Uva-ursi extract and ibuprofen as alternative treatments for uncomplicated urinary tract infection in women (ATAFUTI): a factorial randomized trial.

OBJECTIVES: The aim was to investigate if offering symptomatic therapy (Uva-ursi or ibuprofen) alongside a delayed prescription would relieve symptoms and reduce the consumption of antibiotics for adult women presenting with acute uncomplicated urinary tract infection (UTI). METHODS: A 2 × 2 factorial placebo controlled randomized trial in primary care. The participants were 382 women aged 18-70 years with symptoms of dysuria, urgency, or frequency of urination and suspected by a clinician to have a lower UTI. The interventions were Uva-ursi extract and/or ibuprofen advice. All women were provided with a delayed or 'back-up' prescription for antibiotics. Missing data were imputed using multiple imputation methods (ISRCTN registry: ISRCTN43397016). RESULTS: An ITT analysis of mean score for frequency symptoms assessed on Days 2-4 found no evidence of a difference between Uva-ursi vs. placebo -0.06 (95% CI -0.33 to 0.21; p 0.661), nor ibuprofen vs. no ibuprofen advice -0.01 (95% CI -0.27 to 0.26; p 0.951). There was no evidence of a reduction in antibiotic consumption with Uva-ursi (39.9% vs. placebo 47.4%; logistic regression odds ratio (OR) 0.59 (95% CI 0.22-1.58; p 0.293) but there was a significant reduction for ibuprofen advice (34.9% vs. no advice 51.0%; OR 0.27 (95% CI 0.10 to 0.72; p 0.009). There were no safety concerns and no episodes of upper tract infection were recorded. CONCLUSIONS: We found no evidence of an effect of either intervention on the severity of frequency symptoms. There is evidence that advice to take ibuprofen will reduce antibiotic consumption without increasing complications. For every seven women given this advice, one less will use antibiotics.

Professional kinesiology practice for chronic low back pain: single-blind, randomised controlled pilot study.

BACKGROUND: Chronic low back pain is a highly prevalent condition with no definitive treatment. Professional Kinesiology Practice (PKP) is a little known complementary medicine technique using non-standard muscle testing; no previous effectiveness studies have been performed. METHODS: This is an exploratory, pragmatic single-blind, 3-arm randomised sham-controlled pilot study with waiting list control (WLC) in private practice UK (2007-2009). 70 participants scoring ≥4 on the Roland and Morris Disability Questionnaire (RMDQ) were randomised to real or sham PKP receiving 1 treatment weekly for 5 weeks or a WLC. WLC's were re-randomised to real or sham after 6 weeks. The main outcome was a change in RMDQ from baseline to end of 5 weeks of real or sham PKP. RESULTS: With an effect size of 0.7 real treatment was significantly different to sham (mean difference RMDQ score = -2.9, p = 0.04, 95% CI -5.8 to -0.1). Compared to WLC, real and sham groups had significant RMDQ improvements (real -9.0, p < 0.01, 95% CI -12.1 to -5.8; effect size 2.1; sham -6.1, p < 0.01, 95% CI -9.1 to -3.1; effect size 1.4). Practitioner empathy (CARE) and patient enablement (PEI) did not predict outcome; holistic health beliefs (CAMBI) did, though. The sham treatment appeared credible; patients did not guess treatment allocation. 3 patients reported minor adverse reactions. CONCLUSIONS: Real treatment was significantly different from sham demonstrating a moderate specific effect of PKP; both were better than WLC indicating a substantial non-specific and contextual treatment effect. A larger definitive study would be appropriate with nested qualitative work to help understand the mechanisms involved in PKP.

Antibiotic prescribing for adults with acute cough/lower respiratory tract infection: congruence with guidelines.

