[Use of fixed-combination preparations of regular BHI and basal BHI (NPH) in type I diabetics].
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Biomedical subjects
Publications and source records attributed to R Landgraf.
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In cows, plasma oxytocin and vasopressin were determined by specific and sensitive radioimmunoassays before, during and after parturition. In no case, oxytocin is elevated until the forelimbs of the foetus were distending the vagina and presenting at the vulva, supporting the view that endogenous maternal oxytocin does not primarily induce parturition. This finding is confirmed by simultaneous recording of myometrial electrical activity in 3 animals. Maximal oxytocin levels of 60.4 to 116 pg/ml plasma were measured at delivery of the foetus. The elevation in plasma vasopressin (peak values at delivery: 4.74 to 41.5 pg/ml) might be due, at least partially, to the increase in plasma osmolality during parturition.
Oral glucose tolerance, plasma insulin and basal levels of glucagon, hGH, hPRL, hPL, TSH, T4, T3, thyroxine-binding globulin (TBG), cortisol, corticosteroid-binding globulin (CBG) and estriol were measured in 23 normal pregnant women in late gestation (31 +/- 0.4 weeks of pregnancy). Twelve of these subjects could be re-examined 14 +/- 2 weeks postpartum. Blood glucose was lower basal and after glucose load (100 g) in the pregnant group. Fasting plasma insulin and glucose-induced insulin release were higher in pregnancy. The insulinogenic index and the beta cell response were significantly greater antepartum, while peripheral insulin activity was unchanged. The insulin:glucagon ratio as well as TSH and hGH showed no significant differences between ante- and postpartum values. However, T4, T3, TBG, cortisol, CBG, estriol, hPRL and hPL were significantly higher during gestation than after delivery. T4:TBG and T3:TBG ratios were much lower antepartum, while the cortisol:CBG ratio was comparable ante- and postpartum. To our knowledge this is the first report in which such an extensive hormonal and metabolic analysis was performed in the same women ante- and postpartum. It could be shown that glucose tolerance is not worsened during pregnancy in healthy subjects. The higher gestational insulin values are discussed with respect to the various significant hormonal changes.
After intracarotid injection of [3H]beta-casomorphin-5 (beta CM5) in rats, the accumulation of radioactivity was determined in 18 brain regions and the anterior pituitary. The relative accumulation in all regions significantly exceeded that of [3H]inulin by a factor of 2.5, indicating a low but measurable brain uptake of the peptide. In blood-brain barrier-free areas, the accumulation of radioactivity was 15-fold higher than in blood-brain barrier-protected areas. The relative accumulation was not dependent on the total beta CM5 concentration in the range of 0.3-1.1 microM, and was not depressed by 400 microM L-tyrosine. We conclude that beta CM5, like other peptides, is accumulated in the blood-brain barrier-free areas to a relatively high but differing degree, whereas in the areas with a tight endothelium the accumulation is relatively low and nearly uniform. A binding to endothelial cells may contribute to the low accumulation of beta CM5, especially in blood-brain barrier-protected areas.
The studies concerning the problem of whether an exogenous neuropeptide is able to enter the brain tissue were extended to the undecapeptide Substance P (SP). The amount of radioactivity 15 s after intracarotid injection of [3H] Nle11-SP or [14C] inulin was determined in 18 brain regions and the anterior pituitary of male rats. As compared to the reference [14C] inulin (mean +/- SD: 0.143 +/- 0.009% of the injected radioactivity per g tissue wet weight), the amount of radioactivity was higher after [3H]Nle11-SP injection (0.233 +/- 0.039%, p less than 0.001). Statistically significant differences could be found particularly in cortical and caudal areas as well as in the circumventricular organs studied. These observations do not refute the assumption that a low brain uptake of the labelled neuropeptide occurred due to an accumulation within structures of the blood-brain barrier and/or a penetration of the barrier system.
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Vasopressin and oxytocin were determined simultaneously by a radioimmunoassay in cerebrospinal fluid and plasma of conscious, unrestrained rabbits. An elevation of neuropeptide levels in plasma, but not in cerebrospinal fluid, in response to dehydration or haemorrhage suggests an independent regulation of vasopressin and oxytocin concentration in both body fluids.
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About 8%-15% of the patients with organic hyperinsulinism have an islet cell carcinoma (13% in our series). In addition to a history of complaints of relatively recent onset, the patients present clinically the typical intermittent neurologic-psychiatric symptoms concurrently associated with hypoglycemia. The diagnosis is established biochemically on the basis of hypoglycemia, with inadequate incrementation of the insulin concentration subsequent to suppression and provocation tests. Elevated serum proinsulin and, in most patients, an increased insulin secretion rate are usually found after administration of agents such as glucose or leucine. Localization of the tumors is achieved by selective coeliacography as well as abdominal computerized axial tomography. The islet cell carcinoma is found most frequently in the tail of the pancreas, less frequently in the body and head of the pancreas. Metastatic spread is seen early into adjacent lymph nodes and especially in the liver. The treatment of choice is surgical resection of the tumor. Even in cases with advanced metastatic involvement, surgical intervention appears indicated. Medical treatment includes the administration of diazoxide, long-acting glucagon as well as the cytostatic agent streptozotocin. The average survival time is 30-40 months after diagnosis (in our series 79 months). Thus, the prognosis of patients with islet cell carcinoma appears relatively favorable, especially when compared with adenocarcinoma of the pancreas.
