Toxaphene and other persistent organochlorine pesticides in three species of albatrosses from the north and south Pacific Ocean

Toxaphene and other persistent organochlorine (OC) pesticides (chlordane-related compounds [sigmaCHL], DDT-related compounds [sigmaDDT], hexachlorocyclohexanes [sigmaHCH], tris(p-chloro-phenyl)methane, hexachlorobenzene, octachlorostyrene, dieldrin) were determined in fat of Laysan albatross (Diomedea immutabilis) and in fat and eggs of blackfooted albatross (Diomedea nigripes) from the central north Pacific Ocean. The HCH isomers and chlordane- and DDT-related compounds were also determined in eggs of northern royal albatross (Diomedea sanfordi) collected in New Zealand. Toxaphene was detected in fat samples at mean +/- standard deviation (SD) levels ranging from 243 +/- 61 ng/g wet weight in Laysan albatross to 1,020 +/- 237 ng/g wet weight in blackfooted albatross. These levels were higher than sigmaCHL and sigmaHCH but lower than sigmaDDT. In eggs of blackfooted albatross, toxaphene was the major OC pesticide, averaging 513 ng/g wet weight in two pooled samples compared with 293 ng/g wet weight for sigmaDDT. Two toxaphene congeners, the octachloroborane B8-1413 (Parlar 26) and the nonachlorobornane B9-1679 (P50), comprised about 38% of total toxaphene in both albatross species. All OC compounds were present at significantly higher levels in blackfooted than Laysan albatross fat with the exception of sigmaHCH, dieldrin, and octachlorostyrene. Mean levels of sigmaDDT and sigmaHCH in northern royal albatross eggs from New Zealand were 4 and 60 times lower, respectively, than in blackfooted albatross eggs. The pattern of OC pesticide accumulation was consistent with differences in distribution of the three species in the Pacific Ocean, with highest levels in blackfooted albatross, which feed off the west coast of North America, intermediate levels in Laysan albatross, which frequent the western Pacific, and lowest levels in northern royal albatross, which are confined to the southern oceans surrounding the Antarctic.     

Bioaccumulation of Organochlorine Contaminants in Bowhead Whales (Balaena mysticetus) from Barrow, Alaska

Bowhead whale (Balaena mysticetus) blubber (n = 72) and liver (n = 23) samples were collected during seven consecutive subsistence harvests (1997–2000) at Barrow, Alaska, to investigate the bioaccumulation of organochlorine contaminants (OCs) by this long-lived mysticete. The rank order of OC group concentrations (geometric mean, wet weight) in bowhead blubber samples were toxaphene (TOX; 455 ng/g) > polychlorinated biphenyls (ΣPCBs; 410 ng/g) > dichlorodiphenyltrichloroethane-related compounds (ΣDDT; 331 ng/g) ≥ hexachlorocyclohexane isomers (ΣHCHs; 203 ng/g) ≥ chlordanes and related isomers (ΣCHLOR; 183 ng/g) > chlorobenzenes (ΣCIBz; 106 ng/g). In liver, ΣHCH (9.5 ng/g; wet weight) was the most abundant ΣOC group, followed by ΣPCBs (9.1 ng/g) ≥ TOX (8.8 ng/g) > ΣCHLOR (5.5 ng/g) > ΣCIBz (4.2 ng/g) ≥ ΣDDT (3.7 ng/g). The dominant analyte in blubber and liver was p,p′-DDE and α-HCH, respectively. Total TOX, ΣPCBs, ΣDDT, and ΣCHLOR concentrations in blubber generally increased with age of male whales (as interpreted by body length), but this relationship was not significant for adult female whales. Biomagnification factor (BMF) values (0.1–45.5) for OCs from zooplankton (Calanus sp.) to bowhead whale were consistent with findings for other mysticetes. Tissue-specific differences in OC patterns in blubber and liver may be attributed to variation of tissue composition and the relatively low capacity of this species to biotransform various OCs. Principal component analysis of contaminants levels in bowhead blubber samples suggest that proportions of OCs, such as β-HCH, fluctuate with seasonal migration of this species between the Bering, Chukchi, and Beaufort Seas. Received: 10 October 2001/Accepted: 14 December 2001     

