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Biomedical subjects

S L Andersen

Publications and source records attributed to S L Andersen.

52 records · Page 3Linked to original sources

Ontogeny of the stretch response in the rat fetus: kappa opioid involvement.

Previous studies have demonstrated that the kappa opioid system is functional and plays a role in mediating the stretch response of the rat fetus on Day 21 of gestation. In this study, a kappa opioid agonist (U50,488) was administered on Days 19, 20, or 21, and fetal behavior was recorded after infusion of either milk or saline. Activation of the kappa opioid system promoted stretching in response to saline on Days 20 and 21. Although fetuses on Day 19 did not stretch, videotape analysis indicated that kappa opioid manipulation promoted modest increases in rearlimb activity and changes in fetal body posture that typically occur antecedent to the stretch. These findings suggest that functional maturity, of the kappa opioid system may be a limiting factor in the expression of the fetal stretch response.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

The ontogeny of apomorphine-induced alterations of neostriatal dopamine release: effects on spontaneous release.

The effects of apomorphine (0.05, 0.1, and 1.0 mg/kg, s.c.) on the extracellular levels of dopamine and the dopamine metabolite 3,4-dihydroxyphenylacetic acid were studied through the use of in vivo microdialysis in the neostriatum of developing and adult rats. Fifteen-minute samples were collected from urethane-anesthetized rats 5, 10-11, 21-22, and 35-36 days old and adults and quantified by HPLC with electrochemical detection. Apomorphine attenuated extracellular levels of dopamine in all age groups, suggesting that the dopamine autoreceptor modulating release in the neostriatum is functional by 5 days of age. A dose-response effect of apomorphine on extracellular dopamine was observed in all age groups except at 10-11 days of age. Extracellular levels of 3,4-dihydroxyphenylacetic acid were also significantly decreased in all age groups, consistent with the hypothesis that synthesis-modulating dopamine autoreceptors in the neostriatum are functional by 5 days of age. Apomorphine had a significantly greater effect on extracellular 3,4-dihydroxyphenylacetic acid levels at the 0.05 and 0.1 mg/kg doses in the 5- and 10-11-day-old age groups compared with the other ages. Absolute levels of extracellular dopamine were significantly attenuated at 5 days of age compared with the other ages, and absolute levels of extracellular 3,4-dihydroxyphenylacetic acid monotonically increased with age.

3,4-Dihydroxyphenylacetic Acid↗

Na(+)-K+ pump stimulation elicits recovery of contractility in K(+)-paralysed rat muscle.

1. This study explores the role of active electrogenic Na(+)-K+ transport in restoring contractility in isolated rat soleus muscles exposed to high extracellular potassium concentration ([K+]o). This was done using agents (catecholamines and insulin) known to stimulate the Na(+)-K+ pump via different mechanisms. 2. When exposed to Krebs-Ringer bicarbonate buffer containing 10 mM K+, the isometric twitch and tetanic force of intact muscles decreased by 40-69%. The major part of this decline could be prevented by the addition of salbutamol (10(-5) M). In the presence of 10 mM K+, force could be restored almost completely within 5-10 min by the addition of salbutamol or adrenaline and partly by insulin. 3. In muscles exposed to 12.5 mM K+, force declined by 96%. Salbutamol (10(-5) M), adrenaline (10(-6) M) and insulin (100 mU ml-1) produced 57-71, 61-71 and 38-47% recovery of force within 10-20 min, respectively. The effects of these supramaximal concentrations of salbutamol and insulin on force recovery were additive. Salbutamol and adrenaline produced significant recovery of contractility at concentrations down to 10(-8) M (P < 0.005). 4. In soleus, the same agents stimulated 86Rb+ uptake and decreased intracellular Na+. These actions reflect stimulation of active Na(+)-K+ transport and both showed a highly significant correlation to the recovery of twitch as well as tetanic force (r = 0.80-0.88; P < 0.001). 5. The force recovery induced by salbutamol, adrenaline and insulin was suppressed by pre-exposure to ouabain (10(-5) M for 10 min or 10(-3) M for 1 min) as well as by tetrodotoxin (10(-6) M). 6. The observations support the conclusion that the inhibitory effect of high [K+]o on contractility in skeletal muscle can be counterbalanced by stimulation of active electrogenic Na(+)-K+ transport, the ensuing increase in the clearance of extracellular K+ and in the transmembrane electrochemical gradient for Na+.

