Drug-induced brain monoamine depletion and its behavioral correlates in Caiman sclerops

Author(s):  
E. Doshi ◽  
S.E. Huggins
CNS Spectrums ◽  
2007 ◽  
Vol 12 (7) ◽  
pp. 545-552 ◽  
Author(s):  
Andrea E. Cavanna

ABSTRACTThis article reviews the rapidly growing literature on the functional anatomy and behavioral correlates of the precuneus, with special reference to imaging neuroscience studies using hamodynamic techniques. The precuneus, along with adjacent areas within the posteromedial parietal cortex, is among the most active cortical regions according to the “default mode” of brain function during the conscious resting state, whereas it selectively deactivates in a number of pathophysiological conditions (ie, sleep, vegetative state, drug-induced anesthesia), and neuropsychiatric disorders (ie, epilepsy, Alzheimer's disease, and schizophrenia) characterized by impaired consciousness. These findings, along with the widespread connectivity pattern, suggest that the precuneus may play a central role in the neural network correlates of consciousness. Specifically, its activity seems to correlate with self-reflection processes, possibly involving mental imagery and episodic/autobiographical memory retrieval.


2002 ◽  
Vol 4 (4) ◽  
pp. 342-350

Sleep laboratory investigations constitute a unique noninvasive tool to analyze brain functioning, Polysomnographic recordings, even in the very early phase of development in humans, are mandatory in a developmental plan of a new sleep-acting compound. Sleep is also an interesting tool for the development of other drugs acting on the central nervous system (CNS), Indeed, changes in sleep electroencephalographic (EEG) characteristics are a very sensitive indication of the objective central effects of psychoactive drugs, and these changes are specific to the way the drug acts on the brain neurotransmitter systems. Moreover, new compounds can be compared with reference drugs in terms of the sleep EEG profile they induce. For instance, cognitive enhancers involving cholinergic mechanism have been consistently demonstrated to increase rapid eye movement (REM) sleep pressure, and studying drug-induced slow wave sleep (SWS) alteration is a particularly useful tool for the development of CNS compounds acting at the 5-HT(2A/C) receptor, such as most atypical antipsychotics and some antidepressant drugs. The sleep EEG profile of antidepressants, and particularly their effects on REM sleep, are specific to their ability to enhance noradrenergic or serotonergic transmission, it is suggested that the effects of noradrenergic versus serotonergic reuptake inhibition could be disentangled using specific monoamine depletion tests and by studying drug effects on sleep microsiructure.


Author(s):  
F. G. Zaki ◽  
E. Detzi ◽  
C. H. Keysser

This study represents the first in a series of investigations carried out to elucidate the mechanism(s) of early hepatocellular damage induced by drugs and other related compounds. During screening tests of CNS-active compounds in rats, it has been found that daily oral administration of one of these compounds at a dose level of 40 mg. per kg. of body weight induced diffuse massive hepatic necrosis within 7 weeks in Charles River Sprague Dawley rats of both sexes. Partial hepatectomy enhanced the development of this peculiar type of necrosis (3 weeks instead of 7) while treatment with phenobarbital prior to the administration of the drug delayed the appearance of necrosis but did not reduce its severity.Electron microscopic studies revealed that early development of this liver injury (2 days after the administration of the drug) appeared in the form of small dark osmiophilic vesicles located around the bile canaliculi of all hepatocytes (Fig. 1). These structures differed from the regular microbodies or the pericanalicular multivesicular bodies. They first appeared regularly rounded with electron dense matrix bound with a single membrane. After one week on the drug, these vesicles appeared vacuolated and resembled autophagosomes which soon developed whorls of concentric lamellae or cisterns characteristic of lysosomes (Fig. 2). These lysosomes were found, later on, scattered all over the hepatocytes.


Author(s):  
R. H. Liss

Piperacillip (PIP) is b-[D(-)-α-(4-ethy1-2,3-dioxo-l-piperzinylcar-bonylamino)-α-phenylacetamido]-penicillanate. The broad spectrum semisynthetic β-lactam antibiotic is believed to effect bactericidal activity through its affinity for penicillin-binding proteins (PBPs), enzymes on the bacterial cytoplasmic membrane that control elongation and septation during cell growth and division. The purpose of this study was to correlate penetration and binding of 14C-PIP in bacterial cells with drug-induced lethal changes assessed by microscopic, microbiologic and biochemical methods.The bacteria used were clinical isolates of Escherichia coli and Pseudomonas aeruginosa (Figure 1). Sensitivity to the drug was determined by serial tube dilution in Trypticase Soy Broth (BBL) at an inoculum of 104 organisms/ml; the minimum inhibitory concentration of piperacillin for both bacteria was 1 μg/ml. To assess drug binding to PBPs, the bacteria were incubated with 14C-PIP (5 μg/0.09 μCi/ml); controls, in drug-free medium.


Author(s):  
Sarah A. Luse

In the mid-nineteenth century Virchow revolutionized pathology by introduction of the concept of “cellular pathology”. Today, a century later, this term has increasing significance in health and disease. We now are in the beginning of a new era in pathology, one which might well be termed “organelle pathology” or “subcellular pathology”. The impact of lysosomal diseases on clinical medicine exemplifies this role of pathology of organelles in elucidation of disease today.Another aspect of cell organelles of prime importance is their pathologic alteration by drugs, toxins, hormones and malnutrition. The sensitivity of cell organelles to minute alterations in their environment offers an accurate evaluation of the site of action of drugs in the study of both function and toxicity. Examples of mitochondrial lesions include the effect of DDD on the adrenal cortex, riboflavin deficiency on liver cells, elevated blood ammonia on the neuron and some 8-aminoquinolines on myocardium.


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