Cranial cruciate ligament repair in a calf

A 1-month-old calf was unable to use its right pelvic limb because of rupture of the cranial cruciate ligament. The ligament was replaced with a wedge of bone from the cranial one-third of the patella and the attached portion of the middle patellar tendon. Postoperative complications limited function of the joint.     

An introduction to expert systems

The paper considers the features of expert systems which make them of educational interest, and discusses issues of knowledge representation through rule sets, and how such systems can be used to give explanation and advice. Working systems are outlined in Medicine, Geology and Computing. Some limitations of expert systems are noted and their future potential assessed.     

The effects of coronary vasodilatation on cardiac performance during endotoxin shock

Results of studies have suggested that endotoxin and lowered coronary arterial perfusion pressures are detrimental to cardiac performance and lead to failure. Prevention of cardiac failure in the isolated canine heart preparation confronted with endotoxin and decreased coronary perfusion pressure was possible by perfusing these hearts with sodium nitroprusside. Prevention of failure was manifested by a lowered left ventricular endiastolic pressure and was associated with increased coronary flow and decreased coronary resistance with increased oxygen delivery and decreased oxygen extraction. Possible explanations for improved performance by dilator perfusion include increased delivery of oxygen and nutrients to myocardial tissue as well as a reduction of ventricular wall tension by dilating the coronary vascular skeleton. Prevention of extravasation of interstitial fluid into myocardial tissue by reducing overperfusion of potentially damaged coronary vessels could serve to maintain myocardial integrity and ventricular compliance. The potential use of such therapy warrants further study, with emphasis on evaluating the hemodynamics of the intact animal.     

Proton resonance assignments and ligand exchange kinetics in high-spin and mixed-spin myoglobin complexes using two-dimensional exchange spectroscopy

Local lymph node activation and increased total serum IgE levels are suggested to be predictive parameters of airway hypersensitivity caused by low molecular weight (LMW) chemicals. Whether increases of total serum IgE are indicative of actual induction of specific airway reactions (morphological and functional) after inhalation challenge was examined in the present study. In Brown Norway (BN) and Wistar rats, serum IgE concentrations were examined following topical exposure of chemicals with known diverse sensitization potential in humans: trimellitic anhydride (TMA), a dermal and respiratory sensitizer; dinitrochlorobenzene (DNCB), a dermal sensitizer with no known potential to cause respiratory allergy; and methyl salicylate, a skin irritant devoid of sensitizing properties. Functional and histopathological changes in the respiratory tract were examined after subsequent inhalatory challenge with these chemicals. Of the three tested chemicals, only topical exposure to TMA resulted in a significant increase in total serum IgE concentrations in the high-IgE-responding BN rat. Upon subsequent inhalatory challenge of these rats, TMA induced specific airway reactions which included a sharp decrease in respiratory rate during challenge, followed by an increase in breathing rate with a concomitant decrease in tidal volume 24 and 48 h after inhalatory challenge, and histopathological changes in the larynx and lungs of animals necropsied 48 h after challenge. Interestingly, despite low IgE levels, TMA induced histopathological changes in the larynx and lungs of Wistar rats too. Laryngeal changes were also observed in Wistar rats upon sensitization and challenge with DNCB. These data suggest that increased total serum IgE after topical sensitization is associated with immediate-type specific airway reactivity after inhalation challenge in BN rats and thus may be a valuable parameter in testing for respiratory sensitization potential of LMW compounds. Histopathological examination upon subsequent inhalation challenge of sensitized low-IgE-responders may provide information on other allergic inflammatory airway reactions.     

Dihydroxyacetone levels in electronic cigarettes: Wick temperature and toxin formation

Recently, we reported the presence of dihydroxyacetone (DHA), the active ingredient in sunless tanners, in the aerosol of an electronic cigarette. DHA has been shown to react with DNA in vitro. The FDA restricts the use of DHA to external application only. It states that it should not be inhaled, ingested, or come into contact with any areas containing mucous membranes, due to unknown risk. Herein, the quantification of DHA in the aerosols of three brands of e-cigarettes has been carried out. These included two devices with horizontal heating coil configurations as well as one with a sub-ohm resistance vertical heating coil. In order to understand and begin to address the origin of DHA and related aerosol products, the wicking properties of the three e-cigarettes were compared. DHA levels were analyzed by a combination of GS/MS and ¹H NMR. DHA was found in all three e-cigarettes, with substantially less in the sub-ohm, vertical coil device as compared to the horizontal coil devices (e.g., 0.088 µg/puff vs. 2.29 µg/puff, respectively). Correspondingly, the temperature of the wet layer of the wick for the vertical coil was relatively stable, compared to the wicks for the horizontal coils, upon increasing battery power output. This result is in agreement with prior studies of e-cigarette wicking efficiency and aerosol toxin formation. The temperature measurements reported are a simple means for comparing devices with different design properties during operation.

