[Migraine in children and adolescents-brain and muscle? : Another example of why children are not small adults]. / Migräne im Kindes- und Jugendalter ­ Gehirn und Muskel? : Warum Kinder einmal mehr keine kleinen Erwachsenen sind.

Migraine as primary headache is a life-long disease which is relevant for the quality of life and is based on complex genetics. It often starts in childhood with symptoms typical for the specific age. These show different nuances compared to the migraine symptoms in adults, for example, regarding (bilateral/unilateral) localization of the acute migraine headache. Only over the course of years-during adolescence and young adulthood-do the more specific symptoms as defined by the International Classification of Headache Disorders (ICHD 3 beta) develop. In this article we focus on the clinical specifics of children and adolescents with migraine. We elaborately refer to the trigeminocervical complex (TCC) because it forms a conceptual bridge for the understanding of migraine, for psychoeducation, and for therapeutic options. We pragmatically discuss options and limits of treatments.

Investigations on the heat lability of enzyme activities in bovine lenses following incubation under various culture conditions.

The quality of different culture media and incubation procedures has occasionally been tested by measurements of the specific enzyme activities in incubated lenses. New methodology developments in the field of enzymology, such as partial heat denaturation of enzyme activities have so far rarely been used in the investigations on the physiologic conditions of incubated lenses. Investigations with bovine lenses separated into cortex and nucleus, involving different media and incubation periods, indicate that tests on the heat lability of the enzyme phosphofructokinase (PFK) allow early recognition of intra-molecular alterations which lead to changes in the stability. The method is based on the fact that the PFK in the lens nucleus forms a metastable component (metazyme) during aging, which is more susceptible to heat (50 degrees C) than the native PFK component.

Glycogen concentration changes in retina, vitreous body and other eye tissues caused by disturbances of blood circulation.

The glycogen content in the individual eye tissues is strongly correlated to blood supply. Our investigations on the retina of bovines, which have not been fully evaluated, show that the time interval between interruption of blood supply and preparation of the retina is of special importance. Pressure ischemia affects a decrease in glycogen content in the retina and vitreous of rabbits, which is, however, less distinct in the vitreous. Decrease of glycogen with ischemia also takes place in the cornea and, to a lesser degree, in iris and choroid. In contrast, there is no decrease in the glycogen content of the lens. Changes in glycogen content of the rabbit retina after ligation of the A. carotis communis is less distinct than with pressure ischemia. In the vitreous, changes in glycogen content could not be observed. Values measured in both tissues of the ligated eye decrease with additional pressure ischemia.

Alterations of lens metabolism with experimentally induced cataract in rats.

Rat lenses with experimentally induced cataract (either by naphthalene or by streptozotocin) were analyzed biochemically. Both noxae had some effects in common. Water-soluble protein and aldose reductase activity decreased, and glucose-6-phosphate dehydrogenase, phosphofructokinase and glutathione reductase activity increased. A specific effect of streptozotocin was the rise in glucose, fructose and sorbitol. A specific effect of naphthalene was increased amounts of water-insoluble protein.

Enhancement of the stimulating effect of fructose-1.6-diphosphate on the metabolic energy balance of carbohydrate-deficient bovine lenses by additional supply with ADP.

The energy supply in carbohydrate-deficient bovine lenses was disturbed, as could be demonstrated by measuring the content of free adenine nucleotides. It could be regenerated in part by a 3-hour-incubation in TCM 199 in the presence of fructose-1.6-diphosphate (FDP). Additional supply of ADP enhanced the stimulating effect of FDP towards formation of ATP, providing sufficient receptor molecules for the activated rate of glycolysis and probably also for the citric acid cycle.

Studies on the influence of leucomycine on the carbohydrate metabolism of the lens in vitro.

The influence of leucomycine (10(-5) M--5 X 10(-3) M) on enzyme activities, free adenine nucleotides, and some intermediates of glycolysis in bovine lenses has been investigated. After a 48 h incubation in TCM 199, 6 out of 9 enzymes activities tested were decreased. Concentrations of energy rich nucleotifes, glucose, fructose, and fructose-6-phosphate as well as those of fructose-1,6-diphosphate and lactate were also decreased, whereas adenine monophosphate was increased.

A comparison of two buffering systems for lens organ culture.

Bovine lenses were incubated in a pairwise assay for 24 h in TC 199 which was buffered with Hepes or NaHCO3, respectively. In lenses incubated with Hepes, the content of ATP was higher and that of AMP lower than in those incubated with NaHCO3. The specific activity of phosphofructokinase (PFK), was higher in the lenses from the Hepes medium than in lenses incubated with NaHCO3. A heat-labile metazyme of the PFK which is found in the nucleus of unincubated lenses disappeared when the lenses were incubated in the presence of bicarbonate, but remained intact after 22 h incubation with Hepes.

[Aldose reductase inhibitor--a new way for preventing diabetic lens changes?]. / Aldose Reduktase-Hemmer--ein neuer Weg zur Vermeidung diabetischer Linsenveränderungen?

Increased blood sugar levels may influence the refractive power of the lens in juvenile diabetics, and can lead to the rare true diabetic cataract ("snow-storm cataract"). Surplus glucose induces accumulation of the sugar alcohol within the cells, thus generating disturbances of the osmotic balance and finally causing cataract. The enzyme aldose reductase catalyzes the formation of sorbitol. Experiments with animals have shown that aldose reductase inhibitors can prevent the formation of such opacities with streptozotocin-induced diabetes in rats. Numerous aldose reductase inhibitors are now known, but we still have insufficient knowledge to determine whether systemic or local administration is preferable. The mechanisms reported here are not relevant with respect to the frequent occurrence of senile cataract in older diabetics, which has often been described.

