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Biomedical subjects

F J White

Publications and source records attributed to F J White.

At least 19 recordsLinked to original sources
PubMed2006

Randomised controlled trial of essential fatty acid supplementation in phenylketonuria.

OBJECTIVE: The long-chain polyunsaturated fatty acids (LC-PUFA) status of children with PKU is often compromised. LC-PUFA, which are important fatty acids in the development of the CNS, can be synthesised endogenously from the parent essential fatty acids (EFA) provided dietary intakes are adequate. This study was designed to assess the biochemical effect over a 20-week period of a phe-free protein substitute that has been supplemented with a balanced blend of n-3 and n-6 EFAs on LC-PUFA status of children with PKU. DESIGN, SETTING AND SUBJECTS: Fifty three community-living children aged 1-10 years diagnosed with PKU in the newborn period were recruited from seven tertiary centres in the UK and France and randomised to a fat-free control formula or the EFA-supplemented test-treatment formula in an open, prospective study. Forty four children completed the study (20 controls, 24 test-treatments). Fatty acid status was assessed at entry and 20-weeks follow-up. Three day dietary diaries were recorded at 20 weeks' follow-up. The safety, efficacy and palatability of the test-treatment formula were also assessed. RESULTS: The test-treatment group had significantly higher intakes of fat and EFA than the control group. There was a significant between group difference (P=0.04) in increases in median docosahexaenoic acid (DHA) concentrations in erythrocyte phospholipids, which increased by 19% in the test-treatment group and by 0.5% in the control group over the study period. Growth and phe control were satisfactory in all subjects. CONCLUSIONS: Supplementing the diets of children with PKU with a balanced blend of n-6 and n-3 EFA improves DHA status without compromising AA status.

Child↗
PubMed2006

Excitability of dopamine neurons: modulation and physiological consequences.

This aim of this chapter is to review literature on the excitability and function of dopamine neurons that originate in the midbrain and project to cortico-limbic and motor structures (A9 and A10 dopamine pathways). Electrophysiological studies on rodent or non-human primates have shown that these dopamine neurons are silent or spontaneously active. The spontaneously active neurons show slow regular firing, slow irregular firing or fast bursting activity. In the first section, we will review how neuronal firing is modulated by intrinsic factors, such as impulse-regulating somatodendritic dopamine autoreceptors, a balance between inward voltage-gated sodium and calcium currents and outward potassium currents. We will then review the major excitatory and inhibitory pathways that play important roles in modulating dopamine cell excitability. In the second section, we will discuss how, in addition to being modulated by intrinsic and synaptic factors, excitability of dopamine neurons can also be modulated by life experiences. Dopamine neurons change their firing rate throughout the developmental period, their activity can be modified by stressful life events, and the firing mode can change as a consequence of acute or repeated exposure to psychoactive drugs. Finally, these cells change their firing pattern in response to behaviorally relevant stimuli and learning experiences. We will conclude by discussing how changes in the physiology of the dopamine neurons could participate in the development or exacerbation of psychiatric conditions such as drug addiction.

Action Potentials↗
PubMed2006

Maternal recognition of pregnancy signal or endocrine disruptor: the two faces of oestrogen during establishment of pregnancy in the pig.

Timing of conceptus growth and attachment to the uterine luminal epithelium is regulated by progesterone secretion from the corpus luteum and by expression of progesterone receptor in the uterine epithelia and stroma. Conceptus growth and uterine attachment are temporally associated with the disappearance of progesterone receptors from uterine epithelia. While the loss of progesterone receptor from the endometrial epithelia on day 10 of the oestrous cycle and pregnancy has been well documented, the factors involved with cell specific down-regulation of progesterone receptor are yet to be established. We propose that several progesterone stimulated factors activate nuclear factor kappa B (NF-kB) within the uterine epithelia, which leads to inhibition of progesterone receptor and concomitant stimulation of endometrial genes expressed during early conceptus development. Although oestrogens secreted by pig conceptuses function to establish pregnancy, timing of endometrial exposure to oestrogen is critical. Early oestrogen administration alters the pattern of gene expression through the NF-kB system desynchronising the uterine environment for conceptus implantation resulting in later embryonic loss.

Animals↗
PubMed2005

Influence of nutrient intake and body fat on concentrations of insulin-like growth factor-I, insulin, thyroxine, and leptin in plasma of gestating beef cows.

