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PubMed1998

Larval tolerance in the Drosophila melanogaster species complex toward the two toxic acids of the D. sechellia host plant.

The toxicity of hexanoic (C6) and octanoic (C8) acids, the two major components of the host plant of Drosophila sechellia, was investigated upon larvae of the four species included in the D. melanogaster complex and on interspecific hybrids between D. sechellia and D. simulans. Specific methods had to be devised for obtaining reproducible toxicity results. The three generalist species (D. melanogaster, D. mauritiana and D. simulans) were found to be very sensitive, as indicated by low lethal concentrations and an increase in development duration. By contrast D. sechellia was much more tolerant, especially toward C8 which is the most abundant product in the natural resource. Interspecific hybrids (F1 and backcrosses) exhibited intermediate characteristic, but a dominance of D. simulans sensitivity was observed for both acids and especially for C8. Data on larvae are quite different from those previously obtained on adults, and are more likely to reflect the natural selective pressures existing in the wild.

Animals↗
PubMed1975

Polyunsaturated fatty acid lipidosis. II. Lipid biochemical studies.

Lipid analyses were performed on cerebral tissue from three children who had died of a progressive encephalopathy and from one living child in an early stage of the disease. In the terminal stage of the disease, the cortex and white matter content of all lipid classes, particularly the sphingolipids, were very low. The concentration of gangliosides of the cerebral cortex was 10%, and of cerebrosides in white matter, 2-3% of the normal values for the age. The porportion of the minor gangliosides with short carbohydrate chains was increased because the reduction affected mainly the four major brain gangliosides GM1, GD1a, GD1b and GT1. In the child from whom the biopsy specimen was obtained in an early phase of the disease the cerebral lipid pattern appeared to be normal. A patient who had died of neuronal ceroid-lipofuscinosis (Janský-Bielschowsky) did not show any major lipid changes. The fatty acid patterns of the phosphoglycerides showed such changes as have never been observed in any other disease. In the three advanced cases the fatty acid compositions in cerebral cortex and white matter were identical. In ethanolamine phosphoglycerides the proportions of 18: 1 and 20: 4 (n-6) were increased, while those of 22: 4 (n-6) and 22: 6 (n-3) were markedly diminished. Similar changes in the fatty acid patterns were found in the other phosphoglycerides. In the early phase of the disease 22: 4 (n-6) was decreased and 18: 1 increased. We propose that this new disease be termed polyunsaturated fatty acid lipidosis (PFAL).

Adolescent↗
PubMed2006

Population-based case-control teratogenic study of hydroxyprogesterone treatment during pregnancy.

Hydroxyprogesterone, a synthetic progestin, was used for the treatment of pregnant women with threatened abortion and preterm delivery. Previous studies showed some association between hydroxyprogesterone use during early pregnancy and some specific congenital abnormalities. The population-based large Hungarian data set seemed to be appropriate to check this possible association. The Hungarian Case-Control Surveillance of Congenital Abnormalities between 1980 and 1996 includes 22 843 cases with congenital abnormalities and 38 151 controls without any defect. 318 (1.4%) cases, while 433 (1.1%) controls had mothers with hydroxyprogesterone treatment during pregnancy (adjusted POR with 95% CI: 1.3, 1.1-1.5). However, there was no association between risk for any congenital abnormality group and a higher use of maternal hydroxyprogesterone treatment during the second and third month of gestation. On the other hand hydroxyprogesterone is not effective in the prevention of preterm delivery. In conclusion, there was no detectable risk for congenital abnormalities in the offspring of mothers with hydroxyprogesterone treatment during early pregnancy, however, there is no reasonable indication of this treatment during pregnancy.

17 alpha-Hydroxyprogesterone Caproate↗
PubMed2006

Identification of human dim1 as a peptidase with autocleavage activity.

Dim1 is a highly conserved splicing factor. It is encoded by an essential gene in fission yeast and the Caenorhabditis elegans. It may also be involved in tissue-specific or pathway-specific alternative splicing. Here, we report that besides its function in pre-mRNA splicing, human dim1 is a peptidase and has autocleavage activity. Its autocleavage results in a thioredoxin-like core that was shown previously to act as a dominant negative in fission yeast. The truncated form retains its peptidase activity. Future studies will be needed to identify residues important for dim1-peptidase activity and to characterize its substrate specificity. The biologic importance of dim1's peptidase function and its natural substrate(s) also need to be determined. However, if one or more of its substrates is involved in the pathogenesis of a human disease, dim1 may become a new target for drug development.

