Does exposure to thyroxine-mimics cause feline thyroid hyperplasia?

Over the past four decades, the incidence of feline thyroid hyperplasia (FTH) has steadily increased. Concomitantly, cats' exposure to thyroxine (T4)-mimicking environmental contaminants and food additives has also increased. KATE HILL: and IAN SHAW: hypothesise that the two could be linked.

The toxic chemistry of methyl bromide.

Methyl bromide (MeBr) is a chemically reactive compound that has found use as a fire retardant and fumigant used for wood, soil, fruits and grains. Its use is banned in many countries because of its ozone-depleting properties. Despite this ban, the use of MeBr persists in some parts of the world (e.g. New Zealand) due to its important role in maintaining strict biosecurity of exported and imported products. Its high chemical reactivity leads to a broad toxicological profile ranging from acute respiratory toxicity following inhalation exposure, through carcinogenicity to neurotoxicty. In this article, we discuss the chemistry of MeBr in the context of its mechanisms of toxicity. The chemical reactivity of MeBr clearly underlies its toxicity. Bromine (Br) is electronegative and a good leaving group; the δ+ carbon thus facilitates electrophilic methylation of biological molecules including glutathione (GSH) via its δ- sulphur atom, leading to downstream effects due to GSH depletion. DNA alkylation, either directly by MeBr or indirectly due to reduction in GSH-mediated detoxification of reactive alkylating chemical species, might explain the carcinogenicity of MeBr. The neurotoxicity of MeBr is much more difficult to understand, but we speculate that methyl phosphates formed in cells might contribute to its neurone-specific toxicity via cholinesterase inhibition. Finally, evidence reviewed shows that it is unlikely for Br⁻ liberated by the metabolism of MeBr to have any toxicological effect because the Br⁻ dose is very low.

Can thyroid hormone mimics affect thyroid hormone measurement by immunoassay?

OBJECTIVES: This study aims to determine whether the environmental pollutant and thyroid mimic, tetrabromobisphenol A (TBBPA), interferes with thyroid hormone measurement by immunoassays. DESIGN & METHODS: Hormone-relevant concentrations of TBBPA were added to thyroid hormone-stripped human serum and subjected to 6 different thyroid hormone immunoassays. RESULTS: TBBPA was negative in all of the thyroid hormone immunoassays tested except at very high concentration (above that expected in serum of TBBPA-exposed workers) where it gave a marginally positive result in one immunoassay (in house T4 radioimmunoassay (RIA)). CONCLUSIONS: Serum TBBPA present as a result of workplace exposure or its use as a fabric flame retardant is very unlikely to give false positive results in thyroid hormone immunoassays.

Does the oestrogen receptor encourage oestrogenicity in environmental pollutants? The case of 4-nonylphenol.

A computer-aided docking study was conducted to explore in detail the binding interactions between the structurally unlikely environmental oestrogen 4-nonylphenol (4NP) and three of its metabolites with the human oestrogen receptor alpha (hERα). Docking was done within the Schrodinger Suite 2008 using both a conventional rigid receptor with flexible ligand and the induced-fit docking protocol. Induced-fit docking allows side-chain and backbone movement in the receptor to accommodate the ligand. This study has revealed unconventional interactions between the ligands and the hERα binding pocket that could explain the observed oestrogen-like behaviour of 4NP and suggests some of the metabolites of 4NP may also be oestrogenic.

Stability of the insecticide cypermethrin during tomato processing and implications for endocrine activity.

The thermal and pH stabilities of cypermethrin during food processing were investigated using tomato as a model food system and high-performance liquid chromatography as the analytical method. Cypermethrin was thermally unstable in aqueous conditions, where the hydrolysis of the pesticide was accelerated by heat. The mean proportion remaining after heating cypermethrin in water for 10 min was 66%, falling to 27% after 1 h. Similarly, thermal processing of canned tomatoes caused cypermethrin to degrade, with remaining levels in the final product ranging from 30 to 60% of the original. Cypermethrin was unstable at extreme pHs, with acid hydrolysis occurring faster than alkaline hydrolysis in phosphate buffers. The acidity of tomato paste (pH 4.3) caused cypermethrin levels to decrease by 30% within 12 days at 5 degrees C. The studies indicate that cypermethrin residues are likely to degrade by hydrolysis during food processing, thus reducing the exposure of consumers to cypermethrin. 3-Phenoxybenzaldehyde, a hydrolysis breakdown product of cypermethrin, was detected in the tomato paste and from the heating of cypermethrin in water at 100 degrees C. There is concern that the risk of breakdown products in terms of endocrine activity is unknown since in vitro studies reported that cypermethrin breakdown products display endocrine activity.

