Behavioral and electrophysiological changes induced by acetyl-L-carnitine in aged freely-moving rats

In chronically-implanted, drug-free, behaving aged Fischer rats, intracerebroventricularly (i.c.v.) and intraperitoneally (i.p.) acetyl-L-carnitine (ALCAR) injections powerfully enhanced motor behavior and head movements aimed at attention and exploratory activity. This effect was dose-dependent and associated with the abolition or substantial reduction of the incidence and duration of the spontaneous EEG generalized hypersynchronous patterns termed High Voltage Spindle (HVS), with an increase in EEG monitored theta activity. The results suggest that ALCAR may stimulate the motivational system and disrupt the hypersynchronous processes by inhibiting the GABAergic thalamic reticular neurons and/or activating the brain stem cholinergic reticular system (pedunculo pontine tegmental, PPT and laterodorsal tegmental, LDT nuclei).     

鬼笔环肽对心肌梗死大鼠离体心脏牵张所致电生理学改变的影响

本文旨在探讨肌动蛋白稳定剂--鬼笔环肽(phalloidin)对心肌梗死(myocardial infarction,MI)大鼠离体心脏牵张所致电生理学改变的影响.将32只Wistar大鼠随机分为正常对照组(n=9)、鬼笔环肽组(n=7)、MI组(n=9)、MI 鬼笔环肽组(n=7).离体心脏经Langendorff灌流后,通过改变水囊容积,以△V=0.1、0.2、0.3 mL对心室牵张5 S,观察牵张后效应30 s,记录左心室内压力变化[左心室收缩压(left ventricular systolic pressure,LVSP)、左心室舒张末压(left ventricular end-diastolic pressure,LVEDP)、室内压最大上升,下降速率(±dp/dt max)]、单相动作电位复极90%的时程(monophasic action po-tential duration at 90%repolarization,MAPD 90)、室性期前收缩(premature ventricular beats,PVB)及室性心动过速(ventriculartachycardia,VT)发生率.结果显示,牵张使正常对照组及MI组大鼠MAPD 90明显延长(P<0.05,P<0.01),MI组大鼠MAPD 90延长更显著(P<0.05,P<0.01).鬼笔环肽(1 μmol/L)对正常及MI心肌基础状态下的MAPD 90无影响,但使MI心肌牵张后已延长的MAPD90缩短(△V=0.3 mL时,P<0.05).牵张后MI组大鼠PVB、VT的发生率明显高于正常对照组(均P<0.01).鬼笔环肽对正常大鼠心肌牵张后PVB、VT的发生率无显著影响,但使MI心肌PVB、VT的发生率明显下降(均P<0.01).MI组大鼠LVSP及 ap/dt max 较正常对照组显著降低(P<0.01);鬼笔环肽可使MI心肌LVSP轻度回升,但无统计学意义.结果表明,MI后牵张加重恶性心律失常的发生和持续,鬼笔环肽可以明显抑制其发生.     

Placental changes in rats with streptozotocin diabetes]

Placentas of rats with diabetes mellitus induced by streptozotocin are investigated. Histologically, in the spongiosa zone we find dilated and congested maternal sinus as well as cysts of different size and number. These cysts contain granular eosinophilic material and cytotrophoblastic cells with large amount of glycogen. In our opinion, these cysts are large glycogen islets of the spongiosa zone respectively their remnants. However, similar findings we see in smaller extension in normal rat placentas too. The glycogen content in placentas of diabetic rats is in all localisations higher than in control cases. Comparable histological changes like in diabetic human placenta such as placental disturbances of maturation we don't find in the placental labyrinth of diabetic rats.     

Thorium induced testicular changes in rats.

Daily intraperitoneal administration of thorium nitrate produced progressive morphological and biochemical alterations with the increase in thorium concentration in rat testis. The degenerative changes in the seminiferous tubules increased with the duration of treatment and after 90 days calcification occurred in about 25% of the tubules and in the connective tissue of the tunica albuginea. The activity of adenosine triphosphatase and alkaline phosphatase increased markedly as a result of thorium administration. An attempt has been made to interrelate histopathological and enzymatic changes and the metal concentration in the testicular tissue.     

