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Biomedical subjects

B K Lewis

Publications and source records attributed to B K Lewis.

31 records · Page 2Linked to original sources
PubMed1993

Acute effects of calcitonin gene-related peptide on the mechanical and electrical responses of the rat hemidiaphragm.

Calcitonin gene-related peptide (CGRP) acutely augments the contractile response of skeletal muscle to both direct and indirect stimulation. However, studies in whole muscle tissues have produced extremely variable results. To determine if differences in stimulation parameters are the source of this variation, the effects of increasing stimulus duration were evaluated in the isolated perfused rat hemidiaphragm. The effect of CGRP on the maximum force of contraction (Fc) was dependent upon the stimulus duration. CGRP (10(-6) M) produced an 11% increase in Fc with a 0.1-msec duration stimulus and a 32% increase with a 1.0-msec stimulus. In contrast, CGRP decreased the time for twitch relaxation and this effect was independent of stimulus duration. Additional studies demonstrated that CGRP shortened the relative refractory period. Compound muscle action potential recordings revealed that stimulus durations greater than 0.5 msec produced a second peak of electrical activity with an associated increased Fc. The effects of CGRP on Fc corresponded to the effects of CGRP on this second peak of compound muscle action potential activity. We conclude that, by decreasing the relative refractory period of the muscle tissue, CGRP enhances the potential for repetitive stimulation with commonly used experimental parameters.

Action Potentials↗
PubMed1990

Are postsynaptic nicotinic end-plate receptors involved in lead toxicity?

The effects of Pb2+ on the postsynaptic nicotinic end-plate receptor were examined in the perfused mouse hemidiaphragm preparation. Postsynaptic nicotinic responses, evoked by pressure ejection of ACh, were blocked by Pb2+ in a transient way. After 9-12 min of exposure to 1 microM Pb2+ the amplitude of the depolarization induced by 1 mM ACh was reduced to 39.5 +/- 11% of the control value. During continued exposure to Pb2+ this blocking effect was reversed and after 30 min of exposure to 1 microM Pb2+ the amplitude of the ACh-induced depolarization had returned to the control value. The amplitude and the frequency of miniature end-plate potentials were not altered in the presence of 1 microM Pb2+. Under voltage clamp conditions the effects of Pb2+ on the ACh-induced inward current were similar to those of Pb2+ on the ACh-induced depolarization. After 12 min of exposure to 1 microM Pb2+ the inward current induced by 1 mM ACh was reduced to 44% of the control value and after 30 min the ACh-induced inward current had recovered to 94% of the control value. It is concluded that, in addition to the generally established mechanism of action of Pb2+ at the muscle end-plate, Pb2+ blocks the postsynaptic nicotinic receptor-mediated response at a relative low concentration. The contribution of these postsynaptic effects to the neurotoxic symptoms of Pb2+ remains to be established.

Acetylcholine↗
PubMed1975

Serum insulin changes in arteriosclerotic breeder female rats versus non-arteriosclerotic virgin rats.

Immunoreactive serum insulin (IRI), glucose, free fatty acids (FFA), and corticosterone (Cmpd. B) were measured in non-arteriosclerotic virgin versus arteriosclerotic, breeder female rats exhibiting normal 4-day cycles. In the arteriosclerotic breeder females, the normal increase in IRI during proestrus and estrus did not occur. The IRI levels during these times were comparable to the minimal levels found during metestrus in the non-arteriosclerotic virgin rats and were even lower than the IRI levels or ovariectomized rats. Since both young and old non-arteriosclerotic virgin rats had similar IRI patterns, the lack of cyclic insulin change in the arteriosclerotic breeder rats is not considered to be age-related. Instead, these changes are ascribed to hypothalamic-pituitary-adrenal hyperactivity associated with repeated reproductive activity and the development of arteriosclerosis.

Animals↗
PubMed1975

Metabolic response after isoproterenol-induced myocardial infarction in arteriosclerotic breeder vs nonarteriosclerotic virgin intact and gonadectomized male rats.

Male, nonarteriosclerotic (virgin) intact and castrated, Sprague-Dawley rats and male, arteriosclerotic (breeder) rats were subjected to an acute and massive myocardial infarct, by treating them with two large, subcutaneous doses of isoproterenol, spaced 24 hr apart. Serum insulin and glucose rose abruptly after the first injection of isoproterenol, but not after the second injection. Free fatty acids rose, most markedly, in the intact, nonarteriosclerotic rats, less in the arteriosclerotic breeders, and least in the castrates. These changes in free fatty acids coincided with numerical survival, i.e., greatest number of survivors in castrates. The castrated males also manifested the least amount of congestive heart failure and showed the greatest capacity to affect myocardial repair. It is suggested that reduced androgen levels may have an ameliorative effect on the usual pathogenesis of isoproterenol-induced myocardial infarction in rats.

Animals↗
PubMed1975

Serum prolactin levels in rats following isoproterenol-induced myocardial infarction.

