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PubMed1979

Metabolic studies in rats under glucose and glycerol loading.

It has been found in rats that 40% glycerol, when added to standard diet, reduces the food intake and thus prevents weight gain. The subcutaneous application (40 mg/kg three times daily) has no effect. Under pair feeding conditions the oxygen consumption, the RQ value and body weight remain unaffected as compared with controls receiving glucose. It is concluded that reduction of body weight induced by glycerol feeding is due to reduced amount of food intake and not due to any alterations of energy metabolism.

Animals↗
PubMed1976

[Effect of clofibrate on glucose tolerance and insulin secretion in patients with endogenous hypertriglyceridemia (author's transl)].

In 22 patients with endogenous hypertriglyceridemia, oral and intravenous glucose tolerance showed significant improvement under clofibrate treatment which was in no way correlated to the fall in triglycerides. Basal and stimulated insulin, cholesterol and fasting blood sugar did not change, body weight remained constant and was not correlated to the degree of hypertriglyceridemia. On the other hand a positive correlation between body weight and insulin concentrations was found. Improvement of glucose tolerance independently of body weight and insulin may be due to a direct effect of clofibrate on glucose metabolism without any correlation to its triglyceride-lowering.

Administration, Oral↗
PubMed1979

Activities of enzymes of fat and ketone-body metabolism and effects of starvation on blood concentrations of glucose and fat fuels in teleost and elasmobranch fish.

1. Activities of 3-oxo acid CoA-transferase and carnitine palmitoyltransferase together with tri- and di-acylglycerol lipase were present in red and heart muscles of the teleost fish. However, d-3-hydroxybutyrate dehydrogenase activity was not detectable. These results suggest that the heart and red muscles of the teleosts should be able to utilize the fat fuels triacylglycerol, fatty acids or acetoacetate, but not hydroxybutyrate. The muscles from the elasmobranchs differed in that d-3-hydroxybutyrate dehydrogenase and 3-oxo acid CoA-transferase activities were present, but carnitine palmitoyltransferase activity was not detectable. This suggests that ketone bodies are the most important fat fuels in elasmobranchs. 2. The concentrations of acetoacetate, 3-hydroxybutyrate, glycerol, non-esterified fatty acids and triacylglycerols were measured in blood or plasma of several species of fish (teleosts and elasmobranchs) in the fed state. Teleosts have a 10-fold higher concentration of plasma non-esterified fatty acids, but a lower blood concentration of ketone bodies; both acetoacetate and 3-hydroxybutyrate are present in blood of elasmobranchs, whereas 3-hydroxybutyrate is absent from that of the teleosts. 3. The effects of starvation (up to 150 days) on the concentrations of blood metabolites were studied in a teleost (bass) and an elasmobranch (dogfish). In the bass there was a 60% decrease in blood glucose after 100 and 150 days starvation. In dogfish there was a large increase in the concentration of ketone bodies, whereas in bass the concentration of acetoacetate (the only ketone body present) remained low (<0.04mm) throughout the period of starvation. The concentration of plasma non-esterified fatty acids increased in bass, but decreased in dogfish. These changes are consistent with the predictions based on the enzyme-activity data. 4. Starvation did not change the activities of ketone-body-utilizing enzymes or that of phosphoenolpyruvate carboxykinase in heart and red skeletal muscles of both fish, but it decreased markedly the activity of phosphoenolpyruvate carboxykinase in white skeletal muscle of both fish. However, in the liver of the dogfish, starvation resulted in a twofold increase in the activities of 3-hydroxybutyrate dehydrogenase and acetoacetyl-CoA thiolase, whereas in bass liver it decreased the activity of acetoacetyl-CoA thiolase and increased that of 3-oxo acid CoA-transferase. The activity of phosphoenolpyruvate carboxykinase was increased twofold in the liver of bass, but was unchanged in that of the dogfish. 5. The difference in changes in concentrations of blood metabolites and enzyme activities in the two fish support the suggestion that, in starvation, ketone bodies, but not non-esterified fatty acids, are an important fuel for muscle in elasmobranchs, whereas non-esterified fatty acids, but not ketone bodies, are an important fuel in teleosts. The results are discussed in relation to the evolution of a discrete lipid-storing adipose tissue in teleosts and higher vertebrates.