European guidelines for treating acute cough/lower respiratory tract infection (LRTI) aim to reduce nonevidence-based variation in prescribing, and better target and increase the use of first-line antibiotics. However, their application in primary care is unknown. We explored congruence of both antibiotic prescribing and antibiotic choice with European Respiratory Society (ERS)/European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines for managing LRTI. The present study was an analysis of prospective observational data from patients presenting to primary care with acute cough/LRTI. Clinicians recorded symptoms on presentation, and their examination and management. Patients were followed up with self-complete diaries. 1,776 (52.7%) patients were prescribed antibiotics. Given patients' clinical presentation, clinicians could have justified an antibiotic prescription for 1,915 (71.2%) patients according to the ERS/ESCMID guidelines. 761 (42.8%) of those who were prescribed antibiotics received a first-choice antibiotic (i.e. tetracycline or amoxicillin). Ciprofloxacin was prescribed for 37 (2.1%) and cephalosporins for 117 (6.6%). A lack of specificity in definitions in the ERS/ESCMID guidelines could have enabled clinicians to justify a higher rate of antibiotic prescription. More studies are needed to produce specific clinical definitions and indications for treatment. First-choice antibiotics were prescribed to the minority of patients who received an antibiotic prescription.

The safety and effectiveness of different methods of earwax removal: a systematic review and economic evaluation.

BACKGROUND: Build-up of earwax is a common reason for attendance in primary care. Current practice for earwax removal generally involves the use of a softening agent, followed by irrigation of the ear if required. However, the safety and benefits of the different methods of removal are not known for certain. OBJECTIVES: To conduct evidence synthesis of the clinical effectiveness and cost-effectiveness of the interventions currently available for softening and/or removing earwax and any adverse events (AEs) associated with the interventions. DATA SOURCES: Eleven electronic resources were searched from inception to November 2008, including: The Cochrane Library; MEDLINE (OVID), PREMEDLINE In-Process & Other Non-Indexed Citations (OVID), EMBASE (OVID); and CINAHL. METHODS: Two reviewers screened titles and abstracts for eligibility. Inclusion criteria were applied to the full text or retrieved papers and data were extracted by two reviewers using data extraction forms developed a priori. Any differences were resolved by discussion or by a third reviewer. Study criteria included: interventions - all methods of earwax removal available and combinations of these methods; participants - adults/children presenting requiring earwax removal; outcomes - measures of hearing, adequacy of clearance of wax, quality of life, time to recurrence or further treatment, AEs and measures of cost-effectiveness; design - randomised controlled trials (RCTs) and controlled clinical trials (CCTs) for clinical effectiveness, cohort studies for AEs and cost-effectiveness, and costing studies for cost-effectiveness. For the economic evaluation, a deterministic decision tree model was developed to evaluate three options: (1) the use of softeners followed by irrigation in primary care; (2) softeners followed by self-irrigation; and (3) a 'no treatment' option. Outcomes were assessed in terms of benefits to patients and costs incurred, with costs presented by exploratory cost-utility analysis. RESULTS: Twenty-six clinical trials conducted in primary care (14 studies), secondary care (8 studies) or other care settings (4 studies), met the inclusion criteria for the review - 22 RCTs and 4 CCTs. The range of interventions included 16 different softeners, with or without irrigation, and in various different comparisons. Participants, outcomes, timing of intervention, follow-up and methodological quality varied between studies. On measures of wax clearance Cerumol, sodium bicarbonate, olive oil and water are all more effective than no treatment; triethanolamine polypeptide (TP) is better than olive oil; wet irrigation is better than dry irrigation; sodium bicarbonate drops followed by irrigation by nurse is more effective than sodium bicarbonate drops followed by self-irrigation; softening with TP and self-irrigation is more effective than self-irrigation only; and endoscopic de-waxing is better than microscopic de-waxing. AEs appeared to be minor and of limited extent. Resuts of the exploratory economic model found that softeners followed by self-irrigation were more likely to be cost-effective [24,433 pounds per quality-adjusted life-year (QALY)] than softeners followed by irrigation at primary care (32,130 pounds per QALY) when compared with no treatment. Comparison of the two active treatments showed that the additional gain associated with softeners followed by irrigation at primary care over softeners followed by self-irrigation was at a cost of 340,000 pounds per QALY. When compared over a lifetime horizon to the 'no treatment' option, the ICERs for softeners followed by self-irrigation and of softeners followed by irrigation at primary care were 24,450 pounds per QALY and 32,136 pounds per QALY, respectively. LIMITATIONS: The systematic review found limited good-quality evidence of the safety, benefits and costs of the different strategies, making it difficult to differentiate between the various methods for removing earwax and rendering the economic evaluation as speculative. CONCLUSIONS: Although softeners are effective, which specific softeners are most effective remains uncertain. Evidence on the effectiveness of methods of irrigation or mechanical removal was equivocal. Further research is required to improve the evidence base, such as a RCT incorporating an economic evaluation to assess the different ways of providing the service, the effectiveness of the different methods of removal and the acceptability of the different approaches to patients and practitioners.

