Identification of sex pheromone components of the painted apple moth: a tussock moth with a thermally labile pheromone component.

The sex pheromone of the painted apple moth, Teia anartoides (Lymantriidae) was investigated using GC-EAD and GC-MS analysis, derivatization, TLC analysis, and field cage and field trapping bioassays. The major sex pheromone components were identified as (6Z,9Z)-henicosa-6,9-dien-11-one and (6Z,9Z)-henicosa-6,9-diene. Other minor components of pheromone gland extracts included (6Z)-9R, 10S-epoxyeicos-6-ene, (6Z)-9R,10S-epoxyhenicos-6-ene, (6Z,9Z)-henicosa-6,9-dien-11-ol, (6Z)-henicos-6-en-11-one, and (6Z, 8E)-henicosa-6,8-dien-11-one, but the roles of these minor components remain equivocal. In field cage and field experiments, a blend of all seven identified components [(6Z,9Z)-henicosa-6,9-dien-11-one (relative amount 100), (6Z,9Z)-henicosa-6,9-diene (100), (6Z)-9R,10S-epoxyeicos-6-ene (5), (6Z)-9R,10S-epoxyhenicos-6-ene (10), (6Z,9Z)-henicosa-6,9-dien-11-ol (5), (6Z)-henicos-6-en-11-one (1), and (6Z,8E)-henicosa-6,8-dien-11-one (25)] was as attractive to males as calling females, but tests with blends of the major component(s) with subsets of the minor components did not produce consistent results that unequivocally showed the various minor components to be critical components of the active blend. (6Z,9Z)-henicosa-6,9-dien-11-one is thermally labile and rearranges to (6Z,8E)-henicosa-6,8-dien-1-one and other products at ambient temperature, rendering the synthetic pheromone lure inactive after two days of field exposure.

A prevalidation study on the in vitro skin irritation function test (SIFT) for prediction of acute skin irritation in vivo: results and evaluation of ECVAM Phase III.

A prevalidation study sponsored by the European Centre for the Validation of Alternative Methods (ECVAM) on in vitro tests for acute skin irritation is aimed at identifying non-animal tests capable of discriminating irritants (I) from non-irritants (NI), as defined according to European Union and OECD. This paper reports on Phase III for one of the methods, the skin integrity function test (SIFT), assessing the protocol performance of the SIFT, in terms of reproducibility and predictive ability, in three laboratories. The barrier function properties of excised mouse skin were determined using a set of 20 coded chemicals (10 I, 10 NI), using the endpoints of trans-epidermal water loss (TEWL) and electrical resistance (ER). The basis of the SIFT prediction model is if the ratios of the pre- and post-application values for either TEWL or ER are greater than five-fold, then the test chemical is deemed irritant (I). If the ratio of both parameters is less than five-fold then the chemical is deemed non-irritant (NI). Analysis of variance (ANOVA) indicated that the intra-lab reproducibility was acceptable but that the inter-lab reproducibility was not. Overall, the SIFT test under-predicted the irritancy of the test chemicals chosen for Phase III with an overall accuracy of only 55%. The sensitivity value (ability to correctly predict I) was only 30%. The specificity (ability to predict NI) of the test was better at 80%. A retrospective examination of the SIFT results was undertaken using Student's t-test and a significance level of P<0.05 to predict an irritant based on changes in the TEWL ratio values. This improved the predictivity of the SIFT test, giving a specificity of 60%, a sensitivity of 80% and an overall accuracy of 70%. Appropriate modifications to the prediction model have now been made and the SIFT will be re-examined in a new validation exercise to investigate the potential of this non-animal method to predict acute skin irritation potential.

Rapid integrity assessment of rat and human epidermal membranes for in vitro dermal regulatory testing: correlation of electrical resistance with tritiated water permeability.