Animals↗
PubMed1979

[Possibilities of calculating the fat-free body mass and its reaction to a carbohydrate-poor, fat-rich diet].

9 healthy medical students got an isocaloric fat-rich carbohydrate-reduced diet during 14 days. Body-weight and lean body mass were registrated. We calculated lean body mass from measurement of skinfold thickness, total body potassium and total body water. Body-weight was reduced highly significantly by 3.4 kg on an average. Body potassium and body water remained unchanged. It can be concluded from these results that weight loss was caused by an exclusive reduction of the fat mass.

Adult↗
PubMed2026

Anatomical location defines distinct molecular subtypes of mucosal melanoma.

BACKGROUND: Mucosal melanoma (MM) is a rare and aggressive melanoma subtype that is understudied. The relationships between anatomical location, genomic alterations, stage at presentation, and survival remain incompletely characterized. METHODS: We carried out a retrospective single tertiary center study of 105 patients with histologically confirmed MM diagnosed between 1996 and 2025. Clinical and genomic data were analyzed to evaluate associations between anatomical location, mutational profile, stage at presentation, and survival outcomes, including melanoma-specific mortality. RESULTS: Lower-body tumors arising in the anus or genital areas were enriched for KIT and splicing factor 3 subunit B1 alterations, whereas NRAS mutations were distributed across anatomical regions. Among the two most common mutated genes, NRAS-mutant tumors were more likely than KIT-mutant tumors to present with metastatic disease [53% versus 19%; P = 0.046, odds ratio (OR) 4.7, 95% confidence interval (CI) 1.15-19.41]. Lower-body tumors were associated with worse overall survival (OS) than upper-body tumors (median 2.81 versus 8.40 years; OR = 0.05) and with higher melanoma-specific mortality. In multivariable analyses, upper-body location remained independently associated with improved OS (hazard ratio 0.14, 95% CI 0.05-0.36, P < 0.001). CONCLUSIONS: Anatomical location of MMs and genomic alterations define biologically and clinically distinct subtypes.

KIT mutation↗
PubMed1978

Potentiation of hyperphagia and relief of hypothermia in the genetically obese mouse (genotype, ob/ob) by alpha-methyl tyrosine.

DL-alpha-methyl-p-tyrosine methyl ester hydrochloride affected the hyperphagia and hypothermia characteristic of the genetically obese mouse (genotype, ob/ob) throughout an experimental period of 5 days. Intraperitoneal injections of 100 mg/kg body weight, daily, resulted in a significant increase in the average daily food consumption by 60 per cent, already elevated 35 per cent above that of lean litter-mates. The drug, administered at the same dose, caused a similar percentage elevation of food intake in the lean litter-mates. Rectal temperatures of obese mice were raised significantly throughout the 5-day period by an average of 0.95 degrees C, following administration of the drug. There was a significant rise of 0.75 degrees C in the rectal temperature of lean mice on 2 of the 5 days in the period. Body weight remained unchanged. Further experiments are necessary to determine the site of action at which DL-alpha-methyl-p-tyrosine brings about these effects at this dose in lean and obese mice.

Animals↗
PubMed1975

[Glucose tolerance, insulin and lipids after one week's administration of fenfluramine to overweight patients (author's transl)].