Clinical relevance of laboratory-reported antibiotic resistance in acute uncomplicated urinary tract infection in primary care.

OBJECTIVES: To determine whether patients with an uncomplicated community-acquired urinary tract infection (UTI) and an isolate resistant to trimethoprim had worse clinical outcomes following empirical treatment with trimethoprim 200 mg twice daily for 3 days than did those with a susceptible isolate. PATIENTS AND METHODS: This was a prospective cohort study of clinical outcome. We enrolled 497 women (>or=18-70 years) presenting to general practitioner surgeries in Norwich and Gloucester with at least two symptoms of acute (<7 days) uncomplicated UTI. Significant bacteriuria was defined as >or=10(4) cfu/mL from a mid-stream urine (MSU). RESULTS: Of enrolled patients 75% (334/448) had significant bacteriuria, and trimethoprim resistance was present in 13.9% (44/317) of isolates. Patients with resistant isolates had a longer median time to symptom resolution (7 versus 4 days, P=0.0002), greater reconsultation to the practice (39% versus 6% in first week, P<0.0001), more subsequent antibiotics (36% versus 4% in first week, P<0.0001) and higher rates of significant bacteriuria at 1 month (42% versus 20% with susceptible isolate, P=0.04). Half of patients reconsulting in the first week had a resistant organism. CONCLUSIONS: Patients with uncomplicated UTI caused by trimethoprim-resistant organisms had significantly worse clinical outcomes than those with trimethoprim-susceptible organisms. Nevertheless, trimethoprim resistance was rarer than predicted from routine laboratory submissions and we calculate that 23 women require microbiological investigation to prevent one reconsultation arising from resistance-based treatment failure. We therefore suggest empirical antibiotic treatment in acute, uncomplicated UTIs. If patients reconsult in the first week, we suggest a change of antibiotic treatment with urine culture and susceptibility testing then done. More generally, laboratory resources should concentrate on resistance surveillance to inform empirical antibiotic choice.

Preclinical studies of opioids and opioid antagonists on gastrointestinal function.

Opioid receptors in the gastrointestinal (GI) tract mediate the effects of endogenous opioid peptides and exogenously administered opioid analgesics, on a variety of physiological functions associated with motility, secretion and visceral pain. The studies reviewed or reported here describe a range of in vivo activities of opioid receptor antagonists upon GI function in rodents, focusing on mu receptors. Naloxone, and the peripherally acting mu-opioid receptor antagonists alvimopan and methylnaltrexone, reverse morphine-induced inhibition of GI transit in mice and rats, and morphine- or loperamide-induced inhibition of castor oil-induced diarrhoea in mice. At doses producing maximal reversal of morphine-induced effects upon GI transit, only the central nervous system (CNS) penetrant antagonist naloxone was able to reverse morphine-induced analgesia. Both central and peripheral opioid antagonists may affect GI function and/or visceromotor sensitivity in the absence of exogenous opioid analgesics, suggesting a constitutive role for endogenous opioid peptides in the control of GI physiology. Furthermore, in contrast to naloxone, alvimopan does not produce hypersensitivity to the visceromotor response induced by nociceptive levels of colorectal distension in a rodent model of post-inflammatory colonic hypersensitivity, suggesting that in the periphery endogenous mu-opioid receptor-mediated mechanisms do not regulate colonic sensitivity. The data support the hypothesis that peripherally acting opioid antagonists may be able to selectively block opioid receptors in the GI tract, thereby preserving normal GI physiology, while not blocking the effects of endogenous opioid peptides or exogenous opioid analgesics in the CNS. These findings suggest that the primary sites of action of mu-opioid agonists with respect to inhibition of GI function are in the periphery, whereas analgesic activity resides primarily in the CNS.

