Pharmacological characterization of performance on a concurrent lever pressing/feeding choice procedure: effects of dopamine antagonist,cholinomimetic, sedative and stimulant drugs

This experiment was undertaken to provide a pharmacological characterization of performance on a task involving food-related instrumental and consummatory behavior. Rats were tested in an operant chamber in which there was a choice between pressing a lever to receive a preferred food (Bioserve pellets) or approaching and consuming a less-preferred food (Lab Chow). The lever pressing schedule was a fixed ratio 5 (FR5). Rats usually pressed the lever at high rates to obtain the preferred food, and typically ate little of the lab chow even though it was freely available in the chamber concurrently with the lever pressing schedule. Previous work has shown that injection of dopamine (DA) antagonists, or depletion of DA in the nucleus accumbens, caused a substantial shift in behavior such that lever pressing was reduced but chow consumption increased. In the present study it was shown that the DA antagonist haloperidol decreased lever pressing and increased chow consumption at doses of 0.1 and 0.15 mg/kg. The D1 antagonist SCH 23390 (0.05, 0.1 and 0.15 mg/kg) and the non-selective DA antagonistcis-flupenthixol (0.3 and 0.45 mg/kg) decreased lever pressing and produced substantial increases in chow consumption. The D2 antagonist sulpiride decreased lever pressing, but produced only slight increases in chow intake at the highest dose. Pentobarbital reduced lever pressing and increased chow consumption at 10.0 mg/kg. The muscarinic agonist pilocarpine produced dose-related decreases in lever pressing, but failed to increase chow consumption. Amphetamine produced dose-related decreases in both lever pressing and chow consumption. These results indicate that low/moderate doses of the DA antagonists haloperidol,cis-flupenthixol and SCH 23390 can suppress lever pressing in doses that leave the animal directed towards food acquisition and consumption.     

Objective cervical portio length measurements: consistency and efficacy of screening for a short cervix

OBJECTIVE: To determine the consistency of 4-quadrant cervical portio length measurements with an objective cervical measuring device and to identify patients who may benefit from transvaginal ultrasound. STUDY DESIGN: Prenatal patients (12-34 weeks) derwent 4-quadrant cervical portio measurements and transvaginal ultrasound by different, blinded examiners. Cervical portio quadrant measures were analyzed by correlation analysis, and the predictive ability of cervical portio length measurements to identify short cervices with transvaginal ultrasound was assessed. RESULTS: The right and left lateral cervical portio measurements were consistently available and correlated highly with each other. Cervical portio length had excellent sensitivity (88%), specificity (92%) and negative predictive value (99%) in identifying patients with a short cervix (< 30 mm) by transvaginal ultrasound. CONCLUSION: Right and left lateral cervical portio length measurements are highly consistent and provide an effective screen for patients with short cervixes who may benefit from transvaginal ultrasound.     

Breastfeeding perceptions in communities in Mangochi district in Malawi

Aim: To investigate mothers’ perceptions of breastfeeding and influences from their social network. Methods: A cross‐sectional survey was carried out in Mangochi district, Malawi where questionnaire data from 157 rural and 192 semi‐urban mother–infant pairs were obtained. Results: The proportion of mothers who thought that exclusive breastfeeding should last for 6 months and those who reported to have actually exclusively breastfed were 40.1% and 7.5% respectively. Of those who reported practising exclusive breastfeeding for 6 months, 77.5% stated that exclusive breastfeeding should last for 6 months. This opinion was independently associated with giving birth in a Baby‐Friendly facility, OR = 5.22; 95% CI (1.92–14.16). Among the mothers who thought that exclusive breastfeeding should last for less than 6 months, 43.9% reported having been influenced in their opinion by health workers. Infant crying was the most common (62.4%) reason for stopping exclusive breastfeeding. Conclusion: The findings illustrate the positive impact health workers can have, as well as the need to raise awareness of the benefits of exclusive breastfeeding among both health workers and mothers. Furthermore, continued counselling of mothers on how to deal with stressful infant behaviour such as crying may assist to prolong exclusive breastfeeding.     

Effects of prenatal nicotine exposure on primate brain development and attempted amelioration with supplemental choline or vitamin C: neurotransmitter receptors, cell signaling and cell development biomarkers in fetal brain regions of rhesus monkeys.

Studies in developing rodents indicate that nicotine is a neuroteratogen that disrupts brain development by stimulating nicotinic acetylcholine receptors (nAChRs) that control neural cell replication and differentiation. We administered nicotine to pregnant Rhesus monkeys from gestational day 30 through 160 by continuous infusion, achieving maternal plasma levels comparable to those in smokers (30 ng/ml). Fetal brain regions and peripheral tissues were examined for nAChR subtypes, other neurotransmitter receptors, and indices of cell signaling and cell damage. Nicotine evoked nAChR upregulation, but with distinct regional disparities indicative of selective stimulatory responses. Similarly, indices of cell loss (reduced DNA), cell size and neuritic outgrowth (protein/DNA and membrane/total protein ratios) were distinct for each region and did not necessarily follow the rank order of nAChR upregulation, suggesting the involvement of additional mechanisms such as oxidative stress. We then attempted to offset the adverse effects of nicotine with standard dietary supplements known to interact with nicotine. By itself, choline elicited nicotine-like actions commensurate with its promotion of cholinergic neurotransmission. When given in combination with nicotine, choline protected some regions from damage but worsened nicotine's effects in other regions. Similarly, Vitamin C supplementation had mixed effects, increasing nAChR responses while providing protection from cell damage in the caudate, the brain region most susceptible to oxidative stress. Our results indicate that nicotine elicits neurodevelopmental damage that is highly selective for different brain regions, and that dietary supplements ordinarily thought to be neuroprotectant may actually worsen some of the adverse effects of nicotine on the fetal brain.     