Copyright © 2018 American Association for Aerosol Research     

Subpicogram per milliliter determination of the tobacco-specific carcinogen metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol in human urine using liquid chromatography-tandem mass spectrometry

Exposure to secondhand tobacco smoke (SHS) has been linked to increased risk for a number of diseases, including lung cancer. The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is of particular interest due to its potency and its specificity in producing lung tumors in animals. The NNK metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) in urine is frequently used as a biomarker for exposure. Due to its long half-life (40-45 days), NNAL may provide a long-term, time-averaged measure of exposure. We developed a highly sensitive liquid chromatography-tandem mass spectrometry method for determination of NNAL in human urine. The method involves liquid-liquid extraction followed by conversion to the hexanoate ester derivative. This derivative facilitates separation from interfering urinary constituents by extraction and chromatography and enhances detection with electrospray ionization mass spectrometry. The lower limit of quantitation is 0.25 pg/mL for 5-mL urine specimens. Applications to studies of people with a range of different SHS exposure levels is described.     

Cocaethylene formation following ethanol and cocaine administration by different routes.

Ethanol alters the hepatic biotransformation of cocaine, resulting in transesterification to a novel active metabolite, cocaethylene. Because of first pass metabolism, oral drug administration might be expected to produce relatively larger concentrations of cocaethylene than would intravenous or smoked administration. We, therefore, compared the effects of route of cocaine administration on the formation and elimination of cocaethylene. Six experienced cocaine users were tested in 6 sessions, approximately 1 week apart. Deuterium-labeled cocaine (d?) was administered in all conditions. Oral cocaine-d? 2.0 mg/kg, intravenous cocaine-d? 1.0 mg/kg, and smoked cocaine-d? (200 mg) were administered after oral ethanol 1.0g/kg or placebo. A small, intravenous dose of deuterated cocaethylene (d?) also was administered with all conditions for determination of cocaethylene formation. Physiologic and subjective effects were recorded and plasma cocaine-d?, cocaethylene-d?, cocaethylene-d?, and benzoylecgonine-d? were measured by gas chromatography-mass spectrometry. About 24% (± 11) of intravenous cocaine was converted to cocaethylene. The oral route (34% ± 20) was significantly greater than from the smoked route (18% ± 11) and showed a trend toward significance for greater formation of cocaethylene compared to the intravenous route. Within each route, the cocaine-ethanol combination produced greater increases in heart rate and rate-pressure product than cocaine alone. Global intoxication effects across time after smoking or intravenous administration were significantly greater when cocaine and ethanol were both given. Administration of cocaine by different routes alters the amount of cocaethylene formed through hepatic first-pass effects. Increased cardiovascular and subjective effects might explain the toxicity and popularity of the combined drugs. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Binding of phenylphosphocholine-carrier conjugates to the combining site of antibodies maintains a conformation of the hapten

The structural basis of the binding of phenylphosphocholine haptens to antibodies was studied. This was done by preparing antibodies and testing binding to conjugates of phenylphosphocholine. The choice of haptens was made in order to evaluate the contribution of the carrier to binding, and its effect on hapten conformation in the active site. Thus, phosphocholine (PC) was diazophenyl-linked to tyrosine or histidine as single amino acid carriers and to tripeptides or octapeptides containing tyrosine or histidine as central amino acids to which PC was attached. Relative affinity was assessed by inhibition enzyme-linked immunosorbent assay (ELISA) and binding constants were determined by fluorescence quenching. Fluorinated haptens were used to determine the kinetics of binding using 19F nuclear magnetic resonance. The transferred nuclear Overhauser effect was used to characterize conformation of the bound hapten. We had previously shown that nitrophenylphosphocholine unlinked to carrier is bound in the active site as a bent structure [Bruderer, U., Peyton, D. H., Barbar, E., Fellman, J. H., & Rittenberg, M. B. (1992) Biochemistry 31, 584-589]. We show here that this same bent conformation is retained in the active site regardless of the neighboring carrier or the conformation of the hapten in the unbound conjugate. The presence of the carrier residues in the bound state does, however, influence affinity.