Ultrastructure of the macula densa in streptozotocin diabetic rats

Morphometric analyses of the macula densa in streptozotocin diabetic rats have revealed, that the volume density of the large lateral intercellular spaces, which are present in normal animals between the macula densa cells, decreases significantly in magnitude from 8.7 to 1.5% in diabetic animals. The volume density of cytoplasmic glycogen in the macula densa cells increases significantly from 5.4% in the controls to 14.8% in the diabetic animals, but the total volume density of mitochondria is the same in the two groups. The contact area between macula densa cells and the Goorgmaghtigh cells is increased by 38% in the diabetic animals compared with controls. The structural abnormalities in the macula densa in response to diabetes might be considered a structural counterpart to the alterations in the tubuloglomerular feedback mechanism and the increase in glomerular filtration rate in diabetes.     

实验性糖尿病大鼠心肌细胞膜完整性的改变

应用电生理和辣根过氧化物酶示踪技术观察链脲佐菌素引起的实验性糖尿病大鼠心肌细胞膜完整性的变化。实验结果表明,糖尿病大鼠心肌细胞动作电位波幅、最大舒张电位,阈电位和最大除极速度均比对照动物明显减低(P<0.001),而复极不同水平的动作电位时程比对照动物显著延长(P<0.001),糖尿病大鼠心肌中辣根过氧化物酶阳性的肌细胞数明显多于对照动物(P<0.05)。这些结果说明,糖尿病大鼠心肌细胞膜存在损伤的电位变化,并有肌膜通透性增大。提示心肌细胞膜完整性的损害在糖尿病性心肌病的发生机理中可能起一定作用。     

实验性糖尿病肺形态学及氧自由基研究

目的:了解早期糖尿病肺形态学及氧化应激的变化。方法:应用体视学方法对四氧嘧啶诱导的糖尿病28d大鼠肺进行定量研究、观察超微结构变化并测定血清和肺组织的超氧化物歧化酶(SOD)活性及丙二醛(MDA)含量。结果:糖尿病大鼠肺泡体密度和平均截线长度减少,肺泡壁体密度、肺泡表面积密度、肺泡数密度、肺泡面数密度和肺泡比表面增加。糖尿病大鼠Ⅱ型肺泡细胞粗面内质网扩张,其体密度、面密度、平均截面积和平均周长增加,而比表面减少。肺上皮和毛细血管基底膜增厚。糖尿病大鼠血清SOD活性下降,MDA含量增加;肺组织MDA含量明显升高。结论:糖尿病早期大鼠肺已发生形态学变化且受到氧化应激的危害,提示肺脏是糖尿病损害的"靶器官"之一。     

衰老晚期海马CA1区锥体细胞线粒体改变──电镜定量分析

选用成年健康SD大鼠20只.分为青年组（3个月）和老年组（34～36个月）二个实验组，每组10只。应用透射电镜结合体视学方法观察并比较了海马CA1区锥体细胞线粒体的变化，结果如下：和青年组相比，老年组肿胀、变性线粒体增多，体视学分析显示老年组线粒体密度和平均体积增大，线粒体数密度和比表面减少，线粒体切面积大小频数分布图向右侧迁移，显示到衰老晚期较小的线粒体数减少.较大的线粒体数增多。本研究结果表明，衰老晚期海马CA1区锥体细胞线粒体严重退变，进入失代偿状态。     

Effects of the type of dietary fat at two levels of vitamine in wistar male rats during development and aging. II. Biochemical and morphometric parameters of the brain

