d-Amphetamine-induced increase in catecholamine synthesis in the corpus striatum of the rat: Persistence of the effect after tolerance

Summary The effect ofd-amphetamine onin vivo catecholamine synthesis in four regions of rat brain was determined by measuring the accumulation of dopa after inhibition of dopa decarboxylase. In doses up to 2.5 mg/kg,d-amphetamine caused dose-dependent increases in striatal dopa accumulation to a maximum of 280% of control; further increases in dose resulted in smaller effects until 10 mg/kgd-amphetamine was not significantly different from control.d-Amphetamine did not alter dopa accumulation in telencephalon, in diencephalon-mesencephalon, or in pons-medulla oblongata.d-Amphetamine did not affect either dopamine levels in striatum or NE levels in pons-medulla oblongata; at high doses,d-amphetamine did reduce norepinephrine levels in telencephalon and in diencephalon-mesencephalon.Daily administration of pre-session but not of post-sessiond-amphetamine produced tolerance to the effects ofd-amphetamine on milk consumption in rats. The ability ofd-amphetamine to increase striatal catecholamine synthesis was not altered by the development of tolerance tod-amphetamine. These results suggest that tolerance tod-amphetamine is not related to its effect on catecholamine synthesis but instead occurs via changes in aspects of catecholamine metabolism other than synthesis via change in catecholamine release, reuptake, or receptor sensitivity, or via changes in non-catecholaminergic mechanisms.This research was supported by U.S. Public Health Service National Institute of Mental Health Grant MH-011191-12.Supported by Training Grant USPHS 2 TO5 GM 01939-07 (MSTP).Supported by Research Career Development Award 5 KO2 MH-10562-01.     

Combination of soy protein and high dietary calcium on bone biomechanics and bone mineral density in ovariectomized rats

OBJECTIVE: To determine if feeding soy in combination with a high-calcium diet would preserve bone mineral density and biomechanical bone strength to a greater extent than either soy or calcium alone. DESIGN: Rats were sham-operated (n = l0) and fed a control diet (AIN93G containing 0.2% calcium, 20% casein) or ovariectomized (n = 40) and randomized to one of the following diets (n = 10 per group): control, high calcium (2.5% calcium, 20% casein), soy (0.2% calcium, 20% soy protein), or soy plus high calcium (2.5% calcium, 20% soy protein) for 8 weeks. Bone mineral density of femurs and lumbar vertebrae 1 through 6 were measured by dual energy x-ray absorptiometry. Biomechanical strength properties of femurs and the fifth lumbar vertebrae were measured by three-point bending and compression, respectively. RESULTS: The dietary combination of soy and high calcium did not result in higher femur bone mineral density compared with other ovariectomized groups, and there were no differences in femur yield load or peak load among groups. In contrast, soy plus high calcium resulted in a higher (P < 0.05) vertebral bone mineral density compared with all other ovariectomized groups. Vertebral strength was preserved among rats fed either soy plus high calcium, soy, or high calcium whereas the ovariectomized group fed a control diet had lower (P < 0.05) vertebral strength than the sham-operated group. CONCLUSION: Bone mineral density of the lumbar spine was the only bone outcome that significantly benefited from the combination of soy and high calcium compared with soy or high calcium alone.     

Methylphenidate HCl: therapy for attention deficit hyperactivity disorder

Methylphenidate is a first-line therapy for attention deficit hyperactivity disorder, the most prevalent neuropsychiatric disorder of childhood. The compound is a piperidine and the D-threo-isomer is considered the biologically active form. The compound is available in multiple short- and long-acting preparations, having different delivery systems leading to varying kinetics without clear superiority in efficacy or tolerability at the group level. Common adverse effects are insomnia, appetite disturbance, stomach ache, headache and dizziness. Its mechanism of action is linked to the monoamines dopamine and norepinephrine. The compound appears to predominantly increase the synaptic concentration of dopamine, presumably via inhibition of the dopamine transporter DAT1. There also appears to be effects on presynaptic vesicular trafficking and distribution of dopamine. Both immediate- and sustained-release preparations of methylphenidate have proven efficacy in children and adults with attention deficit hyperactivity disorder. Analysis of the National Institutes of Health-sponsored multimodal treatment study of attention deficit hyperactivity disorder supports a combined medication and behavioral therapy approach.     

Seizures and metabolic disease

Seizures represent an important clinical manifestation of inborn errors of metabolism. The presence of myoclonic seizures and very early onset are clues to a metabolic disorder. Specific correlations between age of seizure onset and electroencephalogram patterns with inborn errors of metabolism are discussed. The explosion of information in neurogenetics and metabolism mandates increasing awareness of appropriate metabolic diagnostic and therapeutic strategies in the setting of certain epilepsies. Specific laboratory, imaging, and treatment considerations are included to present updated material in a field that continues to expand rapidly.     

