Unaltered insulin sensitivity during calcium channel blockade with amlodipine

Summary The sensitivity of peripheral tissues to insulin is of pathophysiological, therapeutic and possibly also of prognostic relevance. Calcium channel blockers are widely used in the treatment of cardiovascular disorders that are commonly associated with decreased insulin sensitivity (S_I). To evaluate the effects of calcium channel blokkade on S_I, glucose homoeostasis and lipid profiles, studies were made of S_I (determined by the Minimal Model Method of Bergman), basal glucose and insulin levels, serum total triglyceride (Tg) and lipoprotein cholesterol (C) fractions and certain other variables in 38 healthy young men (24 y) during placebo and after 3 weeks of calcium channel blockade with amlodipine 5 mg once daily. Measurements were made after 3 days on a standard diet (2200 kcal · day^–1, 45% carbohydrates, 40% fat and 15% proteins) and after an overnight fast. Compared to placebo, amlodipine decreased supine systolic blood pressure (P<0.01). Heart rate, body weight and 24 h urinary sodium excretion were unaltered, and so were fasting plasma glucose (placebo vs amlodipine: 4.86 vs 4.83 mmol·1^–1, respectively) and insulin levels (7.7 vs 7.9 U·ml^–1), S_I (10.5 vs 9.6·10^–4 × min^–1 pro U·ml^–1), serum total Tg, C and lipoprotein C fractions.The findings demonstrate unchanged insulin sensitivity and secretion, as well as lipoprotein regulation, during maintenance administration of 5 mg amlodipine daily to healthy young men.This work was supported in part by the Swiss National Science Foundation     

Modulation of BUdR labeling index in rat brain tumors following intracarotid ACNU administration

Summary Chloroethy1nitrosourea (CENU) chemotherapy has yielded limited benefit on survival of malignant brain tumors. Intracarotid administration of CENU is expected to have the advantage of increasing drug concentration reaching tumors. To understand basic knowledge of intracarotid chemotherapy, we monitor changes of proliferating rate after intracarotid injection of 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2chloroethyl)-3-nitrosourea hydrochloride (ACNU), using a bromodeoxyuridine (BUdR) labeling index (LI) in transplanted brain tumors of three cell strains.C6-2 tumor cells were in vitro sensitive to ACNU, and C6-2/ACNU and C6-1 cells were resistant. The drug sensitivity to ACNU was as follows: 11.9 tM in the C6-2 cells, 46.0 M in the C6-2/ACNU cells, and 49.7 M in the C6-1 cells at SD10, which gives 10% survival of clonogenic cells. The intracarotid ACNU at a dose of 30 mg/kg abruptly decreased the LI to 11% (mean) from 36% in C6-2 transplanted tumors. The LI remained low between 12 and 48 hours after, and then increased to the pretreatment level by 96 hours. In contrast, the LI of C6-1 tumors transiently fell to 15% from 42% at 12 hours after the injection, and subsequently increased to 36% at 24 hours and 37% at 48 hours.These results indicate that intracarotid ACNU administration shortly suppresses proliferating activity of tumors and that combined and alternating chemotherapy are mandatory for enhancing effectiveness of brain tumor chemotherapy.     

A new approach to hybrid hybridoma construction based on the use of an actinomycin D-resistant myeloma cell line

Institute of Higher Nervous Activity and Neurophysiology, Academy of Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR E. A. Zotikov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 112, No. 11, pp. 511–514, November, 1991.     

Devices for the treatment of diabetes: today

Although single or multiple daily subcutaneous injections of insulin with syringes are the mainstay of insulin delivery techniques for the treatment of diabetes mellitus, several other methods are now available. The present paper will review the main problems occurring with the classical subcutaneous insulin therapy and the possible solutions given by the use of new devices, including more particularly insulin jet injectors, pens, and portable pumps. This review has to be considered as an introduction to the presentations of this symposium devoted to implantable pumps, glucose sensors, and artificial pancreas, respectively.     

视屏作业对心理的影响

本研究采用“艾森克个性问卷”(EPQ)和“康乃尔医学调查表”(CMI)方法,对655名视屏作业人员和571名对照人员进行了心理测试,结果表明:视屏作业人员个性呈外向型的人数减少,趋于内向型的比例增加;情绪稳定型的百分率降低,不稳定型的百分率升高;个性表现为外向不稳定型和内向不稳定型的比例增加,外向稳定型的比例减少;易患神经症的倾向增加等。另按工龄长短进行分组比较,上述变化均表现为在高工龄组明显,提示与工作有关。     

Receptor-recycling model of clearance and distribution of insulin in the perfused mouse liver

