Changes in the pulmonary uptake and binding of drugs in an experimental model of lung fibrosis.

To investigate the effect of lung fibrosis on the pulmonary uptake and binding of drugs, rats were given weekly ip injections of 20 mg/kg paraquat dichloride for 6 weeks, and drug uptake and efflux in tissue slices from paraquatdamaged and control lungs were compared. Histologically, lungs from paraquat-treated animals showed multifocal areas of obliterative fibrosis, which appeared to involve 10–20% of the lung. Compared to controls, wet and dry weights of fibrotic lungs were increased 2.4- and 2.3-fold, respectively. Total lung protein per kilogram body weight was increased 85% in the paraquat-treated animals. Tissue/medium concentration ratios for [¹⁴C]benzylpenicillin in paraquat-damaged tissues were not significantly different from control values over a 15 to 240-min incubation period; the antibiotic did not appear to accumulate in lung slices. In contrast, [³H]isoniazid and [³H]dexamethasone were accumulated after 15 min, and uptake by paraquat-damaged tissues was significantly decreased (14–22%) for both drugs. In efflux studies with [³H]isoniazid and [³H]dexamethasone, slow-component rates for the drugs were not significantly different in control and fibrotic tissues; however, the fraction of the drugs that washed out at the slow component rate in the paraquat group was decreased 10–15% compared to controls. Differences in drug accumulation could not be accounted for by either a direct effect of residual lung paraquat on binding or metabolism by the lung. The results suggest that sites for drug accumulation in normal lung may be replaced by nonfunctional tissue in this model of lung fibrosis.     

A retrospective mortality study of substituted anthraquinone dyestuffs workers

ABSTRACT Because short-term bacterial tests have previously shown that about one-third of substituted anthraquinones tested are capable of causing reverse mutation, and two-year feeding studies of three such dyestuffs in rats have shown an excess of hepatocellular carcinomas, a retrospective cohort mortality study was carried out on a population of 1975 male workers employed in a dyestuffs manufacturing plant in Scotland. The population was identified as having worked for more than six months within the factory during the decade 1 January 1956-31 December 1965, and their mortality experience was followed up to 30 June 1980. Age-standardised mortality rates did not show any excess in total or cancer-related mortality.     

Agouti related protein (AgRP) is upregulated in Cushing's syndrome.

Alpha melanocyte-stimulating hormone (alpha-MSH) is an agonist at the melanocortin 3 (MC3-R) and melanocortin 4 (MC4-R) receptors. Alpha-MSH stimulates corticosterone release from rat and human adrenal cells. Patients with Cushing's syndrome have elevated levels of serum alpha-MSH. Agouti related protein (AgRP) is an endogenous antagonist at the MC3-R and MC4-R and is expressed in the rat adrenal cortex. AgRP antagonises alpha-MSH-induced corticosterone release from rat and bovine adrenal cells. This suggests that AgRP may have an inhibitory paracrine role in the adrenal gland. We measured adrenal AgRP mRNA expression and circulating AgRP in 2 patients with Cushing's syndrome and controls. Adrenal AgRP mRNA expression and plasma AgRP were higher in the patients with Cushing's syndrome compared to controls. Plasma AgRP in the patients with Cushing's syndrome following bilateral adrenalectomy and hydrocortisone replacement were similar to the levels seen in controls. Our results suggest that AgRP may have a novel inhibitory paracrine role in the human adrenal gland.     

What is the problem with breast‐feeding? A qualitative analysis of infant feeding perceptions

Aims and objectives Breast‐feeding rates are low in Northern Ireland (NI) compared with other regions of Europe. The aim of this study has therefore been to define and explore factors determining infant feeding decisions with a view to the planning of future research and intervention needs. Method Participants were approached at convenience from the throughput of women attending a large teaching hospital antenatal clinic to take part in focus group discussion. Results Dominant themes indicated that the main barriers to breast‐feeding are restricted freedom and independence associated with family issues, return to work, societal embarrassment and perceived social isolation. The dialogue suggested that breast‐feeding leads to inability to carry out everyday activities and social exclusion. Conclusions Incompatible social norms make it difficult for mothers to breast‐feed successfully. This implies that future promotional efforts should take a societal approach.     

Eosinophilic meningoencephalitis due to Angiostrongylus cantonensis as the cause of death in captive non-human primates

Fatal eosinophilic meningoencephalitis due to Angiostrongylus cantonensis is reported in captive non-human primates. A howler monkey (Alouatta caraya) at the Audubon Park and Zoological Gardens, New Orleans, LA, died 21 days after initial clinical symptoms. A white-handed gibbon (Hylobates lar) died at the Ardastra Gardens and Zoo, Nassau, Bahamas, 17 days after onset of symptoms. Both had access to free-ranging gastropods within the zoos. These are the first reported cases of natural infection by A. cantonensis in non-human primates in the western hemisphere.