Biliary excretion of [C]succinylsulphathiazole in the rat and rabbit

1. After intravenous injection about 30% of the dose (20mg./kg.) of succinylsulphathiazole is excreted unchanged in the bile in 3hr. by the rat, whereas only about 1% is excreted by the rabbit. When the renal pedicles are ligated the biliary excretion of succinylsulphathiazole in the rat increases to about 80% of the dose, but in the rabbit under these conditions the biliary excretion is only 2% of the dose. 2. In the rat, the sulphonamide readily enters the liver and biliary excretion occurs against a concentration gradient from liver to bile; further, the excretory process can be saturated, and can be depressed by the simultaneous administration of phenolphthalein glucuronide or bile salts. 3. In the rabbit, these conditions have not been found; succinylsulphathiazole does not readily enter the liver from the plasma, there is no transfer of the drug from the liver cells to the bile against a concentration gradient, and no saturation or depression of the biliary excretion of succinylsulphathiazole is found. 4. It is suggested that two factors responsible, at least partly, for the low biliary excretion of succinylsulphathiazole in the rabbit are the poor entry of the sulphonamide into the liver in this species and a deficiency of the concentrative mechanism for its excretion in the bile.     

Protein synthesis in the intestine of goldfish acclimatized to different temperatures

1. The incorporation of [¹⁴C]valine and [³H]threonine has been studied in mucosa of goldfish acclimatized to different temperatures. 2. [¹⁴C]Valine was incorporated more rapidly than [³H]threonine at acclimatization temperatures below 15°; this distinction disappeared at higher temperatures. 3. The rate of amino acid incorporation rose as the environmental temperature was increased. 4. The number of valine residues in mucosal protein fell and the number of methionine residues rose as the acclimatization temperature was raised. 5. The concentration of free methionine was closely related to the amount in protein in goldfish mucosa; both increased at higher acclimatization temperatures. 6. An attempt is made to show that these changes are integrated with possible homoeostatic mechanisms in the goldfish intestine.     

The fate of the hydrolysis products of thalidomide in the pregnant rabbit

1. The fate in the pregnant New Zealand White rabbit of oral doses of four ¹⁴C-labelled hydrolysis products of thalidomide, namely α-(o-carboxybenzamido)-glutarimide, 2-phthalimidoglutaramic acid, 2-phthalimidoglutaric acid and 2-(o-carboxybenzamido)glutaramic acid, administered on the 192nd hour of pregnancy has been studied. 2. About 60–95% of the administered ¹⁴C of each compound appears in the urine in 58hr. and the remainder is found in the faeces and in the gut and its contents. 3. Radioactivity is present in the plasma, liver, kidney, brain, muscle, fat and embryo. 4. The ¹⁴C-labelled substances in the plasma and embryo consist of the unchanged compounds and their further hydrolysis products. 5. Since the above four thalidomide hydrolysis products are found in the rabbit conceptus together with their further hydrolysis products after their oral administration to the pregnant rabbit, it appears that the teratogenic activity of thalidomide is due to the compound itself rather than to one or more of its hydrolysis products.     

Growth and gas-vacuole development in vegetative cells of Anabaena flos-aquae

Summary Gas-vacuoles consisting of collections of gas-cylinders, and continuity of the plasma membrane with lamellae, are observed at all stages of growth of Anabaena flos-aquae. In day+4 cells, increased numbers of invaginations of the plasma membrane are observed and the lamellae tend to lie parallel to the cell wall. Some evidence is presented which suggests an associated synthesis of -granules and gas-cylinders by lamellae. Features of older cells are increased numbers of gascylinders, -granules, structured granules, and large intralamellar vesicles which appear to correlate with the presence of pinkish vacuoles as observed with the light microscope. The mean percentage of the volume of cells occupied by gas-vacuoles is about 20% during exponential growth when the doubling time is 56.5 hours, increasing to 34% in day+24 cells when growth is stationary.     

Comparative structure of the gas-vacuoles of blue-green algae

Summary An investigation was made of 5 species of blue-green algae reported to contain gas-vacuoles. All organisms were grown and harvested under standard conditions. Gas-vacuoles were characterised as reddish structures which are destroyed by applying pressure. Using a simple direct preparation technique gascylinders were observed with the transmission electron microscope in gas-vacuolate cells. Gas-vacuoles were present in the strains of Anabaena flos-aquae, Gloeotrichia echinulata and Oscillatoria agardhii studied and absent from Microcystis aeruginosa and Nostoc linckia. The reddish, refractile central area of N. linckia and M. aeruginosa cells was tentatively identified as nucleoplasm. Gas-vacuoles are collections of gas-cylinders 70 m wide, which in A. flos-aquae and G. echinulata are clearly bounded by photosynthetic lamellae and associated with -granules. The presence of bounding photosynthetic lamellae in these species is suggested as a causal factor of the unusual optical properties of their gas-vacuoles. The range of lengths of gas-cylinders in G. echinulata and O. agardhii is from 100 m to 500 m and in A. flos-aquae it is from 100 m to 1300 m. The percentage of cell volume occupied by gas-vacuoles was estimated by direct measurement. In A. flos-aquae and G. echinulata it was 22%. In O. agardhii gas-cylinders were not clearly associated with photosynthetic lamellae and -granules and occupied 39% of cell volume. Gascylinder membranes showed reasonable preservation in KMnO₄ and excellent preservation in OsO₄. The widths of membranes after treatment with these two fixatives was 3 m and 2 m respectively.     

