Biomechanical Properties of Esophagus during Systemic Treatment with Epidermal Growth Factor in Rats

The epidermal growth factor (EGF) is a growth factor with effects on many cell types and tissue. Morphometric and passive biomechanical properties were studied in isolated segments of the esophagus in 22 EGF-treated rats and 12 control rats. The rats were divided into groups with EGF treatment for 2, 4, 7, and 14 days (n=6 for each group except n=4 for the 14 days EGF-treatment group) or saline treatment (n=3 for each group). The mechanical test was performed as a distension experiment in vitro where the whole esophagus was stretched to its in situ length and distended with pressures up to 10 cm H₂O using a ramp distension protocol. The pressure and outer diameter were recorded. Circumferential stress (force per area) and strain (deformation) were computed from the diameter and pressure data using the zero-stress state as reference. The zero-stress state was obtained by cutting esophageal rings radially. This caused the rings to open up into a sector. EGF induced pronounced morphometric changes, e.g., the wall thickness, wall cross-sectional area, and inner and outer circumferential lengths significantly increased during the EGF treatment. Histological analysis showed mucosa and submucosa growth during EGF treatment. The opening angle and residual strains increased with the highest value in the 14 days EGF-treated group (P < 0.05). The change in opening angle depended largely on the change in mucosa thickness. Furthermore, the circumferential stiffness of the esophagus reached a maximum after 7 days EGF treatment (P < 0.01). © 2003 Biomedical Engineering Society. PAC2003: 8719Rr, 8717Ee     

Organ distribution of severe acute respiratory syndrome (SARS) associated coronavirus (SARS-CoV) in SARS patients: implications for pathogenesis and virus transmission pathways

We previously identified the major pathological changes in the respiratory and immune systems of patients who died of severe acute respiratory syndrome (SARS) but gained little information on the organ distribution of SARS-associated coronavirus (SARS-CoV). In the present study, we used a murine monoclonal antibody specific for SARS-CoV nucleoprotein, and probes specific for a SARS-CoV RNA polymerase gene fragment, for immunohistochemistry and in situ hybridization, respectively, to detect SARS-CoV systematically in tissues from patients who died of SARS. SARS-CoV was found in lung, trachea/bronchus, stomach, small intestine, distal convoluted renal tubule, sweat gland, parathyroid, pituitary, pancreas, adrenal gland, liver and cerebrum, but was not detected in oesophagus, spleen, lymph node, bone marrow, heart, aorta, cerebellum, thyroid, testis, ovary, uterus or muscle. These results suggest that, in addition to the respiratory system, the gastrointestinal tract and other organs with detectable SARS-CoV may also be targets of SARS-CoV infection. The pathological changes in these organs may be caused directly by the cytopathic effect mediated by local replication of the SARS-CoV; or indirectly as a result of systemic responses to respiratory failure or the harmful immune response induced by viral infection. In addition to viral spread through a respiratory route, SARS-CoV in the intestinal tract, kidney and sweat glands may be excreted via faeces, urine and sweat, thereby leading to virus transmission. This study provides important information for understanding the pathogenesis of SARS-CoV infection and sheds light on possible virus transmission pathways. This data will be useful for designing new strategies for prevention and treatment of SARS.     

Pattern of mtDNA Variation in Three Populations from São Tomé e Príncipe

We have analysed the matrilineal genetic composition of three self‐reported ethnic groups from São Tomé e Príncipe (Gulf of Guinea), an African archipelago whose settlement begun in the late fifteenth century. Sequence data from the hypervariable segments I (HVS‐I) and II (HVS‐II) were obtained for 30 Angolares, 35 Forros and 38 Tongas. The repertory of mtDNA lineages in São Tomé e Príncipe denoted a fully African maternal pool, primarily arisen from a Central/Southwestern substratum. The absence of any lineages of putative European descent means that the European impact at the mitochondrial pool was virtually nil. Angolares showed a clear reduction of mtDNA diversity and a slight genetic differentiation relative to Tongas or Forros, whereas the latter two groups did not present any signs of genetic boundaries between each other. The data obtained here reinforce the depiction of genetic substructuring in São Tomé e Príncipe previously derived from Y‐chromosome STRs. In addition, the crossing of mtDNA and Y‐STR information led to the inference that the female mediated gene flow within the archipelago was less restricted than the male, a pattern that could be framed in the cultural traditions and socio‐historical interactions among the groups.     