Caproates↗
PubMed1988

Hepatotoxicity to dogs of horse meat contaminated with indospicine.

An outbreak of liver disease which killed more than 30 dogs at Alice Springs was associated with feeding meat from horses, some of which had developed Indigofera linnaei poisoning (Birdsville horse disease). Affected livers were small, nodular and yellow. There was associated jaundice, ascites, elevation of alanine aminotransferase levels in serum, a tendency to bleed, and signs of hepatic encephalopathy. Histologically, livers showed periacinar necrosis, collapse and haemorrhage, with severe swelling, vacuolation and cholestasis in remaining hepatocytes. Indospicine, a toxic amino acid found in the genus Indigofera, was detected in samples of suspect horsemeat. Experimental feeding of horsemeat containing 16 mg indospicine/kg for 32 days produced periacinar necrosis and hepatocellular swelling in 2 dogs, although neither died nor showed clinical illness. In another experiment, intakes of as little as 0.13 mg indospicine/kg bodyweight/day for 70 days produced periacinar liver lesions, and indospicine concentrations in serum, muscle and liver rose during this period to 3.9, 7.9 and 17.5 mg/kg, respectively. It was concluded that meat from horses grazing I. linnaei can be hepatotoxic for dogs, and that this toxicity may be related to its indospicine content.

Amino Acids↗
PubMed1968

A relation between the chain length of fatty acids and the slowing of gastric emptying.

1. Test meals of solutions and suspensions of potassium and sodium salts of a series of saturated fatty acids, from C(2) to C(18), were given to healthy subjects.2. From the volume of these meals recovered after a fixed interval the relative effectiveness of the salts of the acids in slowing gastric emptying was assessed.3. On a molar basis the salts of fatty acids from acetic up to decanoic were relatively ineffective in slowing gastric emptying.4. The salts of fatty acids with 12-18 carbon atoms were much more effective than those with up to 10 carbon atoms. Myristate was the most effective of the salts.5. Buffering the test meals with 33 mM sodium citrate increased the effectiveness of the salts in slowing gastric emptying.

Acetates↗
PubMed1969

The slowing of gastric emptying by nine acids.

1. Test meals containing a range of concentrations of nine different acids were given to twenty healthy subjects. The acids used were hydrochloric, acetic, lactic, tartaric, phosphoric, citric, propionic, butyric and hexanoic.2. The greater the concentration of acid in the meal the greater was the volume of the meal recovered after a fixed interval.3. A rectilinear relationship between the mean concentrations of acid (m-equiv/l.) required to give a recovery of 450 ml. and the molecular weights of the acids used was found. The acids with high molecular weights were less effective than those with low molecular weights.4. The results indicate that the molecular weights of the anions play the dominant part in determining the effectiveness of the various acids. Slowing of gastric emptying by acids does not seem to be dependent upon their pK values provided they are less than 5. The oil/water partition coefficients are also apparently irrelevant to effectiveness.5. These findings are considered to be consistent with the view that a barrier to movement of the anions in an aqueous system limits the access of the hydrogen ions to duodenal receptors, which activate the mechanism slowing gastric emptying.

Acetates↗
PubMed1972

The slowing of gastric emptying by four strong acids and three weak acids.

1. Test meals of 750 ml. water containing a range of concentrations of hydrochloric, nitric, sulphuric, cyclamic (cyclohexylsulphamic), tartaric, L-ascorbic and citric acids were instilled into the stomachs of sixteen healthy subjects.2. The greater the concentration of an acid in the instilled meal, the greater was the volume of meal recovered after a fixed interval.3. For the weak acids, tartaric, ascorbic and citric, the concentrations which gave a recovery of 450 ml., out of the 750 ml. instilled, increased with increase in the molecular weight of the acid.4. For the strong acids, hydrochloric, nitric, sulphuric and cyclamic, the concentrations which gave a recovery of 450 ml., out of the 750 ml. instilled, were approximately equal. These concentrations were less than those for weak acids.5. The strong acids with high molecular weights were slightly more effective in slowing gastric emptying than were those with low molecular weights.6. The approximate equality of effectiveness of nitric, sulphuric and cyclamic acids to hydrochloric acid is attributed to the presence of chloride ion in the duodenal contents. Thus all the strong acids instilled produce an environment of hydrochloric acid around the receptor.7. A model for a duodenal receptor responding to acids is proposed.