The effect of oral administration of the amphetamine derivative, fenfluramine for one week was investigated in comparison to a placebo for the same period in 28 overweight patients, 57% of whom showed a reduced glucose tolerance. In addition to glucose and insulin, the lipid fractions were also measured. In the series with pathological glucose tolerance in which the body weight remained unchanged, fenfluramine produced a lowering of the basal levels of blood sugar and insulin. After oral loading with glucose the total rise in glucose and the rise in insulin in the late phase were diminished. Free fatty acids, free glycerol, triglycerides and cholesterol were not affected.

Adult↗
PubMed1979

Sodium, potassium and water metabolism in the rabbit: the effect of sodium depletion and repletion.

1. Dietary sodium depletion and subsequent repletion was studied in rabbits. Potassium intake was maintained constant. 2. during sodium depletion and repletion blood pressure, packed cell volume, food consumption and body weight remained at control values. 3. Decreased sodium excretion was observed in both urine and faeces during sodium depletion and the physiological control of these changes is discussed in relation to the renin-angiotensin-aldosterone system. 4. Potassium excretion during sodium depletion initially fell as a result of reduced urine volume and gradually returned to normal. Urine potassium concentration remained constant. 5. Faecal excretion of potassium rose by 63% during sodium depletion and there was a rise from a control value of 17-25% in the proportion of total potassium excretion accounted for by the faecal component. 6. Water consumption and urine volume both decreased in the initial phase of sodium depletion and then returned to control levels. 7. It is important to consider both urinary and faecal excretion of sodium and potassium when calculating balance status for either ion. Faecal excretion, as well as kidney function, shows important physiological adaptations.

Animals↗
PubMed1979

Methods of assessing diabetic control.

Control of diabetes from complete normalisation to less adequate degrees of metabolic regulation needs to be assessed with regard to conditions of evaluation and to severity of the disease. Under optimal conditions the therapeutic events should occur with well-timed regularity. Different assessment criteria are appropriate depending on the severity of the deficiency of endogenous insulin. Plasma and urine glucose and ketone body measurements remain the practical standards for assessing diabetic control. Abnormalities of lipid and protein metabolites serve to augment the scope of the assessment. Triglycerides and haemoglobin AIc are also useful indicators of control. In mild (Type II) diabetes it may be possible to achieve normal plasma glucose measurements two hours after meals. Such aims carry a risk of hypoglycaemia in severe (Type I) diabetes. Normoglycaemia and aglycosuria in severe diabetes are feasible only preprandially in most cases. The use of urine glucose tests requires evaluation of blood-to-urine glucose relationships. Practical and convenient methods for identifying patients with high or low "renal thresholds" are described. Investigational methods for characterising diabetic patients assess the variability of glucose and other variables during therapy, as well as the degree to which normal values are attained. Such assessment methods may gain increasing practical importance as therapeutic approaches to diabetic control which are experimental at present come into practice.

Blood Glucose↗
PubMed2026

Evaluation of bone preparation approaches using length-based analysis and targeted sequencing for forensic human identification of historic skeletal remains.

Advances in DNA technology have significantly enhanced the forensic community's ability to develop genetic profiles from unidentified human skeletal remains. However, sampling requires mechanical grinding of hard tissues before DNA isolation. This processing can compromise genetic profiles, particularly in aged bones. We compared the industry-standard pulverization method with an alternative powder-free preparation involving prolonged demineralization and subsequent slicing of 19th-century cortical bone. Data from DNA quantification, STR genotyping, and targeted SNP sequencing were used to evaluate powdered samples versus demineralized slices from paired human bones. Average human DNA yields for pulverized samples and demineralized slices were 0.032&#x2009;ng and 0.692&#x2009;ng, respectively. Demineralized slices recovered more amplifiable DNA than traditional homogenization methods (p&#x2009;<&#x2009;0.05). No pulverized samples produced STR profiles, whereas demineralized slices from the same bone samples yielded partial profiles. Samples underwent DNA repair, library preparation, and hybridization capture using the FORensic Capture Enrichment (FORCE) panel. Applying low-coverage (1X) analysis of high-throughput sequencing (HTS) data, demineralized slices outperformed those prepared by traditional pulverization methods (p&#x2009;<&#x2009;0.05) and substantially increased the information recovered compared with conventional STR analysis methods. Based on HTS data from pulverized samples, DNA fragment length ranged from 27 to 95&#x2009;bp, and FORCE SNP recovery was 33.23%. In contrast, for demineralized slices, DNA fragment length ranged from 85 to 114&#x2009;bp, and FORCE SNP recovery was 83.24%. The required reagents and equipment are typically available in forensic labs, and the workflow outlined herein significantly increases the success of DNA recovery from challenging skeletal samples.

