Evaluation of the effectiveness of 3D vascular stereoscopic models in anatomy instruction for first year medical students.

The head and neck region is one of the most complex areas featured in the medical gross anatomy curriculum. The effectiveness of using three-dimensional (3D) models to teach anatomy is a topic of much discussion in medical education research. However, the use of 3D stereoscopic models of the head and neck circulation in anatomy education has not been previously studied in detail. This study investigated whether 3D stereoscopic models created from computed tomographic angiography (CTA) data were efficacious teaching tools for the head and neck vascular anatomy. The test subjects were first year medical students at the University of Mississippi Medical Center. The assessment tools included: anatomy knowledge tests (prelearning session knowledge test and postlearning session knowledge test), mental rotation tests (spatial ability; presession MRT and postsession MRT), and a satisfaction survey. Results were analyzed using a Wilcoxon rank-sum test and linear regression analysis. A total of 39 first year medical students participated in the study. The results indicated that all students who were exposed to the stereoscopic 3D vascular models in 3D learning sessions increased their ability to correctly identify the head and neck vascular anatomy. Most importantly, for students with low-spatial ability, 3D learning sessions improved postsession knowledge scores to a level comparable to that demonstrated by students with high-spatial ability indicating that the use of 3D stereoscopic models may be particularly valuable to these students with low-spatial ability. Anat Sci Educ 10: 34-45. © 2016 American Association of Anatomists.

Rethinking CME: an imperative for academic medicine and faculty development.

To help address the clinical care gap, a working group discussed the future of faculty development in academic medicine, explored problems within the large, current enterprise devoted to continuing medical education (CME), and described four domains core to its revitalization and reformation. These domains are (1) preparing and supporting an engaged clinician-learner, (2) improving the quality of knowledge or evidence shared, (3) enhancing the means by which to disseminate and implement that knowledge and evidence, and (4) reforming the patient, health care, and regulatory systems in and for which the process of CME exists. Reshaping these domains requires the consideration of a more seamless, evidence-based, and patient-oriented continuum of medical education. Revitalizing CME also requires the full engagement of the academic medical community and its faculty. To achieve the goal of creating a new, more effective, seamless process of CME, the working group recommended an active faculty development process to develop strong clinician-learners, strong involvement of academic health center leaders, the development of an educational home for clinician-learners, and a meaningful national conversation on the subject of CME.

Gender differences in the antinociceptive effect of tramadol, alone or in combination with gabapentin, in mice.

Gender difference in the antinociceptive effect of tramadol and gabapentin (alone or in combination) were investigated in mice. For investigation of acute antinociceptive effect, tramadol and gabapentin were administered to mice by intraperitoneal injection and per os, respectively, and antinociceptive activity was measured by the tail-flick test 30 min after drug administration. For investigation of the development of antinociceptive tolerance to analgesics, mice were injected with tramadol (60 mg/kg), alone or in combination with gabapentin (75 mg/kg), twice daily for seven consecutive days and the tail-flicks were tested on experimental days 1, 3, 5 and 7. Results showed there was a lower ED(50) value of tramadol antinociception in males than in females, indicating that females were less sensitive to the drug. Gabapentin produces a limited antinociception in both males and females. The combination of gabapentin and tramadol produced synergistic effect without gender difference. Repeated administration of tramadol produced antinociceptive tolerance in both genders. Gabapentin produced synergistic effect in tramadol-tolerant mice and repeated administration of gabapentin did not alter the synergistic effect in tramadol-tolerant mice. Because females show a higher overall prevalence of pain and less sensitivity to opioids, our finding may suggest a clinical significance of combined use of the two drugs.

Linear acceleration-evoked cardiovascular responses in awake rats.

It has been well documented that vestibular-mediated cardiovascular regulation plays an important role in maintaining stable blood pressure (BP) during postural changes. But the underlying neural mechanisms remain to be elucidated. In particular, because the vestibular stimulation employed in previous animal studies activated both semicircular canals and otolith organs, the contributions of the otolith system has not been studied selectively. The goal of the present study was to characterize cardiovascular responses to natural otolith stimulation in awake rats that were subjected to pure linear motion. In any of the four directions tested, transient linear motion produced a short-latency ( approximately 520 ms) increase in mean BP with a peak of 8.27 +/- 0.66 mmHg and was followed by a decrease in BP. There was an initial small biphasic response in heart rate (HR) that was followed by a longer duration increase. The short-latency increase in BP was absent in rats that were pentobarbital sodium anesthetized or that were labyrinthectomized bilaterally, but it was unaffected by baroreceptor denervation, indicating that it was of otolith origin. The increase in BP was linear acceleration intensity dependent and was not affected by absence of visual cues. Furthermore, the BP response was attenuated by inactivation of the medial and inferior vestibular nuclei by microinjections of muscimol, indicating that the otolith-driven cardiovascular responses are mediated by the neurons in these areas. These results not only demonstrate the otolith specific influences on the cardiovascular system but also they establish the first rodent model for examining the neural mechanisms underlying the otolith-mediated cardiovascular regulation.

