibition in flown dams but not in their pups. The response of bone marrow cells to colony-stimulating factor showed a trend toward inhibition after spaceflight in dams, but the response of fetus and pup liver cells was not inhibited. Total serum IgG was not affected by spaceflight. None of the examined immune parameters that were altered in rat dams after spaceflight was found to be altered in their offspring.     

The reproductive stage and experience of sexually receptive mothers alter their preference for pups or males.

Female rats show postpartum estrus, a unique stage in their reproductive cycle in which they are able to display maternal and sexual responses at the same time. To assess the relative value of pups or males for sexually receptive mothers with different hormonal profiles and reproductive experiences, we employed a 3-point star maze with 3 choice compartments containing: pups, a sexually active male, or no stimulus (neutral). Cycling maternal and nonmaternal females in late proestrus, independently of their previous reproductive experience, strongly preferred the male to the pups, although most postpartum estrous dams did not exhibit preference for the male. The majority of the postpartum primiparous females did not prefer the litter's chamber either, but a previous reproductive experience strongly determined their preference for the pups. These results suggest that the hormonal changes of the proestrus, in contrast to those of the postpartum estrus, promote a strong preference for the male that is not diminished by the maternal condition. Conversely, the endocrine changes of the postpartum facilitate the effect of previous reproductive experience in strengthening the incentive value of the pups. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Postnatal patterns of fatty acids in brain of progeny from vitamin B-6 deficient rats before and after pyridoxine supplementation

The influence of deficient and adequate maternal intakes of pyridoxine on lipid profiles in brains of progeny at 5, 10, 15, 25 and 50 days of age was studied. The effects of supplementing deficient dams at two different times with pyridoxine on the brain development of progeny were also examined. Three groups of weanling, female rats were fed diets deficient in pyridoxine (1.2 mg pyridoxine-HC1/kg diet) and another group received a control diet (30.0 mg pyridoxine-HC1/kg diet). One deficient group and the control group were fed their diets throughout growth, gestation and lactation. Two groups of dams were fed the deficient diet through growth, gestation and until 5 or 10 days postpartum when pyridoxine was supplemented by feeding the control diet. Body and brain weights were significantly lower in 15, 25 and 50 day-old progeny of deficient dams and deficient dams supplemented at 10 days postpartum. Cerebroside content at 15 days and ganglioside content at 15 and 25 days were significantly lower in brains of pups from unsupplemented deficient dams and deficient dams supplemented at 10 days postpartum. The postnatal development of cerebroside and ganglioside levels in brain was delayed or retarded in brain of pups from unsupplemented deficient dams. Supplementation of dams fed a low level of pyridoxine (1.2 mg/kg diet) with the vitamin beginning at 5 days postpartum reversed all observed effects of the low vitamin intake on brain lipids in progeny.     

Intravenous gestational cocaine in rats: effects on offspring development and weanling behavior

Pregnant rats were injected with cocaine (CN; 6 mg/kg) or an equal volume of saline (SAL), via the tail vein, on gestation days 8-20. A third group was untreated (UT). Maternal weight gain was not affected by dam treatment despite slight differences in food intake. Litter characteristics (e.g., litter size, pup weight) did not differ among groups. Indices of fetal mortality were not affected by the treatments. Developmental tests, initiated on postnatal day (PND) 2, indicated slight delays in the negative geotaxic response and eye opening in cocaine-exposed pups. Open-field and tail-flick tests were performed on PND 21. Pups were acutely injected with cocaine (10 mg/kg, IP), saline, or received no treatment before placement in a novel open field; morphine (1.5 mg/kg, SC) or saline was injected prior to the tail flick test. Pups from CN dams exhibited a significant decrease in spontaneous exploratory behavior compared to both controls, and a time-dependent increase in rearing compared to pups from UT dams. The acute cocaine injection prior to placement in the open field did not alter locomotion or rearing among dam treatment groups. However, the acute cocaine injection did increase stereotypy ratings for female pups from CN dams compared to similarly treated males, and females from SAL and UT dams. No differences were observed among groups in the tail-flick test. These data suggest that the IV route of administration provides a viable method of cocaine delivery in pregnant rats, and provides further evidence of the developmental and behavioral teratogenicity of prenatal cocaine exposure.     