Humans↗
PubMed1979

Effects of chronic intraventricular administration of angiotensin II on drinking behavior and blood pressure.

Angiotensin II was continuously infused into the lateral cerebral ventricle of rats, and the effects on daily food and water consumption, urine volume, and aortic blood pressure were studied. All was infused at a rate of 10 ng/hr for seven days, using subcutaneously implanted osmotic minipumps. An intraventricular (IVT) control group was infused with only the saline vehicle, while a third group received AII subcutaneously. IVT AII rats showed a four-fold increase in water consumption, to a mean of 171 ml/day during Days 2-4 of infusion, whereas water intake of the other groups did not change from preinfusion levels. Urine volume showed a similar pattern to water intake, increasing five-fold in the IVT AII group during Days 2-4. These measures declined during the final three days of AII infusion, but significant tolerance was not observed. Food intake decreased markedly in both saline and IVT AII groups after implantation of the pumps, but the latter resumed normal food intake more slowly than the former, and body weight remained below preinfusion levels throughout the AII period. Aortic blood pressure of the IVT AII rats showed a slight, but progressive, rise during the infusion period, but it did not significantly exceed that of the saline rats. These results indicate that continuous, low-level, intraventricular infusion of AII may markedly increase water intake without significantly increasing fluid retention or blood pressure.

Angiotensin II↗
PubMed1979

[Regression of left ventricular hypertophy in the ECG during antihypertensive treatment: preliminary observations (author's transl)].

Typical signs of left ventricular hypertrophy (LVH) were present in the ECG of 36 (10 women, 26 men) of 127 persons with essential hypertension (46 women, 81 men). After a two-year course of combined drug treatment (chlortalidone, reserpine, methyl-dopa, hydralazine) with effective blood-pressure reduction LVH was still present in the ECG of 29, after a four-year course of only 15 among 36, i. e. a reduction in the presence of LVH of nearly 60%. Since the patients' body-weight remained unchanged during this period, the regression in ECG changes is ascribed to the effectiveness of the drug treatment.

Adult↗
PubMed1978

Histopathologic effects of dietary cadmium on kidneys and testes of mallard ducks.

Mallard ducks fed 2, 20, or 200 ppm cadmium chloride were sacrificed at 30, 60, and 90 d. No mortality occured during the study and body weights remained unchanged. Kidney weights of the 200-ppm group were significantly greater after 60 and 90 d than those of controls; also, testis weights were significantly lower after 90 d. Kidneys of ducks fed 2 and 20 ppm cadmium were relatively unaffected; however, slight to severe kidney lesions were found in the 200-ppm group after 60 d of treatment. No significant lesions were found in mallard testes after feeding 2 ppm cadmium in the diet, and only a few birds in the 20-ppm group showed slight to moderate gonad alterations. After 90 d of treatment, however, testes of males fed 200 ppm had atrophied and the spermatogenic process had ceased. This study should provide important information for the interpretation of cadmium levels found in kidneys and testes of wild ducks.

Animals↗
PubMed1979

Cytologic observations on axotomized feline Betz cells. 1. Qualitative electron microscopic findings.

