Chemical and biological dynamics of tetracyclines.
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Anti-Bacterial Agents↗
Biomedical subjects
M L Nelson
Publications and source records attributed to M L Nelson.
Dynamic imaging of structural changes in silver catalysts by environmental scanning electron microscopy.
Polycrystalline silver catalysts are used extensively for the partial oxidation of methanol to formaldehyde, which is then primarily incorporated in the synthesis process for adhesives and resins. In order to maximize formaldehyde production it is essential to gain a comprehensive understanding of the complex microstructural changes which occur in the catalyst during reaction conditions. However, conventional electron microscopic techniques are incapable of imaging catalysts at high temperatures and in the presence of a gaseous atmosphere. Therefore, an environmental scanning electron microscope (ESEM) has been used to image polycrystalline silver catalysts during simulated industrial conditions. The most dramatic effect of heating various catalysts to 700 degrees C in the ESEM chamber was the formation of "pinholes" in the silver surface. These "pinholes" occur at specific temperatures and are inherently associated with the catalytic process, resulting from near-surface explosions caused by subsurface hydroxyl recombination. Of particular interest was the nature and location of the holes, which preferentially occur in the vicinity of surface defects such as platelets and edge structures. To the best of our knowledge, this study represents the first time that the progress of a catalytic reaction has been observed under in situ conditions by scanning electron microscopy.
Microscopy, Electron, Scanning↗
Ruminal undegradability of blood meal and effects of blood meal on ruminal and postruminal digestion in steers consuming vegetative orchardgrass hay.
Four crossbred steers (360 +/- 3 kg) cannulated at the rumen and duodenum were used in a 4 x 4 Latin square design to examine the effects of supplemental blood meal (BM) on voluntary intake, digesta kinetics, ruminal fermentation, site and extent of digestion, and bacterial protein synthesis in steers fed vegetative orchardgrass hay (Dactylis glomerata L.). The levels of BM supplementation were 0, .07, .13, and .20 kg/d. Voluntary intake of OM (8.35 kg/d) was not significantly affected by BM supplementation. No significant effects of BM supplementation were detected for OM flow to the duodenum or digestion in the rumen or lower tract. However, total tract OM digestibility decreased 2.2 percentage units at .20 kg/d of BM intake (lower with vs without BM; P < .10). Total N intake and flow to the duodenum linearly increased (P < .10) with increasing BM level from 251 to 277 g/d and from 158 to 199 g/d, respectively. Ammonia N and bacterial N flows to the duodenum were not affected (P > .10) by BM supplementation. As a result, nonammonia N flow to the duodenum increased linearly (P < .10) with increasing BM supplementation. Ruminal escape N from BM was 83.5, 85.3, and 87.2% for .07, .13, and .20 kg/d of BM, respectively. Apparent bacterial efficiency and true bacterial efficiency were not affected (P > .10) by BM supplementation. Total amino acid and total essential amino acid flows to the duodenum were increased (P < .10) by dietary inclusion of BM. Duodenal flows of all essential amino acids except lysine and valine and of all nonessential amino acids except alanine and proline were increased (P < .10) by BM inclusion in the diet. In summary, supplementation with BM increased ruminal escape N and duodenal flows of total and most essential amino acids.
Amino Acids↗
Escape protein supplementation of steers fed grass silage-based diets.
