Cocaine impairs maternal nest building in pregnant rats

The present study investigated the onset of maternal nest building in pregnant Fischer rats following chronic repeated cocaine administration. Pregnant Fischer rats were injected with saline or cocaine, 15 mg/kg, three times daily at 1-h intervals for 10 days starting on gestation day 8. Cocaine-exposed females incorporated less material into their nests and built fewer fully completed circular nests than control animals. The overall quality of the nest in cocaine exposed dams was significantly lower than that of control animals. Furthermore, cocaine exposed dams gained less weight than control females. However, no difference in number of pups, weight, or length of pups was observed between groups. Thus, it seems that cocaine disrupts the interest and skill in nest building of pregnant rats.     

Cocaine transiently impairs maternal behavior in the rat.

This paradigm distinguished between two hypotheses not previously directly addressed. Do repeated exposures to cocaine at critical times during pregnancy, when the neural mechanisms that support maternal behavior are being readied, alter some fundamental neural underpinning of maternal behavior in rats? Alternatively, does cocaine alter maternal behavior only when circulating? During the 4 hr after cocaine injection (20 or 40 mg/kg), there were significant deficits in maternal behavior. In contrast, 16 hr after cocaine injection, drug-injected females, in which plasma cocaine had fallen to nondetectable levels, showed the normal maternal behavior of saline-injected controls. This pattern of impaired maternal behavior after cocaine injection, followed by normal behavior as blood levels returned to zero, was replicated over 8 days. It was concluded that cocaine impairs maternal behavior only when circulating and does not have a residual effect in the transiently drug-free, chronically drug-treated dam. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cocaine impairs follicular phase pulsatile gonadotropin secretion in rhesus monkeys

BACKGROUND: Ménière's disease is a medical condition that involves hearing loss, tinnitus and attacks of vertigo. The attacks can be severely disabling with nausea, dizziness, and aural sensations. METHOD: Three scales assessing the correlates of vertigo attacks in Ménière's disease were developed and completed by 514 subjects diagnosed with the disease. The three scales measured were somatic sensations (SOM), psychological state (PSYCHOL), and situational characteristics (SIT) associated with an attack. RESULTS: Psychometric properties of the three scales were investigated showing Cronbach's alphas of 0.76, 0.80, and 0.62 for the three scales respectively. The results on the scales were related to disease progression. Principal components factor analyses showed that the SOM scale could be divided into two subscales: dizziness/vertigo/anxiety and sensations in the ear. The PSYCHOL scale showed an energy/awareness factor and a negative emotional state factor. The SIT scale, finally, showed two factors: environmental disturbances and stressful conditions. CONCLUSIONS: Knowledge of somatic, psychological and situational premonitory characteristics of attacks in Ménière's disease could lead to improved therapy and counselling.     

Cocaine does not compromise cerebral or myocardial oxygen delivery in fetal sheep

Aprikalim, a K+ ATP channel opener, is a potent vasodilator with demonstrated cardioprotective properties against ischemia/reperfusion injury. It is still unknown if K+ ATP channel openers exert their beneficial effects via interaction with oxygen-derived free radicals. Therefore, we investigated the cardioprotective effects of aprikalim against oxygen-derived free radicals. Isolated rabbit hearts were perfused at constant pressure (85 cm H2O) or constant flow (30-35 ml/min). Heart rate, left ventricular developed pressure (LVDP), and either coronary flow or coronary perfusion pressure (CPP) were monitored. Free radicals were produced by electrolysis of the perfusate (0.6 mA, direct current), and 10 microM aprikalim was infused before and after exposure to free radicals. In the constant perfusion pressure experiments, 10 min of exposure to free radicals resulted in a significant reduction of heart rate (137 to 129 beats/min), LVDP (112 to 91 mmHg) and coronary flow (37 to 29 ml/min); coronary flow was more markedly impaired than contractile function. Acetylcholine-induced coronary dilation was also significantly attenuated in the presence of free radicals. After 30 min of recovery, both coronary flow and LVDP were still significantly decreased while acetylcholine-induced coronary dilation had fully recuperated. Aprikalim completely abated the coronary and cardiac depressant actions of free radicals. Constant flow experiments indicated that exposure to free radicals increased CPP (+40%, p < 0.05), an effect totally suppressed by aprikalim. These results demonstrate that aprikalim reverses the cardiodepressant actions of free radicals. The cardioprotection it afforded involves both contractile function and the coronary vasculature. Acetylcholine-induced coronary dilation was blunted by free radicals, an indication of complex interactions at the coronary endothelial level.     

