Rumen-protected methionine supplementation during the transition period under artificially induced heat stress: impacts on cow-calf performance.

Dairy cows experiencing heat stress (HS) during the pre-calving portion of the transition period give birth to smaller calves and produce less milk and milk protein. Supplementation of rumen-protected methionine (RPM) has been shown to modulate protein, energy, and placenta metabolism, making it a potential candidate to ameliorate HS effects. We investigated the effects of supplementing RPM to transition cows under HS induced by electric heat blanket (EHB) on cow-calf performance. Six weeks before expected calving, 53 Holstein cows were housed in a tie-stall barn and fed a control diet (CON, 2.2% Met of MP) or a CON diet supplemented with Smartamine®M (MET, 2.6% Met of MP, Adisseo Inc., France). Four weeks pre-calving, all MET and half CON cows were fitted with an EHB. The other half of the CON cows were considered thermoneutral (TN), resulting in 3 treatments: CONTN (n = 19), CONHS (n = 17), and METHS (n = 17). Respiratory rate (RR), skin temperature (ST), and rectal temperature (RT) were measured thrice weekly and core body temperatures recorded bi-weekly. Post-calving body weights (BW) and BCS were recorded weekly, and DMI was calculated and averaged weekly. Milk yield was recorded daily and milk components were analyzed every third DIM. Biweekly AA and weekly nonesterified fatty acids (NEFA), ß-hydroxybutyrate (BHB), insulin, and glucose were measured from plasma. Calf birth weight and 24 h growth, thermoregulation, and hematology profile were measured and apparent efficiency of absorption (AEA) of immunoglobulins was calculated. Data were analyzed using the MIXED procedure of SAS with 2 preplanned orthogonal contrasts: CONTN vs. the average of CONHS and METHS (C1) and CONHS vs. METHS (C2). Relative to TN, EHB cows had increased RT during the post-calving weeks and increased RR and ST during the entire transition period. Body weight, BCS, DMI, and milk yield were not impacted by the EHB or RPM. However, protein % and SNF were lower in CONHS, relative to METHS cows. At calving, METHS dams had higher glucose concentrations, relative to CONHS, and during the post-calving weeks, the EHB cows had lower NEFA concentrations than TN cows. Calf birthweight and AEA were reduced by HS, while RR was increased by HS. Calf withers height tended to be shorter and RT were lower in CONHS, compared with MTHS heifers. Overall, RPM supplementation to transition cows reverts the negative impact of HS on blood glucose concentration at calving and milk protein % in the dams and increases wither height while decreasing RT in the calf.

Obese sedentary patients with dyspnoea on exertion who are at low risk for coronary artery disease by clinical criteria have a very low prevalence of coronary artery disease.

Dyspnoea, a much less specific symptom of ischaemia than chest discomfort, is common among obese patients. Patients with dyspnoea often undergo stress testing as part of their evaluation. We sought to examine the yield of stress testing in non-elderly, obese, sedentary patients with dyspnoea on exertion (DOE) as a chief complaint.We reviewed stress echocardiograms carried out on 203 patients in a stress testing laboratory at a major tertiary care centre. Of these, 81 (40%) fell into a group that was at low risk for coronary artery disease (CAD) by clinical criteria. Ischaemia was detected in two patients in the low-risk group (2.5%), and these results were likely false positives. In the higher risk group, 9.0% of functional tests showed ischaemia; after further testing, 2.5% of the higher risk patients were found to have obstructive coronary lesions. Clinical follow-up was performed for a mean of 815 days. New obstructive coronary disease was detected in 1.6% of all patients, and these patients were from the higher risk group. In obese sedentary patients with DOE but otherwise at low risk of coronary disease stress testing is of very low yield. DOE is generally not an anginal equivalent in this patient population.

High performance imaging streak camera for the National Ignition Facility.

An x-ray streak camera platform has been characterized and implemented for use at the National Ignition Facility. The camera has been modified to meet the experiment requirements of the National Ignition Campaign and to perform reliably in conditions that produce high electromagnetic interference. A train of temporal ultra-violet timing markers has been added to the diagnostic in order to calibrate the temporal axis of the instrument and the detector efficiency of the streak camera was improved by using a CsI photocathode. The performance of the streak camera has been characterized and is summarized in this paper. The detector efficiency and cathode measurements are also presented.