Beef steers (Trials 1 and 2, 280 +/- 2 kg; Trial 3, 330 +/- 2 kg) were fed diets of 67.5% wheat (Trial 1) or oat silage (Trials 2 and 3), 20.5% barley, and 12% supplement in randomized complete block design growth trials. Dietary treatments were graded levels of supplemental escape protein (EP) from corn gluten meal (Trial 1, 0 to 213 g/d escape protein) or animal by-products (1:1:1 DM mixture of blood, feather, and meat and bone meals, 0 to 223 or 0 to 317 g/d of escape protein in Trials 2 and 3, respectively) to titrate amounts needed to maximize steer live weight gain. As supplemental EP from corn gluten meal increased, steer live weight gain increased linearly (P < .001) and feed-to-gain decreased linearly (P < .001). Supplementation with 135 g/d of corn gluten meal EP (335 g/d of corn gluten meal) increased average daily gain from .76 to .91 kg/d. As supplemental EP from animal by-products increased, steer live weight gain increased quadratically (P < .05) and feed-to-gain decreased linearly (P < .01). Supplementation with 223 or 317 g/d of animal by-product EP increased live weight gain by .27 kg/d. Supplemental escape protein was needed to increase live weight gain of steers consuming ensiled forage diets due to low EP contents of silages (7, 3, and 23% of CP in Trials 1, 2, and 3, respectively) and barley (15, 27, and 22% of CP in Trials 1, 2, and 3, respectively) and limited microbial protein synthesis.
Animals↗
Torsion of the tendon of peroneus brevis.
The authors present a previously undescribed torsion located within the tendon of peroneus brevis. The musculotendinous unit of peroneus brevis was isolated from 46 lower extremities of cadavers. A goniometer was constructed and utilized to quantify the degree of torsion located within each peroneus brevis tendon. Torsion was present in all 46 cadaver specimens, with a mean of 38.5 degrees and a range of 26 degrees to 56 degrees. The regional anatomy and biomechanical functions of peroneus brevis are discussed, and proposed bases for the embryologic origins and functional significance of the torsion are presented.
Adult↗
Differential stimulation of cortisol and dehydroepiandrosterone levels by food in obese and normal subjects: relation to body fat distribution.
BACKGROUND: It has been previously shown that food intake elevates circulating ACTH and cortisol levels, but no report has been published regarding the changes in circulating dehydroepiandrosterone (DHEA). DHEA was originally described as a weak androgen, but more recently it has been associated with a wide range of metabolic functions. In addition, previous studies have described a hyper-responsive hypothalamo-pituitary-adrenal axis in obese subjects in response to various stimuli, but the specific response to food has not been studied. SUBJECTS AND DESIGN: We studied the effect of food on the hypothalamo-pituitary-adrenal axis in 20 subjects of normal body mass index (BMI range 18-25) and also in a group of 12 obese subjects (BMI range 34-61). Levels of glucose, insulin, ACTH, cortisol and dehydroepiandrosterone were measured every 20 minutes. RESULTS: A small rise in DHEA accompanies the rise in circulating ACTH and cortisol in response to food in both lean and obese subjects, but DHEA rose independently of cortisol and ACTH on the fasting day. In the obese subjects, food induced a significantly greater change in serum cortisol (peak cortisol rise (mean +/- SEM); normal-weight group, 169 +/- 14%; obese group, 294 +/- 23%) and in the cortisol/DHEA ratio (area under the curve; normal-weight group, 202 +/- 15%; obese group, 292 +/- 29%) than in the normal-weight subjects. This difference was particularly notable in those with central-type obesity (waist/hip ratio > 0.80). A group of the normal, jean female subjects showed no cortisol rise after food intake. CONCLUSION: Our results suggest that DHEA may vary independently of circulating cortisol, and that the cortisol response to food is enhanced in obese subjects, particularly in those with central obesity. We speculate that there may be a caused connection between the cortisol response to food in normal subjects, and the subsequent distribution of fat if such subjects overeat sufficiently to become obese.
Adipose Tissue↗
Effect of storage temperature and time on fiber content of fresh and ensiled alfalfa.
