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Biomedical subjects

P Singer

Publications and source records attributed to P Singer.

At least 163 records · Page 9Linked to original sources

Ototoxicity of intraventricularly administered gentamicin in adult rabbits.

To determine whether daily intraventricular injection of gentamicin sulfate is ototoxic, adult male rabbits were given 0.2 ml of saline (group 1; n = 8) or 0.25 mg/kg of gentamicin sulfate in 0.2 ml of saline (group 2; n = 7) by intraventricular infusion once a day for 21 d. All rabbits were also given intramuscular gentamicin sulfate, 2 mg/kg, twice daily. Before and after antibiotic treatment, brainstem auditory evoked responses (BAERs) were recorded. During the experimental period, neurologic examinations were performed on all rabbits. After treatment, the animals were euthanized; brain tissue and cochleas were then removed for histopathologic examination. The ratios of neurologic abnormalities observed in group 1 and 2 animals, respectively, were 0/8 and 5/7; of abnormal BAERs, 0/8 and 5/7; of abnormal brain morphology, 2/5 and 6/6; and of abnormal cochlear morphology, 0/6 and 7/7. The electrophysiologic evidence of auditory deficit and the structural evidence of ototoxic insult are significantly associated (p less than or equal to 0.006) with intraventricularly administered gentamicin sulfate. These data suggest that intraventricular gentamicin should be used with caution.

Animals↗

Changes of blood pressure in spontaneously hypertensive rats dependent on the quantity and quality of fat intake.

The effect of diets rich or deficient in polyunsaturated fatty acids (PUFA) on blood pressure of spontaneously hypertensive rats (SHR) and normotensive Wistar rats (WR) was studied. The diets contained either sunflower oil (PUR-SOL), linseed oil (PUR-LIN), cod-liver oil or hydrogenated palm-kernel oil (PUFA-deficient) amounting to 15 or 3 weight percent of fat. They were started at weaning (4 weeks of age) for 22 weeks or prenatally one week before mating of the parents. During the development of hypertension in SHR, systolic blood pressure was decreased in animals of all dietary groups fed 15% fat when compared to SHR on normal food (pellets), i.e. independent of the various diets loaded, all diets containing 15% fat led to a marked delay in the onset of high blood pressure as compared to SHR on normal pellet food. After manifestation of hypertension, obviously a more differentiated effect on blood pressure could be shown in SHR in dependence on different amounts of PUFA loaded. In normotensive Wistar rats (WR) after feeding linseed oil or sunflower oil also a significant lowering in blood pressure could be observed in comparison to controls fed pellets. But after feeding cod-liver oil there was no decrease in blood pressure of normotensive Wistar rats, whereas palm-kernel oil resulted in a blood pressure lowering effect only at the later age of normotensive Wistar rats. Moreover, in SHR after prenatal feeding of a LA-rich, but also a PUFA-deficient diet the blood pressure lowering effect was more pronounced as compared to postnatal feeding of the diets. SHR fed a 15% fat diet showed a significantly lower body weight in comparison to SHR fed a 3% fat diet. In both dietary groups SHR were significantly smaller than SHR fed pellets. In WKY fed a 3% or a 15% fat diet the same body weight could be confirmed. Food intake in SHR fed a 3% fat diet ad libitum appeared higher than in SHR fed a 15% fat diet ad libitum. However, considering the uptake of energy no differences between the groups could be seen. Therefore, in SHR fed a 15% fat diet, body weight and blood pressure were lowest when compared with the other groups of SHR indicating that body weight in SHR might be nearly connected with blood pressure level.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗

Age-dependent alterations of linoleic, arachidonic and eicosapentaenoic acids in renal cortex and medulla of spontaneously hypertensive rats.

The lipid content as well as the fatty acid pattern of triglycerides, free fatty acids (FFA), phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were estimated in renal cortex and medulla of spontaneously hypertensive rats (SHR) and normotensive Wistar rats (WR) at 4, 8, 26 and 52 weeks of age. In general, the level of triglycerides in renal medulla appeared higher when compared with the cortex. On the other hand, PC and PE, increasing with age, were usually higher in the cortex. A decreased percentage of linoleic acid (LA) in triglycerides, of arachidonic acid (AA) in PC and of eicosapentaenoic acid (EPA) in triglycerides, FFA, PC and PE could be found in the kidneys of SHR at 8 weeks of age, i.e. during the development of hypertension. This was accompanied with a rise of AA in FFA of SHR at 8 weeks of age, which occurred with delay in WR (at 26 weeks of age). From the data presented it can be concluded that systematic alterations in the availability of individual polyunsaturated fatty acids (PUFA) in various renal lipids might be related to the onset of hypertension in SHR which should be elucidated in more detail.