Characterization of Eyjafjallajokull volcanic ash particles and a protocol for rapid risk assessment.

On April 14, 2010, when meltwaters from the Eyjafjallajökull glacier mixed with hot magma, an explosive eruption sent unusually fine-grained ash into the jet stream. It quickly dispersed over Europe. Previous airplane encounters with ash resulted in sandblasted windows and particles melted inside jet engines, causing them to fail. Therefore, air traffic was grounded for several days. Concerns also arose about health risks from fallout, because ash can transport acids as well as toxic compounds, such as fluoride, aluminum, and arsenic. Studies on ash are usually made on material collected far from the source, where it could have mixed with other atmospheric particles, or after exposure to water as rain or fog, which would alter surface composition. For this study, a unique set of dry ash samples was collected immediately after the explosive event and compared with fresh ash from a later, more typical eruption. Using nanotechniques, custom-designed for studying natural materials, we explored the physical and chemical nature of the ash to determine if fears about health and safety were justified and we developed a protocol that will serve for assessing risks during a future event. On single particles, we identified the composition of nanometer scale salt coatings and measured the mass of adsorbed salts with picogram resolution. The particles of explosive ash that reached Europe in the jet stream were especially sharp and abrasive over their entire size range, from submillimeter to tens of nanometers. Edges remained sharp even after a couple of weeks of abrasion in stirred water suspensions.

Outstanding survival and regeneration process by the use of intelligent acellular dermal matrices and mesenchymal stem cells in a burn pig model.

A pig model with a deep large burn was used to study the regeneration process induced by mesenchymal stem cells (MSCs) and acellular pig dermal matrices, made intelligent by the combination with biodegradable nanofibers loaded with growth factors (granulocyte-macrophage colony-stimulating factor and epidermal growth factor) and coated with the anti-CD44 monoclonal antibody (intelligent acellular dermal matrices, IADMs). These IADMs are specially designed to integrate in the wound bed as new biological scaffolds as well as to specifically recruit and attach circulating and/or externally applied MSCs through the anti-CD44 antibody while delivering precise amounts of growth factors. In this way, the reparative process as well as the aesthetic and functional results were enhanced in our burn model. The animal survived, the wound was completely closed, and total regeneration of the skin was obtained without much scarring. Surprisingly, hair follicles and other skin appendages developed despite the severity and deepness of the burn. Even burned muscles and ribs seemed to have undergone a regenerative process by the end of the study. Based on these findings, we have proposed the use of IADMs and autologous, allogeneic or xenogeneic MSCs, as a new paradigm for the future treatment of large burns and probably other dermatological and cosmetic human conditions.

The next generation of burns treatment: intelligent films and matrix, controlled enzymatic debridement, and adult stem cells.

We describe a novel technology based on nanoengineered multifunctional acellular biologic scaffolds combined with wound dressings and films of the same kind. This method allows selective delivery and release of shielded biomaterials and bioactive substances to a desired wound or damaged tissue while stimulating the selective anchoring and adhesion of endogenous circulating repairing cells, such as mesenchymal stem cells, to obtain a faster and more physiologic healing process. We also present a new controlled enzymatic debridement process for more effective burned tissue scarolysis. In light of our preliminary in vitro and in vivo data, we are convinced that these approaches can include the use of other kinds of adult stem cells, such as endometrial regenerative cells, to improve the vascularization of the constructs, with great potential in the entire tissue and organ regeneration field but especially for the treatment of severely burned patients, changing the way these lesions may be treated in the future.

Absorption, distribution, metabolism and excretion (ADME) study with 2,2',4,4',5,6'-hexabromodiphenyl ether (BDE-154) in male Sprague-Dawley rats.