Pregnant Angus x Hereford cows (n = 73) were used to determine the effects of amount of nutrient intake and BCS on concentrations of IGF-I, insulin, leptin, and thyroxine in plasma. At 2 to 4 mo of gestation, cows were blocked by BCS and assigned to one of four nutritional treatments: high (H = a 50% concentrate diet fed ad libitum in a drylot) or adequate native grass pastures and one of three amounts of a 40% CP supplement each day (M = moderate, 1.6 kg; L = low, 1.1 kg; or VL = very low, 0.5 kg; as-fed basis). After 110 d of treatment, all cows grazed dormant native grass pasture and received 1.6 kg/d of a 40% CP supplement. At 68, 109, and 123 d of treatment, cows were gathered, and plasma samples were collected by tail venipuncture (fed sample). After 18 h without feed and water, a second plasma sample was collected (fasted sample). At 109 d of treatment, BCS was greatest (P < 0.05) for H cows, similar for M and L cows, and least for VL cows. Concentrations of insulin and leptin were greater (P < 0.05) for H cows than for M and VL cows at 68 and 109 d, but similar for all groups at 123 d. Thyroxine in plasma was greatest (P < 0.05) for H cows at 68 d and similar for cows on all treatments at 123 d. Concentrations of IGF-I, insulin, and leptin in fed and fasted cows were positively correlated with BCS at 109 d. Body condition was predictive of concentrations of IGF-I, insulin, and leptin when cows had different nutrient intakes, but BCS accounted for less than 12% of the variation in plasma concentrations of IGF-I, insulin, and leptin when nutrient intake was the same for all cows. We conclude that amount of nutrient intake has a greater influence than body energy reserves on IGF-I, insulin, and leptin concentrations in the plasma of gestating beef cows.

Animal Nutritional Physiological Phenomena↗
PubMed2005

Effects of grazing program and subsequent finishing on gene expression in different adipose tissue depots in beef steers.

This experiment was conducted to examine the effects of grazing program and subsequent finishing on gene expression in adipose tissue from steers. Twenty Angus x Angus-Hereford steer calves (initial BW = 231 +/- 25 kg) were allotted randomly to one of two winter grazing treatments: 1) grazing winter wheat pasture to achieve a high rate of BW gain (HGW); or 2) grazing dormant tallgrass native range (NR). Steers in the NR treatment were provided 0.91 kg.steer(-1).d(-1) of a 41% CP (as-fed basis) cottonseed meal supplement. Following the grazing period, steers were assigned randomly to feedlot pens. Steers were fed to a common endpoint of 1.27 cm of backfat between the 12th and 13th rib. Four steers from each treatment were slaughtered at the end of the grazing period, and the remaining steers from each treatment (n = 6) were slaughtered at the predetermined compositional endpoint. Intramuscular and s.c. fat samples were collected from LM sections of each steer at the 12th-/13th-rib interface on the left side. Pools of RNA were prepared for HGW and NR s.c. adipose tissue from steers slaughtered immediately after grazing. Suppression subtractive hybridization was performed followed by dot-blot hybridization screening to confirm differential expression of subtracted transcripts. Transcripts confirmed to be differentially expressed were subjected to dideoxy chain-termination sequencing. Quantitative reverse transcription PCR was performed on three differentially expressed clones: osteonectin, ferritin heavy chain, and decorin. Osteonectin, ferritin heavy chain, and decorin gene expression was greater (P < 0.05) in s.c. than in i.m. adipose tissue of finished steers. A depot x background interaction for osteonectin (P < 0.01) and ferritin heavy chain (P = 0.03) gene expression was observed for steers slaughtered after grazing, indicating that nutritional management can affect gene expression in adipose tissue depots differently. No differences resulting from prefinishing nutritional background (HGW or NR) were noted in osteonectin, ferritin heavy chain, or decorin gene expression in i.m. adipose tissue collected from finished steers, which might have resulted from feeding steers to the same compositional endpoint. Our data suggest that nutritional background alters gene expression in adipose depots, and that depots are influenced differently.

Adipose Tissue↗
PubMed2003

Influence of body condition at calving and postpartum nutrition on endocrine function and reproductive performance of primiparous beef cows.