Prenatal cocaine but not prenatal malnutrition affects foster mother-pup interactions in rats

The separate and combined effects of prenatal cocaine exposure and malnutrition on mother-pup interactions in rats were assessed daily from postnatal day 2 to day 21. Sprague-Dawley dams were fed a diet of low protein content (6% casein), an isocaloric diet of adequate protein content (25% casein, control), or a laboratory chow diet prior to mating and throughout pregnancy. Within each diet group, rats received either cocaine injections (30 mg/kg IP two times per week prior to mating and then 30 mg/kg SC daily from days 3 to 18 of pregnancy) or saline injections. Litters were fostered on the day of birth to control mothers (i.e., nondrug-exposed dams fed the control or chow diet). Foster mothers fed the 25% casein diet showed increased contact with cocaine-exposed pups compared with nondrug-exposed pups in the second postnatal week but lower levels as the pups approached weaning. Passive nursing was increased in dams caring for prenatally malnourished, cocaine-exposed pups compared with those caring for similar pups with no drug exposure. Chow-fed mothers did not differ in their behavior towards pups with or without prenatal cocaine treatment. Prenatal cocaine and malnutrition independently compromised birth weight and various reflexive milestones but the attainment of physical milestones was affected only by prenatal cocaine. There were no additive effects of the two prenatal insults on any measure of mother-pup interaction or pup development.     

Hypothermic vocalizations of rat pups (Rattus norvegicus) and direct maternal search behavior.

Emissions of ultrasonic vocalizations (USVs) by rat pups (Rattus norvegicus) during hypothermia have consequences for recovery and warming. The effects on dam behavior of USVs emitted by 3- to 11-day-old pups during hypothermia at rectal temperatures between 18 and 22°C was investigated Rat dams were tested in a Y maze with the home cage as a start box. Dams were given, in one condition, a choice between a hypothermic pup emitting USVs or a hypothermic, silent (anesthetized) pup and, in the other, a choice between 2 hypothermic, silent pups. Although differing in some acoustic properties from normal isolation calls, USVs emitted by hypothermic pups both elicited maternal search behavior and acted as directional cues for dams, in comparisons with control dams exposed only to silent pups. Thus USVs of pups recovering from extreme hypothermia have communicative as well as physiological significance. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Endocrine mechanisms underlying reproductive toxicity in the developing rat chronically exposed to dietary lead

A dose-response study was conducted in a rat model to examine the effects of lifetime lead exposure on the development of the reproductive system and the endocrine mechanisms underlying these effects. Time-impregnated female Sprague-Dawley rats (n = 10-15/group) were exposed to lead acetate in the drinking water at levels of 0.05%, 0. 15%, or 0.45% (w/v) initiated on gestational day 5. At birth, litters were culled to four male and four female pups. Exposure of dams to lead was continued until weaning, following which, the pups continued to be exposed to lead acetate in drinking water until sacrifice. One male and one female pup from each litter were sacrificed at age 21, 35, 55, and 85 d. A significant dose-responsive decrease in birth weight and crown-to-rump length was observed in all lead-exposed litters. However, no marked effects were observed on anogenital distance/crown-to-rump length ratios. Lead exposure resulted in a delay in sexual maturity as measured by prostate weight in male pups and time of vaginal opening in female pups, which increased with lead dose. These disruptions in reproductive physiology were accompanied by a significant decrease in neonatal sex steroid levels and suppression of the plasma concentrations of testosterone (male) and estradiol (female) during puberty. In male pups, this was accompanied by a significant decrease in plasma luteinizing hormone (LH), elevated pituitary LH content, and a decrease in plasma testosterone/LH ratios at the highest dose. In female pups, although no effects were observed on plasma LH concentration, a similar significant elevation in pituitary LH content was observed during early puberty. Postpuberty, plasma LH and sex steroid concentrations were unaffected at any dose in spite of continued lead exposure. No significant effects were observed on epididymal sperm count in male pups at 85 d of age. In female pups, estrus cycling was only significantly disrupted at the highest lead dose. These data suggest that the reproductive axis is particularly sensitive to lead during specific developmental periods, resulting in delayed sexual maturation produced by suppression by sex steroid biosynthesis. The mechanisms underlying this appear to involve lead actions on both LH release and gonadal function. At low, environmentally relevant blood lead concentrations, adaptation to the continuous presence of the metal ion occurs and surprisingly little effect is observed on adult reproductive endocrinology and physiology.     