A metabolism study of orally administered 2,2',4,4',5,6'-hexabromodiphenyl ether (BDE-154; 11.3 micromoles kg(-1)) was conducted in conventional and bile duct-cannulated male Sprague-Dawley rats. In conventional rats, approximately 31% of the radiolabelled dose was retained at 72 h, and lipophilic tissues were the preferred sites for disposition. Urinary excretion of BDE-154 was very low (1.0%), and parent compound was detected. Cumulative biliary excretion was 1.3%, and glutathione conjugates were suggested. Over 62% of the dose in conventional male rats was excreted in faeces, and was composed of parent compound (7.3%), free metabolites (13.1%), and covalently bound residues (41.4%). Faecal metabolites characterized by gas chromatography/mass spectrometry included multiple isomers of monohydroxylated hexa-/penta-/tetrabromodiphenyl ethers, and di-hydroxylated hexa/pentabromodiphenyl ethers. The adipose tissue 14C was extractable BDE-154, but 40% of liver 14C was bound to macromolecules. The study demonstrated the importance of performing individual polybrominated diphenyl ether (PBDE) metabolism studies to understand fully PBDE pharmacokinetics.

Enhanced satellite cell proliferation with resistance training in elderly men and women.

In addition to the well-documented loss of muscle mass and strength associated with aging, there is evidence for the attenuating effects of aging on the number of satellite cells in human skeletal muscle. The aim of this study was to investigate the response of satellite cells in elderly men and women to 12 weeks of resistance training. Biopsies were collected from the m. vastus lateralis of 13 healthy elderly men and 16 healthy elderly women (mean age 76+/-SD 3 years) before and after the training period. Satellite cells were visualized by immunohistochemical staining of muscle cross-sections with a monoclonal antibody against neural cell adhesion molecule (NCAM) and counterstaining with Mayer's hematoxylin. Compared with the pre-training values, there was a significant increase (P<0.05) in the number of NCAM-positively stained cells per fiber post-training in males (from 0.11+/-0.03 to 0.15+/-0.06; mean+/-SD) and females (from 0.11+/-0.04 to 0.13+/-0.05). These results suggest that 12 weeks of resistance training is effective in enhancing the satellite cell pool in skeletal muscle in the elderly.

Classifying undetermined poisoning deaths.

OBJECTIVE: To classify poisoning deaths of undetermined intent as either suicide or unintentional and to estimate the extent of underreported poisoning suicides. METHODS: Based on 2002 statewide death certificate and medical examiner data in Utah, the authors randomly selected one half of undetermined and unintentional poisoning deaths for data abstraction and included all suicides. Bivariate analyses assessed differences in demographics, death characteristics, forensic toxicology results, mental health history, and other potentially contributing factors. Classification and regression tree (CART) analysis used information from unintentional and suicide poisoning deaths to create a classification tree that was applied to undetermined poisoning deaths. RESULTS: The authors analyzed 41 unintentional, 87 suicide, and 84 undetermined poisonings. Undetermined and unintentional decedents were similar in the presence of opiates, physical health problems, and drug abuse. Although none of the undetermined decedents left a suicide note, previous attempt or intent to commit suicide was reported for 11 (13%) of these cases. CART analysis identified suicidal behavior, drug abuse, physical health problems, depressed mood, and age as discriminating between suicide and unintentional poisoning. It is estimated that suicide rates related to poisoning are underreported by approximately 30% and overall suicide rates by 10%. Unintentional poisoning death rates were underreported by 61%. CONCLUSIONS: This study suggests that manner of death determination relies on circumstance dependent variables that may not be consistently captured by medical examiners. Underreporting of suicide rates has important implications in policy development, research funding, and evaluation of prevention programs.

Volatile anaesthetics depolarize neural mitochondria by inhibiton of the electron transport chain.