Enhanced transcription factor DNA binding and gene expression induced by arsenite or arsenate in renal slices

Although the kidney represents a target for the accumulation and toxicity of arsenic, little is known about the molecular targets of arsenic in this organ. Therefore, these studies were designed to examine the molecular impact of arsenite [As(III)] and arsenate [As(V)] at low (nanomolar) concentrations. Precision-cut rabbit renal cortical slices were challenged with As(III) or As(V) for up to 8 h. Neither form of the metal induced overt cytotoxicity as assessed by intracellular K+ levels over this time period at concentrations from 0.01-10 microM. In addition, no alterations in the expression of Hsp 60, 70, or 90 were observed. However, induction of heme oxygenase-1 (Hsp 32) was seen following a 4-h challenge with As(III), but not with As(V). As(III) and As(V) induced DNA binding of AP-1 at 2- and 4-h exposure; following a 6-h exposure there was no difference. Although no alteration in the DNA binding activity of ATF-2 was induced by As(III) or As(V), both forms enhanced the DNA binding activity of Elk-1. Enhanced DNA binding activity of AP-1 and Elk-1 correlated with increased gene expression of c-fos, but not c-jun, at 2 h. c-myc gene expression was also induced by As(III) and As(V), albeit at a later time point (6 h). These results suggest that acute arsenic challenge, by either As(III) or As(V), is associated with discrete alterations in the activity of signaling pathways and gene expression in renal tissue.      

The haemodynamic effect of the 5HT1 agonist BMS-180048: a class effect of triptans?

AIMS: To investigate the effects of an intravenous infusion of BMS-180048, a novel 5HT1-like agonist, on the systemic, pulmonary and coronary circulations in patients undergoing diagnostic cardiac catheterisation. METHODS: Ten patients (mean age 55 years (range 41-65)) were studied during diagnostic cardiac catheterisation. The haemodynamic response to an intravenous (i.v.) infusion for 30 min of BMS-180048 (0.56 mg kg(-1) h(-1) for 10 min and 0.39 mg kg(-1) h(-1) for 20 min) was assessed via a 7F Swan Ganz catheter and thermodilution cardiac output system. Quantitative coronary angiography was performed at 10 min intervals. RESULTS: BMS-180048 caused a significant increase in systemic arterial systolic blood pressure (rise of 32.5 mmHg, 95% CI 24,44.5) P=0.009), pulmonary artery systolic (12.2 mmHg, 95% CI 6.8,18.5; P=0.009) and diastolic pressures (8.5 mmHg, 95% CI 5.0,13.8; P=0.009), right atrial pressure (4 mmHg, 95% CI 1.5,5.2; P=0.013) and pulmonary capillary wedge pressure (9.5 mmHg 95% CI 5.2,14.0; P=0.09). There was no significant change in cardiac output (0.1 l min(-1), 95% CI -0.17,0.57, P>0.05). Mean coronary artery diameter in the proximal coronary segments decreased by 0.73 mm (95% CI -1.22,-0.15; P=0.03) at 35 min. The corresponding reduction in middle segments was 0.26 mm (95% CI -0.395,-0.08; P=0.02). There was a non-significant trend to constriction in the most distal segments of 0.28 mm (95% CI -0.68,0.015); P=0.06). One patient experienced chest pain with ECG changes suggestive of ischaemia. CONCLUSIONS: BMS-180048 displayed a cardiovascular profile similar to that previously reported for sumatriptan. These changes appear to reflect a class effect of these agents.     

Lead exposure and children's intelligence: Do low levels of lead in blood cause mental deficit?

It has come to be generally accepted that low levels of lead exposure may result in mental deficit. This causal inference is based on claimed time precedence of the lead exposure and on biological plausibility. The objective of this study is to argue that mental deficit causes pica which causes lead exposure (i.e. to support the theory of reverse causation).

Methodology:

The literature since the 1930s has been interpreted in the light of our own long experience in the investigation of lead exposure in children and adults to support the arguments in favour of reverse causation.