Endotoxin differentially impairs receptor-mediated relaxation in rat isolated pulmonary and thoracic aortic vessels

PURPOSE: The purpose of this study was to determine the effect of endotoxin on vasorelaxation in the pulmonary and systemic circulations in response to the following agonists that require generation of cyclic adenosine monophosphate: (1) beta-adrenergic receptor stimulation with isoproterenol; (2) H2 receptor stimulation with dimaprit; and (3) adenylate cyclase stimulation with forskolin. METHODS: Male Sprague-Dawley rats weighing 250 to 350 g were injected with endotoxin (20 mg/kg intraperitoneal) or saline. Six hours later, the cumulative dose response to beta-adrenergic receptor stimulation (isoproterenol), H2 receptor stimulation (dimaprit), and adenylate cyclase stimulation (forskolin) was determined in isolated rat pulmonary artery and thoracic aortic rings preconstricted with phenylephrine. RESULTS: Endotoxin caused significant impairment of relaxation to isoproterenol in the pulmonary artery, but the response in the aorta was not different from the control response. In the pulmonary circulation, endotoxin converted the response to dimaprit from vasorelaxation to vasoconstriction. On the other hand, dimaprit resulted in vasorelaxation in the thoracic aorta after endotoxin; however, the response was impaired compared with the control response. Endotoxin did not affect the dose response to forskolin in either the pulmonary artery or the thoracic aorta. CONCLUSION: From these data, we conclude that endotoxin causes regional specific changes in vascular reactivity. These changes in vascular reactivity result in preserved vasorelaxation in the systemic circulation and impairment of vasorelaxation in the pulmonary circulation in response to endotoxin.     

Reduced left ventricular relaxation velocity after acute myocardial infarction

The full length porcine granulocyte/macrophage colony stimulating factor (GM-CSF) cDNA, including secretion signal peptide coding region was recloned into baculovirus transfer vector pAcYM1. The vector was then transfected with Autographica californica nuclear polyhedrosis virus (AcNPV) DNA into SF21AE cells and the recombinant virus AcPGM was recovered. Recombinant porcine GM-CSF (rpGM-CSF) was obtained from the serum-free culture medium of Tn5 cells infected with the AcPGM virus, and was shown to be a glycosylated 21 kDa protein as confirmed by tunicamycin treatment and [3H]-glucosamine uptake. The biological activities of rpGM-CSF in AcPGM-infected cell culture supernatants were demonstrated by porcine bone marrow cell proliferation and haematopoietic cell colony formation assays. The use of rpGM-CSF enabled us to culture porcine monocytes/macrophage and dendritic-like cells, derived from either porcine bone marrow or peripheral blood, for up to 4 months.     

Prolonged myocardial hibernation exacerbates cardiomyocyte degeneration and impairs recovery of function after revascularization

OBJECTIVES: We sought to define the effects of time on contractile function, morphology and functional recovery after coronary revascularization in patients with dysfunctional but viable (hibernating) myocardium. BACKGROUND: Functional recovery after coronary artery bypass graft surgery in patients with chronic myocardial hibernation is incomplete or delayed. The proposed cause is a progressive temporal degeneration of cardiomyocytes. METHODS: In 32 patients with multivessel coronary disease, regional wall motion analysis was performed in hypoperfused but metabolically active areas before and 6 months after bypass surgery. During bypass surgery, transmural biopsy samples were obtained from the center of the hypokinetic zone for light and electron microscopic analyses. The proposed duration of myocardial hibernation was retrospectively assessed. RESULTS: Patients with a subacute hibernating condition (<50 days) demonstrated a higher preoperative ejection fraction (EF, 50+/-8%), and a better preserved wall motion (WM) in the supraapical wall (-1.4+/-0.4) than did patients with intermediate-term (>50 days, EF 37+/-9%, p < 0.05; WM -2.4+/-1.5, p = 0.08) or chronic (>6 months, EF 40+/-14%, WM -2.7+/-0.9, p < 0.005) ischemia. Structural degeneration correlated with the duration of ischemia (r = 0.56, p < 0.05). Postoperative recovery of function was enhanced in patients with a short history of hibernation compared with patients with an intermediate-term or chronic condition (EF 60+/-10% vs. 40+/-10%, p < 0.001, and vs. 47+/-14%, p < 0.05). CONCLUSIONS: Hibernating myocardium exhibits time-dependent deterioration due to progressive structural degeneration with enhanced fibrosis. Early revascularization should be attempted to salvage the jeopardized tissue and improve postoperative outcome.     

