Serum levels of vitamin D metabolites and bone remodelling in hyperthyroidism

Serum levels of 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D and 1,25-dihydroxyvitamin D were measured in 25 untreated hyperthyroid patients in whom histomorphometric evaluations of iliac crest bone biopsies were performed after in vivo tetracycline doublelabeling. The serum concentration of 25-hydroxyvitamin D was normal. The serum concentration of 1,25-dihydroxyvitamin D was reduced (p < 0.02) compared to normal whereas the serum concentration of 24,25-dihydroxyvitamin D was increased (p < 0.02). The bone changes were characterized by an enhanced turn-over in trabecular and cortical bone leading to an increased porosity of cortical bone and mobilisation of bone mineral. The observed changes in vitamin D metabolism could be explained by a reduced renal 1-alpha-hydroxylase activity secondary to hypercalcaemia with suppressed parathyroid secretion and hyperphosphataemia. The bone changes were unrelated to the serum levels of vitamin D metabolites. In trabecular bone the appositional rate and mineralization rate of osteoid were increased and the mineralization lag time was shortened showing that the mineralization and formation of osteoid in the hyperthyroid state can progress with an enhanced rate in spite of a reduced mean serum level of the active vitamin D metabolite, 1,25-dihydroxyvitamin D.     

Creatine kinase in the serum of patients with acute infections of the central nervous system

Serum creatine kinase was assessed in 94 consecutive patients without convulsions admitted to hospital due to suspicion of infection of the central nervous system. No reliable discrimination between patients with aseptic and those with bacterial meningitis was obtained. Patients with bacterial meningitis and brain oedema, as well as patients with encephalitis, had significantly higher values (P less than 0.01) than patients with meningism, aseptic meningitis and bacterial meningitis without cerebral oedema. Very high values, above 2500 U/1, were encountered in only the most severe cases of bacterial meningitis. The highest serum CK value found in patients with encephalitis was 725 U/l. Reference values for control patients with meningism were 16-269 U/1. In a subset of 9 patients creatine kinase isoenzyme analysis was performed. In all cases only muscle type (MM) isoenzyme was found.     

Insulin receptor binding and insulin action in human fat cells: effects of obesity and fasting

We have studied (125I)-insulin binding and insulin dose response relationships of (14C)-methylglucose transport conversion of (14C)-glucose to CO2 and total lipids, and lipolysis at 37 degrees C and pH 7.4 in adipocytes from obese patients before (n = 15) and after fasting for 10 days (n = 6). Studies of adipocytes from obese before fasting showed a significant reduction of insulin binding when expressed to cell surface area and rightward shifts of the insulin dose response curves (decreased insulin sensitivity) for glucose transport, glucose oxidation, lipogenesis and antilipolysis. The decreased insulin sensitivity of adipocytes from obese was most likely the functional consequence of the impaired insulin binding. Moreover, decreased maximal glucose transport capacities were present in rat cells from obese both in the basal and maximally insulin stimulated states. Similarly, the percentage response above basal level to maximal insulin stimulation of glucose oxidation and lipogenesis was impaired to these cells. The latter findings suggest post receptor defects localized both to the transport system per se and to intracellular mechanisms involved in the metabolism of glucose. Conversely, the post receptor pathways for the insulin induced antilipolysis was intact in fat cells from obese man. Studies after fasting showed an increase of adipocyte insulin binding accompanied by an increased sensitivity to the antilipolytic effect of insulin with unchanged maximal responsiveness. However, due to marked post receptor alterations, the insulin stimulated glucose utilization was severely blunted. Thus, the glucose transport system of adipocytes from all fasted subjects was totally unresponsive to insulin, while some of the fasted patients had a slight response of glucose oxidation and lipogenesis in the presence of insulin in maximally effective concentrations.     