BACKGROUND: The mitochondrial membrane potential (DeltaPsim) controls the generation of adenosine triphosphate (ATP) and reactive oxygen species, and sequesteration of intracellular Ca2+[Ca2+]i. Clinical concentrations of sevoflurane affect the DeltaPsim in neural mitochondria, but the mechanisms remain elusive. The aim of the present study was to compare the effect of isoflurane and sevoflurane on DeltaPsim in rat pre-synaptic terminals (synaptosomes), and to investigate whether these agents affect DeltaPsim by inhibiting the respiratory chain. METHODS: Synaptosomes were loaded with the fluorescent probes JC-1 (DeltaPsim) and Fura-2 ([Ca2+]i) and exposed to isoflurane or sevoflurane. The effect of the anaesthetics on the electron transport chain was investigated by blocking complex I and complex V. RESULTS: Isoflurane 1 and 2 minimum alveolar concentration (MAC) decreased the normalized JC-1 ratio from 0.92 +/- 0.03 in control to 0.86 +/- 0.02 and 0.81 +/- 0.01, respectively, reflecting a depolarization of the mitochondrial membrane (n = 9). Isoflurane 2 MAC increased [Ca2+]i. In Ca2+-depleted medium, isoflurane still decreased DeltaPsim while [Ca2+]i remained unaltered. The effect of isoflurane was more pronounced than for sevoflurane. Blocking complex V of the respiratory chain enhanced the isoflurane- and sevoflurane-induced mitochondrial depolarization, whereas blocking complex I and V decreased DeltaPsim to the same extent in control, isoflurane and sevoflurane experiments. CONCLUSIONS: Isoflurane and sevoflurane may act as metabolic inhibitors by depolarizing pre-synaptic mitochondria through inhibition of the electron transport chain, although isoflurane seems to inhibit mitochondrial function more significantly than sevoflurane. Both agents inhibit the respiratory chain sufficiently to cause ATP synthase reversal.

Tissue disposition, excretion and metabolism of 2,2',4,4',6-pentabromodiphenyl ether (BDE-100) in male Sprague-Dawley rats.

The absorption, disposition, metabolism and excretion study of orally administered 2,2',4,4',6-pentabromodiphenyl ether (BDE-100) was studied in conventional and bile-duct cannulated male rats. In conventional rats, >70% of the radiolabelled oral dose was retained at 72 h, and lipophilic tissues were the preferred sites for disposition, i.e. adipose tissue, gastrointestinal tract, skin, liver and lungs. Urinary excretion of BDE-100 was very low (0.1% of the dose). Biliary excretion of BDE-100 was slightly greater than that observed in urine, i.e. 1.7% at 72 h, and glucuronidation of phenolic metabolites was suggested. Thiol metabolites were not observed in the bile as had been reported in other PBDE metabolism studies. Almost 20% of the dose in conventional male rats and over 26% in bile-duct cannulated rats was excreted in the faeces, mainly as the unmetabolized parent, although large amounts of non-extractable radiolabel were also observed. Extractable metabolites in faeces were characterized by mass spectrometry. Monohydroxylated pentabromodiphenyl ether metabolites were detected; mono- and di-hydroxylated metabolites with accompanying oxidative debromination were also observed as faecal metabolites. Tissue residues of [(14)C]BDE-100 in liver, gastrointestinal tract and adipose tissue contained only parent material. The majority of the 0-72-h biliary radioactivity was associated with an unidentified 79-kDa protein or to albumin.

Sevoflurane depolarizes pre-synaptic mitochondria in the central nervous system.

BACKGROUND: Volatile anaesthetics protect the heart from ischaemic injury by activating mitochondrial signalling pathways. The aim of this study was to test whether sevoflurane, which is increasingly used in neuroanaesthesia, affects mitochondrial function in the central nervous system by altering the mitochondrial membrane potential (DeltaPsi(m)). METHODS: In order to correlate free cytosolic Ca(2+) ([Ca(2+)](i)) and DeltaPsi(m), rat neural presynaptic terminals (synaptosomes) were loaded with the fluorescent probes fura-2 and JC-1. During sevoflurane exposure, 4-aminopyridine (4-AP) 500 micro M to induce pre-synaptic membrane depolarization or carbonylcyanide-p-(trifluoromethoxy)-phenylhydrazone (FCCP) 1 micro M to induce maximum mitochondrial depolarization was added. In order to block mitochondrial ATP-regulated K(+)-channels (mitoK(ATP)), the antagonist 5-hydroxydecanoate (5-HD) 500 micro M was added. RESULTS: In Ca(2+)-containing medium, both sevoflurane 1 and 2 MAC gradually decreased the normalized JC-1 ratio from 0.96 +/- 0.01 in control to 0.92 +/- 0.01 and 0.89 +/- 0.01, representing a depolarization of DeltaPsi(m) (n = 9, P < 0.05). Sevoflurane 2 MAC increased [Ca(2+)](i). In Ca(2+)-depleted medium, sevoflurane 1 and 2 MAC depolarized DeltaPsi(m), while [Ca(2+)](i) remained unaltered. Sevoflurane 2 MAC attenuated the 4-AP-induced depolarization of DeltaPsi(m). When mitoK(ATP) was blocked, the sevoflurane-induced depolarization of DeltaPsi(m) was attenuated, but not blocked. The depolarizing effect of sevoflurane on DeltaPsi(m) compared with FCCP was calculated to 13.2 +/- 1.3% in Ca(2+)-containing and 15.1 +/- 1.2% in Ca(2+)-depleted medium (n = 7). CONCLUSIONS: Sevoflurane depolarizes DeltaPsi(m) in rat synaptosomes, and the effect is not dependent on Ca(2+)-influx to the cytosol. Opening of mitoK(ATP) is partly responsible for the depolarizing effect of sevoflurane.