The object of this study was to explore the possible influence of the type of dietary fat at two extreme levels of vitamin E on several biochemically determined changes in the whole brain as well as on a number of quantitatively analyzed ultrastructural variations with age in neurons of the dorso-lateral parietal cortex and in the cerebellar Purkinje cells. For this purpose, six groups of weaning Wistar male rats were fed ad libitum isoenergetic diets containing similar amounts (15 g per 100 g of diet) of saturated fat (coconut oil), unsaturated fat (safflower oil) or a combination of both at two levels of dl-α-tocopherol (2 or 200 mg per 100 g of diet). The determinations were carried out in rats killed at 3, 6, 12, 18 and 24 months. Although in relation to age and irrespective of the type of diet several of the biochemical parameters significantly fluctuated with time, comparisons of the results between the youngest and oldest rats showed no changes in the concentration of RNA, triglycerides, phospholipids, cholesterol and collagen, a significant increase in DNA and vitamin E, and a significant decrease in total protein. While in vitro lipoperoxidation of whole brain homogenates (malonaldehyde production) increased from 3 to 18 months, there was a precipitous decline at 24 months. None of these biochemical changes were consistently influenced by the type of diet. In vivo peroxidation in the total lipids of the whole brain (conjugated dienes) was never observed in rats fed the saturated fat diets and was only detected at 6, 12 and 18 months in some of the rats fed unsaturated or combined fat diets. At 24 months, however, none of the rats from the various dietary groups showed in vivo lipoperoxidation. It would appear that the dietary levels of vitamin E had no effect on the extent of in vivo lipoperoxidation in rats fed the unsaturated fat diets but may have had some preventive effect in rats fed the combined fat diets for 18 months. The possible nosologic implications, if any, of the eventual occurrence of in vivo lipoperoxidation remained uncertain since no correlation could be found between this phenomenon and the other biochemical and morphometric parameters. In the cerebral cortex, the numerical density of neurons, astrocytes and dark oligodendrocytes did not change with age, but microglial cells increased and light oligodendrocytes significantly decreased. No major quantitative variations were found in mitochondria and rough endoplasmic reticulum of cortical neurons with age. The numerical density of Purkinje cells decreased with age and, while in these cells the numerical density of mitochondria decreased, the fractional volume of these organelles as well as the density of rough endoplasmic reticulum remained unchanged with age. The fractional cytoplasmic volume of lipofuscin significantly increased almost linearly with time in cortical neurons and Purkinje cells. While no correlation was found between lipofuscin accumulation in the cerebral cortical neurons and the variations in the other morphometric parameters of these cells, a highly significant negative correlation was detected between the increment of lipofuscin and the decrement of Purkinje cell number (r = ?0.96) as well as with the decrement in the number of mitochondria in these cells (r = ?0.90), suggesting a possible deleterious effect of this pigment. None of the morphometric parameters, including lipofuscin, were clearly influenced by either the type of dietary fat or by the levels of vitamin E.     

Pilocarpine-stimulated salivary flow rate and salivary glucose concentration in alloxan diabetic rats. Influence of severity and duration of diabetes

Pilocarpine-stimulated salivary flow rate and glucose concentration were estimated in short-term (1 month) and long-term (12 months) alloxan diabetic rats and in age-matched nondiabetic controls. Diabetic rats had significantly decreased salivary flow rate which was negatively correlated to blood glucose concentration. They also had increased salivary glucose levels, which were positively correlated to blood glucose values, when the blood glucose values were above 15 mmol l-1, suggesting a threshold mechanism for salivary glucose excretion. The long-term diabetic rats had significantly higher salivary flow rates than the short-term diabetics. Insulin therapy in short-term diabetic rats improved the salivary parameters and normalized blood glucose levels, indicating that the salivary abnormalities are reversible - at least in the short-term perspective - and reflect the metabolic derangements of the diabetes. The results suggest that reduced salivary flow rate and increased salivary glucose concentration might be of importance for the development of the periodontal disease and caries seen in diabetic rats.     

Study on the capillary permeability of myocardium in diabetic rats]

The alteration of myocardial capillary permeability (MCP) in experimental diabetic rat was investigated by using cationic ferritin as a tracer. Diabetes was induced by injection of streptozocin (70mg/kg b.w.ip.). Vehicle injected, age and body weight-matched rats were served as the controls. The myocardial tissue was examined by the end of 2,7, and 9 months or even longer after diabetes induction. Results showed that (1) MCP was significantly increased in diabetic rats in comparing with that of the controls; (2) The increase of permeability became more pronounced with prolongation of the course of diabetes; and (3) the increase of MCP preceded the capillary basal laminar thickening demonstrated by electron microscopy. These findings suggest that increased MCP may play a role in the pathogenesis of basal laminar thickening and myocardial complications in diabetic state.     

Effects of combined renovascular hypertension and diabetes mellitus on myocardial cells,non-vascular interstitium and capillaries: a stereological study on rat hearts