Developmental and behavioral effects of postnatal amitraz exposure in rats

The effects of postnatal amitraz exposure on physical and behavioral parameters were studied in Wistar rats, whose lactating dams received the pesticide (10 mg/kg) orally on days 1, 4, 7, 10, 13, 16 and 19 of lactation; control dams received distilled water (1 ml/kg) on the same days. A total of 18 different litters (9 of them control and 9 experimental) born after a 21-day gestation were used. The results showed that the median effective time (ET50) for fur development, eye opening, testis descent and onset of the startle response were increased in rats postnatally exposed to amitraz (2.7, 15.1, 21.6 and 15.3 days, respectively) compared to those of the control pups (1.8, 14.0, 19.9 and 12.9 days, respectively). The ages of incisor eruption, total unfolding of the external ears, vaginal and ear opening and the time taken to perform the grasping hindlimb reflex were not affected by amitraz exposure. Pups from dams treated with amitraz during lactation took more time (in seconds) to perform the surface righting reflex on postnatal days (PND) 3 (25.0 +/- 2.0), 4 (12.3 +/- 1.2) and 5 (8.7 +/- 0.9) in relation to controls (10.6 +/- 1.2; 4.5 +/- 0.6 and 3.4 +/- 0.4, respectively); the climbing response was not changed by amitraz. Postnatal amitraz exposure increased spontaneous motor activity of male and female pups in the open-field on PND 16 (140 +/- 11) and 17 (124 +/- 12), and 16 (104 +/- 9), 17 (137 +/- 9) and 18 (106 +/- 8), respectively. Data on spontaneous motor activity of the control male and female pups were 59 +/- 11 and 69 +/- 10 for days 16 and 17 and 49 +/- 9, 48 +/- 7 and 56 +/- 7 for days 16, 17 and 18, respectively. Some qualitative differences were also observed in spontaneous motor behavior; thus, raising the head, shoulder and pelvis matured one or two days later in the amitraz-treated offspring. Postnatal amitraz exposure did not change locomotion and rearing frequencies or immobility time in the open-field on PND 30, 60 and 90. The present findings indicate that postnatal exposure to amitraz caused transient developmental and behavioral changes in the exposed offspring and suggest that further investigation of the potential health risk of amitraz exposure to developing human and animal offsprings may be warranted.     

Milking procedure alters the electrolyte composition of spontaneously hypertensive and normotensive rat milk

A number of groups, including our own, have shown that the severity of hypertension expressed by the adult spontaneously hypertensive rat (SHR), which is primarily considered to be a genetic model of hypertension, can be reduced as a result of exposure to the behavioural and nutritional environment provided by a normotensive foster mother. It has been suggested that the hypertensive influence of the SHR dam may involve increased sodium delivery to the pups and there have been some reports of elevated sodium concentrations in the milk of SHR dams. However, these studies used either a long (> or =6 h) dam-pup separation period before collecting milk or repeated milking of the same dams, both of which have been shown to alter the trace element content of rat milk. Therefore, we have compared the electrolyte content of milk collected by these methods with milk derived from SHR and normotensive Wistar-Kyoto (WKY) dams separated from their litters for 2 h prior to a single-milking session. Long separation and repeated milking resulted in variable effects on the electrolyte content of both SHR and WKY dams' milk, compared with milk collected after 2 h from dams which had not previously been milked. The most notable effects were the abolition of significant strain differences, observed following 2-h separation, for milk sodium (WKY 22.1+/-1.4 vs. SHR 27.5+/-2.1 mmol/liter, p < 0.05) and calcium (WKY 92.3+/-4.3 vs. SHR 69.4+/-2.9 mmol/liter, p < 0.05) when dams were separated for 6 h or were serially milked. These data suggest that the electrolyte content of SHR and WKY dams' milk can be altered by the collection procedure and it is recommended that dams be milked on only one occasion following a short separation period from their litter.     