An approach is presented that allows for rapid selection of robust rat and human epidermal membranes for use on in vitro dermal regulatory studies. Tritiated water (THO) permeability was correlated with electrical resistance (ER) and the results used to propose ER values to judge membrane integrity. Rat and human epidermal membranes were prepared and mounted onto in vitro glass static diffusion cells (0.64 cm(2)) maintained at 32 degrees C. THO permeability coefficients (Kp) were determined and compared with ER measurements. Electrical resistance was also determined for various in vitro cell exposure areas from 0.64 cm(2) to 2.54 cm(2). Our results show that rat epidermal membrane THO Kp values exhibited a lognormal distribution with a median value of 2.76 x 10(-3) cm/h. Human epidermal membrane THO Kp values were best described by a Weibull distribution with a median value of 1.13 x 10(-3) cm/h. The corresponding median electrical resistance measurements were 5.59 kOmega for rat and 23 kOmega for human epidermal membranes. Based on the widely used and accepted single point THO Kp thresholds of /=5.87 kOmega and >/=17.1 kOmega were calculated and proposed as acceptable benchmarks for pre-qualifying membranes. In our research exploring the relationship between ER and exposure area we report that an inverse relationship exists between ER and in vitro cell exposure area; as cell area increased, ER decreased. The use of electrical resistance provides a rapid and reliable method for evaluating the integrity of rat and human epidermal membranes for in vitro dermal kinetic testing.

A survey of diabetes services in hospitals in Papua New Guinea.

AIM: To determine the number and distribution of diabetic persons in Papua New Guinea (PNG), and to document available services. METHODS: Survey of the 19 hospitals thought to be the most significant centres for care of diabetes. RESULTS: 16 hospitals were successfully surveyed. Type 1 diabetes is very rare, with 18 known cases in the country (6 less than 15 years old). Known type 2 cases totalled around 4600 with almost all cases in coastal centres, particularly Port Moresby, East New Britain and Manus. There were very few cases in the highlands. Insulin is generally available, along with oral hypoglycaemic drugs. Testing for complications is very limited, and glycosylated haemoglobin (HbA1c) testing is available in only one centre. Only 3 trained diabetes educators are available in the country, with 1 dietitian and no specialist endocrinologists. CONCLUSIONS: The vast majority of persons with type 2 diabetes in PNG are undiagnosed and are not receiving treatment: based on the lower of two country prevalence estimates, less than 3% of the diabetic persons in the country are seen at health facilities. Services are limited, with only a handful of health professionals specially trained in diabetes. Expansion of services and awareness and prevention programs are urgently needed.

High-affinity nasal extraction of vinyl acetate vapor is carboxylesterase dependent.

Vinyl acetate induces nasal tumors in rats, but not mice. Species differences in airflow patterns, physiology, and biochemistry complicate extrapolation of nasal dosimetry from rats to humans. Physiologically based pharmacokinetic modeling of vinyl acetate dosimetry in rats suggested the presence of a saturable metabolic removal pathway in rat nasal mucus. We explored the possibility that this pathway is either a cytochrome P-450 2E1 (CYP2E1) or high-affinity carboxylesterase. Nasal extraction of vinyl acetate vapor (150 ppm) was measured in the surgically isolated nasal cavity of anesthetized rats. Vinyl acetate (150 ppm) was extracted with 73% efficiency in controls. Pretreatment of rats with the CYP2E1 inhibitor diallyl sulfide (DAS) had no effect on extraction, despite significantly reducing CYP2E1 activity. Pretreatment with bis(p-nitrophenyl) phosphate (BNPP), a carboxylesterase inhibitor, reduced extraction to approximately 41%. Acetaldehyde production was similarly unaffected by DAS but was reduced to 55% of control by BNPP. Rat nasal mucus carboxylesterase activity had a K(m) value (32 microM) similar, within a factor of 2, to the value predicted by the physiologically based model, although V(max) was significantly lower than the model prediction. Histochemical observations support the inference that the high-affinity carboxylesterase is bound to the luminal plasma membrane of nasal tissue and is not readily released by nasal lavage, providing an explanation for the low V(max) of the lavage enzyme. This high-affinity isoenzyme could be important in the removal of odorants from the sensory cell-rich nasal olfactory epithelium.

Morphometric analysis of the muscle fibres of the soleus muscle of the ageing rat: long-term effect of hypophysectomy and food restriction.