Transfusion related acute lung injury: a pediatric perspective

Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-associated mortality. TRALI occurs in children and adults, but the syndrome has not been reviewed from a pediatric perspective. We reviewed the literature on TRALI from a pediatric perspective. TRALI has been documented in pediatric patients, especially in the setting of hematologic malignancy. Additional TRALI cases have been reported in pediatric patients with a variety of diagnoses. TRALI is likely to be much more common than previously appreciated in the pediatric patient population. TRALI should be considered in the differential diagnosis of all pediatric patients who develop new acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) during or within six hours of a blood product transfusion. When a case of TRALI is suspected, a transfusion reaction report to the blood bank is important to initiate the investigation and identify the implicated donor.     

Choosing abdominal incision and closure techniques: a review

This review summarizes contemporary concepts of abdominal surgical incision creation and closure. The Ovid computerized database was searched for articles published in English from 1996 to 2003 using keywords pertaining to the specific topic of interest (e.g., suture, drain, surgical technique, fascia). Human prospective, randomized trials; meta-analyses; and evidence-based-focused reviews were assessed and data abstracted. Several earlier and animal-based studies on specific issues were included. The data indicate that: (1) the direction of the incision should be based upon obtaining adequate exposure; (2) hair should either be left in place or clipped at the time of surgery; (3) a single dose of prophylactic antibiotics should be given 30 minutes prior to surgery; (4) using a "deep" scalpel is unnecessary; (5) a scalpel and electrocautery are comparable for deepening the incision; (6) minimal peritoneal lavage with non-antibiotic containing solutions is adequate; (7) the peritoneum should not be routinely closed; (8) the fascia should be loosely approximated by a continuous mass closure using a slowly absorbable, monofilament suture with the smallest possible caliber and a suture:wound length ratio of at least 4:1; (9) retention sutures, subcutaenous sutures and drains do not appear to reduce the risk of wound complications; and (10) the skin may be closed in a variety of methods, but a semiocclusive dressing should be applied. As scientific evidence accumulates to refute traditional dogma, management of the surgical patient has undergone substantial changes. Surgeons should now be able to create and close an abdominal wound based upon sound scientific principles rather than simply "doing what I always do."     

Preoperative glucocorticoids decrease pulmonary hypertension in piglets after cardiopulmonary bypass and circulatory arrest

BACKGROUND: Glucocorticoids during cardiopulmonary bypass benefit pediatric patients undergoing repair of congenital heart defects and are routine therapy, but underlying mechanisms have not been fully examined. The hypothesis was that glucocorticoids could improve cardiopulmonary recovery after cardiopulmonary bypass and deep hypothermic circulatory arrest. METHODS: Crossbred piglets (5 to 7 kg) were cooled with cardiopulmonary bypass, followed by 120-min deep hypothermic circulatory arrest. Animals were then warmed to 38 degrees C, removed from bypass, and maintained for 120 min. Methylprednisolone (60 mg/kg) was administered in the cardiopulmonary bypass pump prime (intraoperative glucocorticoids) or 6 hours before bypass (30 mg/kg) in addition to the intraoperative dose (30 mg/kg; preoperative and intraoperative glucocorticoids). Controls (no glucocorticoids) received saline. RESULTS: Pulmonary vascular resistance in controls increased from a baseline of 152 +/- 40 to 364 +/- 29 dynes. s/cm(5) at 2 hours of recovery (p < 0.001). Intraoperative glucocorticoids did not alleviate the increase in pulmonary vascular resistance (301 +/- 55 dynes. s/cm(5) at 2 hours of recovery, p < 0.001). However, animals receiving pre and intraoperative glucocorticoids had no increase in pulmonary vascular resistance (155 +/- 54 dynes. s/cm(5)). Plasma endothelin-1 in controls increased from 1.3 +/- 0.2 at baseline to 9.9 +/- 2.0 pg/mL at 2 hours recovery (p < 0.01), whereas glucocorticoid-treated animals had lower endothelin-1 levels (4.5 +/- 2.1 pg/ml, preoperative and intraoperative glucocorticoids; 4.9 +/- 1.7 pg/mL, intraoperative glucocorticoids) at the end of recovery (p < 0.05). Intracellular adhesion molecule-1 in lung tissue was lower in animals receiving pre and intraoperative glucocorticoids (p < 0.05). Myeloperoxidase activity was elevated in control lungs at 2 hours of recovery compared with glucocorticoid-treated groups (p < 0.05). Inhibitor kappaBalpha, the inhibitor of nuclear factor-kappaB, was higher in lungs of animals receiving glucocorticoids compared with controls (p < 0.05). CONCLUSIONS: Glucocorticoids prevented pulmonary hypertension after cardiopulmonary bypass and deep hypothermic circulatory arrest, which was associated with reduced plasma endothelin-1. Glucocorticoids also reduced pulmonary intercellular adhesion molecule-1 and myeloperoxidase activity. Inhibition of nuclear factor-kappaB, along with reduced neutrophil activation, contributed to glucocorticoid alleviation of pulmonary hypertension after cardiopulmonary bypass and deep hypothermic circulatory arrest.