Distribution of house dust mite allergen: comparing house dust mite allergen levels in dust samples collected from different sites on living room floors with smooth coverings

BACKGROUND: The distribution of house dust mite allergen (Der p1) in living rooms with smooth floor coverings, as measured in the middle compared with the border of the floor was investigated. It was hypothesized that activity causes displacement of Der p1, from the middle towards the border. METHODS: Dust samples from the middle and border of 50 floors with smooth coverings were collected and analysed on Der p1 content in a standardized way. RESULTS: The Der p1 exposure expressed as per unit area (ng/m2) showed that border samples contained significantly more Der p1 compared with middle samples (median: 2.57 vs 0.27, respectively, P = 0.023). Presence of pets and presence of more than two inhabitants increased the difference. When expressed as per unit weight of dust (ng/g), significant differences were only detected when comparing Der p1 content of samples collected in households with three or more inhabitants [median: 2 (border) vs 53 (middle), respectively; P = 0.035]. CONCLUSIONS: The Der p1 is unequally distributed on living room floors with smooth coverings, most likely because of displacement of dust from the middle towards the border due to activity. Expression as ng/g of dust and ng/m2 could not obviously be interchangeable.     

Narrowly Distributed Surfactant‐Free Polystyrene Latex with a Water‐Soluble Comonomer

Summary: The surfactant‐free synthesis of latex polymers of styrene and sodium styrenesulfonate (NaSS) was investigated. The development of size and size distribution of the particles was studied by photo‐correlation spectroscopy (PCS) and transmission electronic microscopy (TEM). The effects of NaSS concentration and the order of addition of reactants were examined in detail. The results showed that the particle size decreases with an increase in the styrene sulfonate concentration. The polydispersity index can be reduced by mixing NaSS with styrene homogeneously before adding initiator, but this leads to a slightly larger mean particle size.

TEM image of surfactant‐free polystyrene latex made by the modified method.     

Intracellular acetylcholinesterase of adult rat myofibers is more concentrated in endplate than non-endplate regions

The intracellular distribution of acetylcholinesterase (AChE) was determined in adult rat anterior gracilis muscles. Echothiophate iodide (ECHO), a water-soluble cholinesterase inhibitor, was applied to muscles in situ to eliminate extracellular and/or extracellularly oriented enzyme. Control and ECHO-treated muscles were either cut into 1-mm segments and assayed for AChE activity or cytochemically stained for AChE. Subsequent analysis by light and electron microscopy showed that the AChE stain inside myofibers was highly localized and clearly visible only in the zone immediately underlying the point of nerve-muscle contact. Biochemical assay of muscle segments showed intracellular AChE to be most highly concentrated in regions containing large numbers of endplates (approximately twice the activity of endplate-free areas). Since such "endplate-rich" segments are in fact mostly extra-synaptic tissue, we conclude that intracellular AChE of adult rat gracilis myofibers, although present along the length of the cell, is more than two times as concentrated in sub-synaptic areas as compared to extra-synaptic areas. This result must be carefully considered when attempting to identify "endplate-specific" AChE activity of mammalian muscle, and further points to the importance of neural influences on AChE metabolism/regulation.     

Distribution of the [3H]-label from low doses of radioactive ochratoxin a ingested by rats,and evidence for DNA single-strand breaks caused in liver and kidneys

The distribution of a single low dose of [³H]ochratoxin A (OTA) in different tissues of male Wistar rats, after administration by intubation, was investigated after 5 h, 24 h and 48 h. This dose corresponds to concentrations encountered in naturally contaminated feed (4 ppm). The distribution of [³H]-label varied with the time elapsed after administration; at 5 h the highest specific label was found in the stomach contents and in decreasing order in: intestinal contents, lung, liver, kidney, heart, fat, intestine, testes, and the lowest in muscles, spleen and brain. With exception of brain, fat, stomach and lung, all tissues showed maximum levels at 24 h, after which time the label decreased steadily, whereas in fat it increased.After a 12-week feeding experiment, with doses of 288.8 g/kg corresponding to an intake of 4 ppm in feed each 48 h, the DNA in liver and kidneys was investigated for damage. By the alkaline elution method combined with micro-spectrofluorimetric determinations of DNA, evidence for DNA single-strand breaks was obtained. These findings support reports on the carcinogenic action of OTA.     