The influences of body condition score (BCS) at calving and postpartum nutrition on endocrine and ovarian functions, and reproductive performance, were determined by randomly allocating thin (mean BCS = 4.4 +/- 0.1) or moderate condition (mean BCS = 5.1 +/- 0.1) Angus x Hereford primiparous cows to receive one of two nutritional treatments after calving. Cows were fed to gain either 0.45 kg/d (M, n = 17) or 0.90 kg/d (H, n = 17) for the first 71 +/- 3 d postpartum. All cows were then fed the M diet until 21 d after the first estrus. A replication (yr 2; M, n = 25; H, n = 23) was also used to evaluate reproductive characteristics. Concentrations of IGF-I, leptin, insulin, glucose, NEFA, and thyroxine were quantified in plasma samples collected weekly during treatment and during 7 wk before the first estrus. Estrous behavior was detected by radiotelemetry, and luteal activity was determined based on concentrations of progesterone in plasma. All cows were bred by AI between 14 and 20 h after onset of estrus, and pregnancy was assessed at 35 to 55 d after AI by ultrasonography. Cows that calved with a BCS of 4 or 5 had similar endocrine function and reproductive performance at the first estrus. During treatment, H cows gained BW and increased BCS (P < 0.01), and had greater (P < 0.05) concentrations of IGF-I, leptin, insulin, glucose, and thyroxine in plasma than M cows. However, during the 7 wk before the first estrus, plasma concentrations of IGF-I, leptin, insulin, glucose, NEFA, and thyroxine were not affected by time. Cows previously on the H treatment had a shorter (P < 0.01) interval to first postpartum estrus and ovulation, and a larger dominant follicle (P < 0.01) at first estrus, than M cows, but duration of estrus and the number of mounts received were not influenced by nutrient intake. Pregnancy rate at the first estrus was greater (P < 0.03) for H (76%, n = 38) than for M (58%, n = 33) cows. Increased nutrient intake after calving stimulated secretion of anabolic hormones, promoted fat deposition, shortened the postpartum interval to estrus, and increased pregnancy rate at the first estrus. Concentrations of IGF-I and leptin in plasma were constant during 7 wk before the first estrus, indicating that acute changes in these hormones are not associated with the resumption of ovarian function in primiparous beef cows.

Animal Nutritional Physiological Phenomena↗
PubMed2002

How practical are recommendations for dietary control in phenylketonuria?

In patients with phenylketonuria, blood phenylalanine concentration during childhood is the major determinant of cognitive outcome. Guidelines provide age-related recommendations for treatment. To ascertain the extent to which these aims are achievable, we audited results from four centres for the years 1994-2000. The median proportion of samples with phenylalanine concentrations above those recommended was less than 30% for those younger than age 10 years but almost 80% for those aged 15 years and older. Similarly, the median frequency of blood sampling, expressed as a proportion of that recommended, was more than 80% for patients younger than 10 years but less than 50% by age 15 years. Our results indicate the difficulty of maintaining control in phenylketonuria, especially in older rather than younger children.

Adolescent↗
PubMed2002

Seasonal effects on estrous behavior and time of ovulation in nonlactating beef cows.

Estrous behavior and time of ovulation relative to the onset of estrus were determined in mature Angus x Hereford cows (n = 17 to 21 each season) during summer, winter, and spring for 2 yr. Estrous behavior was evaluated during the first of two consecutive estrous periods, and time of ovulation was determined during the second estrus. Concentrations of progesterone were quantified in twice weekly blood samples to ensure all cows had normal estrous cycles. The HeatWatch system was used to measure the duration of estrus, number of mounts received per estrus, and duration of the longest interval between mounts received. Commencing 16 h after the onset of the second estrus, transrectal ultrasonography was performed every 4 h until the dominant follicle was no longer present on the ovary, and time of ovulation was defined as 2 h preceding the absence of the dominant follicle. There was a seasonal effect on the duration of estrus; cows were estrus longer in summer (17.6 +/- 0.8 h) than in winter (15.5 +/- 0.8 h; P = 0.07) or spring (13.9 +/- 0.9 h; P < 0.05). Cows were mounted more times per estrus (P < 0.05) in winter (59.0 +/- 5.3) than in summer (43.6 +/- 5.3) or spring (38.2 +/- 5.8). Intervals between mounts of estrous cows were longer (P < 0.05) in summer (4.1 +/- 0.4 h) than in spring or winter (2.7 +/- 0.4 h). During all seasons, cows were mounted more times (P < 0.01) between 0600 to 1200 (3.2 +/- 0.2 mounts received/h of estrus) than during other times of the day (2.1 +/- 0.2 mounts received/h of estrus). Cows ovulated 31.1 +/- 0.6 h after the onset of estrus, and time of ovulation was not influenced by season. We conclude that season influences estrous behavior of beef cows; cows are mounted more times per estrus in winter than in summer or spring. Time of ovulation relative to the onset of estrus is constant during all seasons and averages 31.1 h.

Animals↗
PubMed2001

Enhanced reactivity and vulnerability to cocaine following methylphenidate treatment in adolescent rats.