Cytochrome complex essential for photosynthetic oxidation of both thiosulfate and sulfide in Rhodovulum sulfidophilum.

Many photosynthetic bacteria use inorganic sulfur compounds as electron donors for carbon dioxide fixation. A thiosulfate-induced cytochrome c has been purified from the photosynthetic alpha-proteobacterium Rhodovulum sulfidophilum. This cytochrome c(551) is a heterodimer of a diheme 30-kDa SoxA subunit and a monoheme 15-kDa SoxX subunit. The cytochrome c(551) structural genes are part of an 11-gene sox locus. Sequence analysis suggests that the ligands to the heme iron in SoxX are a methionine and a histidine, while both SoxA hemes are predicted to have unusual cysteine-plus-histidine coordination. A soxA mutant strain is unable to grow photoautotrophically on or oxidize either thiosulfate or sulfide. Cytochrome c(551) is thus essential for the metabolism of both these sulfur species. Periplasmic extracts of wild-type R. sulfidophilum exhibit thiosulfate:cytochrome c oxidoreductase activity. However, such activity can only be measured for a soxA mutant strain if the periplasmic extract is supplemented with purified cytochrome c(551). Gene clusters similar to the R. sulfidophilum sox locus can be found in the genome of a green sulfur bacterium and in phylogenetically diverse nonphotosynthetic autotrophs.

Interaction between physical activity and diet: implications for blood pressure management in primary care.

OBJECTIVES: This review summarises the evidence for the effectiveness of primary care based interventions of diet and physical activity aimed at reducing blood pressure. BACKGROUND: As blood pressure rises so does the risk of heart disease and stroke. There is a large literature on the effects on blood pressure of changing various aspects of diet either as single nutrient interventions, patterns of food consumption, or the addition of dietary supplements (potassium, magnesium, and fish oil). Controlled trials have been undertaken to assess the relative benefits of lifestyle changes in activity (walking etc) compared with more structured exercise programmes. There is sufficient evidence to suggest that changes in diet and activity under controlled conditions can reduce blood pressure and delay or reduce the need for drug treatment in subjects who are hypertensive. What is less clear is how to achieve these lifestyle changes in the primary care setting as part of routine clinical management. RESULTS: There have been a number of systematic reviews undertaken to evaluate the evidence. The interventions were either delivered alone or in combination with other advice, either with or without aids, and by various practice nurse staff (GP, nurse, dietitian); follow-up varied from 3 months to a year. Compliance with the advice was generally not measured. The variability in the quality of the studies and interventions made it difficult to draw conclusions: any effects seen tended to be small. CONCLUSIONS: Equivocal results (non statistically significant reductions) should not be considered as proof of no effect without careful consideration of the effects of chance, bias and confounding, and without better measures of compliance. There is little debate that, under investigator control, blood pressure can be reduced by changes in diet and activity. Changes to a 'healthy' diet (low in total and saturated fat; energy intake balanced with expenditure to maintain or achieve optimal body weight; low in salt: high in fruits, vegetables, legumes; and whole grains) and increases in modest levels of physical activity (walking etc) would be expected to reduce blood pressure by between two and four mmHg. A shift in the population distribution of this order would be expected to have a substantial impact on population mortality patterns and could be achieved cost-effectively in primary care.

Characterization of a KRAB family zinc finger gene, ZNF195, mapping to chromosome band 11p15.5.