Aging↗

Changes of arachidonic acid in phosphatidylcholine different from other lipids in kidneys of spontaneously hypertensive rats after feeding a linoleic acid-rich diet.

In spontaneously hypertensive rats (SHR) fed a linoleic acid-rich (LAR) diet over 22 weeks blood pressure could not be influenced when compared with SHR on linoleic acid-deficient (LAD) food. On the other hand, normotensive Wistar rats (WR) revealed a significantly lower blood pressure after feeding a LAR diet. The percentages of LA and AA were markedly increased in triglycerides and free fatty acids (FFA) in renal cortex and medulla of LAR-fed SHR and WR in comparison to LAD-fed animals. In renal phosphatidylethanolamine (PE) LA was also increased whereas AA remained unchanged. On the contrary, in phosphatidylcholine (PC) LA was only slightly augmented (in SHR) or even lowered (in WR), AA appearing decreased in SHR but increased in WR. These different changes in PE and PC indicate that individual phospholipids show a dissimilar behavior after dietary interventions, which can be masked by the evaluation of total phospholipids and might be of pathophysiological relevance.

Animals↗

Defective desaturation and elongation of n-6 and n-3 fatty acids in hypertensive patients.

Hypertensive patients had higher levels of linoleic acid (LA) in serum lipids than normal controls. Administration of large doses of LA failed to raise the percentage of its metabolite arachidonic acid (AA) in serum lipids. Similarly, intake of large amounts of alpha-linolenic acid (alpha-LNA) failed to increase the amount of eicosapentaenoic acid (EPA). The percentage of EPA in serum lipids could readily be increased by direct administration of comparably low doses in a mackerel diet. Hypertensive subjects seem to desaturate and elongate LA and alpha-LNA only very slowly.

Animals↗

Decrease of arachidonic acid in phosphatidylcholine from renal medulla of SHR after feeding a linoleic and linolenic acid-rich diet.

Linoleic acid-rich (LAR), linolenic acid-rich (LNAR) and linoleic acid-deficient (LAD) diets in spontaneously hypertensive rats (SHR) and normotensive rats (NR) resulted in various changes in n-6 and n-3 fatty acids of lipids in renal medulla. After LAR diets the percentage of linoleic (LA) and arachidonic acids (AA) was high only in triglycerides (TG) and free fatty acids (FFA). In phosphatidylethanolamine (PE) LA was increased after LAR diet, whereas AA remained unchanged. In phosphatidylcholine (PC) LA was higher, but AA appeared lower as compared to LAD fed SHR. After LNAR diet linolenic (LNA) and eicosapentaenoic acids (EPA) were increased, but AA appeared significantly lower. Consequently, the lowest percentage of AA was found after LNAR diet. Blood pressure could not be influenced by the diets.

Animals↗

Alterations of linoleic, arachidonic and eicosapentaenoic acids in renal cortex and medulla of SHR during the onset of hypertension.

104 spontaneously hypertensive rats (SHR) and 107 normotensive control rats (WR) fed a commercial diet were sacrificed at 4, 8, 26 and 52 weeks of age. The kidneys were immediately removed and carefully separated into cortex and medulla. In general, the triglyceride levels in renal medulla appeared higher when compared with the cortex. On the other hand, phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were usually higher in the cortex and increased with age. In the kidneys of SHR at 8 weeks of age, i.e. during the development of hypertension, the percentage of linoleic acid (LA) in triglycerides and of arachidonic acid (AA) in PC was decreased. This was associated with an increase of AA in free fatty acids (FFA), indicating an enhanced activity of phospholipase A2. Furthermore, a fall of eicosapentaenoic acid (EPA) in triglycerides, FFA, PC and PE of kidneys in SHR at 8 weeks of age could be found. The data suggest that systematic alterations in the availability of individual polyunsaturated fatty acids in various renal lipids might be related to the onset of hypertension in SHR. Age-dependent changes in enzymes involved in prostaglandin formation should be considered as an adaptive mechanism which is insufficient to reduce or abolish genetically determined hypertension in SHR.

Aging↗

Clinical studies on lipid and blood pressure lowering effect of eicosa-pentaenoic acid-rich diet.