Concentration andpH dependent steady-state volume of distribution of methotrexate estimated by a simple physiologically based method

The effects of plasma concentration and pH on the steady-state volume of distribution, V_ss,of methotrexate (MTX) were studied in five conditioned male beagle-mongrel dogs. Steady-state plasma MTX concentrations of approximately 1, 20, and 100g/ml were targeted for by i.v. bolus doses followed by i.v. infusions. An isotonic solution of sodium bicarbonate or ammonium chloride was simultaneously infused for the purpose of inducing plasma pH change, while the infusion of an isotonic solution of sodium chloride served as a control. Plasma and urine concentrations of MTX were quantitated by a sensitive high-performance liquid chromatographic method, and the V_ss of MTX was estimated by a recently reported physiologically based method of Chiou and Lam. Statistically significant (p<0.05) concentration and plasma pHdependent V_ss of MTX were observed. Concentration dependence of V_ss was noted in sodium chloride and ammonium chloride infused dogs, but not in bicarbonate treated dogs. There was an average 50.0 and 44.8% increase in V_ss at 1 g/ ml relative to the two higher concentrations (20 and 100 g/ ml) for dogs treated with ammonium and sodium chloride, respectively. However, V_ss of MTX at the targeted concentrations of 20 and 100 g/ml was relatively constant. Plasma pHdependence of V_ss was observed only at the plasma concentration of 1 g/ml, and on the average, ammonium chloride and sodium chloride treatments resulted in 50.0 and 31.3% higher V_ss,respectively, when compared with the bicarbonate treatment. These phenomena appear to be adequately explained by the reported tissue uptake kinetics of MTX.This research was supported in part by a grant from the National Cancer Institute, CA-29754.Abstracted from a dissertation submitted in 1984 by Chung Y. Lui to the Graduate College, University of Illinois at Chicago, in partial fulfillment of Doctor of Philosophy Degree requirements.     

Association of Opioid Use Disorder With 2016 Presidential Voting Patterns: Cross-sectional Study in New York State at Census Tract Level

BackgroundOpioid overdose-related deaths have increased dramatically in recent years. Combating the opioid epidemic requires better understanding of the epidemiology of opioid poisoning (OP) and opioid use disorder (OUD).ObjectiveWe aimed to discover geospatial patterns in nonmedical opioid use and its correlations with demographic features related to despair and economic hardship, most notably the US presidential voting patterns in 2016 at census tract level in New York State.MethodsThis cross-sectional analysis used data from New York Statewide Planning and Research Cooperative System claims data and the presidential voting results of 2016 in New York State from the Harvard Election Data Archive. We included 63,958 patients who had at least one OUD diagnosis between 2010 and 2016 and 36,004 patients with at least one OP diagnosis between 2012 and 2016. Geospatial mappings were created to compare areas of New York in OUD rates and presidential voting patterns. A multiple regression model examines the extent that certain factors explain OUD rate variation.ResultsSeveral areas shared similar patterns of OUD rates and Republican vote: census tracts in western New York, central New York, and Suffolk County. The correlation between OUD rates and the Republican vote was .38 (P<.001). The regression model with census tract level of demographic and socioeconomic factors explains 30% of the variance in OUD rates, with disability and Republican vote as the most significant predictors.ConclusionsAt the census tract level, OUD rates were positively correlated with Republican support in the 2016 presidential election, disability, unemployment, and unmarried status. Socioeconomic and demographic despair-related features explain a large portion of the association between the Republican vote and OUD. Together, these findings underscore the importance of socioeconomic interventions in combating the opioid epidemic.