We report the cDNA sequence of the zinc finger gene, ZNF195, which maps to chromosome 11p15.5. ZNF195 contains an N-terminal KRAB domain and 14 tandemly repeated Krüppel type zinc finger motifs at its C-terminus. Northern analysis shows expression of ZNF195 in adult heart, brain, placenta, skeletal muscle, and pancreas with a predominant transcript size of 4.3 kb. There is little expression in adult lung, liver, and kidney. In fetal lung, liver, kidney, and brain, the predominant transcript is 3.5 kb. Fetal brain also expresses a 4.3-kb transcript. RT-PCR analysis shows that two exons, 4a, which contains an inverted Alu sequence, and 4b, are differentially spliced and absent from the major transcript.

Genomic organization and chromosomal localization of a member of the MAP kinase phosphatase gene family to human chromosome 11p15.5 and a pseudogene to 10q11.2.

Mitogen-activated protein kinase phosphatases (MKPs) play a central role in a variety of signaling pathways. We recently described a novel murine MKP, M3/6, which is uniquely specific for c-Jun N-terminal kinase/stress-activated protein kinase and p38 kinase. Here we report the localization of the human orthologue of this gene, HB5, to within 150 kb of H19 on human chromosome 11p15.5. The gene consists of six exons. Two of the introns in HB5 are not found in other genes of this family, suggesting an evolutionary split between MKPs displaying specificity toward different MAP kinases. An intronless pseudogene is present on chromosome 10q11.2. Although 11p15.5 is an imprinted region, HB5 is almost entirely unmethylated on both alleles in lymphocytes. Chromosome 11p15 has been implicated in the development of a number of tumor types, including lung, a tissue known to express this gene. Loss of heterozygosity was found in one of eight informative lung tumors studied.

Underexpression of the 43 kDa inositol polyphosphate 5-phosphatase is associated with cellular transformation.

The 43 kDa inositol polyphosphate 5-phosphatase (5-phosphatase) hydrolyses the second messenger molecules inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] and inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P4]. We have underexpressed the 43 kDa 5-phosphatase by stably transfecting normal rat kidney cells with the cDNA encoding the enzyme, cloned in the antisense orientation into the tetracycline-inducible expression vector pUHD10-3. Antisense-transfected cells demonstrated a 45% reduction in Ins(1,4,5)P3 5-phosphatase activity in the total cell homogenate upon withdrawal of tetracycline, and an approximately 80% reduction in the detergent-soluble membrane fraction of the cell, as compared with antisense-transfected cells in the presence of tetracycline. Unstimulated antisense-transfected cells showed a concomitant 2-fold increase in Ins(1,4,5)P3 and 4-fold increase in Ins(1,3,4,5)P4 levels. The basal intracellular calcium concentration of antisense-transfected cells (170 +/- 25 nM) was increased 1.9-fold, compared with cells transfected with vector alone (90 +/- 25 nM). Cells underexpressing the 43 kDa 5-phosphatase demonstrated a transformed phenotype. Antisense-transfected cells grew at a 1.7-fold faster rate, reached confluence at higher density and demonstrated increased [3H]thymidine incorporation compared with cells transfected with vector alone. Furthermore, antisense-transfected cells formed colonies in soft agar and tumours in nude mice. These studies support the contention that a decrease in Ins(1,4,5)P3 5-phosphatase activity is associated with cellular transformation.

Transforming growth factor-beta 1 regulates the expression of ryanodine-sensitive Ca2+ oscillations in cardiac myocytes.

Factors which regulate sarcoplasmic reticulum (SR) gene expression are largely unknown. We investigated whether Transforming Growth Factor-beta 1 (TGF-beta 1) plays a role in the maintenance of Ca2+ handling mechanisms in isolated neonatal rat cardiomyocytes. Myocytes cultured in the presence of serum were found to beat continuously and undergo spontaneous Ca2+ oscillations whereas in the absence of serum the cells lost the ability to undergo cyclical Ca2+ oscillations. The oscillations were restored when serum-free medium was supplemented with TGF-beta 1. Both caffeine-induced Ca2+ elevations and the inhibitory effect of ryanodine on spontaneous activity were also dependent on the continued presence of TGF-beta 1; in its absence these indices of SR function were severely compromised. TGF-beta 1 therefore appears to play a critical role in the maintenance of Ca2+ oscillations in the heart by regulating the expression of the ryanodine-sensitive Ca2+ release mechanism.