Treatment of attention deficit hyperactivity disorder with the psychostimulant drug methylphenidate (MP) has increased dramatically among schoolchildren. We tested whether repeated exposure to moderate doses of MP (5 and 10 mg/kg IP for 5 or 7 days) in adolescent rats increased reactivity to cocaine measured by motor responses (ambulations and rearing) to a cocaine challenge in adulthood. We later tested whether repeated exposure to a low dose of MP (2 mg/kg IP for 7 days) enhanced the psychomotor effects of cocaine, measured by different challenge doses (0-30 mg/kg) as well as to the reinforcing effects of cocaine, measured by self-administration of low-dose infusion (75 microg/kg, IV). We found that exposure to moderate doses of MP enhanced psychomotor responses to cocaine but exposure to a low dose only increased cocaine self-administration. These results suggest that adolescent exposure to low doses of MP in rats may increase the incentive value of low reinforcers, thereby rendering adult rats more susceptible to cocaine self-administration.

Animals↗
PubMed2000

Enhanced vulnerability to cocaine self-administration is associated with elevated impulse activity of midbrain dopamine neurons.

Individual differences in responding to a novel environment predict behavioral and neurochemical responses to psychostimulant drugs. Rats with a high locomotor response to a novel environment (HRs) exhibit enhanced self-administration (SA) behavior, sensitization, and basal or drug-induced dopamine release in the nucleus accumbens compared with rats with a low response to the novel context (LRs). In this study, we determined whether such differences in vulnerability to drug addiction might be related to differences in dopamine (DA) neuron activity. Rats were divided into HRs and LRs according to their response to a novel environment and then tested for acquisition of cocaine SA. HRs rapidly acquired cocaine SA (175 microg/kg per infusion), whereas LRs did not. Differences in cocaine SA were not caused by differences in exploratory behavior or sampling because these behaviors did not differ in HRs and LRs self-administering a saline solution. In a separate experiment, we used extracellular single-unit recordings and found that HRs exhibit higher basal firing rates and bursting activity of DA neurons in the ventral tegmental area and, to a lesser extent, in the substantia nigra pars compacta. The greater activity of midbrain DA cells in HRs was accompanied by reduced sensitivity to the inhibitory effects of a DA D2-class receptor agonist, indicating possible subsensitivity of impulse-regulating DA autoreceptors. These results demonstrate that differences in the basal activity of DA neurons may be critically involved in determining individual vulnerability to drugs of abuse.

Action Potentials↗
PubMed2000

L-type calcium channels modulate glutamate-driven bursting activity in the nucleus accumbens in vivo.

The majority of adult nucleus accumbens medium spiny neurons exhibit a bistable membrane potential that fluctuates between a relatively hyperpolarized (Down) state (average=-76 mV) and a less hyperpolarized (Up) state (average=-60 mV) near firing threshold. During in vivo extracellular recordings from nucleus accumbens neurons, we used microiontophoresis to apply glutamate and selected neurons that fired in bursting patterns reflecting a subthreshold bistable membrane potential. The average frequency of bursts events was 0.85 Hz. The average burst duration was 392+/-3.5 ms, with an average of 13.4 spikes and an average spike frequency of 30.6+/-3.1 Hz per burst. To determine the involvement of the L-type calcium channel in the bursting pattern, we applied the benzothiazepine L-type calcium channel blocker, diltiazem. Diltiazem rapidly (<2 min) and reversibly decreased the burst duration by 29% and the frequency of spikes within a burst by 30% without changing the overall burst event frequency. The results provide the first in vivo electrophysiological evidence implicating an L-type calcium channel that modulates glutamate-induced burst firing of nucleus accumbens neurons.

Animals↗
PubMed2000

Altered responsiveness of medial prefrontal cortex neurons to glutamate and dopamine after withdrawal from repeated amphetamine treatment.

Using in vivo extracellular single-cell recording and microiontophoresis, we compared the responsiveness of medial prefrontal cortex (mPFC) neurons (layers V-VI) to dopamine and glutamate in rats that had received repeated amphetamine or saline injections. Neurons from amphetamine-pretreated rats showed increased responsiveness to glutamate and decreased responsiveness to dopamine after three days of withdrawal, suggesting that the mPFC is transiently hyperexcitable during amphetamine withdrawal. Published 2000 Wiley-Liss, Inc.

Amphetamine↗
PubMed2000

Pharmacological reversal of behavioral and cellular indices of cocaine sensitization in the rat.