15 volunteers were put on a mackerel (MD) and herring diet (HD) for 2 weeks in a cross-over design. At the end of the dietary periods eicosa-pentaenoic acid (EPA) was predominantly incorporated into cholesterol esters (CE), whereas docosahexaenoic acid (DHA) appeared more in triglycerides (TG). This was more pronounced after MD as compared to HD. After MD a significant decrease of serum TG, total cholesterol (C) and lecithin cholesterol acyl transferase (LCAT) activity could be observed returning to the initial levels 3 months later. After HD only a decrease of LCAT was significant. In addition, a marked decrease in blood pressure (BP) was associated with lower plasma noradrenaline levels after MD, but not after HD. In 14 patients with mild essential hypertension an enhanced percentage of EPA and DHA in the lipids of VLDL, LDL and HDL could be confirmed. After MD serum TG, C, LDL-C and LCAT were significantly decreased, whereas HDL-C appeared increased. After HD the changes were of minor degree. Systolic BP was significantly lower at the end of MD. In 8 patients with type IV and V hyperlipoproteinemia (HLP) similar changes could be seen, the most striking finding being a fall in serum TG, especially if initial values were extraordinarily high. The data suggest a beneficial effect of MD on several parameters known as risk factors of atherosclerosis.

Adult↗

Negative correlation of eicosapentaenoic acid and lipid accumulation in hepatocytes of diabetics.

In 130 type I and II diabetics with normal serum lipids and in 98 diabetics with type IIa-V hyperlipoproteinemia (HLP), liver biopsies were performed if clinically indicated. During histological examinations of one half of the biopsy specimen lipid droplet size was classified into 4 categories, which were proved by morphometric studies, independent of the amount of fat. From the remaining part the fatty acid composition of triglycerides was analyzed by gas liquid chromatography. Moreover, the fatty acid pattern of serum triglycerides and subcutaneous adipose tissue from the abdominal wall was estimated. The percentage of eicosapentaenoic acid (EPA) in triglycerides of normal diabetic liver (no visible fat) was remarkably high (greater than 30 per cent). In adipose tissue it was low (less than 1 per cent). In serum triglycerides it remained between liver and depot fat (about 3 per cent). EPA decreased with rising lipid droplet size in hepatocytes. Liver diseases, like chronic hepatitis, had no influence on the results. One year after clofibrate treatment, the percentage of EPA in liver appeared increased. In adipose tissue, however, it remained constant. In general, EPA in liver and serum triglycerides was higher in diabetics with normal serum lipids as compared to diabetics with HLP. The decreased availability of EPA in liver and serum triglycerides of diabetics with HLP suggests a significant correlation between this fatty acid and hepatic lipid accumulation which itself is associated with diseases known as risk factors of atherosclerosis.

Adipose Tissue↗

Mono-, di- and triglycerides in serum of spontaneously hypertensive and normotensive rats in relation to age.

Serum triglycerides appeared significantly lower in spontaneously hypertensive as compared to normotensive rats except in 8-week-old animals. Tri-, di and monoglycerides decreased continuously with age in the former but revealed only a transient fall in the latter. The remarkably high portion of partial glycerides (about 30% of total glycerides) in serum should be considered in all studies on lipolysis in rats.

Aging↗

The treatment of newborn infants with major handicaps. A survey of obstetricians and paediatricians in Victoria.

We report the results of a survey of the attitudes and practices of obstetricians and paediatricians in Victoria with respect to the treatment of infants born with severe handicaps. Eighty-seven obstetricians and 111 paediatricians either completed questionnaires or agreed to be interviewed during the period 1981-1982. The treatment of severely handicapped infants is a matter of increasing concern to members both of the public and of the medical profession. The principal question is whether every infant should have its life prolonged by all available means, or whether some infants born with severe handicaps should be allowed to die. We attempt to identify areas of consensus and disagreement. We do not propound any particular point of view--our intention is rather to stimulate debate.

Attitude of Health Personnel↗

Role of electrical activity in axotomy-induced increased glucose use.

Glucose use as demonstrated by 2-deoxyglucose autoradiography increases in the hypoglossal nucleus after axotomy of the hypoglossal nerve. There are several possible explanations for this increase, including increased energy metabolism to support increased protein, RNA, and lipid synthesis during regeneration or, alternatively, increased electrical activity associated with the site of nerve transection or alterations in the neurolemma. To evaluate the possible role of electrical activity, we recorded spike activity in the hypoglossal nucleus after axotomy and evaluated glucose uptake in the hypoglossal nucleus after xylocaine application to the proximal nerve stump. There was no evidence from these experiments that an increased number of action potentials is responsible for the increased glucose use after axotomy.

Action Potentials↗