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
Comparative StudyEndothelin-1 influences the efficacy of inhaled nitric oxide in experimental acute lung injury.
Beneficial effects of inhaled nitric oxide (iNO) on arterial oxygenation in acute lung injury (ALI) suggest the presence of vasoconstriction in ventilated lung regions and this may be influenced by endothelin-1 (ET-1). We studied a possible interaction between ET-1 and iNO in experimental ALI. Sixteen piglets were anesthetized and mechanically ventilated (inspired O2 fraction, 1.0). ⋯ PaO2 changes induced by iNO revealed a moderate and significant correlation with ET-1 plasma levels (R = 0.548, P = 0.001). Our data suggest that endogenous ET-1 production influences the efficacy of iNO in ALI. Furthermore, iNO reduced ET-1 plasma levels, possibly indicating anti-inflammatory properties of iNO in the early phase of ALI.
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Endothelin (ET)-1 evokes a burning pruritus sensation when injected intradermally in humans and nocifensive behavior when injected into the hind paw of rodents. Because pain and pruritus are clearly distinct nociceptive sensory modalities in humans, the current study evaluates the potential of ET-1 to elicit scratching behavior in mice. Mice received an intradermal injection of 1-30 pmol ET-1; 10 microg of the mast cell degranulator compound, 48/80; 100 nmol histamine; or vehicle into the scruff, and the number of scratching bouts displayed during the first 40 mins was recorded. ⋯ Responses to compound 48/80 or responsiveness of vehicle-treated mice were unaffected by these antagonists. Thus, ET-1 displays potent pruritic actions in the mouse mediated to a substantial extent via local ET(A) receptors. The findings with IRL-1620 and BQ-788 suggest that local ET(B) receptors exert an antipruritic role, but, for reasons still unknown, the results obtained using systemic A-192621 injection are at variance with this view.