To determine effects of storage temperature and time on fiber content, fresh alfalfa (late vegetative) was hand-clipped from three locations (blocks) and stored fresh or ensiled at -20 degrees C or +60 degrees C for 0, 24, 48, 96, 168, or 336 h. The experimental design was a randomized complete block with a 2 x 2 factorial arrangement of treatments. Main effects were method of forage conservation (fresh or ensiled) and temperature of storage (-20 degrees C or + 60 degrees C). Length of storage (0, 24, 48, 96, 168, or 336 h) was in the subplot. Conservation method x storage temperature x time interactions were detected (P < .05) for NDF, IVDMD, ADIN, and N content of NDF. Large increases in alfalfa NDF were observed up to 168 h of storage at 60 degrees C, whereas when fresh alfalfa was stored at -20 degrees C, small increases were observed up to 48 h but a large increase was observed after 168 h. Ensiled alfalfa stored at -20 degrees C had no change in NDF content. Contributors to increased NDF seemed due to changes in protein solubility and glycosylamine formation when fresh forage was stored at 60 degrees C, and changes in protein solubility, glycosylamine formation, and Maillard product formation when ensiled forage was stored at 60 degrees C. At -20 degrees C, formation of adducts with arabinose and glucose from nonstructural carbohydrates as well as polymerization and fragmentation of cell wall monosaccharides probably contributed to altered NDF content of alfalfa.
Arabinose↗
Health care worker incidents reported in a rural health care facility: a descriptive study.
About eight million workers, or 6.4% of the total United States work force, are employed by the health care industry. Frequency of injury has continued to rise from 6 per 100 full time workers in 1980 to over 10 in 1992 (US Department of Labor, 1994). This descriptive, retrospective study characterizes host, agent, and environmental variables for 120 incidents reported in 1990 at a rural nursing home and acute care hospital with 290 employees. Incident is defined as an event that results in injury or has the potential to result in an injury. Based on an estimate of full time equivalents (190.4 FTE) calculated at 9 months, the incident rate per 100 FTEs was 63 for this facility. Injury was reported in 114 incidents, resulting in an overall injury rate per 100 FTEs of 59.9. Sprains and strains were the most frequently reported nature of injury followed by cuts, lacerations, and punctures. Female and male workers reported similar proportions of incidents. At midyear, 85% of the employee population was female, 15% male. Females represented 83.3% of the subjects reporting incidents; males represented 16.7%. These data from a small rural facility differ from many of the findings on the injury experience of health care workers reported in the literature.
Accidents, Occupational↗
Molecular requirements for the inhibition of the tetracycline antiport protein and the effect of potent inhibitors on the growth of tetracycline-resistant bacteria.
Forty-seven compounds and tetracycline (Tc) structural analogues were tested for their ability to interfere with [3H]Tc uptake in everted inner membrane vesicles derived from Tc-resistant Escherichia coli D1-209, bearing the class B tetracycline resistance efflux protein (Tet protein). For effective inhibition of Tc uptake, the molecule had to have an intact ABCD tetracyclic carbon skeleton and a conjugated phenolic beta-diketone substructure at positions 10-12a with the subsequent development of keto-enol tautomerization. Molecular variations at carbon positions 2, 4, 5, 6, 7, 8, and 9 did not decrease, and some increased, the inhibitory activity as compared to that of Tc. Among these compounds, the highest inhibition of uptake occurred with certain position 6 and 13 derivatives of 5-hydroxytetracycline. In a group of 13-(propylthio) derivatives of 5-OH-Tc [13-propyl, 13-(3-chloropropyl), and 13-(2-carboxyethyl)] there was a correlation between uptake inhibitory activity and antibacterial activity. The 13-(3-chloropropyl) derivative, with the best efflux inhibitory activity, exhibited synergistic activity when tested in combination with doxycycline against Tc-resistant E. coli bearing the class A or B determinant, against Staphylococcus aureus bearing class K, and against Enterococcus faecalis bearing the class L determinant. The 13-propyl analogue also showed high transport blocking activity and showed synergistic antibacterial activity against E. coli bearing the class A determinant and additive activity against the other Tc-resistant bacteria. The synergistic antibacterial activity of these compounds was not shown by the 13-[(2-carboxyethyl)thio] homologue, whose efflux blocking activity was 70-fold less. These findings suggest that multiple sites on the Tc molecule are available for synthetic modification toward the development of an effective Tc blocking agent. Such compounds, used alone or in combination with a standard tetracycline, show improved antibacterial activity.