Summary The effects of combined renovascular hypertension and diabetes mellitus on the rat heart were investigated in order to detect possible synergistic effects of the two conditions. Hypertensive diabetic and hypertensive non-diabetic animals were compared to diabetic and non-diabetic controls. Hypertension was established for 12 weeks by a surgical stenosis of the left renal artery; diabetes mellitus was maintained for 8 weeks by a single intraperitoneal injection of 60 mg/kg streptozotocin. Light microscopic stereology did not reveal significant divergences between diabetic hypertensives and non-diabetic hypertensives. Hypertension induced a focal perivascular and interstitial fibrosis with increased volume densities of non-vascular interstitium and fibrosis (P<0.001). Capillary density (Q_A) was decreased in transverse sections (P<0.01) and increased in longitudinal sections (P<0.01). This indicates a three-dimensional remodelling of the capillary bed with an increased number of obliquely running capillaries. At least the length density (L_V) of capillaries (mm/mm³) tends to be normalized in long-term renovascular hypertension. At the ultrastructural level, a synergism of hypertension and diabetes mellitus was observed: the volume ratio of mitochondria to myofibrils was significantly decreased in hypertensive diabetics, but not in non-diabetic hypertensives or in diabetics. This may enhance the risk of cardiac deterioration. We conclude that the primary target of the synergistic damage in hypertensive diabetic heart muscle disease is the myocardial cell and not the cardiac interstitium.Preliminary results of this study have been published in: Mall G (1991) Morphometric study on the rat heart in combined renovascular hypertension and diabetes mellitus. In: Nagano N, Dhalla NS (eds) The diabetic heart. Raven Press, New York, pp 115–124Dedicated to Prof. Dr. med. G. Seifert on the occasion of his 70th birthday     

Ultra-structural changes in cells from the CNS in offspring from diabetic rats

This study was conducted to evaluate the cytological effects of maternal diabetes in the central nervous system (CNS). Sixteen adult female rats were divided in two groups and diabetes was induced in one group using alloxan. Both groups became pregnant by natural mating. At day?7 after birth, the cerebrum, cerebellum and spinal cord were collected from offspring of all rats. The weight of the neonates and their blood glucose were measured. Various cellular parameters were determined using transmission electron microscopy. Results revealed changes in the neurons of the grey matter of the cerebrum, cerebellum and spinal cord in the offspring of diabetic mothers (ODM) compared to controls. Mitochondrial abnormalities were also detected; mitochondrial cristae were destroyed and the mitochondria showed signs of vacuolation whilst increased heterochromatin was also noted. The density of neurons and neuroglial cells in the cerebrum, cerebellum and spinal cord was decreased in ODM compared with the control group. The body weight and blood glucose of ODM were significantly higher than that of controls (p?<?0.05). Maternal hyperglycaemia exhibits deleterious effects on the cells of the CNS during foetal life that affects the density of neurons, mitochondria and nuclei which persist through the post-neonatal period.     

Synergistic effects of diabetes mellitus and renovascular hypertension on the rat heart - stereological investigations on papillary muscles

Summary The effects of combined renovascular hypertension and diabetes mellitus on the rat heart were investigated in order to detect possible synergistic effects of the two conditions. Hypertensive diabetic and hypertensive nondiabetic young male Wistar rats were compared with diabetic and nondiabetic controls. Since the normal body weight increase of the diabetic animals was markedly suppressed a weight-matched nondiabetic control group was introduced in addition. Hypertension was established for eight weeks by a surgical stenosis of the left renal artery, diabetes mellitus was maintained for four weeks after a single intraperitoneal injection of 75 mg/kg streptozotocin. Light and electron microscopic stereological parameters were obtained for the left ventricular papillary muscles. The whole hearts were also investigated histologically. Qualitative morphology failed to substantiate synergistic effects in the hypertensive diabetic rats. Vascular abnormalities were not observed. The stereological parameters, however, revealed microstructural reactions which were observed exclusively in the hypertensive diabetic group: the volume ratio of mitochondria-to-myofibrils was decreased, the surface-to-volume ratio of mitochondria was increased (reduction of mitochondrial size) and the mean cross sectional area of capillaries was decreased. Similar quantitative mitochondrial changes have been frequently described in long-standing hypertension, but in the present investigation, they were not found in the nondiabetic hypertensive group. It is therefore concluded that diabetes mellitus potentiates the effects of chronic pressure overload on myocardial cells. However, the myocardial fibrosis which has been found by other groups at later stages of hypertension and/or diabetes mellitus was not detected in the present study. The reduced mean cross sectional area of capillaries in hypertensive-diabetic rats may be correlated with early molecular changes of the myocardial interstitium or with early abnormalities of small arteries. Thus our stereological results support the hypothesis that a non-coronary hypertensive diabetic cardiomyopathy occurs in mammalian hearts.The results were presented in part at the Erwin Riesch Symposium,The results were presented in part at the Erwin Riesch Symposium,Dedicated to Prof. Dr. Drs.h.c.mult. G. Schettler on theDedicated to Prof. Dr. Drs.h.c.mult. G. Schettler on the