Reversibility of electrophysiological changes induced by chronic high-altitude hypoxia in adult rat heart

Recent studies indicate that regression of left ventricular hypertrophy normalizes membrane ionic current abnormalities. This work was designed to determine whether regression of right ventricular hypertrophy induced by permanent high-altitude exposure (4,500 m, 20 days) in adult rats also normalizes changes of ventricular myocyte electrophysiology. According to the current data, prolonged action potential, decreased transient outward current density, and increased inward sodium/calcium exchange current density normalized 20 days after the end of altitude exposure, whereas right ventricular hypertrophy evidenced by both the right ventricular weight-to-heart weight ratio and the right ventricular free wall thickness measurement normalized 40 days after the end of altitude exposure. This morphological normalization occurred at both the level of muscular tissue, as shown by the decrease toward control values of some myocyte parameters (perimeter, capacitance, and width), and the level of the interstitial collagenous connective tissue. In the chronic high-altitude hypoxia model, the regression of right ventricular hypertrophy would not be a prerequisite for normalization of ventricular electrophysiological abnormalities.     

Ultrastructural and ultracytochemical changes in the lungs of rats with diabetes mellitus

Diabetes mellitus was produced in Rats by means of a single streptozotocin injection. The evolution of the lung ultrastructure and of the state of the alveolar epithelium glycocalix was followed during two months. Among the different cellular types of the lung parenchyma, the main alterations were revealed in the pneumocytes of type II. They consisted in severe enlargement of the endoplasmatic rough net channels, diminution of the quantity of the lamellated corpuscles and delay of their output out of the cytoplasm, the reduction of microvilli and thinning of the glycocalix. As an answer to the epithelium alteration, a regeneration of the type II pneumocytes was discovered. A structural insufficiency of the phagocyte system--polymorph nuclear leucocytes and alveolar macrophages was noted.     

Ceramide profiles in the brain of rats with diabetes induced by streptozotocin

Diabetes is associated with disturbances of brain activity and cognitive impairment. We hypothesize that ceramides may constitute an important contribution to diabetes-linked neuro-dysfunction. In our study we used rats injected with streptozotocin (STZ) as a model of severe hyperglycemia. Using the gas-liquid chromatography technique we found a significant increase of ceramide content in brains and a decrease in plasma of diabetic rats. The inhibitor of serine palmitoyltransferase, myriocin, reduced ceramide generation in hyperglycemic brains, although injected alone it exerted a paradoxical effect of ceramide upregulation. Myriocin had no impact on ceramide concentration in the plasma of either control or diabetic rats. The level of ceramide saturated fatty acids was elevated whereas the level of ceramide poly-unsaturated fatty acids was downregulated in brains of all experimental groups. The concentration of ceramide mono-unsaturated fatty acids remained unchanged. The pattern of individual ceramide species was altered depending on treatment. We noted an STZ-evoked increase of brain ceramide C16:0, C18:0 and C20:0 and a strong decline in ceramide C18:2 fatty acid levels. Some changes of brain ceramide pattern were modified by myriocin. We found a decreased amount of total ceramide-ω-6 fatty acids in STZ-treated rat brains and no changes in ceramide-ω-3 concentration. We conclude that ceramides may be important mediators of diabetes-accompanied brain dysfunction.     

Quantitative morphological changes in endocrine pancreas of rats with spontaneous diabetes mellitus

The present study describes the cytopathology of the pancreatic islets in 18-old male eSS rats with spontaneous diabetes mellitus as compared to aged-matched normal animals. Light-microscopic immunocytochemical and morphometric techniques were used to study islet-cell populations, while quantitative methods were employed specifically for the analysis of B-cell ultrastructure. The diabetic rats showed disruption of the islet structure and fibrosis in the stroma. The volume density (Vvi) of endocrine tissue and the Vvi and percentage of B cells were diminished, whereas the Vvi of exocrine tissue and the Vvi and percentage of D cells were increased. The number of medium and large islets as well as their mean volume (micron3) decreased in these animals. Pancreatic B cells from eSS rats showed an increase in the Vvi of endoplasmic reticulum, immature secretory granules and lysosomes. Conversely, the Vvi of total secretory granules and microtubules appeared diminished. The current observations contribute to our understanding of this useful animal model of diabetes mellitus, in the attempt to clarify the pathogenesis of the disease.     

