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At least 91 records · Page 5Linked to original sources
PubMed2006

Post-translational enzyme activation in an animal via optimized conditional protein splicing.

Control over the timing, location and level of protein activity in vivo is crucial to understanding biological function. Living systems are able to respond to external and internal stimuli rapidly and in a graded fashion by maintaining a pool of proteins whose activities are altered through post-translational modifications. Here we show that the process of protein trans-splicing can be used to modulate enzymatic activity both in cultured cells and in Drosophila melanogaster. We used an optimized conditional protein splicing system to rapidly trigger the in vivo ligation of two inactive fragments of firefly luciferase in a tunable manner. This technique provides a means of controlling enzymatic function with greater speed and precision than with standard genetic techniques and is a useful tool for probing biological processes.

Animals↗
PubMed1981

Specific norepinephrine and serotonin uptake inhibitors in man: a crossover study with pharmacokinetic, biochemical, neuroendocrine and behavioral parameters.

Eight depressed patients with major affective illness were treated with both zimelidine, a selective serotonin-uptake inhibitor, and with desipramine, a selective norepinephrine uptake inhibitor, following a double-blind crossover design. At steady-state the active metabolite of zimelidine, norzimelidine, predominated in the CSF by a factor of 7 to 1 over parent drug. As predicted, even high concentrations of norzimelidine were not associated with decreased 3-methoxy-4-hydroxy-phenylglycol (MHPG) in the CSF. In the same individuals, desipramine concentrations were highly correlated with decreases of MHPG in the CSF. Despite specific effects on monoamine neurotransmitter systems which have been implicated in the control of neuroendocrine secretion, neither drug had consistent effects on plasma cortisol, luteinizing hormone, growth hormone or prolactin. Both drugs had a marked and unexpected common effect on the 24-hour rest-activity cycle. The excess activity during the normal rest period (0--700 hr.) which has been noted in severely depressed individuals was significantly reduced by both the serotonergic zimelidine and the noradrenergic desipramine. These findings suggest that effects on the rest-activity pattern may be a common pathway for antidepressant effect.

Adolescent↗
PubMed1982

Antimanic, antidepressant, and antipanic effects of opiates: clinical, neuroanatomical, and biochemical evidence.

These clinical data may offer some support for the hypothesis that opiates have antidepressant, antimanic, and antipanic effects. This hypothesis should be studied directly by double-blind studies of the effects of exogenous and synthetic endogenous opioid peptides in patients with major depressive illness, panic and anxiety states, schizophrenia, and schizo-affective illness. These clinical data support our studies in nonhuman primates and man which suggest a common LC or NE hyperactivity may underly both drug withdrawal and spontaneous panic states. Whether endorphin deficiency or derangements account for the postulated NE hyperactivity needs additional study and we will discuss our preliminary work later. Failure of endorphins to terminate bursts in LC firing rate and NE release may be responsible for both of these types of panic states. In addicts, this mechanism could exist prior to opiate use, or abuse of potent exogenous endorphinomentic compound may cause an endorphin-abnormality. Both of these possibilities would be compensated by continuous opiate maintenance. Methadone maintenance is a complicated psychiatric, psychological, and social phenomenon. Further studies are necessary to evaluate the role of opiate maintenance in treating or suppressing the emergence of underlying psychopathology. Previous psychiatric hospitalization or treatment for a schizophrenic or affective illness may contraindicate absolutely the use of clonidine or other rapid detoxification methods. These data suggest the possibility of substituting a nonaddicting psychotropic medication for opiates in some patients who are self-medicators. The clinical data support other data suggesting the potential antipsychotic, antidepressant, and antianxiety/antipanic effects of the endogenous opioids, endorphins, and exogenous opioids, endorphins, and exogenous opiates. These and other data suggest potential utility for opioid agonists and endorphin testing in psychiatric treatment and diagnosis.

Adult↗
PubMed1979

State and trait in psychiatric practice.

The authors present a schema for conceptualizing psychiatric illness in terms of state and trait disorders. These disorders are relatively independent components, one or both of which can be present in one patient. They usually require treatment by different methods. State disorders, such as schizophrenic psychosis, mania, and depression, are time-limited and autonomous and respond better to pharmacological than psychosocial therapy. Trait disorders, such as neurotic and characterological disturbances, are long-lasting and respond better to psychosocial therapies. The authors discuss the implications of this schema for the integration of pharmacological and psychosocial treatments.

Humans↗
PubMed1980

Failure of naloxone to reduce manic symptoms.

The authors conducted a double-blind placebo-controlled study in which patients with a wide range of manic symptoms were administered 20 mg of naloxone subcutaneously. Naloxone failed to improve manic severity, activation-arousal, or elation-grandiosity for intervals up to 3 hours. Global nurse ratings of mania did not improve over an 8-hour period. The authors suggest that the question of endorphin involvement in mania has not been resolved and recommend clinical studies with longer acting oral narcotic antagonists such as naltrexone.

Affective Disorders, Psychotic↗