Levels of polychlorinated dibenzo-p-dioxins and dibenzofurans in cattle raised at agricultural research facilities across the USA and the influence of pentachlorophenol-treated wood.

Adipose tissue samples from 158 cattle raised locally at experiment stations across the USA were analysed for polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/F). While 80% of the samples had PCDD/F concentrations that fell within the range of a previous US survey of beef animals (not detected -4.1 ppt toxic equivalency), several animals had exceptionally high concentrations (8-54 ppt toxic equivalency). The investigations of three facilities where highly contaminated animals were raised found pentachlorophenol-treated wood at each site. The congener pattern in the animals' tissues and the lack of elevated PCDD/F levels in other environmental samples, i.e. hay and soil, indicated that the treated wood was the source of contamination. A congener pattern similar to that of pentachlorophenol-exposed animals was seen for the means and medians of the entire data, i.e. OCDD, HpCDD and 1,2,3,6,7,8-HxCDD dominated, the PCDD concentrations equalled or exceeded the furan concentrations, and the concentration of 1,2,3,6,7,8-HxCDD was six times that of the other HxCDD isomers. This suggested that pentachlorophenol-treated wood contributed measurably to many of the animals in this survey. The largest contributors to the median toxic equivalencies were 1,2,3,7,8-PeCDD (40%) and 1,2,3,6,7,8-HxCDD (16%). No clear geographical trends emerged from the data.

Covalent binding of PCB metabolites to lipids: route of formation and characterization.

1. After an oral dose of (14)C-labelled 3,3',4,4'-tetrachlorobiphenyl (CB-77), the conventional germ-free and bile-duct cannulated male Sprague-Dawley rat excreted approximately 80% of the dose in faeces and/or bile within 3 days. 2. For the germ-free and conventional rat, 15% of the dose was excreted via the faeces as metabolites covalently bound to lipids. Bile-duct-cannulated rats excreted similar amounts of lipid-bound metabolites in the bile. The lipid-bound metabolites appear to be formed in the liver and excreted via the bile, and the microflora did not seem essential for the formation of lipid-bound metabolites. 3. The novel CB-77 metabolites had chemical and physical properties similar to those of lipids with regard to solubility and polarity, as determined by partition characteristics on various chromatographic systems. 4. In addition to identification of hydroxylated CB-77 metabolites, several fatty acid esters of hydroxy-chlorobiphenyls were indicated and one hydroxy-tetrachlorobiphenylol palmitoate was identified, but fatty acid esters were minor metabolites. 5. Approximately 70% of the lipid-bound metabolites were present in the fraction that contained phospholipids. The formation of lipid-bound CB-77 metabolites seems a spontaneous reaction rather than an enzymatically catalysed reaction, as indicated by the large number of different lipid-bound metabolites.

Tissue disposition, excretion and metabolism of 2,2',4,4',5-pentabromodiphenyl ether (BDE-99) in the male Sprague-Dawley rat.