Acetates↗
PubMed1981

Regulation of 86Rb outflow from pancreatic islets: the dual effect of nutrient secretagogues.

1. An increase in the concentration of extracellular D-glucose from zero to 1.7 mM or more (up to 16.7 mM) causes a rapid and sustained decrease in 86Rb fractional outflow rate (FOR) from prelabelled and perifused pancreatic rat islets. The 86Rb FOR also decreases when the concentration of D-glucose is raised from 1.7 mM or more (up to 5.6 mM) to higher values not exceeding 8.3 mM. 2. However, when the glucose concentration is raised from 8.3 mM (or 11.1 mM) to higher values, no decrease in 86Rb FOR is observed and, instead, a transient increase in 86Rb FOR now takes place. 3. Such a dual effect on 86Rb FOR is also observed when alpha-ketoisocaproic acid is used as the nutrient secretagogue or when the latter keto acid is used in combination with D-glucose. 4. The transient increase in 86Rb FOR evoked by D-glucose in islets already exposed to alpha-ketoisocaproate is abolished by mannoheptulose, suggesting that it depends on the integrity of glucose metabolism. 5. The transient increase in 86Rb FOR evoked, under suitable experimental conditions, by D-glucose of alpha-ketoisocaproate is abolished in the absence of extracellular Ca2+ and mimicked by theophylline and tolbutamide, suggesting that it is attributable to an increase in cytosolic Ca2+ concentration. The latter view is supported by the fact that the increase in 86Rb FOR coincides with an increase in 45Ca FOR, provided that Ca2+ is not removed from the extracellular medium. 6. It is concluded that, in contrast to the situation found when the concentration of the nutrient secretagogue is increased from a non-insulinotropic to a higher value, the stimulation of Ca2+ entry into islet cells and the subsequent increase in insulin secretion evoked by D-glucose or alpha-ketoisocaproate when the concentration of these nutrients is increased from intermediate (8.3-10.0 mM) to higher values is not attributable to a decrease in K+ conductance.

Animals↗
PubMed1984

Anaesthetic action of esters and ketones: evidence for an interaction with the sodium channel protein in squid axons.

The effects of methyl butyl ketone, methyl heptyl ketone and methyl pentanoate on the sodium current of the squid giant axon have been examined. The peak inward current in intact axons was reduced reversibly by each substance. Sodium currents were recorded in intracellularly perfused axons before and during exposure to the test substances and the records were fitted with equations similar to those proposed by Hodgkin & Huxley (1952). Shifts in the voltage dependence of the steady-state activation and inactivation parameters (m infinity and h infinity), reductions in the peak heights of the activation and inactivation time constants (tau m and tau h) and changes in the maximum sodium conductance (gNa) caused by these substances have been tabulated and compared with the effects of methyl octanoate (Haydon & Urban, 1983b). Each compound shifted the voltage dependence of the steady-state inactivation parameter in the hyperpolarizing direction and that of the steady-state activation parameter in the depolarizing direction. The shifts produced by the ketones are compared with those produced by methyl pentanoate and by methyl octanoate. The possible role of an interaction between the carbonyl oxygen of the test substance and the sodium channel protein in producing the h infinity shift is discussed. The peak time constants are reduced and the voltage dependences of tau m and tau h are shifted in a direction commensurate with the shifts in steady-state properties. The maximum sodium conductance is not much affected either by the ketones or by methyl pentanoate. Large reductions in peak inward current coupled with little effect on gNa have been reported for the n-alkanols and other surface-active compounds (Haydon & Urban, 1983b). This lack of a large effect on gNa indicates that whatever direct interaction does take place between the test substance and the channel protein, it does not result in a blockage of the channel.

Animals↗