The effect of Saccharomyces cerevisiae on the stability of the herbicide glyphosate during bread leavening.

AIMS: To investigate the ability of baker's yeast (Saccharomyces cerevisiae) to degrade the herbicide glyphosate during the fermentation cycle of the breadmaking process. METHODS AND RESULTS: Aqueous glyphosate was added to bread ingredients and kneaded by commercially available breadmaking equipment into dough cultures. Cultures were incubated in the breadmaker throughout the fermentation cycle. The recovery of glyphosate levels following fermentation was determined, thus allowing an estimation of glyphosate degradation by yeast. CONCLUSIONS: It was shown, for the first time, that S. cerevisiae plays a role in metabolizing glyphosate during the fermentation stages of breadmaking. Approximately 21% was degraded within 1 h. SIGNIFICANCE AND IMPACT OF THE STUDY: As a result of projected increases in the glyphosate use on wheat and the role of bread as a dietary staple, this may contribute to more informed decisions being made relating to the use of glyphosate on glyphosate-resistant wheat, from a public health/regulatory perspective.

The effect of propofol on airway pressures generated by magnetic stimulation of the phrenic nerves.

OBJECTIVES: To assess the effect of propofol on the change in airway pressure produced by diaphragmatic contraction. DESIGN AND SETTING: Prospective, controlled study in patients anaesthetised with propofol in a university hospital. PATIENTS AND METHODS: We stimulated the phrenic nerves before and immediately after induction of anaesthesia in 11 subjects, using a pair of 43-mm mean diameter double magnetic coils and measured the change in airway pressure at the mouth (TwPmo) produced by the resulting diaphragmatic contraction. Supramaximality of stimulation was confirmed with electromyogram and pressure measurements. We recorded the change in Resting End Expiratory Position (REEP) using a spirometer. We applied an approximate correction for the effect of lung volume on the amplitude of twitch pressure produced by diaphragmatic contraction. INTERVENTION: Following the initial stimulations, the patients were anaesthetised with a propofol infusion. Once stable, repeat measurements were made. MEASUREMENTS AND RESULTS: Following induction, REEP fell by mean 0.3 l standard deviation (SD) 0.2 l. TwPmo fell by mean 14.2% SD 14.0% ( P = 0.01), mean 22.3% SD 11.7% corrected ( P < 0.001). Twitch transdiaphragmatic pressure fell by 18.1% and 20.0% (25.8% and 27.7% corrected) in two further subjects studied with oesophageal and gastric balloon catheters. CONCLUSION: Propofol does reduce the effectiveness with which diaphragmatic contraction produces changes of pressure in the airway.

The influence of intraperitoneal bupivacaine on pain following major laparoscopic gynaecological procedures.

We present the results of a randomised, double-blind controlled trial to determine the effect of adding bupivacaine to intraperitoneal Hartmann's solution, used to reduce the incidence of postoperative adhesions, on postoperative pain and on analgesic consumption in patients presenting for major laparoscopic gynaecological procedures. Fifty-six women were studied and postoperative analgesic requirements and visual analogue scores were used to assess the pain experienced by the treatment group when compared with the control group. There was no statistical difference in the pain scores between the two groups at any time during the study period (Student's t-test; p = 0.29-0.74) nor was there any difference in analgesic consumption (Mann-Whitney U-test; p = 0.34-0.79).

A case of extensive block with the combined spinal-epidural technique during labour.

The increasing use of combined spinal-epidural analgesia in obstetric practice has arisen from a desire to achieve a rapid onset of analgesia while reducing the intensity of the motor block. Although the procedure has an excellent safety profile, as with any technique there are potential problems. Difficulty in assessing the position of the epidural catheter after establishment of the spinal blockade may lead to an abnormally extensive block when a full-strength local anaesthetic solution is used. We present a case in which the use of 0.5% bupivacaine to top-up the epidural component of a combined spinal-epidural resulted in a total spinal block. The possible causes of this complication are discussed.

Thermal stability of organophosphorus pesticide triazophos and its relevance in the assessment of risk to the consumer of triazophos residues in food.