Albuterol↗

Calcitonin gene-related peptide stimulates active Na(+)-K+ transport in rat soleus muscle.

Calcitonin gene-related peptide (CGRP) is found in a wide variety of tissues, including sensory and motor nerve endings in skeletal muscle. After intense electrical stimulation or K(+)-induced depolarization, CGRP can be released from nerve terminals and bound to receptors on sarcolemma. We show here that CGRP (rat and human) and salmon calcitonin stimulate 22Na extrusion and the influx of 86Rb and 42K in isolated rat soleus muscle. This leads to a pronounced (up to 56%) decrease in intracellular Na+, a minor increase in intracellular K+, and hyperpolarization. All these effects were blocked by ouabain or cooling, indicating that they reflect an acute stimulation of active electrogenic Na(+)-K+ transport. Capsaicin, which induces release of CGRP from sensory nerve endings, was found to exert similar effects on Na(+)-K+ transport. Various Na(+)-K+ pump-stimulating agents have been shown to counteract the inhibitory effect of a high extracellular concentration of K+ ([K+]o) on muscle contractility (4, 20). CGRP and capsaicin were likewise found to improve contractile performance of muscles inhibited by high [K+]o, and these effects were blocked by ouabain. CGRP might play a role in the maintenance of Na(+)-K+ gradients and excitability during intensive muscle work, known to be associated with an acute rise in the interstitial K+ concentration.

Animals↗

Effect of milk on dopamine release in the newborn rat: an in vivo microdialysis study.

Newborn rats exhibit a rich behavioral repertoire to access the nipple and obtain milk. In older pups, catecholamines including dopamine (DA) mediate the behavioral effects of milk. In the present study, pups were delivered at term by caesarean section and instrumented with the microdialysis probe. Microdialysis samples were collected at 15 min intervals and K(+)-evoked levels of DA were measured with HPLC-ED. Pups received either no infusion, single or multiple intraoral infusions of saline or milk during subsequent samples. A decrease in K(+)-evoked DA release was evident after the first infusion in all subjects. Repeated milk infusions continued to reduce levels of extracellular DA, which remained evident 30 min after the last milk infusion. The rat neonate's first exposure to milk exerts lasting effects on neostriatal DA activity in the absence of prior suckling experience.

Administration, Oral↗

Dispiro-1,2,4,5-tetraoxanes: a new class of antimalarial peroxides.

Dispiro-1,2,4,5-tetraoxanes 2-4 were synthesized as potential peroxide antimalarial drugs. They had curative activity against Plasmodium berghei in vivo at single doses of 320 and 640 mg/kg which confirms earlier unpublished data. Moreover, artemisinin (1) and 4 had equivalent ED50's against P. berghei in vivo in the multiple-dose Thompson test; neither showed any evidence of acute toxicity at total doses of more than 12 g/kg. Dispiro-1,2,4,5-tetraoxane 4 had IC50's comparable to those of 1 against Plasmodium falciparum clones in vitro. These results confirm the potential of dispiro-1,2,4,5-tetraoxanes as a new class of inexpensive peroxide antimalarial drugs.

Animals↗

Bisquinolines. 1. N,N-bis(7-chloroquinolin-4-yl)alkanediamines with potential against chloroquine-resistant malaria.

On the basis of observations that several bisquinolines such as piperaquine possess notable activity against chloroquine-resistant malaria, 13 N,N-bis-(7-chloroquinolin-4-yl)alkanediamines were synthesized and screened against Plasmodium falciparum in vitro and Plasmodium berghei in vivo. Twelve of the thirteen bisquinolines had a significantly lower resistance index than did chloroquine; the resistance index was apparently unrelated to either in vitro or in vivo activity. Except for two compounds, there was a reasonable correlation between in vitro and in vivo activities. Seven of the thirteen bisquinolines had IC50's of less than 6 nM against both chloroquine-sensitive (D-6) and -resistant (W-2) clones of P. falciparum and were curative against P. berghei at doses of 640 mg/kg. In contrast to chloroquine, these bisquinolines did not show any toxic deaths at curative dose levels. Four bisquinolines, however, caused skin lesions at the site of injection. Maximum activity was seen in bisquinolines with a connecting bridge of two carbon atoms where decreased conformational mobility seemed to increase activity. Bisquinoline 3 (+/-)-trans-N1,N2-bis(7-chloroquinolin-4-yl)cyclohexane-1,2-diamin e was not only the most potent bisquinoline in vitro, but was clearly unique in its in vivo activity--80% and 100% cure rates were achieved at doses of 160 and 320 mg/kg, respectively. In summary, these preliminary results support the premise that bisquinolines may be useful agents against chloroquine-resistant malaria.

