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Biomedical subjects

P M Ryan

Publications and source records attributed to P M Ryan.

10 recordsLinked to original sources

The toxicity profile of a single dose of paroxetine: an alternative approach to acute toxicity testing in the rat.

In this study we have examined the effect of a single administration of the selective serotonin reuptake inhibitor, paroxetine (120-300 mg kg(-1), orally) in a recently developed rodent model of acute toxicity testing. Reduced body-weight, food consumption, water consumption and body temperature were observed in all paroxetine-treated groups, which were reversible within 7 days. Five days after administration, a dose-dependent increase in red blood cells, haemoglobin and haematocrit was observed with the 3 higher dose levels of paroxetine, which was significant in the 240 and 300 mg kg(-1) treatment groups (P < 0.05). Hyperactivity was apparent in the first 24 hr following treatment, as was evidence of the serotonin syndrome. When the animals were sacrificed (11 days after drug administration), an increase in liver weight was observed in the highest dose. These results are in agreement with those previously observed with paroxetine at the preclinical and clinical levels. They demonstrate that this rodent model, because of its multi-parameter nature, is a useful method for examining the consequences of a single high dose of an antidepressant drug.

Animal Testing Alternatives↗

Extracting parity and magnitude from Arabic numerals: developmental changes in number processing and mental representation.

Children from Grades 2, 3, 4, 6, and 8 (7.8, 9.2, 9.8, 11.7, and 13. 6 years old, respectively) made speeded, bimanual parity (odd/even) judgments of the Arabic numerals 0-9. Analysis of response times indicated that from fourth grade on, parity information is retrieved directly from memory rather than being extracted by means of a mental calculation strategy. As early as Grade 3, children exhibited the SNARC (Spatial-Numerical Association of Response Codes) effect, where small numbers were responded to faster with the left hand than with the right hand, while the converse held true for large numbers. This finding, previously demonstrated only in adults, confirms that (a) children represent magnitude information in the form of a left-to-right oriented mental number line, and (b) this information is accessed obligatorily even when irrelevant. Finally, although the SNARC effect remained strong at Grade 4, it was attenuated at Grades 6 and 8 by a linguistic effect based on associations between the unmarked adjectives "even" and "right" and between the marked adjectives "odd" and "left."

Adolescent↗

The characterization of oxotremorine-induced hypothermic response in the rat.

Oxotremorine is a muscarinic receptor agonist that induces a variety of physiological and behavioural effects including hypothermia in mice. These effects are antagonized dose-dependently by classical anticholinergic compounds such as atropine. Although the oxotremorine-induced hypothermic response has been demonstrated in mice, few studies of the effects of this muscarinic agonist have been made in the rat. The following studies were made in male Sprague Dawley rats: 1. an investigation of the dose-response relationship between oxotremorine and hypothermia; 2. an examination of the effect of housing on the oxotremorine-induced hypothermic response, and 3, an investigation of the acute administration of various doses of atropine sulphate on the hypothermia caused by oxotremorine. The results indicate that the dose-response relationship between oxotremorine and the antagonism of hypothermia is similar in rat as it is in mice. The results also showed that this effect did not occur in group-housed animals.

Animals↗

Epidemiology, etiology, diagnosis, and treatment of schizophrenia.

The epidemiology, etiology, diagnosis, and treatment of schizophrenia are reviewed. In the United States, at least 1 in every 100 persons is afflicted with schizophrenia. The theory that schizophrenia is a biochemical disorder has gained wide acceptance, although none of the etiological theories are conclusive. Criteria contained in the Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised, are most commonly used to diagnose schizophrenia. Accuracy in diagnosing schizophrenia is critical because the treatments and prognoses for different types of psychoses can vary considerably. Treatment primarily involves the use of antipsychotic drugs, which are thought to act by blocking central dopamine receptors. The classical antipsychotics are the phenothiazines; of these, the prototype is chlorpromazine. Other classes of antipsychotics are the thioxanthenes, butyrophenones, dihydroindolones, dibenzoxazepines, diphenylbutylpiperidines, and dibenzodiazepines. Selecting an appropriate agent involves consideration of adverse effects, dosage forms, and the agent's ability to relieve target symptoms. Adverse effects of these agents include sedation, extrapyramidal effects, and anticholinergic effects. Tardive dyskinesia is a serious, irreversible condition associated with long-term antipsychotic therapy. Clozapine, a newer atypical antipsychotic, has been shown to be more effective than chlorpromazine and haloperidol and seems to cause few neurological adverse effects. Treatment of schizophrenia has not changed much since the advent of antipsychotic drug use nearly 30 years ago. Newer atypical antipsychotics show promise in improving target symptoms while causing fewer adverse effects.

Antipsychotic Agents↗

The incidence of cancer following total hip replacement.

We have studied the incidence of tumours at remote sites following total hip replacement: 1,358 individuals have been followed up for 14,286 person-years after operation. In the decade following implantation the incidence of tumours of the lymphatic and haemopoietic systems was significantly greater, and that of cancer of the breast, colon, and rectum, significantly less than expected. Whilst the association might be due in part to an effect of the prosthetic implants, other mechanisms, particularly drug therapy, require consideration.

Breast Neoplasms↗

Human triosephosphate isomerase cDNA and protein structure. Studies of triosephosphate isomerase deficiency in man.

Nine cDNA clones of human adult liver triosephosphate (TP) isomerase have been isolated and characterized. All nine appear to be derived from a single mRNA species. DNA sequencing of one clone, designated pHTPI-5a, defined the last two nucleotides of the methionine initiation codon, the entire 744-nucleotide coding region of the mature polypeptide, and the entire 448-nucleotide 3' untranslated region. The frequency of TP isomerase clones in the cDNA library suggests that TP isomerase mRNA is present in adult liver at approximately 25 copies/cell. A single, low abundance TP isomerase mRNA species was detected in RNA isolated from normal human fibroblast cell lines. Analysis of TP isomerase mRNA levels in cultured fibroblasts of individuals that are homozygous for TP isomerase deficiency revealed normal levels in one and approximately 40% of normal levels in another. From this small patient sampling, it can be concluded that the genetic basis for TP isomerase deficiency is heterogeneous.

Amino Acid Sequence↗