Propylthiouracil, ipodate, dexamethasone and periods of fasting induce different variations in serum rT3 in dogs

Fasting or administration of propylthiouracil (PTU), ipodate, or dexamethasone are all known to induce a pattern of low serum triiodothyronine (T3) concentrations and high serum reverse T3 (rT3) concentrations in humans. In the present study it was found that this is not a universal phenomenon. In normal dogs exposed to fasting or these various pharmacologic agents, the serum T3 level was always depressed as in humans. However, different variations in serum rT3 levels were observed. Fasting and PTU administration were accompanied by slight decreases in the serum rT3 concentration. A single dose of ipodate did not alter serum rT3 levels, but serum thyroxine (T4) levels increased by more than 50%. Dexamethasone induced a considerable increase in serum rT3 levels, while serum T4 levels were unaltered. The results suggest that the high serum rT3 level nearly always seen in "the low T3 syndrome" in humans is merely a coincidental character of the human species, and that it has little importance for in vivo homeostasis.     

Aspects of glucose homeostasis in uremia as assessed by the hyperinsulinemic euglycemic clamp technique

A three-step hyperinsulinemic euglycemic clamp was performed in 14 nondialyzed uremic and ten age-matched healthy subjects. Nine of the uremics were restudied for a mean of 42 days (range, 21 to 88 days) after initiation of dialysis therapy. Insulin was infused at the following three rates: 0.5 mU·kg^?1·min^?1, 2.0 mU·kg^?1·min^?1, and 4.0 mU·kg^?1·min^?1. Each dose was given for 120 minutes. Glucose uptake during the last 30 minutes of each clamp were consistently lower in uremic patients pre-dialysis than in controls (2.3 ± 0.3 v 6.6 ± 0.8 mg·kg^?1·min, 7.8 ± 0.6 v 13.2 ± 1.1mg·kg^?1·min^?1 and 9.6 ± 0.7 v 15.5 ± 1.0 mg·kg^?1·min^?1, all P < 0.001). Serum insulin levels wre similar in the two groups, and blood glucose values during steady state were maintained at 79 ± 2, 77 ± 2, and $\text{77 ± 2 mg}\text{100 mL}$ in uremic subjects and at 72 ± 3, 73 ± 2, and $\text{75 ± 2 mg}\text{100 mL}$ in healthy subjects. The insulin levels required to elicit half-maximal biological response in uremics (82 ± 5 μU/mL) were markedly higher than in controls (54 ± 8 μU/mL, P < 0.01). Dialysis therapy enhanced maximal glucose disposal (8.7 ± 0.9 v 11.4 ± 0.8 mg·kg^?1·min^?1, P < 0.01), while insulin concentrations required to achieve half-maximal glucose metabolism were virtually identical in the two situations (86 ± 7 μU/mL and 85 ± 11 μU/mL). No difference in I¹²⁵ insulin binding to monocytes was observed in the uremic patients and a separate control group. In contrast to the impaired glucose uptake in uremia the insulin effect on lipolysis and ketogenesis was normal as estimated by measurement of serum NEFA, blood glycerol and 3-hydroxybutyrate. The response of the gluconeogenic precursors, lactate and alanine, was also similar in the uremic and control subjects. The impaired peripheral glucose uptake in nondialysed uremics could not be ascribed to different levels of cortisol, catecholamines, or NEFA, although a possible participation of growth hormone could not be ruled out. In conclusion, severely impaired peripheral glucose uptake is present in nondialysed uremic subjects. Short-term dialysis therapy (hemodialysis or continuous ambulatory peritoneal dialysis; CAPD) tends to abolish this defect. Since an apparently normal first step in insulin action, namely binding to receptors, was found, the uremic insulin resistance is a result of depressed insulin action at postbinding sites. However, it cannot be excluded that a superimposed intrinsic defect glucose transport system eg an impaired insulin-independent glucose uptake may contribute. In contrast to the abnormal glucose uptake, the responses of key intermediary metabolites were normal in uremia indicating normal insulin action on lipolysis, ketogenesis, and gluconeogenesis.     