RATIONALE AND OBJECTIVES: Behavioral sensitization has been proposed as an animal model for the intensification of drug craving in cocaine addiction. Interactions between dopamine and glutamate systems are important for the induction and maintenance of sensitization. The goal of this study was to determine if established cocaine sensitization could be reversed by pharmacological manipulation of these transmitter systems. METHODS: Rats received 15 mg/kg cocaine (IP) on days 1-10 and were challenged with cocaine (10 mg/kg) on day 13 to verify that sensitization had occurred. On days 14-20, separate groups of sensitized rats received daily injections of dopamine D1- or D2-class agonists, an NMDA receptor antagonist, or a dopamine agonist with an NMDA antagonist. Three days or 2 weeks later, all rats were again tested for their response to cocaine to determine if sensitization had been reversed. RESULTS: Reversal of sensitization was produced by repeated administration of either a D1-class agonist (SKF 81297) or the combination of an NMDA receptor antagonist and a D2-class agonist. Effective combinations were cocaine+MK-801, quinpirole+MK-801, quinpirole+CGS 19755, and pergolide+memantine. The latter drugs are approved for human use. Reversal of sensitization persisted for at least 2 weeks after cessation of drug treatment. Electrophysiological studies revealed that these drug treatments also reversed dopamine D1 receptor supersensitivity in the nucleus accumbens, a cellular correlate of sensitization. CONCLUSIONS: These results demonstrate that pharmacotherapy can reverse behavioral and cellular adaptations associated with repeated cocaine administration, and may do so without the need for continued medication.

Animals↗
PubMed2000

Increased risk of vitamin B12 deficiency in patients with phenylketonuria on an unrestricted or relaxed diet.

OBJECTIVE: To investigate whether dietary relaxation or cessation in patients with phenylketonuria (PKU) predisposes to vitamin B12 deficiency. STUDY DESIGN: Patients with PKU aged 11 to 38 years underwent a neurologic examination and dietetic assessment and were divided according to their diet into 1 of 3 groups: Strict - those on a strict low phenylalanine (phe) diet with amino acid, mineral, and vitamin supplements; Relaxed - those on a total protein intake of approximately 1 g/kg/d with 50% of this from natural protein and 50% from amino acid, mineral, and vitamin supplements; Unrestricted - those on no formal protein restriction and not taking amino acid supplements. Assays of blood samples were taken for vitamin B12 and folate levels by standard assays. Results were analyzed with Student t test. RESULTS: Vitamin B12 levels were significantly lower in the PKU groups on relaxed or unrestricted diets compared with the normal population (P <.0001 [unrestricted] and.0034 [relaxed]). Folate levels were significantly elevated in all PKU groups (<.0001). CONCLUSION: Patients with PKU who are no longer under strict dietary control may be at risk from vitamin B12 deficiency. We recommend that all patients should remain under medical and dietetic supervision and in particular have their vitamin B12 status monitored.

Adolescent↗
PubMed1999

Dopamine D3 receptor mutant and wild-type mice exhibit identical responses to putative D3 receptor-selective agonists and antagonists.

Previous studies using a variety of drugs with different affinities for the dopamine (DA) D3 receptor suggested that this receptor is involved in regulating motor activity and hypothermia. However, the in vivo selectivity of many of these compounds has been repeatedly questioned. To examine the precise roles of the DA D3 receptor in motor activity and hypothermic responses, we used mutant mice lacking the DA D3 receptor to evaluate the in vivo effects of several putative D3 receptor-selective agonists and antagonists. Using automated photocell activity chambers, we observed that the decreases in locomotor activity produced by putative D3 receptor-selective agonists as well as increases in locomotor activity produced by putative D3 receptor antagonists are identical in D3 receptor mutant and wild-type mice. In addition, the hypothermia produced by the putative D3 receptor-selective agonist PD 128907 is identical in both groups of mice. Based on these findings, we propose that D3 receptors are unlikely to be involved in these effects and we caution that the putative D3 ligands that have been used to reach conclusions regarding the functional roles of D3 receptors lack the necessary in vivo selectivity to support such conclusions.

Animals↗
PubMed1999

Changes in behavior in free-ranging Lemur catta following release in a natural habitat.

The adjustment of captive-reared and developmentally deprived ringtailed lemurs (Lemur catta) to supported release on St. Catherine's Island, Georgia, was studied over 7 years to examine if these animals developed behavior comparable to wild populations. Initial changes after release included decreased obesity and increased agility as well as foraging for appropriate novel plants. Ranging, daily behavior cycles, and vocalizations developed more slowly over 1-3 years, but eventually the behavior resembled that of wild groups. Group composition and social structure changed through conflict to resemble wild and captive troops in social organization, including the emergence of matrilineal dominance and male emigration. Since behavior eventually resembled that seen in the wild, some resilience of species-typical wild behavior in captivity is supported.

Animals↗