Lead induced testicular changes in protein malnourished rats

The effect of concurrent low protein (8% casein) diet and lead (Pb) exposure (1 mg/ml lead acetate in drinking water) on testes of weaned rats up to 90 days of age was investigated Histopathological examination of testes of lead treated rats maintained on low protein diet revealed marked pathological changes associated with greatly reduced succinic dehydrogenase, glucose-6-phosphate dehydrogenase and adenosine triphosphatase activity as revealed histochemically compared to lead treated rats fed normal protein diet. It was concluded that higher accumulation of lead may be responsible for altering the enzyme levels and inducing the testicular degeneration to a greater extent in low protein fed rats compared to their counterpart controls.     

Nerve conduction in childhood diabetes

Sixty-nine diabetic children were studied with respect to the motor nerve conduction velocities, duration of illness and adequacy of control.As a group there was a trend for children with diabetes to have slower MNCV than non-diabetic children, and for the slowing to become progressive as the duration of their disease increased. Poorer quality of diabetes control was also associated with progressive slowing of conduction but the exact relationship is uncertain, since no patient who had diabetes for more than four years was well controlled.Theories of causation of peripheral neuropathy in diabetic patients are reviewed; metabolic changes, rather than other factors, are thought most likely in children.     

Age-related changes in cholesterol metabolism in macrosomic offspring of rats with streptozotocin-induced diabetes.

The aim of this study was to determine the impact of diabetic macrosomia on cholesterol and lipoprotein metabolism. Age-related changes in the activities of serum LCAT, hepatic HMG-CoA reductase, cholesterol 7alpha-hydroxylase, and ACAT, the major enzymes involved in cholesterol metabolism, were determined in macrosomic offspring of streptozotocin-induced diabetic rats. Hepatic, serum, and lipoprotein cholesterol contents were also examined. Mild hyperglycemia in pregnant rats was induced by intraperitoneal injection of streptozotocin (40 mg/kg body weight) on day 5 of gestation. Control pregnant rats were injected with citrate buffer. At birth, macrosomic pups had higher serum, LDL-HDL(1), and HDL(2-3) cholesterol levels (P < 0.05) associated with increased LCAT activity (+57%) compared with control values. At 1 and 2 months of life, serum and lipoprotein cholesterol concentrations in macrosomic rats were similar to those of controls, whereas LCAT activity remained elevated about 1.5-fold. In addition, there was no change in hepatic cholesterol contents but hepatic HMG-CoA reductase, cholesterol 7alpha-hydroxylase, and ACAT activities were higher in both macrosomic males and females than in their respective controls (P < 0.01). By 3 months, macrosomic rats had developed hypercholesterolemia with a rise in all lipoproteins. Enzyme activities were still increased in these mature macrosomic rats, and hepatic cholesteryl esters were higher only in macrosomic females.These data demonstrate an overproduction, combined with overutilization, of cholesterol during the phase of rapid growth in macrosomic rats. However, cholesterol oversynthesis exceeded its removal and was a major contributor to hypercholesterolemia in adult macrosomic rats. In conclusion, macrosomia was associated with alterations in cholesterol metabolism through adulthood.     

Hepatic changes during a carrageenan induced granuloma in rats

Hepatic changes during inflammation were studied in rats bearing a carrageenan induced granuloma. In spite of a decrease in the metabolic capacity of microsomes to induce lipid peroxidation during inflammation, the endogenous lipid peroxidation remained unchanged and unrelated with the hepatic activities measured. The continuous increase in hepatic cAMP observed during acute and chronic phases could be related to adenylate cyclase stimulation by mediators, and could be an initial step in the hepatocyte adaptation leading to the increased level of hepatic caeruloplasmin, to the reduction of cytochrome P-450 level and to the modifications of Ca(2+) sequestration by microsomes.     

Effect of physical load on serum protein glycation in rats with induced diabetes]

Decreased levels of early and advanced glycation products were found in exercise-training diabetic rats as compared with sedentary diabetic rats. Adaptation to systemic physical exercise in diabetic animals affects not only enzyme-regulated metabolism but also non-enzymatic processes involving protein glycation.