The degradation of triazophos in aqueous solutions was monitored at 205 and 254 nm after separation using high-performance liquid chromatography. An ODS column was used with a mobile phase of 60% acetonitrile and 0.04% phosphoric acid at a flow rate of 1.4 cm(3) min(-)(1). When dissolved in distilled water, approximately 30% of the original triazophos was detected. The effect of heating time and temperature on a 0.5 mg dm(-3) standard was investigated. Over a 150 min period at 100 degrees C the peak area detected for the standard decreased by 58.67 +/- 6.19 and 65.03 +/- 4.61% when measured at 254 and 205 nm, respectively. The precision of the absorbance detected at 205 and 254 nm was 3.54 +/- 2.8 and 3.86 +/- 3.9%, respectively. There was a significant difference (P = 0.10) between the precision of the results obtained at each wavelength. The t(calcd) value was -2.236 and the t(crit) value was 1.94. The most sensitive wavelength was 205 nm. A 54% difference in the gradients of the calibration graphs obtained at each wavelength was observed. The results suggest that approximately 72% of triazophos is degraded during a 20 min cooking period at 100 degrees C, due to ambient and elevated temperature hydrolysis. Therefore, the dose to the consumer of triazophos residues in cooked food is likely to be approximately 72% lower than in the raw food, with a concomitant reduction in toxicological risk.

Complete airway obstruction during awake fibreoptic intubation.

Awake fibreoptic intubation is well established as the optimum method of securing the airway in patients in whom difficulty is anticipated. We report a patient undergoing awake fibreoptic intubation in whom the use of topical local anaesthetic precipitated acute loss of the airway so that urgent surgical intervention was required.

Identification of brain metabolites by magnetic resonance spectroscopy in MND/ALS.

Magnetic resonance spectroscopy (MRS) has provided a novel means of studying the brain biochemistry of motor neurone disease/amyotrophic lateral sclerosis (MND/ALS) patients in vivo in situ. Previous studies have demonstrated changes in the ratios of areas under specific spectral peaks in MND/ALS patients (Jones et al., 1995). However, the significance of such findings cannot be fully elucidated without first ascertaining the biochemical identity of each peak. Each peak in a MRS spectrum corresponds to the resonance of specific protons in a particular chemical environment. Many biochemicals contain similar protons in similar environments so it is possible that a single spectral peak could represent protons from more than one biochemical. In this study of major brain MRS peaks we have demonstrated that peaks are potentially composed of a number of protons from different chemicals. For example, the peak at chemical shift 2.01 ppm, conventionally recognised as the neurotransmitter N-acetyl aspartate, may actually be a result of the protons of the N-acetyl moiety (Frahm et al., 1991). We have consequently shown that other N-acetylated compounds such as N-acetyl glutamate are also capable of producing a peak here, whereas their non-acetylated derivatives are not. We have also shown GABA is capable of producing a peak at chemical shift 3.00 ppm, a peak which is generally assigned to creatine/phosphocreatine. These findings have important implications in the identification of spectral peaks in MRS studies and in the interpretation of spectral differences between MND patients and controls.

Studies on cellular free radical protection mechanisms in the anterior horn from patients with amyotrophic lateral sclerosis.

There have been no reports of changes in free radical inactivating enzymes in the anterior horn of the spinal cord in ALS despite great interest in the possibility that free radicals might be important in the aetiology of the disease. In this study we have measured copper/zinc superoxide dismutase (Cu/ZnSOD), manganese superoxide dismutase (MnSOD) and glutathione peroxidase (GSHPX) activities in anterior horn tissue obtained from patients with ALS and from controls. Total SOD activity was no different in the anterior horn of ALS cases compared to controls, but Cu/ZnSOD activity was reduced, and that of MnSOD increased, at thoracic cord level only. No detectable activity of GSHPX or cytochrome P450 (unpublished data) was found. These latter negative findings are important because they suggest that generation of free radicals from exogenous chemicals is not important in ALS and further that the neurone (as compared to other cell types) is poorly protected against the toxicity of hydrogen peroxide.

Preliminary results of proton magnetic resonance spectroscopy in motor neurone disease (amytrophic lateral sclerosis).

Possible changes in brain metabolites in motor neurone disease/amytrophic lateral sclerosis (MND/ALS) were investigated using 1H magnetic resonance spectroscopy (MRS). A series of normal, healthy volunteer controls and MND patients have been studied using a spin echo (SE) 135 ms sequence, acquiring spectra from the region of the motor cortex. A further limited series of studies have been made for similar groups of volunteers and MND patients using a STEAM 20 ms sequence (stimulated echo). Analysis of the SE 135 ms spectra indicates there are statistically significant differences in the ratios of N-acetyl-aspartate to creatine and N-acetyl-aspartate to choline between controls and MND patients. Furthermore, metabolites identified using the STEAM 20 ms may be of great importance in the investigations of free radical mediated mechanisms, which have been postulated as being important contributors to the disease process. Preliminary results indicate that 1H MRS may provide important data to help understand the disease processes in MND and it could form a useful method for monitoring the effects of future trial treatment regimens.