Summary After perfusion of mouse livers with A₁₄-¹²⁵I-insulin for designated intervals, an acid-wash technique was employed to separately measure the surface-bound (X_s) and intracellular (X_i) A₁₄-¹²⁵I-insulin, as well as intracellular degradation products (X_deg) of labelled insulin. From the perfusate concentrations (C_p) of A₁₄-¹²⁵I-insulin, the apparent intrinsic hepatic clearance of labelled insulin at a high dose (0.2 nmol/l) was shown to be 60% smaller than that at a low dose (0.018 nmol/l), indicating that the cellular uptake of insulin is remarkably nonlinear at the concentration range examined. From the time courses of C_p, X_s, X_i and X_deg, the hepatic insulin disposition was shown to be largely accounted for by the receptor-mediated endocytosis. The observed data at the low dose were analysed to estimate biochemical parameters, (i.e., total receptor number, endocytotic rate constant and intracellular degradation rate constant) according to receptor-recycling and non-receptor-recycling models, using a computer-aided optimization procedure. The receptor-recycling model could not only adequately explain the C_p, X_s, X_i and X_deg at the low dose, but also predict the C_p at the high dose. On the other hand, a non-receptor-recycling model, in which recycling of receptors was not assumed, could also explain the observed data at the low dose, but failed to predict the C_p at the high dose, indicating that the receptor recycling process is necessary to explain the hepatic insulin clearance at high insulin concentrations, at which hepatic insulin clearance should be limited by the rate of receptor recycling. However, the applicability of our model might be limited within the physiologic insulin concentrations, because of the negative co-operativity of insulin-receptor interaction and a high-capacity, non-degradative and more rapidly recycling pathway for receptors that may occur at high concentrations of insulin. In conclusion, we have developed a mathematical model of hepatic insulin clearance and distribution under physiological conditions, including receptor binding, receptor-mediated endocytosis and receptor recycling, which has been so far demonstrated using isolated hepatocytes.     

Pulmonary mechanics and outcome of neonates on ECMO.

Deciding when to wean neonates from extracorporal membrane oxygenation (ECMO) can be difficult. The usefulness of simple measurements of pulmonary mechanics e.g., dynamic compliance (Cdyn) has been questioned. We investigated the pulmonary mechanics of eight neonates using the interrupter technique, which allows the partitioning of pulmonary mechanics into compartments representing the conducting airways and more peripheral phenomena (viscoelastic properties and "pendelluft"). Three neonates required ECMO for a congenital diaphragmatic hernia (CDH), two for hyaline membrane disease (HMO), two for meconium aspiration syndrome (MAS), and one for pneumonia. All neonates with MAS, HMD, and pneumonia were successfully weaned from ECMO when their Cdyn was 0.3 mL/cmH2O/kg or greater [mean 0.34 +/- 0.06 (SEM)]. All three neonates with CDH died and their highest Cdyn was 0.21, 0.19, and 0.09 mL/cmH2O/kg respectively (mean, 0.16 +/- 0.037). The airway resistance (Raw) and the slower component of pressure change after interruption (delta Pdiff), a measure of the more peripheral phenomena of the lung, were not significantly different in those neonates who survived and those who did not. The values for delta Pdiff in all patients were higher than those in healthy neonates. However, the Raw was not different. This suggests that the major disturbance in pulmonary mechanics was distal to the conducting airways. Those neonates who were successfully weaned from ECMO had a significantly higher Cdyn 24-48 hours prior to decannulation. Considering the lung as a two-compartment model offers no advantages when compared to the one-compartment model for the prediction of the outcome of a neonate on ECMO.     

Mathematical aspects of the paternity index I=X/Y,especially in relation to the chance of non-exclusion of non-fathers

Summary In a previous paper the author mentioned some aspects of the paternity index I (=X/Y): Among false triplets the frequency of those with I equal to or higher than an (observed) I value of I ^x is considerably lower than 1/I ^x; among false triplets the mean value of I is equal to 1, and among non-excluded non-fathers it is equal to the inverse of the chance of non-exclusion; among true triplets the mean value of 1/I (=i) is equal to the chance of non-exclusion of non-fathers. In a statistical material rather strong deviations from some of these expectations were observed.In the present paper further characteristics of the distribution of I values were taken into consideration, and especially those that should hold if lnI would fit in with a normal distribution. It was supposed that with the aid of such a distribution the deviations mentioned above could be recognized as chance variability. It appears, however, that neither the logarithms of the paternity index, nor those of the zygosity index of twins (chosen as an analogous model that is more easily analysable than the paternity index) are really normally distributed. This, in turn, makes that estimates of probability of paternity, based on such a supposition, are of doubtful reliability. Besides it is concluded that also for other reasons other estimates than Essen-Möller's W (or I or i), as probability of first type errors, lead in practice to conclusions that are equally subdue to a priori suppositions as are W values and may be, in fact, much more erroneous than those.Special attention is paid to the statistical analysis of paternity studies with more than one alleged father, and it is concluded that in such cases the general formula that may be considered to be equivalent with Essen-Möller's formula for one-man paternity cases, i.e., W=X/(X+Y) or I/(I+1), must be W ₁=I ₁/(I+n); W ₂=I ₂/(I+n) etc. and certainly not W ₁=I ₁/(I+1); W ₂=I ₂/(I+1) etc.Dedicated to Prof. Dr. Erik Essen-Möller on the occasion of his 80th birthday     

Quantitative analysis of paradoxical inward rib cage movement during sleep in children

Paradoxical inward rib cage movement in children is quantified by the labored breathing index (LBI) on the respiratory inductive plethysmography. Labored breathing index during rapid eye movement sleep (REMS) in 59 children without obvious sleep disordered breathing (SDB) declined with age, and decreased to the mature low level at 35 months of age. The LBI was also found to reflect well the severity of SDB. Paradoxical inward rib cage movement, which was quantified by LBI, is concluded to be an important finding in diagnosing SDB in child patients.