Antiporters↗
The pharmacokinetics and pharmacodynamics of medifoxamine after oral administration in healthy elderly volunteers.
The pharmacokinetics and psychomotor effects of medifoxamine, a 5 HT reuptake inhibitory antidepressant, were studied in healthy elderly volunteers after single and multiple dosing. The elimination half life (t1/2z) after single doses of 300 mg was 2.8 h--almost identical to that found in young volunteers. After seven days of dosing at 100 mg three times daily the mean corrected AUC after 300 mg significantly increased from 1.04 to 1.34 mg.h.l-1 and t1/2z increased to 4.0 h (NS). There were no significant changes in critical flicker fusion frequency, symbol digit substitution, continuous attention or choice reaction times.
Administration, Oral↗
Eating behavior in bulimia nervosa: multiple meal analyses.
Ten bulimic individuals were admitted to an inpatient unit and for 7 consecutive days eating behavior was observed and recorded. Age, sex, and weight-matched control subjects (n = 10) were admitted to the same unit for 4 d. All food and fluid intake, frequency of binge eating and purging, and ratings of appetite and mood before and after eating were recorded every 24 h. Bulimic patients demonstrated chaotic eating patterns that varied within as well as between individuals. Total daily energy intake was significantly higher for bulimic patients (41982 +/- 113 kJ; 10,034 +/- 2701 kcal) than for control subjects (8050 +/- 0427 kJ; 1924 +/- 102 kcal). On average, patients binged 1.6 times, purged three times, and ate one snack or meal without purging daily. Macronutrient analyses of intake revealed significantly less energy from protein and more energy from fat in bulimic patients compared with control subjects. Some improvement of mood was noted after binges, the magnitude of which was greatest after purging.
Adolescent↗
Inhibition of the tetracycline efflux antiport protein by 13-thio-substituted 5-hydroxy-6-deoxytetracyclines.
A series of 13-(alkylthio) and 13-(arylthio) derivatives of 5-hydroxy-6-deoxytetracycline (tetracycline, Tc) were synthesized and compared to the clinically used antibiotics tetracycline, methacycline, and minocycline for their ability to inhibit tetracycline efflux in an everted membrane vesicle assay of bacterial resistance to tetracyclines. The assay screened for the ability of tetracycline analogues to inhibit [3H]tetracycline uptake into everted membrane vesicles, thereby evaluating the molecular prerequisites for inhibition of an efflux-dependent resistant bacterial system. Thiol adducts attached at the exocyclic C13 carbon of methacycline led to an increase in inhibitor potency as compared to the reference antibiotics. The most potent inhibitors of [3H]tetracycline uptake into everted vesicles among these analogues, particularly members of the alkyl series, revealed important structure-activity relationships between inhibitor potency, steric parameters, and lipophilicity at the C13 sulfur position.
Bacterial Proteins↗
Eating pathology in bulimia nervosa.
Degree of eating pathology in bulimia nervosa was assessed using the Eating Behavior Rating Scale (EBRS) across three videotaped eating sessions. Twelve bulimic and 12 non-eating disordered subjects participated in this study. All subjects were filmed during a baseline meal (ad libitum), a high-calorie meal, and a low-calorie meal (both fixed amounts). Mean EBRS scores were significantly higher for bulimics (12.6 +/- 1.7) than for controls (3.9 +/- 0.9), suggesting a higher degree of eating pathology in these patients. Affect during eating was significantly more negative in the bulimic patients. EBRS and affect scores were significantly correlated [r (11) = .813, p < .01]. Bulimics had a slower rate of eating than controls and took significantly longer to initiate eating. Scores of pathological eating correlated with scores on the Eating Attitudes Test and the Bulimic Investigatory Test-Edinburgh, indicating a relationship between objective measures of pathological eating and self-report measures of eating disorder symptoms.
Adult↗
The association of age with gastric emptying.