Cardiodepressant and neurologic actions of Solenopsis invicta (imported fire ant) venom alkaloids.

BACKGROUND: We hypothesized that the alkaloid compounds that are the majority components of fire ant (Solenopsis invicta) venom are capable of producing cardiovascular and central nervous system toxic effects in mammals. OBJECTIVE: To evaluate toxic effects of synthetic S. invicta alkaloids in rodent models. METHODS: Cardiovascular effects of intravenous injection of the racemic (+/-)-cis- and trans-isomers of 2-methyl-6-nundecylpiperidine (isosolenopsin A and solenopsin A, respectively) were evaluated in anesthetized, gallamine-paralyzed rats who had received artificial ventilation and in isolated, perfused rat hearts. RESULTS: (+/-)-Solenopsin A dose dependently (3-30 mg/kg [10 to 104 micromol/kg]) depressed cardiovascular function. Maximal percent changes following injection of 30 mg/kg were -42.96% +/- 5.8% for blood pressure, -29.13% +/- 3.6% for heart rate, and -43.5% +/- 9.2% for left ventricular contractility (dP/dt). (+/-)-Isosolenopsin A (3-15 mg/kg [10 to 52 micromol/kg]) produced responses similar to those seen with the corresponding doses of solenopsin A. In conscious, spontaneously breathing rats, solenopsin A (30 mg/kg intravenously) caused seizures, respiratory arrest, and death. Infusion of working, isolated, perfused hearts with solenopsin A reduced contractile function (dP/dt) at 10 microM and caused cardiac arrest at 100 microM. CONCLUSIONS: Two alkaloid components of imported fire ant venom possess robust cardiorespiratory depressant activity and elicit seizures in the rat. Such effects identify these alkaloids as toxic compounds in biological systems and may explain the cardiorespiratory failure noted in some individuals who experience massive fire ant stings.

Methyl parathion increases neuronal activities in the rat locus coeruleus.

Exposure to organophosphate insecticides induces undesirable behavioral changes in humans, including anxiety and irritability, depression, cognitive disturbances and sleep disorders. Little information currently exists concerning the neural mechanisms underlying such behavioral changes. The brain stem locus coeruleus (LC) could be a mediator of organophosphate insecticide-induced behavioral toxicities since it contains high levels of acetylcholinesterase and is involved in the regulation of the sleep-wake cycle, attention, arousal, memory, and pathological processes, including anxiety and depression. In the present study, using a multi-wire recording technique, we examined the effects of methyl parathion, a commonly used organophosphate insecticide, on the firing patterns of LC neurons in rats. Systemic administration of a single dose of methyl parathion (1 mg/kg, i.v.) increased the spontaneous firing rates of LC neurons by 240% but did not change the temporal relationships among the activities of multiple LC neurons. This dose of methyl parathion induced a 50% decrease in blood acetylcholinesterase activity and a 48% decrease in LC acetylcholinesterase activity. The methyl parathion-induced excitation of LC neurons was reversed by administration of atropine sulfate, a muscarinic receptor antagonist, indicating an involvement of muscarinic receptors. The methyl parathion-induced increase in LC neuronal activity returned to normal within 30 min while the blood acetylcholinesterase activity remained inhibited for over 1 h. These data indicate that methyl parathion treatment can elicit excitation of LC neurons. Such excitation could contribute to the neuronal basis of organophosphate insecticide-induced behavioral changes in human.

The natural treatment of hypertension.

The goal of this review is to evaluate the efficacy of commonly available dietary supplements in the treatment of hypertension, using the average blood pressure reduction achieved with the implementation of lifestyle modifications as a standard. For this reason, the authors focus on the antihypertensive potential of these agents rather than pharmacology, pharmacokinetics, adverse effects, or supplement-drug interactions. For the purpose of this review, dietary supplements are defined as exhibiting some evidence of benefit if a systolic blood pressure reduction of 9.0 mm Hg or greater and/or a diastolic blood pressure reduction of 5.0 mm Hg or greater has been observed in previously published, peer-reviewed trials. These defining limits are based on the average blood pressure reduction associated with the implementation of certain lifestyle modifications. Agents with some evidence of benefit include coenzyme Q10, fish oil, garlic, vitamin C, and L-arginine.

