Abstract: The present study compares hematologic, rheologic and hemodynamic characteristics of red cells from mouse, rat and human. Red cells in these species are biconcave discs that show significant differences in diameter and mean corpuscular volume (MCV). However, differences in mean corpuscular hemoglobin concentration (MCHC) are not significant. Viscosity measurement of washed red cell suspensions (in each case the medium osmolarity adjusted to match plasma osmolarity) showed significant interspecies differences at shear rates of 37.5 and 750 sec−1 as follows: Human > rat > mouse. Hemodynamic and microcirculatory behavior of these red cells was investigated in the artificially perfused ex vivo…mesocecum vasculature of the rat. Hemodynamic measurements in the whole ex vivo mesocecum preparation revealed maximal increase in the peripheral resistance unit (PRU) for the human red cells followed by the rat and mouse red cells, respectively, at a hematocrit (Hct) of 40%. Further, measurements of red cell velocities (Vrbc) in single arterioles of the mesocecum vasculature, during sustained perfusion with washed red cell suspensions, showed that at any given perfusion pressure (Pa), Vrbc for both mouse and rat red cells was higher than that for human red cells, while Vrbc for mouse red cells was higher than that for the rat. These results demonstrate that the microvascular flow behavior of these red cells is likely to be influenced by both physical and rheologic characteristics.
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Keywords: Mammalian red cells, rheology, hemodynamics, ex vivo vasculature, peripheral resistance (PRU), red cell velocity (Vrbc)
DOI: 10.3233/BIR-1994-31109
Citation: Biorheology,
vol. 31, no. 1, pp. 103-113, 1994
Abstract: One of the major neuropathological characteristics of Alzheimer's disease (AD) is the brain depositions of senile plaques that are mainly composed of toxic amyloid β–peptide (Aβ), which is generated from a family of Aβ containing precursor proteins (AβPP; 695-770 amino acids). The role of cytokines and growth factors has been implicated in the pathogenesis of AD. Our goal is to determine the mode of action of cytokines on the regulation of AβPP gene expression. Here we studied the effect of different cytokines on the activity of 5'-untranslated region (5'-UTR) of AβPP mRNA in human astrocytic cells (U-373). We compared AβPP-5'-UTR…activity in the presence of interleukin-1 (IL-1α and IL-1β), transforming growth factor (TGF-β1) and tumor necrosis factor TNF-α1. The astrocytic cells, which were treated separately with these agents, were transfected with either the vector (pSV2CAT) or pSV2UTR-CAT construct containing 90 bp of AβPP 5'-UTR +54 to 144 bp). This region was cloned upstream of a reporter chloramphenicol acetyl transferase gene (CAT). Our results indicate that the treatment of pSV2UTR-CAT-transfected cells with either IL-1α, IL-1β, TGF-β1 or TNF-α1 stimulated reporter gene activity in a factor-specific manner. This was consistent with their effects on elevating AβPP protein levels. Transfection of the same cells with the pSV2CAT vector lacking 5'-UTR resulted in a reduced reporter gene activity with all treatments studied. DNA-gel shift experiments indicate that the 54/144 region binds to a nuclear protein(s) in a cell type specific manner. These results suggest that 5'-UTR of the AβPP gene can respond to the stimulation of different cytokines, which likely regulate AβPP transcription and translation via regulatory elements present in the AβPP promoter and in 5'-UTR, respectively. The characterization of AβPP regulatory elements, including the 5'-UTR, will accelerate the development of novel agents against new targets for AD.
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Abstract: OBJECTIVE: To study the prescribing patterns and usage of antimicrobials in the Neonatal Intensive Care Units (NICU) of Trinidad & Tobago. METHODS: A 3-month prospective observational study was conducted at the three NICUs at the major public hospitals. Data included antimicrobials prescribed, route of administration, culture and sensitivity reports, leukocyte count, length of stay and outcome of patients. RESULTS: 353 patients were studied, 57.5% of the patients were males. Mean birth weight was 2.96 ± 0.94 (Standard Deviation) kg. Admission diagnoses included meconium stained liquor, preterm, respiratory distress, sepsis, etc. Length of stay ranged between 1 to 76 days, (median…4, Interquartile Range 1–8). The mean leukocyte count was 15.7 ± 8.5 × 103 per μL. Overall, 645 culture specimens were sent; umbilical swab (27.6%), throat swab (27.0%) and blood (16.4%) being the most common specimens. 310 (48.1%) showed no bacterial growth. Overall, 16 different antimicrobials were used. First line antibiotic of choice was a combination of ampicillin and gentamicin (85.8 %). Second line antibiotic of choice was cefotaxime. The overall mortality was 7.6%. CONCLUSION: The choice of antimicrobials in the NICUs of major public hospitals is mostly empirical and not primarily dictated by the culture and sensitivity reports, emphasizing the need for antibiotic stewardship programme in Trinidad & Tobago.
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Keywords: Antimicrobials, prescription patterns, usage, neonatal intensive care