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Plasma vasopressin (AVP) and oxytocin (OXT) were determined by radioimmunoassay in healthy young men before, during and after a running exercise until exhaustion. In four of the five test subjects (one subject was underloaded) physical load resulted in a marked increase in plasma AVP with peak values of 11.7 to 57.8 pg/ml at exhaustion. Plasma OXT increased in three test subjects with peak values of 4.5 to 23.9 pg/ml. Within 1 h of recovery, both neuropeptides returned to basal plasma levels. The relationship between plasma AVP and osmolality (p less than 0.001) suggests that changes in osmolality play a dominant role in regulating the secretion of AVP. Besides peripheral effects, the increased levels of AVP and/or OXT during and immediately after the exercise, respectively, might induce a favourable action on the brain function. Determination of plasma AVP and OXT during a day-night cycle in the same test subjects reveals increased AVP levels from 02.00 to 08.00 h as compared to the other time periods chosen (18.00--24.00 h, p less than 0.001; 08.00--16.00 h, p = 0.031). In contrast, OXT does not differ between these time periods but decreased from 08.00 to 16.00 h (p less than 0.01). Accordingly, no correlation exists between both neuropeptides suggesting an independent secretion. It is unclear whether the circadian variations shown are able to influence the neuropeptide response to exercise.
Eleven healthy volunteers, five type I diabetics, and one type II diabetic man were examined. After an overnight fast caerulein (20 ng/kg) was injected intravenously and 60 min later an oral glucose tolerance test was performed with 100 g glucose in the normals and 25 g glucose in the diabetics. Blood pressure, pulse rate, blood glucose, serum insulin, glucagon, prolactin and growth hormone values were measured during the whole period of 240 min and compared with the same parameters in control tests in the same persons without caerulein application. None of the measured parameters were significantly influenced by caerulein. It is therefore concluded that in contrast to the stimulation of the exocrine pancreas functions of the endocrine pancreas, the pituitary gland and glucose tolerance are unchanged after caerulein.
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Arginine vasopressin (AVP) and oxytocin (OXT) were measured simultaneously in the same sample by specific and sensitive radioimmunoassay (RIAs). The antibodies used did not cross-react to a variety of analogues and related peptides. The extraction procedure using Vycor glass powder resulted in mean recoveries of 84.4% (AVP) and 64.6% (OXT). In both assays, the sensitivity was 1 to 2 pg/ml plasma. A preincubation procedure that depresses plasma levels of both AVP and OXT selectively, provided specific blank values for a given plasma sample. To confirm the validity of the RIAs, dehydration experiments were performed. In rats, the basal levels of plasma AVP and OXT (means: 2.63 pg/ml and 6.80 pg/ml, respectively) are increased significantly after 24 h, 48 h and 72 h of water deprivation. Relationships are presented between both neurohormones in the plasma and neurohypophyses of control and dehydrated animals. As shown in cows, a significant correlation exists between plasma AVP and plasma osmolality but not between plasma OXT and osmolality or plasma AVP and OXT. The conclusion is drawn that basal levels as well as physiological changes in plasma and neurohypophyseal AVP and OXT can be measured by the RIAs described.
We have outlined the symptoms, diagnostic procedures and operative treatment of "multiple endocrine adenomatosis" (MEA I, IIa und IIb). The priority of the operative procedure whenever two or more clinical syndromes in a patient with MEA are present and the possibility of multiple tumors has to be considered carefully. When there is a tumor of an endocrine organ, it should always bethought about the MEA-syndrome. We report about 9 patients seen in our hospital.
Using the isolated perfused rat pancreas PGE2 (1 MUM and 10 muM) had no effect on basal or glucose (10 and 20 mM)-induced insulin release (IR). PGF2 alpha stimulated basal IR at 1 muM and inhibited IR at 10 muM. The glucose-induced IR was unaffected by this PG. Furosemide (5 and 10 mM) led to a monophastic IR at low glucose (glu) and to a potentiation of IR at high glu. Only high indomethacin (Indo) (50 microgram/ml) inhibited glu-induced IR. The stimulatory effect of furosemide on IR could not be inhibited by indomethacin. However mepacrine (0.1 mM) abolished the furosemide effect. Also glu-induced IR was inhibited by mepacrine. Acetylsalicylic acid (30 mg/100 ml) had no significant influence on glu-induced IR. These findings provide evidence that phospholipase activation rather than increased PG synthesis might primarily be involved in the secretory process of insulin.
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