Effects of Triton X-100 on acid phosphatases with different substrate specificities

Summary The effect of Triton X-100 on the activities of acid phosphatases from wheat germ, potato and human prostate was tested using -glycerophosphate, p-nitro-phenyl phosphate and naphthol AS BI phosphate as substrates. There was little effect on -glycerophosphatase activity at the concentrations of Triton X-100 tested. However at low concen trations of the detergent there was a stimulation of the activities of p-nitrophenyl phosphatase and naphthol phosphatase which were inhibited with the higher concentrations. Triton X-100 was found to enhance colour production between naphthol AS BI and fast red violet LB.Further evidence is presented confirming the presence of more than one acid phosphatase from each of the sources employed.     

Metabolism of propionate by sheep-liver mitochondria: Effects of α-oxoglutarate, adenosine triphosphate, sodium chloride and potassium chloride

1. A study has been made of the effects of ATP and alpha-oxoglutarate on the rate of metabolism of propionate by whole mitochondria from sheep liver, and by mitochondria disrupted with ultrasonic energy or by freezing and thawing. Whole mitochondria metabolized propionate aerobically; the rate was increased and stabilized by 0.5mm-ATP, and increased at least a further 50% by 1.67mm-alpha-oxoglutarate. 2. Anaerobically, externally added ATP at high concentrations permitted slow consumption of propionate. 3. In the presence of 1.3mm-ATP, but in the absence of alpha-oxoglutarate, there was no significant lag phase in the removal of propionate by whole mitochondria, and the rate declined at concentrations below 2mm. In the additional presence of 1.67mm-alpha-oxoglutarate or -glutamate, propionate was removed at linear rates until the residual propionate concentration was about 0.1mm. 4. Maximum rates of metabolism of propionate by whole mitochondria with 1.3mm-ATP occurred with alkali-metal chloride concentrations of 65-95mm and with K(+)/Na(+) ratios 5-10, both in the presence and absence of alpha-oxoglutarate. 5. With disrupted mitochondria stimulatory effects of alpha-oxoglutarate were obtained only aerobically, only with propionate and not propionyl-CoA as substrate, and only when sufficient mitochondrial structure remained to permit unsupplemented metabolism of propionate to occur. 6. In the presence of ATP and CoA, disrupted mitochondria fixed [2-(14)C]propionate at a rate adequate to explain the rate with whole mitochondria stimulated with ATP and alpha-oxoglutarate. 7. With both whole and partially disrupted mitochondria in the absence of ATP, the rate of metabolism of propionate was inhibited by about 80% by 3.3mm-AMP. The inhibition was partly overcome by alpha-oxoglutarate plus CoA. 8. It is concluded that the ultimate effect of alpha-oxoglutarate was to increase the rate of supply of ATP within the mitochondria. Reasons are given why it is premature to conclude that the extra ATP arose entirely from the oxidation of alpha-oxoglutarate itself.     

Bone breaking stress as a function of weight bearing in bipedal rats

The effect of bipedal stance on the breaking stress in compression of rat femora is investigated as a function of animal weight. It is shown that the breaking stress is a linear function of body weight, bone density and specific calcium content of the femur. In all cases investigated, bipedal femora are shown to have a higher breaking stress than controls. It is concluded that there is a continuous change in the quality as well as the quantity of bone in the rat femur with age and that the increased strength of bone material found in bipedal animals compared to controls as well as large animals as compared to small ones, cannot be explained on the basis of bone mineral content alone.     

Inhibition of Microbial Lipases by Fatty Acids

Addition of lard or sodium oleate to the medium used for lipase production by Pseudomonas fragi resulted in a decreased accumulation of lipase in the culture supernatant fluid without affecting cell growth. The production and activity of lipase was inhibited by lard, sodium oleate, and the salts of other unsaturated fatty acids. Some divalent cations, Tweens, lecithin, and bovine serum prevented oleate inhibition, but did not reverse it. Similar inhibitory actions were observed with Geotrichum candidum lipase, but not with a staphylococcal lipase or pancreatic lipase. A protective effect by protein in crude enzyme preparations is indicated. The ability of oleate to lower surface tension does not appear to be related to its ability to inhibit lipase.