[Hereditary hyperferritinemia-cataract syndrome]. / Hereditäres Hyperferritinämie-Katarakt-Syndrom.

HISTORY AND FINDINGS: Symptom-free brother and sister of Italian descent (age: 31 and 28 years), under examination to exclude haemochromatosis, were found to have increased serum ferritin levels. Both had cataracts removed, as had their mother. Physical examination had been normal in both siblings. INVESTIGATIONS: Serum ferritin levels were raised to 926 and 956 ng/ml, respectively, while blood and differential counts, blood sugar and serum iron levels, iron binding capacity and transaminases were within normal limits. Liver sonography was normal and biopsies excluded haemochromatosis in both cases. The serum ferritin levels were elevated in all family members who had a cataract. DIAGNOSIS: Family history, greatly elevated serum ferritin levels and cataracts established diagnoses of hereditary hyperferritinaemia-cataract syndrome. CONCLUSION: The autosomally inherited hyperferritinaemia-cataract syndrome is a new condition that should be included in the differential diagnosis of hereditary hyperferritinaemia. A single measurement of the serum ferritin level and ophthalmological examination are sufficient to make the diagnosis; liver biopsy is unnecessary and blood letting contraindicated, because it would quickly cause microcytic iron-deficiency anaemia.

"Metabolic switch" for desert survival.

Food, like water, is in short supply in the desert. We report a specialized mechanism used by a desert mouse for surviving prolonged food shortages. The key element of this adaptation is a large reduction in resting metabolism. After about 2 weeks of restricted food intake (50% of normal), the desert mouse "switched down" its resting metabolism and was able to survive and maintain its weight indefinitely on these limited rations. When food was again freely available, resting metabolism "switched up," returning to normal levels in a single day. The reduced metabolism occurred without a decrease in body temperature or in levels of activity. In marked contrast, metabolism of the laboratory white mouse increased during food restriction, and the experiments had to be terminated to avoid starvation. We think this "metabolic switch" is common among desert mammals. It may be an amplification of a general metabolic response for coping with food scarcity common to all mammals, including humans.

Prevalence and control of benzimidazole-resistant small strongyles on German thoroughbred studs.

The prevalence of benzimidazole-resistant small strongyles was determined in a survey, conducted on 14 thoroughbred studs, which compared the faecal egg counts of groups of horses before and after treatment with the recommended doses of cambendazole (20 mg kg-1 b.w.) or febantel (6 mg kg-1 b.w.). Benzimidazole-resistant cyathostomes were found on all farms examined. Pyrantel pamoate (19 mg kg-1 b.w.), oxibendazole (10 mg kg-1 b.w.) and ivermectin (0.2 mg kg-1 b.w.) reduced the strongyle egg counts on these studs by 97-100% at 2 weeks post-treatment. However, 6 weeks after dosing the reduction of the strongyle egg output had decreased to an average of 67.8% (8.7-97.1%) with pyrantel pamoate and 51.2% (0-95.8%) with oxibendazole, whereas ivermectin still suppressed the egg counts by 98.2% (95-100%).

Trial of sulfonylurea in combination with insulin in the therapy of diabetes type I and II. Evidence against a primary extrapancreatic receptor effect.

Recently in vitro evidence has been presented that sulfonylurea derivatives exert their chronic extrapancreatic effect by increasing the number of cellular insulin receptors. To ascertain if this receptor effect holds in vivo, we performed a randomized double-blind study on 21 type I (0.3 ng/ml residual C-peptide secretory capacity after glucose/glibenclamide stimulation), and on 19 insulin treated type II (2.0 ng/ml C-peptide) diabetics. The patients received for six weeks 10 mg/d of glibenclamide in addition to insulin. Insulin binding was initially lower in type II (4.7 +/- 0.75% per 10(7) monocytes and 6.39 +/- 1.08% per 4.5 X 10(9) erythrocytes) than in type I diabetic patients (5.1 +/- 0.48% and 7.95 +/- 0.88% respectively) and in 12 normal subjects (5.25 +/- 0.48 and 8.1 +/- 0.94% respectively). Glibenclamide normalized the number of monocyte receptors (from 4.14 to 5.49 X 10(4) sites/cell) in type II patients, but was without effect in type I diabetics. Blood glucose was significantly reduced (240 to 182 mg/dl; p = 0.02) in the type II group with a concomitant decrease in glycosylated hemoglobin from 12.4 to 10.5% (p = 0.01). Most of the effect occurred during the first week of treatment. Glibenclamide was the more effective the worse the initial metabolic state (r = -0.93; p = 0.001). Erythrocyte insulin receptors decreased markedly in both groups, perhaps due to a sulfonyl urea-induced change in erythrocyte plasma survival time. It is concluded that sulfonylurea treatment is a valuable adjunct in reducing the insulin resistance in insulin treated type II diabetics. The effect depends on the availability of endogenous insulin, thus exhibiting only partly extrapancreatic character.(ABSTRACT TRUNCATED AT 250 WORDS)

Metabolic meaning of elevated levels of oxidative enzymes in high altitude adapted animals: an interpretive hypothesis.

It is commonly observed that during acclimatization to altitude oxidative enzyme activities increase per g wet weight of tissue. To examine this problem in long-term adapted animals we measured citrate synthase (CS), hydroxyacylCoA dehydrogenase (HOAD), pyruvate kinase (PK), and lactate dehydrogenase (LDH) activities/g of myocardium in two domestic species (llama and alpaca) and a high altitude deer, the taruca. In all these species, we found an upward scaling of oxidative capacity (indicated by absolute activities of CS and HOAD) but a downward scaling of anaerobic/aerobic metabolic potentials of the heart (indicated by low ratios of LDH/CS, and LDH/HOAD, but high ratios of PK/LDH). As the direction and magnitude of these long-term adaptations are the same as in shorter-term acclimatizations, we wondered why a similar pattern at the enzyme level correlates with the right shift of the O2 dissociation curve (ODC) in the latter case, but with a left shifted ODC in the former. We hypothesize that in the long term, increased oxidative enzyme activities allow increased maximum flux capacity of aerobic metabolism. This in turn calls for physiological adjustments in O2 transfer systems; flux limits of the former must be matched by flux limits of the latter. Only then can an acceptably high scope for aerobic activity be achieved despite reduced O2 availability in inspired air. Such long-term match-up invariably calls for a left-shifted ODC plus other well known adjustments in O2 transport. In the short term, right shifting the ODC may increase the total amount of aerobic work possible (by favoring O2 unloading and thus raising tissue O2 concentration), yet maximum flux capacity cannot be changed much because mitochondrial metabolism is designed for maintaining stable rates of ATP synthesis even at widely varying O2 tensions. That is why even in short-term acclimatization, in order to increase flux capacity, the activities of oxidative enzymes also must be increased.

Bioluminescent assay for determination of picomole amounts of AMP, ADP, and ATP in adipose and muscle tissue biopsies.

A method is described for quantitative determinations of AMP, ADP, and ATP in tissue samples weighing a few milligrams by utilizing constant bioluminescent light intensity after reagent mixing. The smallest measurable quantity of adenosine nucleotide amounts to 0.2 pmol (coefficient of variation = 0.05) in the bioluminescent assay.