Results:

The arguments for reverse causation are based on: (i) analogy with mental retardation which causes increased lead exposure; (ii) the results of published prospective studies that show a special relationship between blood lead levels at 24 months and intelligence tested later, exactly what would be predicted by the reverse causation theory; and (iii) on an alternative explanation for mental retardation following lead encephalopathy (i.e. that mental retardation following encephalopathy is due to anoxia and not due to a direct destructive effect on the brain neurones). The arguments, which have been proposed for the conventional view, are rejected for the following reasons: (i) none of the prospective studies have found a relationship between cord blood lead levels and intelligence tested later, undermining the argument based on time precedence of lead exposure; and (ii) there is no convincing evidence that lead poisoning, short of encephalopathy, causes mental retardation.

Conclusion:

We believe that the reverse causation hypothesis is a more plausible explanation of the facts.     

Respiratory syncytial virus immune globulin treatment of RSV lower respiratory tract infection in previously healthy children

OBJECTIVE: To evaluate the efficacy of high titer respiratory syncytial virus (RSV) immune globulin (RSVIG) in the treatment of previously healthy children hospitalized with proven RSV lower tract infection (LRI). METHOD: Infants and young children /=2. 5 were enrolled. RESULTS: One hundred and one previously healthy children hospitalized with RSV LRI received either 1500 mg/kg of RSVIG (RespiGam, MedImmune Inc, Gaithersburg, MD) or albumin placebo in a randomized, double-blind, placebo-controlled trial. Forty-six RSVIG and 52 recipients of placebo met all eligibility criteria. Demographic characteristics of the two groups were similar. More RSVIG recipients (46% vs 29%) had an SaO2 /=3.0) had 1.6 fewer hospital days and 2.7 days less ICU stays. CONCLUSION: RSVIG infusions seemed safe and generally well tolerated. Although some beneficial effect trends were seen for those with more severe disease who were treated there was no evidence that treatment with RSVIG resulted in reduced hospitalization and reduced ICU stays in all children with RSV disease.     

Liver transplant for giant cell hepatitis with autoimmune haemolytic anaemia

Giant cell hepatitis (CGH) with autoimmune haemolytic anaemia (AHA) is a distinct entity with an aggressive course. Immunosuppression may help early disease. A case is reported of a child with GCH and AHA with early disease recurrence after liver transplantation for end stage liver disease.     

Changes to the quantity and processing of starchy foods in a western diet can increase polysaccharides escaping digestion and improve in vitro fermentation variables

This study investigated how readily achievable changes to the quantity and processing of starchy foods in a typical Western diet: (1) were reflected in levels of resistant starch (RS) and NSP excreted from the small intestine; and (2) more favourable profiles of butyrate, NH3 and phenol production. Two diets, a low-starch diet (LSD) and a high-starch, low-fat diet (HSLFD) were compared. The LSD with 20% total energy (%E) from starch was based on a 'typical' Australian diet, while the HSLFD (40%E as starch) was the same Australian diet modified by an increased content of legumes, starchy foods and coarsely-ground cereals and by a reduced fat content. Four subjects with iliostomies consumed each diet for 2 d, with ileal effluent collection on the second day. On the HSLFD compared with the LSD, RS in ileal effluent increased from from 0.49 to 1.7 g/MJ per d (P < 0.005) while ileal NSP excretion increased from 2.0 to 3.3 g/MJ per d (P < 0.05). Ileal effluents obtained after each diet were incubated for 24 h in vitro with a human faecal innoculum. After fermentation, ileal effluent from the HSLFD produced more butyrate relative to other short-chain fatty acids (17.5 v. 15.8 molar %, P < 0.005) and less phenol (2.3 v. 5.7 mg/l, P < 0.05) and NH3 (20.3 v. 23.1 mmol/l, P < 0.005) than the LSD diet. The HSLFD also generated a lower pH (6.15 v. 6.27, P < 0.05). On a wt/wt basis, RS was 2.3-fold higher in the HSLFD effluent while NSP did not increase, suggesting that the change in RS largely contributed to the fermentation effects. Changes in in vitro variables when the HSLFD ileal effluent was ground before fermentation indicated the importance of physical structure in determining ileal excretion of RS. We conclude that: (1) readily achievable modifications to the amount and processing of starchy foods in an Australian diet would produce potential benefits for in vitro fermentation variables; and (2) the physical structure of grains and cereals is important in determining access by colonic bacteria to a carbohydrate substrate.