Samples of paraquat dichloride and paraquat dimethosulphate are equitoxic when the LD50 is expressed as mg. paraquat ion/kg. body-weight. There are wide species variations in the LD5o and, of course, variations according to the route of administration in a single species.The pathological lesions attributable to paraquat are described in some detail. Among the most unusual is a peculiar proliferative condition in the lungs, which in an extreme case and in many parts can hardly be recognized as consisting of pulmonary tissue. With slight variations, the same microscopical picture may be seen in the rat, mouse, dog, and man, and less often in the rabbit. The experimental evidence suggests that once the condition is initiated it often proceeds in the absence of further exposure to paraquat until it becomes lethal.There is evidence that much of the mortality resulting from dermal application of paraquat in the rabbit is caused not by percutaneous absorption but by oral contamination from the stratum corneum. This leads to glossitis and oesophagitis and an inability or unwillingness to eat.In this paper we report the effects of paraquat administered to laboratory animals as the dichloride or dimethosulphate, either as a single dose by one or other route, or over a short term of repeated doses. Observations made by others on the effects of very exceptional cases of poisoning in man, arising from accidental imbibition of a solution of the substance rather than from its use in the field, suggest that similar pathological changes may be expected in human beings. Chemical Constitution and UsesParaquat is a dipyridylium compound. The formula and chemical nomenclature of the dichloride are given below.

Isolated rat or hamster liver parenchymal cells or kidney cortex segments were incubated in a medium containing 3HHO and the incorporation and partial distribution of tritium in the glucose formed was determined. Gluconeogenesis from lactate or pyruvate caused about 80 to 90% of the possible amount (7 μatoms per glucose molecule) of fixation of tritium from 3HHO in glucose, with a high percentage labelling on C‐6. Glucose formation from glycogen breakdown under anaerobiosis caused less than 20% of the possible fixation of tritium, with most of the labelling on C‐2. This technique may be of eventual use in determining rates and sources of glucose formation.

This study examined the anaerobic and aerobic contributions to muscle metabolism during high intensity short duration exercise. Six males [mean (SD): age 25.0 (6.0) years, height 179.0 (8.2) cm, mass 70.01 (7.42) kg, VO2max 4.63 (0.53) l.min-1, body fat 12.7 (2.3)%] performed three counterbalanced treatments of 30, 60 and 90 s of maximal cycling on an air-braked ergometer. All treatments were also performed on days when biopsies were not taken from the vastus lateralis muscle and cannulae not inserted into a forearm vein to ascertain whether these procedures adversely affected performance. The mean results can be summarised as follows: (Table: see text). The muscle lactate and O2 deficit data suggested that 60 and 90 s were more appropriate durations than 30 s for assessing the anaerobic capacity on an air-braked cycle ergometer. The mean power outputs also indicated that the invasive procedures did not adversely affect performance [corrected].

Rats from an inbred strain (NZR/Mh) were found to have high concentrations of glycogen in their livers, even after 24 h of starvation. Despite this, blood glucose concentrations were well maintained on starvation for up to 72 h. The primary defect is a deficiency of liver phosphorylase kinase, causing a lack of active glycogen phosphorylase, although total phosphorylase is normal. The intravenous injection of glucagon caused a rapid activation of cyclic AMP-dependent protein kinase in the liver, but no increase in either phosphorylase kinase or phosphorylase a activity. Although total glycogen synthase activity in the livers of affected rats was higher than normal, glycogen synthase in the active form was very low, presumably as a result of the high liver glycogen content. The condition is transmitted as autosomal recessive and, apart from hepatomegaly, the affected rats appear healthy.

Nine 'large-eating ' (approximately 12 MJ/d) and nine 'small-eating ' (approximately 5.3 MJ/d) women were selected from the population on the basis of diet and activity diaries. At rest and in the postabsorptive state the rate of oxygen consumption ( poJ/kg fat-free mass (FFM) and rate of carbon dioxide production (&,)/kg FFM were 9-17% higher (P < 0.05) in the 'large-eaters' than in the 'smalleaters'. As energy expenditure was increased by walking at 2.4,3.9 and 5.4 km/h the differences between the two experimental groups for both & / k g FFM and ec0Jkg FFM were decreased to negligible values, but energy expended on a body-weight basis (MJ/kg per min) remained significantly higher (510 %) in 'large-eaters'. Oral temperature was also consistently higher (up to 0.5") in this group both at rest and during sitting, standing and walking activities. Although the average thermic effect of a standardized liquid meal tended to be higher (27 YO ; not significant) in the 'small-eaters', the other results demonstrate that the 'large-eating' females had a markedly higher rate of energy expenditure at rest and during light physical activities.Energy metabolism : Indirect calorimetry : Women

We have studied the inhibitory action of long-and short-chain fatty acids on hepatic glucose utilization in hepatocytes isolated from fasted rats. The rates of hepatic glucose phosphorylation and glycolysis were determined from the tritiated products of [2-'H] and [6-3H]glucose metabolism, respectively. The difference between these was taken as an estimate of the 'cycling' between glucose and glucose-6-phosphate. In the presence of 40 mM glucose this cycling was estimated at 0.68 pmol/min/g wet wt. Glucose phosphorylation was unaffected during palmitate and hexanoate oxidation to ketone bodies but glycolysis was inhibited. The rate of glucose cycling was increased during this phase to 1.25 pmol/min/g. Following the complete metabolism of the fatty acids, glycolysis was reinstated and cycling rates returned to control levels. Hepatic glucose cycling appears to be an important component of the glucose/fatty acid cycle.

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Long-term study of 21 PNH patients revealed an unexpectedly high incidence of functional and anatomic renal abnormalities. Most patients demonstrated varying degrees of hematuria and proteinuria distinct from hemoglobinuria. Evaluation of renal function revealed hyposthenuria, abnormal tubular function, and declining creatinine clearance. Radiologically these patients had enlarged kidneys, cortical infarcts, cortical thinning, and papillary necrosis which were confirmed by autopsy studies. Hypertension developed in eight patients. Urinary tract infection was uncommon. The renal findings bear striking similarity to those of sickle cell anemia. Contrary to the usual opinion, out studies clearly showed evidence of widespread renal pathology in PNH most likely due to repeated microvascular thrombosis similar to the venous thrombosis involving other organs in this disorder.