Circulating prolactin levels were monitored in nonarteriosclerotic, arteriosclerotic, and hormonally sterilized male and female Sprague-Dawley rats during the acute necrosis and repair phases of myocardial infarction induced by isoproterenol. Male rats are particularly prone to succumb to acute myocardial ischemia but reduction of androgen levels by neonatal sterilization improved survival considerably. Circulating prolactin levels are greatly increased, particularly in females, during acute myocardial ischemia. Since androgens suppress the hypothalamic center for prolactin release, prolactin levels were delayed and transitory in males. It is suggested that the superior survival of female rats may be related to their greater production of prolactin during acute stages of myocardial ischemia, which would dampen the tachycardia-inducing effects of the potent beta-adrenergic stimulating agent, isoproterenol.

Androgens↗
PubMedDate not supplied

Changes in LH and prolactin in arteriosclerotic femal breeder rats.

Serum levels of LH and prolactin were measured in repeatedly-bred, arteriosclerotic female rats. Serum LH was abnormally decreased on the afternoon of proestrus and estrus. The extent of the depression of circulating LH levels parallels the severity of the arteriosclerosis. Serum prolactin was significantly increased above normal at proestrus, and the degree of prolactin increase was also correlated with the degree of severity of arteriosclerosis. It is suggested that frequent and repeated pregnancies affect the hypothalamic-pituitary-adrenal-gonadal axis leading to hormonal and metabolic imbalance, which may play a causal role in the pathogenesis of the spontaneous arteriosclerosis which appears in repeatedly-bred rats.

Animals↗
PubMedDate not supplied

Metabolic responses following isoproterenol-induced myocardial infarction in arteriosclerotic breeder vs. non-arteriosclerotic virgin and ovariectomized female rats.

Intact and ovariectomized, non-arteriosclerotic female rats and arteriosclerotic, breeder female rats were subjected to myocardial infarction by the administration of 2 subcutaneous injections, 24 hr apart, of the beta-adrenergic stimulator, isoproterenol. The animals were sacrificed at regular hourly intervals following each injection and then on days 4, 6, 8, 10, 12, and 16 thereafter. Measurement of serum insulin and free fatty acids (FFA) demonstrated a blunted response in these metabolic parameters in the case of the ovariectomized virgin rats. The non-arteriosclerotic, intact virgin rats exhibited dynamic changes in serum insulin, glucose, FFA and corticosterone (Cmpd. B) following both isoproterenol injections, whereas the arteriosclerotic breeder rats manifested elevated levels of these parameters on Day 1, but did not display any increases in serum levels, except for FFA, following the second isoproterenol injection on Day 2. In spite of the hormonal alterations brought about by the gonadectomy and their differing metabolic response, the ovariectomized females did not have a mortality rate significantly different from the intact females. Thus, the presence or absence of ovarian estrogens seemingly does not affect the progress of an isoproterenol-induced myocardial infarction.

Animals↗
PubMedDate not supplied

Serial MR imaging of experimental autoimmune encephalomyelitis induced by human white matter or by chimeric myelin-basic and proteolipid protein in the common marmoset.

BACKGROUND AND PURPOSE: Experimental autoimmune encephalomyelitis (EAE) in the marmoset was monitored by serial MR imaging to determine correlates to the natural-history MR studies in multiple sclerosis (MS). The relationships of MR-revealed lesions to clinical status and histopathologic findings were also explored. METHODS: We induced EAE by subcutaneous inoculation in two marmosets by human white matter (HWM) and in seven marmosets by MP4 (a chimeric recombinant fusion protein of myelin-basic and proteolipid protein) in adjuvant along with intravenous inactivated pertussis vaccine to facilitate the disease process. The HWM-inoculated animals were induced with Freund's adjuvant as the established model of marmoset EAE. The MP4-inoculated animals were induced with either Freund's incomplete adjuvant or TiterMax as part of a preclinical treatment trial. MR imaging was performed at 1.5 T at baseline, and repeated at 1- to 2-week intervals for a period of up to 16 weeks in six EAE-induced marmosets, and intermittently for up to 70 weeks in three EAE-induced and two control marmosets. Proton density- (PD-) and T2-weighted, pre- and postgadopentetate dimeglumine enhancement, T1-weighted, and magnetization transfer (MT) images were obtained. The brains were prepared for histologic evaluation of lesion distribution and counts, characterization of lesions as demyelinating or inflammatory, and histopathologic scoring. The clinical, MR, and pathologic scoring were done on grading systems, and correlated for evaluation. RESULTS: White matter (WM) changes after EAE induction were observed first at 9 days in the HWM-induced animals and at 2.5 weeks in the MP4-induced animals, with subsequent week-to-week fluctuations on PD- and T2-weighted images. Contrast-enhancing lesions were not observed in all animals. MR-revealed WM lesions correlated to histopathologic analysis of EAE lesions, measuring from 0.5 mm to 1.5 mm. The lesion count and extent of demyelination was greater in the HWM-induced animals than in the MP4-induced animals. Some MR-revealed lesions correlated directly to clinical symptoms, but the majority of lesions were clinically silent. CONCLUSION: On MR images, lesions in the EAE marmoset model were confined to the WM, and their development, resolution, distribution, and enhancing characteristics fluctuated over the duration of the study. The dynamic presentation of MR-revealed lesions confirms the parallels between EAE in the marmoset and relapsing-remitting MS. Clinical symptoms alone were not representative of ongoing pathologic brain lesions. Therefore, serial MR imaging serves as a very important adjunct to clinical and histologic surveillance of the development of new and the persistence of existing brain lesions in this animal model of MS.

Animals↗