Isolation of pathogenic strains of Haemophilus somnus from the female bovine reproductive tract.

The prevalence of Haemophilus somnus in the genital tract of slaughtered and live cows in southern Ontario was investigated. The vagina and uterus of slaughtered cows were swabbed separately. Live cows were examined and sampled in two field surveys: Centre A and Centre B. In the former, aspirated mucus secretions and in the latter, specimens obtained by guarded swabbing were examined bacteriologically. Haemophilus somnus was isolated from 28 genital tracts of 461 slaughtered (6.1%), and seven of 199 live (3.5%) cows during the centre B survey. The isolates were recovered from both normal and diseased reproductive tracts. Fourteen strains isolated from genital organs were examined for pathogenicity in vivo to test the occurrence of pathogenic isolates. In the initial stage of the in vivo study on pathogenicity, each of the fourteen isolates was examined on one calf using an intracisternal inoculation. Subsequently, one pathogenic and one nonpathogenic strain were inoculated into five calves each to statistically confirm their pathogenic potential. Of 14 genital isolates of H. somnus examined in an intracisternal calf assay, six (43%) caused a fatal peracute neurological disease, while eight were nonpathogenic. A comparative pathological study of pathogenic and nonpathogenic isolates showed that the former caused a severe fatal suppurative meningoencephalitis whereas the latter caused no lesions whatsoever or a mild leukocytic leptomeningitis. The salient data obtained in this study indicate that there are pathogenic strains of H. somnus in the genital tract of apparently normal cows as well as of those with inflammatory disease.

Distribution of [3H]diisopropylfluorophosphate, [3H]soman, [3H]sarin, and their metabolites in mouse brain.

The brain area distribution of [3H]diisopropylfluorophosphate, [3H]soman, and [3H]sarin and their metabolites in mice was studied after iv administration of sublethal doses. At the appropriate time after the injection of the radiolabeled organophosphate, the mice were decapitated and their brains were dissected into seven areas. There was a relatively even distribution of the parent compounds and their metabolites in all brain areas except the hypothalamus, which contained concentrations of parent compounds the metabolites that were 2-5 times greater than those in other brain areas. Concentrations of the parent compounds and free metabolites declined steadily throughout the time course, whereas concentrations of the bound metabolites remained relatively constant between 6 and 24 hr. There was no correlation between the disposition of soman, and its metabolites, and cholinesterase inhibition in brain areas, which implicates other central mechanisms in the production of organophosphate effects. However, the higher concentrations of organophosphates and their metabolites in the hypothalamus suggest that this area might be important with respect to the pharmacological effects or the toxicity of these compounds.

1-14C-n-hexadecane disposition in the spiny lobster, Panulirus argus and the American lobster, Homarus americanus.

1-14C-n-hexadecane, a model compound for the non-volatile aliphatic hydrocarbon components of crude oil, was administered by intrapericardial injection to the spiny lobster, Panulirus argus, and the clawed or American lobster, Homarus americanus. Experiments were conducted in Florida (spiny lobster) and Maine (American lobster). The animals were sacrificed at various times from 0.5 hr to 8 wks after administration of the dose. The tissues and fluids were analyzed for 14C content by digestion or catalytic oxidation and liquid scintillation counting. Selected tissues (hepatopancreas, tail muscle and hemolymph) were extracted with ethyl acetate to allow quantitation of the unmetabolized n-hexadecane by thin layer chromatography. n-Hexadecane-derived radioactivity was very persistent in both the spiny lobster (t1/2 = 4.6 wk) and the American lobster (t1/2 = 11.2 wk). In both lobsters, the hepatopancreas (HP) acquired the highest specific activity and the tail muscle had the longest half life for elimination from an individual tissue. Although hexadecane was metabolized more rapidly in the HP of the spiny lobster than in the HP of the American lobster, unmetabolized hexadecane persisted in the HPs of both species for at least 8 weeks after the dose (the longest time studied).