Mechanisms governing the relative proportions of thyroxine and 3,5,3'-triiodothyronine in thyroid secretion

In subjects with normal thyroid function only a minor part of firculating 3,5,3'-triiodothyronine (T3) originates directly from the thyroid; the majority is produced in the peripheral tissues by deiodination of thyroxine (T4). However, T3 of thyroidal origin constitutes a relatively high fraction of the total T3 produced in many patients with thyroid hyperfunction or hypofunction. Such a relatively high T3 content in the secretion of the thyroid could be caused by a low T4/T3 ratio in thyroglobulin. Severe iodine deficiency is a well-known inducer of a low T4/T3 ratio, but a low T4/T3 ratio can also be produced independent of the iodine content. This is seen in in vitro studies of thyroglobulin iodination when small amounts of DIT are added to the incubation mixture and in vivo in TSH-treated animals and in patients with Graves' disease. Another mechanism for high thyroidal secretion of T3 could be an enhanced fractional deiodination of T4 to T3 in the thyroid. In vitro thyroid perfusion studies have shown that the T3 content of thyroid secretions is higher than would be expected from the T4/T3 ratio of thyroid hydrolysate and that the major mechanism is deiodination of T4 to T3. Thyroxine deiodinases are also present in the human thyroid, and the amount of T4 deiodinase is enhanced in the thyroids from patients with medically treated Graves' disease and in the hyperstimulated thyroids of rats. Other factors of possible importance for the mixture of T3 and T4 secreted by the thyroid are a relatively faster liberation of T3 than of T4 from thyroglobulin during partial hydrolysis (this faster release of T3 is probably the mechanism behind the more "rapid" secretion of T3 than of T4), or some kind of thyroid heterogeneity leading to pinocytosis and hydrolysis of thyroglobulin with a lower T4/T3 ratio than that of average thyroglobulin.     

The effect of somatostatin on plasma noradrenaline and plasma adrenaline concentrations during exercise and hypoglycemia.

The effect of somatostatin, on the secretion of noradrenaline and adrenaline was studied in eight normal subjects during exercise and in insulin induced hypoglycemia. Plasma growth hormone response to exercise and hypoglycemia was almost totally suppressed by somatostatin. Plasma noradrenaline during exercise tended to be lower during the infusion of somatostatin but the difference was not significant. During the infusion of somatostatin the secretion of adrenaline was increased. This was seen during exercise but was much more pronounced during hypoglycemia. The blood glucose concentration attained after insulin injection was lower during the infusion of somatostatin and evidence is presented which indicates that the higher adrenaline values during hypoglycemia were due to the lower blood glucose values attained. In conclusion the secretion of catecholamines are not inhibited by a dose of somatostatin which nearly totally suppresses the secretion of growth hormone.     

A double-blind study of the efficacy of neutral human and porcine insulin in type I diabetes using a glucose-controlled insulin infusion system

The comparative potency of equimolar amounts of soluble porcine and semisynthetic human insulin were studied in ten patients with type 1 diabetes in acute experimental situations. In both situations residual subcutaneous insulin depots were eliminated by intramuscular treatment exclusively with soluble insulin four days before the experiments. Then, practically identical metabolic states were achieved by connecting the patients to a glucose-controlled insulin infusion system (Biostator) 12 hours before the study. In one study, 0.5 g/kg body weight of glucose was administered intravenously as a bolus, and thereafter insulin was infused at a rate of 1.0 mU/kg/min. The decline in blood glucose was rectilinear and identical for the two insulins: y = ?1.18x + 206 and y = ?1.17x + 205. The insulin effect is well below maximum, and a 10% increase in the infusion rate of insulin was easily detected. Although changes in blood glucose and pancreatic glucagon were identical, a significantly lower plasma growth hormone level was noted after human insulin infusion. In the second study, 24 hours of near-normoglycemia was attained by the glucose-controlled insulin infusion system, the patients being supine and having identical meals at identical intervals. The diurnal blood glucose, plasma growth hormone, and pancreatic glucagon patterns were identical and the total 24 hour insulin consumption was 47.7 ± 3.5 units and 47.7 ± 3.7 units for the two insulins.     

Increased insulin binding to adipocytes and monocytes and increased insulin sensitivity of glucose transport and metabolism in adipocytes from non-insulin-dependent diabetics after a low-fat/high-starch/high-fiber diet