Animals↗

Antimalarial activity of new dihydroartemisinin derivatives. 5. Sugar analogues.

A series of dihydroartemisinin derivatives containing a sugar moiety was prepared in the search for analogues with good water solubility and high antimalarial activity. The preparation of the new compounds was achieved by treatment of dihydroartemisinin (2) with chlorotrimethylsilane in pyridine solution at -10 degrees C to give a nearly quantitative yield of 10-O-(trimethylsilyl)dihydroartemisinin (3), which was then condensed with 1-hydroxypolyacetylated sugars 5 to give dihydroartemisinin derivatives 7a-d. Deacetylation of intermediates 7 gave the desired sugar derivatives 8. The resulting derivatives, tested in vitro against Plasmodium falciparum, were found to be more effective against W-2 than D-6 clones and were not cross-resistant with existing antimalarials. Trimethylsilylated compound 3 is more effective than derivatives 7a-d, which possess activity comparable to or better than that of artemisinin itself. Deacetylated compounds 8a-d were substantially less active than 7 in both cell lines. In P. berghei-infected mice, 7a-c showed 5/5, 2/5, and 3/5 cures, respectively, at 320 mg/kg per day x 3, whereas 7d showed no activity at the same dosage. However, 7d did prolong the life span in 3/5 of the infected mice at 640 mg/kg per day x 3 dose level. Trimethylsilylated compound 3 was also the most effective among the compounds studied, with 5/5 cures at 80 mg/kg per day x 3. The deacetylated sugar derivatives 8a-d showed only slight in vivo antimalarial activity.

Animals↗

Senior preceptorship: faculty-preceptor collaboration.

The literature on senior preceptorship focuses principally on student outcomes. Little is known about the teaching-learning processes that produce the desired results. This article describes the dynamics of faculty-preceptor collaboration that fostered bicultural adaptation in students taking a senior preceptorship course. Four areas of conflict in normative expectations between education and practice are addressed: documentation, theory application, time management, and priority setting. The close working alliance between the instructor and preceptors was instrumental in helping students reconcile the conflicting norms in all areas except priority setting. In addition to the benefits to students, the collaboration resulted in mutual appreciation and respect between instructor and preceptors.

Adaptation, Psychological↗

The nurse advocate project: a strategy to retain new graduates.

Would you like to have 96% of the newly graduated nurses you hired last year still working for you a year later? Does your staff know how to help new graduates, who have been in the student role for over 20 years, adjust to the world of work? The author discusses the nurse advocate project which increased retention, decreased costs, and fostered a more positive work environment for all staff.

Adaptation, Psychological↗

Project BEGIN: recruiting students from ancillary personnel.

Project BEGIN (Be Envied: Get Into Nursing!) was a joint education-service endeavor to recruit students and boost employee morale. A hospital and its school of nursing worked together in preparing licensed practical nurses, unit receptionists, and nursing assistants with the requisites for entry to nursing school. In a span of 2 weeks, 22 employees were in various stages of completing the requirements. The authors discuss the project's implementation and outcomes.

Curriculum↗

Do student preceptorships affect moral reasoning?

The author examines the effects of a senior preceptorship course on the moral reasoning of senior nursing students. The findings suggest a broadening gap between education and practice resulting from changes in the health care industry, more specifically, in the acute care facility and a compromise of professional role enactment in the hospital. The author suggests we reconsider the following questions: Is the patient still the first priority in nursing? Is the hospital setting an appropriate placement for nursing students?

Adult↗

Preceptor teaching strategies: behaviors that facilitate role transition in senior nursing students.

This article describes the learning outcomes of students who participated in a senior preceptorship course. Data from student logs and course evaluations forms were analyzed descriptively to identify the specific instructional strategies of preceptors that were instrumental in teaching students the roles and functions of the staff nurse. Role modeling was one of the most effective strategies and also the one regarded by preceptors as least significant.

Humans↗