Preputial glands of infant rats (Rattus norvegicus) provide chemosignals for maternal discrimination of sex.

In 4 experiments, dams were presented with simultaneous choice tests of pup odors, and their investigatory sniffing was measured. Dams did not show differential sniffing of male and female bladder urine or urine voided by pups with preputial glands removed (PPX). They preferred urine voided by intact male pups to that voided by intact females, and they preferred urine voided by intact pups to that of PPX pups within each sex. Finally, they preferred water homogenates of preputial glands removed from male pups to those of female pups. It is concluded that the neonatal preputial gland is a source of chemosignals that are attractive to dams and that are used by dams to identify sex of pup. (27 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of antioxidants on streptonigrin-induced DNA damage and clastogenesis in CHO cells

This study evaluates the comparative efficacy of antioxidant vitamins (ascorbic acid and alpha-tocopherol) and non-vitamin antioxidants (glutathione, cysteine and L-2-oxothiazolidine-4-carboxylate (OTZ)) in modulating the detoxification pathway of lactating dams and suckling murine pups. In dams, 100 mg/kg b.w./day treatment of each of the vitamin and non-vitamin antioxidants induced a significant increase in the hepatic level of acid soluble sulfhydryl (-SH) compared to the modulating efficiency of OTZ, glutathione and alpha-tocopherol in the kidney tissue. In the liver and kidney tissues of suckling pups OTZ and alpha-tocopherol were effective in modulating the -SH level. A statistically significant increase in the hepatic glutathione-S-transferase (GST) level was observed by OTZ, glutathione and alpha-tocopherol, while only OTZ was effective in the kidney tissue of dams and pups. In the murine system, the modulation of cellular GST/GSH status, specifically by OTZ, alpha-tocopherol and interacting antioxidant pool, may potentially ameliorate the pathophysiology of oxidative stress.     

Resource partitioning during reproduction in the Norway rat

Rat pups nursed by pregnant dams grow as fast as pups reared by dams that are not pregnant. Moreover, litters that were in utero during a lactation are as numerous at birth and grow as fast as pups developing in a nonlactating, pregnant mother. These litters continue to grow as fast as pups born to nonlactating dams whether or not the first litter remains after the birth of the second litter. When pregnant and lactating dams have a restricted food supply, some dams are capable of extending the duration of their pregnancies by over 2 weeks past that of nonlactating, pregnant dams. This facultative prolongation of pregnancy apparently allows females to carry normal litters to term.     

Effects of chronic and acute cocaine treatment on the onset of maternal behavior and aggression in Sprague-Dawley rats.

Pregnant rats (N?=?17) were treated either throughout gestation (Gestational Day 1–20) with 30 mg/kg per day (chronic cocaine) or with 1 15-mg/kg dose immediately following parturition (acute cocaine). Chronic and acute cocaine treatment delayed or diminished the postpartum onset of some components of maternal behavior, and chronically treated dams were significantly more aggressive toward a male intruder than acute cocaine-treated or saline-treated dams. Cocaine increased the latency to crouch over pups and decreased crouch duration during a 30-min observation period that immediately followed parturition. Latencies to nest build were also longer in more chronic cocaine-treated dams than in saline controls. On Day 6 postpartum, 83% of chronic cocaine-treated dams pinned and attacked an intruder male 8 or more times during a 10-min observation period, whereas only 4% of acute cocaine-treated and none of the saline-treated dams exhibited this much aggression. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Comparison of two positive reinforcing stimuli: Pups and cocaine throughout the postpartum period.