Inhibition by chlordiazepoxide of adenosine-stimulated glucagon secretion

The action of a water soluble benzodiazepine, chlordiazepoxide (CDZ) on the stimulatory effect of adenosine on glucagon secretion from the isolated pancreas of the rat perfused in presence of 2.8 mM glucose was studied. CDZ 10(-7) and 10(-6) M had no effect per se on glucagon secretion under our experimental conditions. In contrast, CDZ 10(-6) M (but not 10(-7) M) markedly reduced the peak of glucagon secretion provoked by adenosine, 2-chloroadenosine (1.65 C 10(-6) M) and by a stable analogue, 5'-N-ethylcarboxamidoadenosine or NECA (1.65 X 10(-8) M). This peripheral interaction between CDZ and adenosine seemed to be specific, since CDZ did not modify the peak of glucagon secretion induced by (-)isoproterenol (10(-8) M). Our results demonstrate an inhibitory effect of CDZ on adenosine-stimulated glucagon secretion.     

A randomized prospective controlled study of the metabolism and hepatotoxicity of halothane in humans

In a randomized prospective controlled study in humans, the metabolism and hepatic effects of a single administration of halothane were compared with enflurane and meperidine. Pre- and postoperative antipyrine pharmacokinetics, intraoperative indocyanine green clearance, liver histology, and postoperative liver function tests were determined in 24 patients undergoing abdominal surgery who were randomly allocated to receive either halothane (0.5%, group I), enflurane (0.8%, group II), or meperidine (group III) as a supplement to a common basal anesthetic regimen consisting of thiopental, nitrous oxide/oxygen/muscle relaxant. In addition, end-tidal concentrations of the volatile reductive metabolites of halothane, chlorodifluoroethylene (CDF), and chlorotrifluoroethane (CTF) were determined in group I patients and serum and urinary inorganic fluoride were determined in both group I and II patients. Indocyanine green clearance was measured before anesthesia (stage I), during basal anesthesia (stage II), in the presence of surgical stimuli (stage III), and after introduction of the selected anesthetic agent (stage IV). CDF and CTF were detectable within 20 min of the start of halothane anesthesia in every patient receiving halothane. Peak serum fluoride concentrations occurred at 2 and 24 hr in the enflurane and halothane groups, respectively, whereas urinary fluoride excretion was elevated postanesthesia in the enflurane group only. There was no difference between the pre- and postoperative disposition of antipyrine in group II or III, but after anesthesia, antipyrine clearance was significantly decreased (P less than 0.02) and plasma half-life increased (P less than 0.05) in group I patients (halothane). Concentrations of serum alanine aminotransferase (ALT) and bilirubin were significantly elevated (P less than 0.5) postoperatively in groups I and II but unchanged from preoperative values in group III patients. Three of the 24 liver biopsies taken at the end of stage IV showed several foci of acute liver cell necrosis; of these, two patients were from group I and one from group II. There were no significant differences in liver cell morphology (P greater than 0.5) in biopsies taken at the end of stage IV compared with biopsies at the end of stage III, from groups I and II. The results of this study show that reductive metabolism of halothane occurs routinely in patients undergoing halothane anesthesia under conditions of normoxia. This may be the cause of the changes in antipyrine clearance after halothane anesthesia.     

Pulmonary embolism after hip or knee replacement: postoperative changes on pulmonary scintigrams in asymptomatic patients

Serial pulmonary imaging has proved to be effective in the evaluation of patients undergoing total joint arthroplasty. A clinical dilemma arises in asymptomatic patients whose postoperative pulmonary images differ from the preoperative images. The authors prospectively evaluated 403 patients with serial imaging to determine the significance of changed postoperative images in asymptomatic patients undergoing total hip or knee arthroplasty. Twenty-two (5.5%) patients had significant changes on postoperative images. Seventeen were asymptomatic; all but one underwent pulmonary angiography. Documented pulmonary emboli were demonstrated in 100% of patients whose postoperative images changed to indicate a high probability of pulmonary embolism, 71% whose images changed to a moderate probability, and 0% whose images changed to indeterminate probability. Overall, pulmonary emboli occurred in 76% of all asymptomatic patients with significantly change postoperative images. Asymptomatic pulmonary embolism is a significant occurrence after total hip or knee repair, and a changed lung scan with appropriate clinical evaluation is an accurate indicator of pulmonary emboli in asymptomatic postarthroplasty patients.