Adult cats survived left lateral funiculotomy 1 to 153 days. The pericruciate cortex was studied electron microscopically in these as well as sham-operated and unoperated animals. Ten days after surgery Betz cells of the right pericruciate cortex displayed disaggregation of cytoplasmic ribosomes; random dispersal and degranulation of the normally compact arrays of cisterns of rough ER; in some cells perinuclear and peripheral disposition of remaining Nissl bodies; retispersion of the Golgi apparatus; and, uncommonly, neurofilamentous hyperplasia. Fourteen days postoperatively cytoplasmic ribosomes were largely regrouped in rosette arrangements and Golgi membranes were evenly distributed in the cytoplasm. Further reversion of the ER toward a normal appearance occurred 28 days postoperatively but substantial perikaryal atrophy had supervened in many neurons by 49-153 days after surgery. Evidence of nerve cell death was not found. Concentric membranous arrays derived from ER and associated with autophagic bodies and mitochondria were identified in dendrites of normals and cats that had been operated upon, perhaps more frequently contralateral to the spinal operation. Electron-dense and electron-lucent degenerative changes in dendrites also occurred, especially early after operation. Degenerating myelin sheaths were detected in the pericruciate cortex of animals that had been operated upon and sometimes were captured in the process of phagocytosis by oligodendrocytes as well as astrocytes and microglia. The long-term persistence of axotomized Betz cells, albeit in an atrophic state, and the reversibility of some of the cytologic responses to axon injury suggest that these neurons may retain a capacity for axon regeneration that could be mobilized, as by pharmacologic means.

Animals↗
PubMed1979

Maintenance of potassium balance during diuretic therapy.

The relative efficacies of potassium chloride, amiloride, triamterene and spironolactone in maintaining potassium balance were studied in 40 patients with essential hypertension receiving diuretic therapy. The preparations were administered in random order in a cross-over manner. In 31 patients treated with 50 mg hydrochlorothiazide daily, addition of 1500 mg potassium chloride daily was the weakest and 50 mg spironolactone daily the most effective agent for maintaining serum potassium. Amiloride (5 mg daily) and triamterene (75 mg daily) were less effective and equally so. Similar results were obtained with 9 patients treated with double dosages of the diuretic and supplements. Despite changes in serum potassium, total body potassium remained constant throughout the trial.

Adult↗
PubMed1978

Influence of chenodeoxycholic acid on the kinetics of endogenous triglyceride transport in man.

Plasma lipids and triglycerides kinetics were studied in ten subjects before and after 6-8 weeks treatment with 1 g/day chenodeoxycholic acid for radiolucent gallstones. Plasma triglyceride concentration fell by 20% and phospholipid concentration rose by 5% on average; there was no change in cholesterol or free fatty acids. Body weight remained constant. Triglyceride kinetics, studied by a precursor-labelling technique, revealed a reduction both of triglyceride plasma pool and turnover rate, accompanied by a decline of more than 35% both of plasma triglyceride precursor pool and of incorporation of plasma free fatty acids into newly synthesized plasma triglycerides. Fractional turnover rates in both pools remained unaltered. The appearance-time for newly synthesized plasma triglycerides after injection of label did not change. These results indicate that chenodeoxycholic acid lowers plasma triglyceride by reducing its synthesis, thereby precluding alternative, and possibly undesired, modes of action, such as impaired secretion or increased peripheral catabolism of endogenous triglyceride. Several biochemical mechanisms may be responsible for this effect, among which stimulation of phospholipid synthesis by bile acids could play a role.

Chenodeoxycholic Acid↗
PubMed1979

Autoradiographic study of distribution patterns of metals which occur as corrosion products from dental restorations.

Radioactive chromium, cobalt, gold and mercury, all of which may occur as corrosion products from dental restorations, were injected in single doses via the tail vein of mice and an in vivo analysis of their distribution was performed using whole-body autoradiography. Gold seemed to be inert and went mainly to the liver and bones. The other elements studied were distributed widely in the body and remained for a long period of time in specific target organs and tissues.

Animals↗