Nine non-insulin-dependent diabetics were studied before and after 3 weeks on an isoenergetic high-fiber/high-starch/low-fat diet (alternative diet), and nine non-insulin-dependent diabetics were studied on their usual diet. In the group that ate the alternative diet, the intake of fiber and starch increased 120% and 53%, whereas fat intake decreased 31%. Diabetes control improved as demonstrated by decreased fasting plasma glucose (P < 0.05) and 24-hour urinary glucose excretion (P < 0.05). The in vivo insulin action increased (K_IVITT increased, P < 0.05) with no change in fasting serum insulin levels. In fat cells obtained from patients in the alternative-diet group, insulin receptor binding increased (P < 0.05) after the change of diet. Insulin binding to purified monocytes (more than 95% monocytes) also increased (P < 0.05), whereas no change was found in insulin binding to erythrocytes. When lipogenesis was studied at a tracer glucose concentration at which glucose transport seems to be rate limiting, insulin sensitivity increased (P < 0.02). This is the predicted consequence of increased receptor binding. Moreover, when CO₂ production and lipogenesis were studied at a higher glucose concentration, where steps beyond transport seem to be rate limiting for glucose metabolism, increased insulin sensitivity was also observed. In contrast, no change was found in maximal insulin responsiveness. Fat and blood cells from the patients who continued on their usual diet showed no changes of the mentioned quantities. In the total group of non-insulin-dependent diabetics, fat cell insulin binding as well as rates (both basal and maximal insulin-stimulated rates) of glucose transport, CO₂ production, and lipogenesis were very heterogeneous, but when results from the first and second fat biopsy from the same patient were compared, these values varied only slightly. We conclude that the beneficial effect of a high-fiber/high-starch/low-fat diet on metabolic control in diabetics may in part be mediated through an increased insulin-binding ability of target cells for insulin, which causes an increased insulin sensitivity in these cells.     

日本血吸虫病与肠线虫病联合化疗的效果

血吸虫病人合并感染肠线虫者(A组)采取;吡喹酮40mg/kg加阿苯达唑200mg和复方甲苯咪唑400mg(尚含左旋咪唑100mg)分2d顿服,1个半月后血吸虫阴转率88.0％,蛔虫、鞭虫和钩虫阴转率分别为77.4％、23.6％及100.0％。对不合并血吸虫病的肠线虫病患者采取两种联合化疗方案:B组—阿苯达唑200mg和复方甲苯咪唑200mg(尚含左旋咪唑50mg)顿服,蛔虫、鞭虫和钩虫的阴转率分别为66.7％、18.8％和62.5％,较A组结果稍低;C组—阿苯达唑100mg和噻嘧啶900mg顿服的驱虫效果差,蛔虫和鞭虫的阴转率分别为50.0％及11.1％。3种驱虫方案对血吸虫和蛔虫的减卵率可达97.0％～99.9％;对钩虫的减卵率达68.9％～100％;对鞭虫的效果差。相应增加药物的剂量及改进服法,当可提高疗效。     

Age-dependent changes of protein structure II. Conformational differences of aldolase of young and old rabbits

Conformational differences between aldolase from old and young rabbit muscle are revealed and described by means of UV difference spectroscopy, thermal perturbation difference spectra, and UV fluorescence. These two objects differ in thermal stability of protein conformation, but similar conformational transitions are observed on substrate binding.     

抗血小板药物在心脑血管疾病中的临床应用

抗血小板治疗是冠心病、缺血性脑卒中、心房颤动等心脑血管疾病的重要治疗措施之一。近年来,随着抗栓领域基础及临床研究的逐步深入,出现了许多新型的抗血小板药物。本文通过对各种抗血小板药物的临床应用进行综述,以期为血栓栓塞性疾病,尤其是心脑血管疾病提供规范化、个体化的抗血小板治疗。     

The effect of hormones on the haemodynamics in animals of different age groups

The investigation was undertaken to study to effect of varying doses of epinephrine, vasopressin, insulin, thyroxin, estradiol-dipropionate on the haemodynamics and contractility of the myocardium of rats in different age groups, as well as the effect of epinephrine and vasopressin on coronary blood circulation in dogs of various age groups. The age group peculiarities of reactions to the hormones were compared with changes in their content in the blood of animals of different age groups.Upon administering small concentrations of the hormones in this study, more pronounced changes in haemodynamics and contractility of the myocardium were observed in senile animals. The administration of larger doses led to more pronounced changes in mature animals. During the process of aging, there is a decrease in the range of the reactions of the cardiovascular system to the action of hormones.In case of long term (14 days) administration of thyroxin, it was found that in senile animals the contractility of the heart was lower than that in short term (4 days) administration. In long term administration of thyroxin, it was found that in mature animals the index for the myocardium's contracting ability was more pronounced than in short term administration.Irregular changes in the concentrations of different hormones in the blood, changes in sensitivity and ability of the myocardium to respond to their action lead to changes in the hormonal regulation of the heart, and to the development of aging metabolic and functional changes.     