Gastric emptying is important as a rate-limiting step in the absorption of orally administered drugs. Paracetamol absorption kinetics were used to compare gastric emptying in 19 fit elderly and 19 fit young volunteers. The results showed no significant difference in any of the derived parameters (t1/2abs, tlag and tmax) between the two groups. These results suggest that ageing does not impair this rate-limiting step in drug absorption.
Acetaminophen↗
Observation of the anterior supracostal muscles.
A pair of anomalous supernumerary muscles has been found in a single cadaver which fit the classic description of the Musculus supracostalis anterior. The muscles took origin from the first rib deep to the two pectoral muscles and between the origins of the pectoralis minor and serratus anterior muscles. They were directed inferiorly to insert on the upper margin of the fourth rib. The nerve supply of one muscle of the pair was determined to be from the collateral branch of the second right intercostal nerve. This supports the theory that these rare muscles may be derived from a single external intercostal muscle which grew to span several intercostal spaces.
Aged↗
Decrease in resting metabolic rate during abstinence from bulimic behavior.
Among eight normal-weight bulimic women studied during 1 week of binge eating and vomiting and 7 weeks of abstinence without weight loss, resting metabolic rate and T3 and T4 levels fell significantly during abstinence. These data suggest that a physiological consequence of binge eating and vomiting is an increase in metabolic rate, in part due to increased thyroid hormone activity.
Adult↗
Effects of rapeseed silage variety and dietary level on digestion and growth performance of beef steers.
A digestion and ruminal fermentation trial involving five ruminally cannulated steers assigned to a 5 x 5 Latin square with a 2 x 2 + 1 arrangement of dietary treatments was conducted to evaluate the effects of variety of rapeseed silage (RS) containing either a high (HG) or a low (LG) glucosinolate concentration when fed at 100 or 50% of diet DM. A bromegrass hay-corn-soybean meal mixture, which was expected to be isocaloric and isonitrogenous with the RS, was used as the control (C) treatment and replaced RS in the 50% diets. In situ disappearance of substrate from both RS varieties was measured in ruminal environments created by each diet. No dietary treatment x RS substrate interactions were observed for any in situ variable. Total tract digestibility and extent of in situ disappearance of both DM and NDF were greater (P less than .01) for HG than for LG. In situ DM and NDF disappearance at 8, 16 and 24 h was greater (P less than .01) for RS than for the C diet. Similarly, total tract DM digestibility was greater (P less than .01) for RS (61.0%) vs C (56.0%) diets. Diets with 50% RS had greater (P less than .01) NDF digestibility (50.4%) than 100% RS (43.6%) diets. Variety of RS had no effect on particulate passage rate. In a 77-d growth trial with 60 beef steers, ADG was greater (P less than .01) for HG vs LG (.46 vs .36 kg), 50 vs 100% (.52 vs .31) and C vs RS (.64 vs .41) diets.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Ovarian histopathology of bitches immunized with porcine zonae pellucidae.
The ovarian histopathology of bitches immunized with crude (cPZP) or partially purified (pPZP) porcine zona pellucida proteins was examined in order to determine the cause of abnormal estrous cycles. The majority of immunized bitches had ovarian cytes. Those immunized with cPZP had follicular cysts lined with a thin layer of granulosa cells, while in those immunized with pPZP, the cysts were lined by a basement membrane with a clump of luteinized cells. In two bitches immunized with cPZP, oocytes were present only in primordial follicles. Similar abnormalities were not found in a bitch immunized with human serum albumin or in 12 untreated bitches. Oocytes flushed from the oviducts of mated, immunized bitches were degenerating, which may have been a primary cause of infertility in such bitches. Ovaries studied 2-6 weeks after immunization showed no loss of gap junctional communication between oocytes and granulosa cells, nor was any inflammatory reaction seen. IgG was bound to the zona as revealed by fluoresceinated protein A staining of frozen sections of those ovaries. Abnormal estrous cycles in PZP-immunized bitches appear to result from follicular dysgenesis or cyst formation, but the etiology of these conditions is unresolved.
Animals↗