Biochemical analysis of bovine lens sections obtained by a new sectioning device.

One mm thick layers were reproducibly sliced from the punched-out inner cylinder of bovine lenses. The layers were obtained by a special designed freeze-sectioning device. Biochemical analysis of these layers revealed a detailed picture of the lenticular distribution of the amount of water-insoluble and urea-insoluble fractions. Furthermore, the distribution of the content of glucose, fructose and sorbitol was established. The results clearly show the usefulness of a microsectioning device to obtain layers for subsequent biochemical analysis which may lead to a comprehensive understanding of age- and/or cataract-related alterations within one lens.

[In vitro incubation of lenses. Model for testing substrate utilization of substances of the energy metabolism, demonstrated with bencyclane-hydrogen-fumarate (author's transl)]. / In vitro Inkubation von Linsen. Modell zur Untersuchung der Substratverwertbarkeit von Substanzen für den Energiestoffwechsel am Beispiel des Bencyclan-hydrogenfumarats.

When bovine lens homogenate was treated with bencyclane-hydrogen-fumarate, the carbohydrate metabolism was activated. This may chiefly be due to the fumarate part of the substance. A 24 H In vitro incubation of whole bovine lenses in TC-199 with and without bencyclane-hydrogen-fumarate did not show the above effect. On the model of former investigations by J.E. Harris et al. we modified the test procedure by selecting the medium and the time of incubation so that the endogenous carbohydrates of the lens were consumed, thus creating new metabolic balances. This metabolic condition allows investigations intended to activate metabolic processes and to restore the steady state of metabolic parameters. We investigated the effect of bencyclane-hydrogen-fumarate using the same method and found that given certain conditions the lens recovers when incubated for 2 h in TC-199 (containing 1 g glucose/1) with addition of a 10(-4) M solution of bencyclane-hydrogen-fumarate. The ATP-content of these lenses in particular gives proof of this result. As already observed in former investigations on homogenates, this effect is probably due to metabolization of the fumarate part of the bencyclane-hydrogen-fumarate by the citric acid cycle. The method used explains the differences observed when using lens homogenates or whole lenses under the same experimental conditions.

Action of bencyclane-hydrogen-fumarate on the carbohydrate metabolism of bovine lens homogenates.

1-Benzyl-1-(3-dimethylaminopropoxy)cycloheptane (bencyclane-hydrogen-fumarate; Fludilat) in a concentration of 10-2 M effects an increase in the O2 consumption and the formation of CO2 in a 10% bovine lens homogenate. This effect is even increased if the glucose-substrate supply is raised from 25 mM to 37 mM. Investigations on the concentrations at ATP, ADP and AMP show that bencyclane is able to stabilize the physiologic distribution pattern of the three free adenine nucleotides. Further, the observed changes in the distribution pattern indicated that the fumaric acid rest of bencyclane may serve as a substrate for this reaction in the same way as fumarate.

[Determination of the KM-value of the fumarase (E.C. 4.2.1.2) with bencyclan-hydrogenfumarate as the substrate (author's transl)]. / Bestimmung des KM-Wertes der Fumarase (E.C. 4.2.1.2) mit Bencyclan-hydrogenfumarat als Substrat.

The Michaelis-Menten constant for fumarase (E.C. 4.2.1.2) has been determined by measuring the enzyme activity by the spectrophotometric method of Racker, which depends on the formation or disappearance of the double bond of fumaric acid. When using Na2-fumarate or bencyclan hydrogenfumarate (Fludilat), respectively, as a substrate, a KM-value of 1.3 X 10(-3) M was found for both substances. In a linked assay where the formation of NADH in the reaction of fumarate leads to malate leads to oxaloacetate was used as a parameter for the reaction rate, a KM-value of 1.35 X 10(-3) M was found.

Is it possible to maintain a normal glutathione level in lenses in vitro?

In most types of experimentally induced cataracts, glutathione (GSH) content decreases considerably before the onset of opacity. GSH may provide a protective function for protein SH groups by scavenging oxidative products that may impair lens metabolism. To avoid impairment of lens metabolism by decreased levels of GSH it may be possible in vitro: (1) to stimulate GSH synthesis by enrichment of the incubation medium with the amino acids necessary for GSH synthesis or (2) to enrich the incubation medium with the tripeptide itself so that it can be taken up by the lens. Both approaches were investigated with bovine lenses. Lenses were incubated in pairs in a salt solution without carbohydrates, so as to deplete lens of GSH. Following starvation, one lens of each pair was incubated for recovery in TCM 199 enriched with MgSO4 and the three amino acids of GSH; the other lens was put into a freshly prepared salt solution. After 6 h, lenses from the recovery solution contained more GSH than the other lenses. Addition of fructose-1,6-diphosphate to the medium enhanced this effect. When, after starvation, lenses were incubated in the presence of different amounts of GSH, GSH lens content rose, with the highest in those lenses incubated in a medium with a final molarity of 4 X 10(-3) M GSH. Therefore, incubation of lenses depleted of GSH in medium with either the amino acids of GSH or GSH itself appear to facilitate recovery of GSH content.

Studies of lens enzyme activities in relation to cataract type and plasma constituents.

The specific activities of glutathione reductase (GR), EC 1.6.4.2, and aldolase, (ALD) EC 4.1.2.13, were determined in the homogenates of 60 cataractous lenses. Concentrations of certain plasma constituents and the morphological types of cataract of the patients were known. Investigations were aimed at establishing a possible correlation between enzyme activities and plasma constituents as well as between the specific activities of GR and ALD and type of cataract. A correlation between the specific activity of GR and the urea content of the blood could be identified. Results also indicated a relationship between the decrease in GR activity and the formation of cortical cataracts.