This set of experiments investigated the appetitive or motivational processes underlying the performance of maternal behavior. The place preference paradigm was adapted to simultaneously investigate the reinforcing properties of cocaine and pups for maternal, lactating dams. These modifications allowed the authors to assess which stimulus, either a 10 mg/kg sc injection of cocaine or 3 pups, had the strongest reinforcing value. At Postpartum Days 10 and 16, the dams preferred the cocaine cue-associated chamber, whereas the dams tested at Postpartum Day 8 preferred the pup cue-associated chamber. Overall, the data revealed an interaction between the postpartum period at testing and the exhibited preference for cocaine or pups. Further testing will investigate the neural circuitry underlying the appetitive processes of each stimulus. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Prenatal alcohol exposure results in hyperactivity of the hypothalamic-pituitary-adrenal axis of the offspring: modulation by fostering at birth and postnatal handling

Exposure of fetal rats to alcohol results in permanent hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis. In contrast, postnatal handling or fostering have been reported to restrain HPA activity. Because of the deleterious consequences of a hyperresponsive HPA axis, we thought that the possibility that postnatal manipulations might be able to reverse the influence of prenatal alcohol treatment deserved investigation. To test this hypothesis, we exposed rat dams to alcohol by inhalation during the second week of gestation. At birth, pups were either fostered or remained with their dam. For the first 3 weeks, litters were handled daily for 15 min or left undisturbed. At 22 days of age, male and female pups were decapitated under basal conditions, after 10 min of mild electro-footshock, or 10 min after footshock had been terminated. As expected, prenatal exposure to alcohol induced increased adrenocorticotropin (ACTH) secretion in response to footshock, and postnatal handling of control pups resulted in a suppression of corticosterone and ACTH release, although changes in this latter hormone did not reach statistical significance. Surprisingly, however, pups exposed to alcohol that were also fostered and handled after birth, showed an ACTH response to footshock stress that was significantly larger than all other groups. This unexpected response may be due to alterations in maternal-pup behaviors and may indicate that these manipulations act on different neuronal substrates within the central HPA of young rats. Further studies are needed to determine whether adrenal regulation is also altered in animals exposed to alcohol prenatally and reared in a similar manner.     

Effects of DDT on reproduction in multiple generations of beagle dogs

The effects of chronic oral exposure to 1, 5, and 10 mg of technical DDT/kg/day on: 1) age at puberty, length of gestation, fertility, success of pregnancy, litter size, and lactational ability of dams; 2) viability, survival to weaning, sex distribution and growth of pups; and 3) morbidity, mortality, organ/body weight ratios, gross and histologic abnormalities in all animals were studied through three generations of Beagle dogs. There were a total of 135 adult female and 63 adult male dogs in the project which produced 650 pups. There were no statistically significant differences among control and DDT-treated dogs in any of the reproductive variables, with the exception of age at puberty of the females. DDT-treated females had their first estrous cycles 2 to 3 months earlier (P less than .001) than the control dogs. Selected DDT-treated females, held for a second breeding period, had normal anestrous periods between their first and second estrous cycles. There was no effect of DDT on survival, growth, and sex distribution of pups, nor was there any influence on morbidity, mortality, gross or histologic findings in any of the dogs. All organ/body weight ratios were normal, with the possible exception of an increase in liver/body weight ratio in some DDT-treated animals.     

The selective estrogen receptor modulator, raloxifene: a segment II/III delivery study in rats

