Intermediate acting insulin given at bedtime: effect on blood glucose concentrations before and after breakfast.

Six C-peptide deficient diabetics receiving twice daily mixtures of short and intermediate acting insulins were selected for study because of persistently raised blood glucose concentrations before and after breakfast. They were investigated to assess the effect of moving their evening injection of intermediate acting insulin to bedtime. The patients'' usual twice daily insulin treatment was optimised and compared with the bedtime regimen during inpatient metabolic studies and an outpatient crossover study. With the conventional injection regimen blood glucose concentration rose sharply from 0500 to reach a fasting mean value of 10 +/- SE 1 . 6 mmol/l (180 +/- 29 mg/100 ml) and 16 . 8 +/- 2 . 2 mmol/l (303 +/- 40 mg/100 ml) after breakfast. By contrast, when the evening dose of intermediate acting insulin was delayed until bedtime the nocturnal rise in blood glucose concentration started later and was significantly lower both fasting (7 . 5 +/- 1 . 1 mmol/l (135 +/- 20 mg/100 ml); p less than 0 . 02) and after breakfast (13 . 2 +/- 1 . 4 mmol/l(238 +/- 25 mg/100 ml); p less than 0 . 02). Fasting blood concentrations of ketone bodies (3-hydroxybutyrate) were also significantly decreased. Plasma free insulin concentrations showed the predicted changes in five of the six patients. Blood glucose profiles collected over four months during the outpatient study confirmed the beneficial effect of giving intermediate acting insulin at bedtime.     

Phosphatase activities in rat liver before and after birth

Synopsis Several phosphatase enzymes have been studied biochemically and cytochemically to ascertain whether there are ontogenic changes in level or location. Nucleoside monophosphatase (5-nucleotidase) and lysosomal acid phosphatase are low in foetal liver and, unlike glucose-6-phosphatase, are still quite low in neonatal liver. Bile canaliculi show strong staining for 5-nucleotidase in adult liver but not in foetal or neonatal liver. Nucleoside diand triphosphatase activities in foetal liver are already near half the adult level. The diphosphatase that is active towards UDP shows the same cytochemical locations in neonatal liver as in adult liver. Triphosphatase activity in foetal and neonatal liver is located largely in star-like cells, rather than in the bile canaliculi of parenchymal cells. Biochemical comparison of foetal, neonatal and adult liver has shown that inorganic pyrophosphatase (assayed without Mg²⁺) parallels glucose-6-phosphatase, but acid ribonuclease does not parallel acid phosphatase. In albino rats injected with thyroxine, glucose-6-phosphatase has shown a more marked increase in foetal liver than in adult liver, although the uptake of thyroxine seemed to be less. In hooded rats, foetal liver showed a negligible uptake of thyroxine and no rise in glucose-6-phosphatase.A. A. El-Aaser is on leave from the Faculty of Medicine, University of Cairo.     

Structural equivalents of latency for lysosome hydrolases.

1. Structure-linked latency, a trait for most lysosome hydrolase activities, is customarily ascribed to the permeability-barrier function performed by the particle-limiting membrane, which shields enzyme sites from externally added substrates. 2. The influence of various substrate concentrations on the reaction rate has been measured for both free (non-latent) and total (completely unmasked by Triton X-100) hydrolase activities in rat liver cell-free preparations. The substrates were: beta-glycerophosphate, phenolphthalein mono-beta-glucuronide. p-nitrophenyl N-acetyl-beta-D-glucosaminide and p-nitrophenyl beta-D-galactopyranoside. The ratio (free activity/total activity) X 100 is called fractional free activity at any given substrate concentration. 3. The fractional free activity of beta-glucuronidase and beta-N-acetylglucosaminidase were clearly independent of substrate concentration, over the range examined, in both homogenates and lysosome-rich fractions. The fractional free activity of acid phosphatase appeared to be either unaffected (homogenate) or even depressed (lysosome-rich fraction) by increasing the beta-glycerophosphate concentration. The fractional free activity of beta-galactosidase consistently showed a non-linear increase with increasing substrate concentration in both homogenates and lysosome-rich fractions. 4. Procedures such as treatment with digitonin, hypo-osmotic shock and acid autolysis, although effective in causing varying degrees of resolution of the latency of lysosome hydrolase activities, were unable to modify appreciably the pattern of dependence or independence of their fractional free activities on substrate concentration, as compared with that exhibited by control preparations. Ouabain did not affect the free beta-N-acetylglucosaminidase activity of liver homogenates at all. 5. Preincubation of control preparations with beta-glycerophosphate or p-nitrophenyl beta-galactoside did not result in any significant stimulation of the free hydrolytic activity toward these substrates. 6. The results consistently support the view that the membrane of "intact" lysosomes is virtually impermeable to all the substrates tested, except for p-nitrophenyl beta-galactoside, for which the evidence is contradictory. Moreover the progressive unmasking of the hydrolase activities produced by these procedures in vitro reflects the increasing proportion of enzyme sites that are fully accessible to their substrates rather than a graded increase in the permeability of the lysosomal membrane.     

Formation of extensor digitorum muscle proportions before and after birth

Studies on the formation of the extensor digitorum muscle morphological characteristics were carried out on material of 85 human fetuses (42 males and 43 females), 16 to 36 weeks old, and 45 adults (31 males and 14 females). Intermediary conclusions were drawn on probable changes occurring in the morphological formation of the muscle after birth, as a result of comparing proportions of the muscle at the fetal stage with its form in adults. In this work, the anthropometric method of study and statistical analysis of results have been applied. Analysis of the results in the fetal group has shown that all metrical characteristics of the muscle reach their maximum values at the end of the investigated ontogenetic space. This is, naturally, a consequence of evolution and growth of all fetal body measures, including elongation of forearms. However, the evolution of the individual muscle characteristics is not regular and though the direction of this growth is similar, its extent varies, and also differs slightly in sexual groups. Comparison of the values of muscle indices for 9 month old fetuses with the same indices for adults shows that relative dimensions of all investigated muscular characteristics decrease during the post-natal period except the relative length of the tendon.     

Lethal osteogenesis imperfecta. Definition and heterogeneity

The lethal form of osteogenesis imperfecta must be more clearly defined than it is. Early death of the child is not a sufficient criteria since it is observed in other forms compatible with survival. The authors therefore insist on the innumerable fractures of the ribs giving the particular aspect described as "bamboo ribs". These are observed in practically all cases. Heterogeneity however is undoubtful and an X-ray film is reproduced showing thin ribs without fractures in another exceptional lethal form. Genetic and very recent biochemical investigations suggest a new heterogeneity of the lethal form, even well defined clinically and radiologically. Contrary to earlier and frequent statements, it results most often from a dominant mutation, while recessive inheritance is much rarer, therefore the overall risk of recurrence much below 25%.     

Lethal progeroid syndrome with osteolysis. Case report.

A particular progeroid syndrome with severe acro-osteolysis, cutaneous changes, failure to thrive, and early death is described in a young boy. Progeria and mandibulo-acral dysplasia are discussed, but early death is unusual in these two syndromes. This observation raises the question of a large spectrum including all of these syndromes.