Cardiorespiratory effects of breathing and relaxation instruction in myocardial infarction patients

The effect of individual instruction in relaxation and breathing, additional to an exercise training program, was investigated in 76 post-myocardial infarction patients after rehabilitation and at 3 months follow-up. Respiration rate (RR), heart rate (HR) and respiratory sinus arrhythmia (RSA) were the outcome variables used to compare experimental (exercise plus relaxation) and control (exercise without relaxation) groups. HR and RR decreased slightly during 20-min sessions of supine measurement. This response did not vary between sessions (pre-rehabilitation, post-rehabilitation and after 3-month follow-up). RSA tended to decrease during the sessions. The within-session reduction in RSA became more apparent in the control group after treatment and less so in the experimental group. RR decreased in the experimental group after rehabilitation, but not in the control group. HR decreased for all patients, but the decrease was larger in the experimental group. This effect was associated with the lower RR. RSA did not change in the control group but increased in the experimental group, during both normal and deep breathing. This effect was also associated with a slower RR and became marginally significant when RR was statistically controlled for. We conclude that the relaxation intervention induced a slower breathing pattern which was associated with beneficial effects on resting HR and RSA. Further study is warranted to clarify the degree to which reduced respiration rate is an indicator of lower sympathetic arousal or merely a concomitant of the learned breathing technique.     

Characteristics of the effect of parathyroid hormone on rat myocardial relaxation]

We report a case of biopsy-proven polyarteritis nodosa (classic type in association with the antiphospholipid syndrome. Medium-sized arteriopathy was confirmed on visceral angiography. Elevated anticardiolipin antibodies were detected before initiating therapy with methylprednisolone and IV pulse cyclophosphamide. Rapid subsidence of symptoms correlated with a gradual normalisation of the erythrocyte sedimentation rate. After 6 months of therapy anticardiolipin antibodies were within normal limits. Only one similar case has been reported so far.     

Cocaine abuse and reproduction

Exposure of Streptococcus pyogenes to 5 x minimum inhibitory concentration of roxithromycin for 1 h produced a significant postantibiotic effect. More than 2.5 h was necessary for roxithromycin-treated bacteria to increase by 1 log10 in colony-forming units after drug removal, compared with the unexposed cells. After exposure to and removal of the drug, treated cells failed to exhibit normal hemolytic activity for at least 4 h. The inhibitory effect persisted for 20 h after drug removal, although the extent of growth for treated and untreated cells was almost the same. Hydrophobicity of treated cells, studied throughout the logarithmic growth phase with a water-hexadecan two-phase system, was markedly decreased by 40%, compared with untreated cells 4 h after drug removal. Cells that had been treated with roxithromycin became more susceptible to the bactericidal activity of human PMNL than untreated bacteria. The data indicate that some of the metabolic activity that contributes to the virulence of S. pyogenes is affected by postexposure to roxithromycin, and its minimum inhibitory concentration and serum level might not be the best indicators of efficacy in this class of drugs.     

Cocaine and the nervous system

Cocaine abuse today has reached greater heights than it did during the first cocaine epidemic in the late nineteenth century. It is estimated that one out of every four Americans has used cocaine and some six million people in the US use it regularly. Although cocaine affects all systems in the body, the central nervous system (CNS) is the primary target. Cocaine blocks the reuptake of neurotransmitters in the neuronal synapses. Almost all CNS effects of cocaine can be attributed to this mechanism. Euphoria, pharmacological pleasure and intense cocaine craving share basis in this system. The effects of cocaine on other organ systems, in addition to its effects on the CNS, account for the majority of the complications associated with cocaine abuse. In this paper, the CNS effects following cocaine administration and their treatment are discussed.     

Cocaine, kindling, and psychosis

The authors review the evidence that repetitive administration of central nervous system stimulants and other compounds may be associated with progressively increasing effects on pathological behavior and seizures rather than tolerance. They suggest that the progressive effects of these compounds may be related to electrical kindling, a phenomenon in which repetitive subthreshold stimulation of the limbic system is eventually associated with major motor seizures. They review the studies supporting a pharmacological kindling mechansim and suggest a kindling model for psychological stimuli that combines neurophysiological, biochemical, and psychological perspectives.     