Cardiorespiratory effects following acute exposure to pyridostigmine bromide and/or N,N-diethyl-m-toluamide (DEET) in rats.

The acute lethal interaction that occurs in rodents when high doses of a peripherally restricted cholinesterase inhibitor, pyridostigmine bromide (PB), and the insect repellent N, N-diethyl-m-toluamide (DEET) are combined was first described during studies of chemical mixtures that were targeted as potential causative agents of Gulf War illnesses. This study was intended to provide insight into possible mechanisms of that lethal interaction. Following a single intraperitoneal injection of PB (2 mg/kg) and/or DEET (300 or 500 mg/kg), respiratory activity was measured in conscious freely moving rats using whole-body plethysmography. Cardiovascular function was also monitored simultaneously through an arterial catheter. PB (2 mg/kg) given alone stimulated respiration and increased blood pressure. Arterial pH levels were decreased, whereas pO(2) and pCO(2) remained at control levels. Administration of DEET (300 mg/kg) alone increased tidal volume and decreased blood pressure. Blood gases and pH levels were unaltered. A higher dose of DEET (500 mg/kg) also decreased respiratory and heart rate. Coadministration of PB (2 mg/kg) and DEET (300 mg/kg) increased tidal volume, decreased arterial pH, and elevated pCO(2). Heart rate and blood pressure declined progressively after drug coadministration. Pretreatment with atropine methyl nitrate (AMN), a peripherally selective competitive antagonist at nicotinic and muscarinic receptor sites, reduced the individual effects of PB or DEET, and significantly increased survival after coexposure to these agents. Although changes in respiratory function may have contributed to the lethal interaction, it was concluded that the primary cause of death was circulatory failure.

Pharmacokinetics of methyl parathion: a comparison following single intravenous, oral or dermal administration.

Assessment of the risks posed by the residential use of methyl parathion requires an understanding of its pharmacokinetics after different routes of exposure. Thus, studies were performed using adult female rats to define the pharmacokinetic parameters for methyl parathion after intravenous injection and to apply the described model to an examination of its pharmacokinetics after single oral or dermal exposure. The pharmacokinetics of methyl parathion after intravenous administration (1.5 mg/kg) were best described by a three-compartment model; the apparent volume of the central compartment was 1.45 liters/kg, clearance was 1.85 liters/h/kg and the terminal half-life was 6.6 h with an elimination constant of 0.50 h(-1). The apparent oral absorption coefficient for methyl parathion (1.5 mg/kg) was 1.24 h(-1), and its oral bioavailability was approximately 20%. The latter likely includes a significant first pass effect. Concentrations of methyl parathion increased during the initial 10-60 min and then declined during the next 15-36 h. After dermal administration (6.25-25 mg/kg), methyl parathion concentrations peaked within 12-26 h and then declined dose dependently. The apparent dermal absorption coefficient was approximately 0.41 h(-1), and only two pharmacokinetic compartments could be distinguished. In conclusion, the pharmacokinetics of methyl parathion are complex and route dependent. Also, dermal exposure, because of sustained methyl parathion concentrations, may pose the greatest risk.

A comparison of cholinesterase activity after intravenous, oral or dermal administration of methyl parathion.

Time-dependent changes in blood cholinesterase activity caused by single intravenous, oral or dermal administration of methyl parathion to adult female rats were defined. Intravenous and oral administration of 2.5 mg/kg methyl parathion resulted in rapid (<60 min) decreases in cholinesterase activity which recovered fully in vivo within 30-48 h. In contrast, spontaneous reactivation of cholinesterase in vitro was complete within 6 h at 37 degrees C. Dermal administration of methyl parathion caused dose-dependent inhibition of cholinesterase activity which developed slowly (> or =6 h) and was prolonged (> or =48 h). Time- and route-dependent effects of methyl parathion on cholinesterase activity in brain and other tissues generally paralleled its effects on activity in blood. In conclusion, pharmacodynamics of methyl parathion differ substantially with route of exposure. Recovery of cholinesterase in vivo after intravenous or oral exposure may partially reflect spontaneous reactivation and suggests a rapid clearance of methyl parathion or its active metabolite methyl paraoxon. The more gradual and prolonged inhibition of cholinesterase caused by dermal administration is consistent with disposition of methyl parathion at a site from which it or methyl paraoxon is only slowly distributed. Thus, dermal exposure to methyl parathion may pose the greatest risk for long-term adverse effects.