1. A disposition, metabolism and excretion study of orally administered 2,2',4,4',5-pentabromodiphenyl ether (BDE-99) was conducted in the conventional and bile duct-cannulated male rat. 2. In the conventional rat, >50% of the radiolabelled dose was retained at 72 h, and lipophilic tissues were the preferred sites for disposition, i.e. adipose tissue, adrenals, gastrointestinal tract and skin. 3. Urinary excretion of BDE-99 was very low (<1% of dose), and glucuronidation of phenolic metabolites was suggested. 4. Biliary excretion of BDE-99 was slightly greater than observed in urine, i.e. 3.6% at 72 h. 5. Over 43% of the dose in the conventional male rat and 86% in the bile duct-cannulated rat was excreted in the faeces, mainly as the unmetabolized parent compound. 6. Metabolites in bile and faeces were not conjugated. Mono- and di-hydroxylated pentabromodiphenyl ether metabolites were characterized by mass spectrometry. Two thiol metabolites were characterized in the bile. Oxidative debromination was also observed in the faecal metabolites. 7. Tissue BDE-99 was readily extractable, except for in the liver. The tissue (14)C was not associated with lipids and was mainly the unmetabolized parent compound. 8. Total thyroxine (T4) plasma levels were elevated at 3 and 6 days, and returned to control levels by day 12.

Binding of brominated diphenyl ethers to male rat carrier proteins.

1. Two [(14)C]-labelled brominated diphenyl ethers, 2,2',4,4',5-pentabromodiphenyl ether (BDE-99) and decabromodiphenyl ether (BDE-209), were separately administered to the male Sprague-Dawley rat as a single oral dose (2.2 mg kg(-1) body weight and 3.0 mg kg(-1), respectively). 2. Very low [(14)C] urine excretion was observed for both congeners (<1% of the dose), and cumulative biliary excretion was approximately 4% for BDE-99 and 9% for BDE-209. 3. More than 6% of the pooled urine from the BDE-99-treated rat was protein-bound to an 18-kDa protein characterized by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and Western immunoblot analysis as alpha(2u)-globulin. Eighteen per cent of the radioactivity from the pooled urine from the BDE-209 treated rat was bound to albumin; no binding to alpha(2u)-globulin was detected. 4. In bile, 27-39% of the radioactivity from the BDE-99-dosed rat was bound to an unidentified 79-kDa protein, whereas essentially all (>87%) of the biliary radioactivity from BDE-209 was bound to the 79-kDa protein. Both parent BDE-99 and-209 and their metabolites were detected by thin layer chromatography in the extracted fraction of this bile protein. 5. By differential centrifugation, the subcellular localization of the (14)C derived from each congener in selected tissues was quantified. The cytosolic [(14)C] from livers of the BDE-209-treated rat was bound to a 14-kDa protein, which was characterized as a fatty acid-binding protein.

Mechanisms of cholinergic dysfunction in rabbits following recurrent aspiration of cow's milk.

Recurrent aspiration of cow's milk has been shown to alter neural control of airways in young rabbits (Gelfand et al., 1997). The purpose of this study was to define the mechanisms responsible for in vitro cholinergic hyperresponsiveness in this model. Beginning at 1 week of age, rabbits received either 0.5 mL/kg whole cow's milk or sterile saline intranasally while under light anesthesia. This was repeated each weekday for 2 weeks. At 8 weeks of age, rabbits were sacrificed. Portions of lungs underwent lavage with sterile saline. Tracheal smooth muscle (TSM) segments were also removed. Segments were assessed for acetylcholine (ACh) release by high-performance liquid chromatography ( HPLC) with electrochemical detection or acetylcholinesterase (AChE) kinetic activity by spectrophotometry. Substance P (SP), a neuropeptide that can increase ACh release from nerves, was also assessed using an enzyme immunoassay to define the content in lavage and TSM segments. Immunohistochemistry for SP within airways was also assessed. We found that recurrent aspiration of milk led to statistically significant alterations in many parameters. Acetylcholine release was significantly greater in segments of airways from rabbits that had aspirated cow's milk (27.5 +/- 1.7 vs. 20.1 +/- 1.6 pmol/min/g tissue) than saline. At the same time, AChE activity was less in the group that aspirated milk (8.7 +/- 0.4 vs. 10.2 +/- 0.5 nmol/min/mg protein) compared to saline. The amount of SP within both lavage as well as tissue homogenates was greater in the group that had aspirated the foreign protein (159.1 +/- 28.9 vs. 41.9 +/- 5.2 pmol/mg protein in lavage; 158.7 +/- 31.9 vs. 80.5 +/- 7.8 pmol/mg protein in tissues) than saline controls. While total cholinergic nerve density as assessed by choline acetyltransferase was not significantly different between groups, SP-positive immunoreactive nerves were easily identified in the group that aspirated cow's milk. This study suggests that cholinergic hyperresponsiveness caused by repeated aspiration of milk is due to several abnormalities, including prejunctional (increase in ACh release) as well as junctional (decrease in AChE) mechanisms within the airways. In addition, an upregulation of SP within airways is part of this process.