Temperature-dependent disposition of [14C]benzo(a)pyrene in the spiny lobster, Panulirus argus.

[14C]Benzo(a)pyrene (BP) (1 mg/kg) was administered by intracardiac injection to groups of spiny lobsters which were killed at various times up to 7 weeks after dosing. Tissues and fluids were evaluated for BP-derived radioactivity. Two studies were conducted in successive summer and winter seasons, when seawater temperatures throughout were 26.5 to 29.0 and 13.5 to 16.5 degrees C, respectively. Highest concentrations of BP-derived radioactivity were found in the hepatopancreas, stomach, intestine, intestinal contents, and the green gland. After an initial distribution phase, the dose was lost from the lobsters in a log linear manner. The elimination half-lives for overall elimination of BP-derived radioactivity were 1.11 weeks in the warmer (summer) and 2.25 weeks in the colder (winter) water. Similarly, for individual organs, elimination was more rapid in the warmer water. For the hepatopancreas, green gland, intestine, and tail muscle, respective t1/2 values (week) were 1.02, 1.26, 1.71, and 1.42 in the summer and 2.50, 1.50, 5.04, and 2.11 in the winter. There was no suggestion of tissue accumulation of BP-derived radioactivity. HPLC analysis of hepatopancreas samples showed that, in summer, unmetabolized BP concentrations fell rapidly, accounting for only 5% of the total label in the hepatopancreas by 3 days. The fall in unmetabolized BP was accompanied by approximately equal increases in the percentages of both polar metabolites and conjugates. Although the time curve for metabolism of BP in the hepatopancreas was not studied in winter, the metabolic capacity was such that, by 3 days after the dose, only 5% of the 14C present in hepatopancreas was unmetabolized BP. Thus, it appears that, for this dose of BP, the more rapid elimination of 14C in summer was due to a more rapid excretion of metabolites, and not to increased metabolism of BP.

3-Methylcholanthrene does not induce in vitro xenobiotic metabolism in spiny lobster hepatopancreas, or affect in vivo disposition of benzo[a]pyrene.

Administration of 3-methylcholanthrene (10 mg/kg) i.m. to spiny lobsters, Panulirus argus, did not cause induction of the cytochrome P-450 content of hepatopancreas microsomes. The rate of oxidation of benzo[a]pyrene or 7-ethoxyresorufin in reductase-fortified preparations of hepatopancreas microsomes was the same for corn oil-treated or 3-methylcholanthrene-treated lobsters. Administration of 3-methylcholanthrene (10 mg/kg) i.m. to spiny lobsters one week prior to an i.v. dose of [14C]benzo[a]pyrene (1 mg/kg) did not influence the disposition of the radiolabelled benzo[a]pyrene in lobsters. At one week after the dose of [14C]benzo[a]pyrene, approximately 40% of the dose of [14C]benzo[a]pyrene remained in the lobsters, regardless of treatment. The digestive tract (hepatopancreas, intestinal contents, stomach and intestine) contained most (86%) of the 14C remaining in the lobsters.

Uptake of lead by vegetable foodstuffs during cooking.

Uptake of Pb by foodstuffs during cooking has been identified as an additional potential source of human exposure to Pb. Vegetables and rice cooked in water containing Pb may adsorb up to 80% of the Pb in the water. The amount of Pb adsorbed was dependent upon the concentration of Pb in the water, type of vegetable, water hardness, salting of the water, duration of cooking and the available surface-area of the vegetables. Substantial deposition of Pb also occurred on the surfaces of the saucepan itself (Al greater than enamel greater than Teflon), with subsequent desorption under certain cooking conditions. During tea-making, the concentration of Pb in water was reduced by 30-40% due to adsorption of Pb by the tea-bags. The dietary significance of the adsorption of Pb by foodstuffs during cooking as an additional source of human Pb uptake is assessed.