Experimental biology and medicine
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Exp. Biol. Med. (Maywood) · Mar 2008
ReviewPromoting collaborations between biomedical scholars in the U.S. and sub-Saharan Africa.
The premise of this piece is that a priority of international health should be to increase the number of investigators in the US and other developed countries who engage in research and other kinds of scholarly work in underdeveloped parts of the world, particularly sub-Saharan Africa where the overall disease burden is the highest and the gap in biomedical research infrastructure is the widest. The author's aim is to encourage medical students, resident doctors, and medical school faculty to devote a part of their career to teach, acquire clinical skills, or participate in research with health professionals at teaching hospitals in Africa. ⋯ Lastly, the piece points out potential pitfalls and problems that are often overlooked or underestimated in the early phases of planning an international partnership, including lukewarm institutional support at home, inflexible institutional review boards, dominance of the program by the US partner, maintaining continuity, and striking the right balance between scholarly work and humanitarian efforts. My hope is that US students and faculty in the health professions who read this piece will be stimulated and encouraged to consider how they might integrate into their curriculum or academic life visits lasting several months or more each year during which they would teach or train others or engage in research at a teaching hospital in some country in Africa.
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Exp. Biol. Med. (Maywood) · Feb 2008
Propofol depresses angiotensin II-induced cardiomyocyte hypertrophy in vitro.
Cardiomyocyte hypertrophy is formed in response to pressure or volume overload, injury, or neurohormonal activation. The most important vascular hormone that contributes to the development of hypertrophy is angiotensin II (Ang II). Accumulating studies have suggested that reactive oxygen species (ROS) may play an important role in cardiac hypertrophy. ⋯ Further studies showed that propofol inhibited the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and mitogen-activated protein kinase/ERK kinase 1/2 (MEK1/2) induced by Ang II via a decrease in ROS production. In addition, propofol also markedly attenuated Ang II-stimulated nuclear factor-kappaB (NF-kappaB) activation via a decrease in ROS production. In conclusion, propofol prevents cardiomyocyte hypertrophy by interfering with the generation of ROS and involves the inhibition of the MEK/ERK signaling transduction pathway and NF-kappaB activation.
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Exp. Biol. Med. (Maywood) · May 2007
Protective role of connexin 32 in steady-state hematopoiesis, regeneration state, and leukemogenesis.
The role of gap junctions formed by connexins (Cxs) has been implicated in the homeostatic regulation of multicellular systems. Primitive hematopoietic progenitor cells form a multicellular system, but a previous report states that Cx32 is not expressed in the bone marrow. Thus, a question arises as to why Cx molecules are not detected in the hematopoietic tissue other than in stromal cells. ⋯ Cx32-KO mice showed increased leukemogenicity compared with wild-type mice after MNU injection; furthermore, in a competitive assay for leukemogenicity in mice that had been lethally irradiated and repopulated with a mixed population of bone marrow cells from Cx32-KO mice and wild-type mice, the resulting leukemias originated predominantly from Cx32-KO bone marrow cells. In summary, the role of Cx32 in hematopoiesis was not previously recognized, and Cx32 was expressed only in HSCs and their progenitor cells. The results indicate that Cx32 in wild-type mice protects HSCs from chemical abrasion and leukemogenic impacts.
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Exp. Biol. Med. (Maywood) · Jun 2006
Endothelin ET(B) receptor antagonist reduces mechanical allodynia in rats with trigeminal neuropathic pain.
Trigeminal neuropathic pain, which is associated with marked orofacial mechanical allodynia, is frequently refractory to currently available drugs. Because endothelins (ETs) can contribute to nociceptive changes in animal models of inflammatory, cancer, and diabetic neuropathic pain, the present study evaluated the influence of ET(A) and ET(B) receptor antagonists on orofacial mechanical allodynia in a rat model of trigeminal neuropathic pain. Unilateral constriction (C) of the infraorbital nerve (ION) caused pronounced and sustained bilateral mechanical allodynia, evaluated by application of von Frey hairs to the vibrissal pad. ⋯ Co-injection of atrasentan plus A-192621 did not modify ION injury-induced mechanical allodynia. Injection of 10 pmol ET-1 into the upper lip of naive rats caused ipsilateral mechanical allodynia lasting up to 5 hrs. Thus, ET(B) receptor-mediated mechanisms contribute to orofacial mechanical allodynia induced by CION injury, but, some-how, functional ET(A) receptors are required for expression of the antiallodynic effect of ET(B) receptor blockade.
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Exp. Biol. Med. (Maywood) · Jun 2006
Endothelin-a receptor blockade does not debilitate the cardiovascular and hormonal adaptation to xenon or isoflurane anesthesia in dogs.
The objective of this study was to investigate whether circulatory and hormonal changes during xenon plus remifentanil or isoflurane plus remifentanil anesthesia are altered by endothelin-A (ET(A)) receptor blockade. Eight beagle dogs were studied in four protocols (n = 7 each). After a 30-min awake period, anesthesia was induced with 8 mg/kg propofol, administered intravenously (iv), and maintained with either 0.8% +/- 0.01% (vol/vol) isoflurane plus 0.5 microg/kg/min remifentanil (Protocol 1) or 63% +/- 1% (vol/vol) xenon plus 0.5 microg/kg/min remifentanil (Protocol 2) for 1 hr. ⋯ We conclude that the hemodynamic and hormonal adaptation after xenon plus remifentanil and isoflurane plus remifentanil anesthesia does not depend on the endothelin system, because it is unaffected by ET(A) receptor inhibition. Therefore, the use of Atrasentan does not impair cardiovascular stability during xenon- or isoflurane-based anesthesia in our dog model. However, the way anesthesia is performed is of crucial importance for hemodynamic and hormonal reactions observed during research in animals because the release of vasopressin and catecholamines may be intensified by xenon plus remifentanil anesthesia.