Metabolism of [14C]1,2,7,8-tetrachlorodibenzo-p-dioxin in a ruminating Holstein calf.

1. [UL-7,8-ring 14C]-1,2,7,8-tetrachlorodibenzo-p-dioxin (1278-TCDD) was administered orally to a ruminating Holstein bull calf (43.6 kg; 1.2 mg kg(-1) body weight). Urine and faeces were collected daily for 96 h, while blood was sampled at multiple time points. Tissues were removed for combustion analysis. 2. Each tissue contained < 0.65 of the dose at 96h. Tissues with highest levels of 1278-TCDD, as a percentage of administered dose, were the large and small intestine, rumen, liver and carcass. 3. Urinary excretion accounted for 10.6% of the dose, and faecal excretion accounted for 81.6% of the administered dose. The major urinary and faecal metabolites were isolated and characterized by mass spectrometry and 1H-NMR. 4. Plasma levels of 14C peaked at 24h, and decreased to near background at 96 h. Detectable plasmal levels of 1278-TCDD were observed by 2 h. 5. A hydroxylated metabolite of 1278-TCDD was detected in calf plasma, which has the potential to interfere with thyroid hormone homeostasis.

Baseline factors predicting early resumption of driving after life-threatening arrhythmias in the Antiarrhythmics Versus Implantable Defibrillators (AVID) Trial.

BACKGROUND: In the Antiarrhythmics Versus Implantable Defibrillators (AVID) Trial, patients with ventricular fibrillation or hemodynamically unstable ventricular tachycardia were randomly assigned to receive either an implantable cardioverter-defibrillator (ICD) or antiarrhythmic drug therapy. As part of the trial, patients were asked to participate in a prospective driving survey. The purpose of the survey was to determine what baseline factors and patient characteristics specifically predicted resumption of driving earlier than advised by current guidelines. METHODS: Patients were surveyed anonymously as to their driving habits in the initial period after random assignment and every 6 months thereafter. AVID study coordinators were independently asked to assess their patients' driving status as well. The relation between baseline factors and time to resumption of driving was explored by means of Kaplan-Meier estimates for univariate analyses and the stepwise Cox proportional hazards regression model for multivariate analyses. RESULTS: There were 802 patients who were eligible for assessment of driving status. The majority of patients (58%) resumed driving an automobile within 6 months of their index arrhythmia regardless of whether they received drug therapy or an ICD. By multivariate analysis, patients who were younger than 65 years of age, male, and college educated were more likely to drive early, as were patients whose index arrhythmia was ventricular tachycardia. CONCLUSIONS: Younger, college-educated men and those whose index arrhythmia is ventricular tachycardia are most likely to resume driving <6 months after the initiation of therapy for a potentially life-threatening ventricular arrhythmia. Patients with an ICD did not appear to resume driving later than those who were discharged on antiarrhythmic drugs alone.

Tissue distribution, excretion, and metabolism of 1,2,7,8-tetrachlorodibenzo-p-dioxin in the rat.

A tissue distribution, excretion, and metabolism study was conducted using a relatively non-toxic dioxin congener, i.e., 1,2,7,8-tetrachlorodibenzo-p-dioxin (1278-TCDD), to gain a better understanding of mammalian metabolism of dioxins. Conventional, bile duct cannulated, and germ free male rats were administered mg/kg quantities as a single oral dose. Elimination of 1278-TCDD was largely complete by 72 h. Distribution of [14C]1278-TCDD was low in all tissues examined. Metabolites were identified in urine, bile, and feces by negative ion FAB-MS and 1H-NMR, or GC/MS. The major fecal metabolite was a NIH-shifted hydroxylated TCDD. The bile contained a glucuronide conjugate of this hydroxy TCDD, and a diglucuronide conjugate of a dihydroxy-triCDD. The major metabolites in urine were glucuronide and sulfate conjugates of 4,5-dichlorocatechol.