Raloxifene is a nonsteroidal, selective estrogen receptor modulator developed by Eli Lilly and Company as a therapeutic agent for postmenopausal osteoporosis. Raloxifene was administered orally by gavage at doses of 0, 0.1, 1, or 10 mg/kg/d to female CD rats (25/group) on Gestation Day 6 (GD 6) through Postpartum Day 20 (PD 20). Females were allowed to deliver and maintain their progeny until PD 21. All dead pups and pups culled on PD 1 were given internal and external examinations. One pup/sex/litter was assigned to each of the following assessment groups: 1) the primary pair for the F1 generation study, in which survival, growth, development, behavior, indicators of sexual maturation, and reproductive performance were evaluated; 2) terminal necropsy evaluations at PD 21; 3) terminal necropsy evaluations at 60 d of age; and 4) assessments of immune function at 5 to 6 weeks of age. At termination on PD 21, 60, or approximately 140, a necropsy was performed; crown rump and tibia lengths were measured; pituitary weights were taken; and a portion of the anterior pituitary was retained for growth hormone, luteinizing hormone, and prolactin content determinations (control and 10-mg/kg groups only). The remainder of the pituitary and reproductive tissues were retained for histologic evaluations. Dose-related depressions in maternal body weight and food consumption occurred during gestation. Mean gestation length was increased at 1 and 10 mg/kg. Delayed, extended, and/or disrupted parturition occurred in dams given 10 mg/kg, which resulted in a high incidence of maternal morbidity and/or death, increased numbers of dead pups, and the survival of only 66% of live pups to PD 21. Progeny body weights were not decreased at birth, but were depressed progressively in a dose-related manner during the 3-week lactation period. Negative geotaxis and incisor eruption were apparently accelerated in the 1- and 10-mg/kg groups, but eye opening was delayed at 10 mg/kg. Postweaning activity levels, auditory startle, and passive avoidance performance were not affected in the raloxifene groups. Dose-related decreases in spleen cellularity and thymus weights occurred in both sexes, but immune system function, as measured by splenic natural killer cell activity and antibody response to sheep red blood cells, was not affected. Postweaning body weights and growth parameters, as well as pituitary hormone content, were affected in both an age- and sex-specific manner. Preputial separation was not affected, but vaginal patency occurred ca 2 d earlier than controls in females from the 10-mg/kg group. Estrous cycles of the F1 females were not affected during the first two weeks after vaginal opening, but were disrupted at 12 to 14 weeks of age in the 10-mg/kg group. These females showed poorer mating and fertility indices, and litter size was reduced in the two females that were pregnant. Histologically, reproductive organs were not affected in males at any age or in females at PD 21. At PD 60, vaginal mucification occurred in females from the 0.1- and 1-mg/kg groups. At PD 140, the only finding was a high rate of uterine hypoplasia in the 10-mg/kg group, and this finding occurred in the absence of any concomitant ovarian or vaginal changes. These reproductive and developmental findings are consistent with estrogen antagonist activity of raloxifene.     

Intragastric intubation: important aspects of the model for administration of ethanol to rat pups during the postnatal period

One technique for the controlled delivery of ethanol to neonatal rat pups is intragastric intubation. Often, the vehicle used for delivery of ethanol is composed of a nutrient mixture to compensate for decreased suckling or other possible nutritional compromise. This study analyzed the selection of nutrient vehicle, the combination of experimental treatment groups within a litter, and the overall litter size on the growth rate of ethanol-intubated and intubated-control pups, compared with mother-raised control pups. Sprague-Dawley rat pups were raised in litters of 8 or 10, and administered ethanol by intragastric intubation with 20% (v/v) Sustacal or 80% (v/v) Intralipid-II nutrient vehicle. Pups were treated between postnatal days 2 and 10, and body weight was analyzed on day 10. Pups were assigned to a treatment group as either intubated ethanol, intubated control, or nonintubated mother-raised controls. Experimental comparison by statistical analyses was performed to identify the optimal treatment design (mixed treatment groups in a single litter or a single treatment group per litter), the optimal vehicle (Sustacal or Intralipid-II), and the optimal number of pups per litter (8 vs. 10). The analyses demonstrate that the mixing of intubated control, intubated ethanol, and nonintubated mother-raised control treatment groups within a single litter introduced an uncontrolled variable that confounded measurement of ethanol-specific alterations. The sensitivity of treatment groups to inclusion in mixed litters was dependent on the nutrient vehicle and thus nutritional adequacy. Our results suggest that an optimal design was achieved with eight pups per litter. Furthermore, ethanol intubated and intubated control pups grow at a rate identical to parallel litters of eight mother-raised control pups when Intralipid-II is used as nutrient vehicle, and a single treatment group is present in a litter. Optimization of these experimental parameters has provided an excellent neonatal rat model for analysis of specific ethanol effects on brain development during the third trimester.