Effects of HIV Infection on Pulmonary Artery Pressure in Children

BackgroundPulmonary hypertension may complicate human immunodeficiency virus (HIV) infection and result in right ventricular (RV) failure and premature death. There are limited data of the effects of childhood HIV infection or antiretroviral therapy (ART) on pulmonary artery pressure (PAP).ObjectivesTo establish if there is an association between childhood HIV infection or its treatment and pulmonary artery pressure.MethodsThe study conducted a cross-sectional study of 102 HIV-infected (48 ART-naïve, 54 ART-exposed) and 51 HIV-uninfected children in Jakarta, Indonesia, to estimate PAP using echocardiography parameters: tricuspid regurgitation peak velocity (TRV), left ventricular systolic index and diastolic eccentricity index (EI), and RV systolic function, assessed by tricuspid annulus plane systolic excursion. The association between either ART-naive or ART-exposed HIV and PAP was explored using general linear modelling adjusted for potential confounders.ResultsART-exposed HIV-infected children had higher TRV (adjusted difference: 0.36 m/s; 95% confidence interval [CI]: 0.12 to 0.60; p = 0.003) and diastolic EI (adjusted difference 0.06; 95% CI: 0.01 to 0.11; p = 0.02) than did uninfected children. The EI in ART-exposed children was significantly higher than normal. ART-naive HIV-infected children had a lower tricuspid annulus plane systolic excursion (adjusted difference: –2.2 mm; 95% CI: –3.73 to –0.71; p = 0.004), despite no difference in TRV (adjusted difference: 0.18 m/s; 95% CI: –0.06 to 0.43 m/s; p = 0.14). Seven (13%) ART-exposed and 4 (8.3%) ART-naïve HIV-infected children had pulmonary hypertension. Within-HIV group comparisons showed that accounting for lower respiratory tract infections attenuated the lower RV systolic function in ART-naïve children but not in ART-exposed children (difference: –1.1 mm; 95% CI:–2.8 to 0.7 mm; p = 0.22), but not the higher left ventricular eccentricity indexes in the ART-exposed children (systolic difference: 0.07; 95% CI: 0.02 to 0.12; p = 0.007; diastolic difference: 0.08; 95% CI: 0.02 to 0.14; p = 0.006).ConclusionsART-exposed HIV infection is associated with higher estimated PAP. Reduced RV systolic function is seen in ART-naïve HIV infection. Lower respiratory tract infection partly explains lower systolic RV function in ART-naïve relative to ART-exposed HIV infection.     

Transvenous endomyocardial biopsy using the gastrointestinal biopsy (Olympus GFB) catheter

The use of a GFB biopsy catheter (Olympus) for endomyocardial biopsy in 23 patients is described. The catheter may be introduced alone or through a Cournand catheter. This technique is simple and safe and has a success rate of 100 per cent. There is little problem with cleaning out the blood. The technique of introducing the biopsy catheter through an already positioned Cournand catheter avoids any damage to the veins or perforation through the vein or right atrium; even in patients with large right atria, the procedure of first manipulating a soft rather than a stiff catheter into the right ventricle, and then introducing the biopsy through the Cournand catheter, becomes technically easy. The biopsy specimens measure 2 by 2.5 mm., which are adequate for microscopic examination and bacterial or viral culture studies. There have been no immediate or late complications.     

隐匿性血吸虫感染的研究

在已达到消灭血吸虫病标准的泰兴市和已达到基本消灭标准的昆山市各为8000余人的2个社区,分别发现隐匿性血吸虫感染111例和74例,预期人群感染检出率分别为2.4％及1.69％。患者检出率为0.04％及0.37％。用COPT、IHA、ELISA和IESA 4种方法检测血清特异性抗体,2项及2项以上同时阳性者达40.0％,吡喹酮抗虫治疗后1年,COPT呈下降趋势。