This communication reports on the effects of ageing, hypophysectomy and food restriction on the fibre sizes of the soleus muscle which is primarily concerned with posture. The results reported here are compared with those previously shown for the gastrocnemius muscle which is involved mainly with locomotion. Muscle fibre size (measured as equivalent circle diameter) in the soleus muscle of the male Wistar rat increased from youth at 130 days (type 1 fibres, 61.2 microns; type 2, 58.3 microns) to middle age at 600 days (type 1 fibres, 70.4 microns; type 2, 68.0 microns) and then underwent atrophy in old age to 1,000 days (type 1 fibres, 54.5 microns; type 2, 38.0 microns). There was no growth or atrophy of these fibres in either hypophysectomized or food-restricted rats. There was an increased range of fibre sizes in control rats between youth and old age being 5-fold for type 1 fibres and 3-fold for type 2 fibres, but there was a loss of type 2 fibres in hypophysectomized rats. This ageing process in the range of fibre size was retarded by hypophysectomy (2-fold increase for type 1 fibres) and to a lesser extent by food restriction (3-fold increase for type 1 fibres). Muscle fibre atrophy and compensatory hypertrophy were not as prominent in the hypophysectomized and food-restricted groups as in the old control groups. In general these effects were similar to those previously shown for the gastrocnemius muscle. However, atrophy of both type 1 and type 2 fibres in old age was more pronounced in the soleus muscle. The retarded ageing of the soleus muscle in hypophysectomized and food-restricted rats was probably due to the absence or reduced circulating levels of hormones known to target muscle cells, such as growth hormone and thyroxine.

Morphometrical analysis of the short-term effects of hypophysectomy and food restriction on skeletal muscle fibers in relation to growth and aging changes in the rat.

Muscle fiber growth is impaired by lack of hormonal influence. In the case of the gastrocnemius muscle of the male Wistar rat, ablation of the pituitary at age 60 days results in cessation of the growth of type 1 muscle fibers, and a reduction in the size of type 2 muscle fibers at 120 days of age, 60 days after hypophysectomy. The effects of food restriction, which are known to reduce pituitary hormone secretion, are not as great as hypophysectomy in inhibiting muscle fiber growth. Food restriction slowed the growth of type 1 muscle fibers (hypophysectomy abolished growth) and caused cessation of growth of type 2 muscle fibers (hypophysectomy caused atrophy).

Morphometrical analysis of skeletal muscle fibre ageing and the effect of hypophysectomy and food restriction in the rat.

Morphometrical analyses were carried out on muscle fibres from cross-sectional areas of the medial head of gastrocnemius muscles from 5 groups each of 4 male Wistar rats representing young (aged approximately 100 days), medium-aged (400 days), old (1,000 days), old hypophysectomized (1,000 days) and old food-restricted (1,000 days) rats. Approximately 18,000 muscle fibres were measured in each group. Rats were hypophysectomized when young at 60-70 days and food restriction began at the same age. The results show that there is a reduction in type 2 fibre size (measured as the mean equivalent circle diameter) from 59.7 micron in medium-aged controls to 50.3 micron in old controls, but there is no significant difference between the sizes of type 2 fibres in controls, hypophysectomized or food-restricted rats in old age. Analysis of type 1 fibres demonstrated no differences between young, medium-aged and old controls and the old food-restricted group, but type 1 fibres in the old hypophysectomized group (45.5 micron) were significantly smaller than in the old controls (54.6 micron) and old food-restricted rats (58.5 micron). In old controls there is a 4-fold increase in the range of fibre sizes (coefficient of variation) for type 1 fibres and a 2-fold increase for type 2 fibres, indicating fibre atrophy and hypertrophy. Long-term hypophysectomy is more effective than food restriction in preserving the smaller range of the coefficient of variation of fibre size seen in young controls.

Conflicts and complexity in inpatient geropsychiatry.

In order to illustrate the principles and practice of inpatient geropsychiatric care, the authors present the case of a 73-year-old woman who developed a paranoid delusional syndrome associated with hypothyroidism. The roots of such care, which lie in the network of biopsychosocial losses of late life, are exemplified in their analysis of this patient's multiple medical, psychiatric and social liabilities. The interrelationships among these problems provide the rationale for integrated multidisciplinary assessment and treatment, which is the central organizational concept for geropsychiatric care. Through effective team leadership, efficient case coordination, firm and flexible interdisciplinary boundaries, and incisive prioritization of limited resources and limited options, the multidisciplinary process is shown to provide the basis for a comprehensive and, ideally, a holistic understanding of the patient's strengths and liabilities. The authors highlight this patient's dramatic benefit from such a comprehensive program of medical, psychiatric, and socioenvironmental interventions in order to indicate the fruitfulness of this complex and gratifying process.