Cocaine abuse counseling as HIV prevention

The synthesis and hemoglobin cross-linking studies of a novel organic reagent, bis[2-(4-carboxyphenoxy)carbonylethyl]phosphinic acid (BCCEP; 2) has been reported. The reagent was synthesized in four steps from hydroxybenzoic acid. The tri-sodium salt of BCCEP was employed to cross-link oxyHb, and the product was purified by DEAE-cellulose chromatography. The purified material was analyzed by SDS-PAGE, IEF, and HPLC analyses, which clearly showed the formation of covalent, intramolecular cross-links. While SDS-PAGE analyses of individual bands pointed to the molecular weight range of 32 kDa, the HPLC analyses suggested that the cross-links had formed between beta 1-beta 2 subunits. The oxygen equilibrium measurements and the Hill plots were performed on the purified bands to assess oxygen affinity as well as cooperativity of oxygen binding of the modified hemoglobins. All bands corresponding to modified hemoglobins showed significantly reduced oxygen affinity as compared with that of cell-free hemoglobin, as desired. The modified hemoglobins, however, exhibited somewhat reduced oxygen-binding cooperativity as contrasted with human stroma-free hemoglobin. Molecular dynamics simulation studies (Insight II/Discover/Biosym) on the Reagent-HbA0 complex suggested that the most likely amino acid residues involved in the cross-linking are Lys82 or N-terminal Val1 on one of the beta chains, and Lys144 on the other.     

Cocaine contamination of United States paper currency

The exchange of illicit cocaine for money by drug dealers is an everyday occurrence in cities in the United States. There is ample opportunity during the exchange, storage, and use of cocaine for paper currency to become contaminated. Because currency is exchanged frequently, it is likely that contaminated currency would be found in common use. We examined ten single dollar bills from several cities in the United States for the presence of cocaine. Individual bills were extracted with methanol (10 mL). Cocaine was purified from the methanol extract by solid-phase extraction (SPE). The SPE extract was analyzed by gas chromatography-mass spectrometry (GC-MS). Standard curves were constructed with new, uncirculated currency. Cocaine was identified qualitatively by full scan and quantitated by selected ion monitoring. Cocaine was present in 79% of the currency samples analyzed in amounts above 0.1 micrograms and in 54% of the currency in amounts above 1.0 micrograms. Contamination was widespread and was found in currency from all sites examined. Cocaine amounts were highly variable and ranged from nanogram to milligram amounts. The highest amount of cocaine detected on a single one-dollar bill was 1327 micrograms. These results indicated that cocaine contamination of currency is widespread throughout the United States and is likely to be primarily a result of cross-contamination from other contaminated currency and from contaminated money-counting machines.     

Cocaine self-administration increased by compounding discriminative stimuli

Presenting independently established discriminative stimuli in compound can substantially increase response rates under food and shock-avoidance schedules. To determine whether this effect extends to drug self-administration, rats were trained to press a lever to receive cocaine intravenously. A tone and a light were independently established as discriminative stimuli for cocaine self-administration, then presented in combination in a stimulus-compounding test. Compared to tone and light alone, the tone-plus-light compound stimulus increased responding approximately three-fold when cocaine was withheld during testing, and it increased drug intake approximately two-fold when cocaine was made available during testing. Compounding did not increase responding after training in a truly random control condition where tone and light were presented uncorrelated with the availability of cocaine. The results obtained with this animal model of drug abuse define conditions under which combinations of environmental stimuli might substantially increase human drug use.     

Cocaine and cocaethylene binding to human milk

The relationship between frequency of intake of different types of fat and breast cancer was investigated in a case-control study conducted in Montevideo, Uruguay, during the time period 1994-1996. Our study comprised 365 cases and 397 controls. A moderate and non-significant increase in risk of breast cancer, associated with total fat intake, was found. Saturated and monounsaturated fat intake were not associated to an increased risk of this malignancy, whereas polyunsaturated fat and linoleic acid were associated with a significantly reduced risk (OR 0.26, 95% CI 0.13-0.53). On the contrary, both alpha-linolenic acid and cholesterol intakes were associated with an increased risk of breast cancer (OR for the upper quartile of intake of alpha-linolenic acid 3.79, 95% CI 1.53-9.40). When alpha-linolenic was examined at different levels of intake, the OR's were significantly higher at low levels of linoleic acid intake (OR 7.5, 95% CI 1.9-28.8).