Cardiovascular autonomic dysfunction in systemic lupus, rheumatoid arthritis, primary Sjögren syndrome and other autoimmune diseases.

Neurological manifestations are known to occur in patients with autoimmune diseases, often subclinically, but autonomic nervous system (ANS) involvement has rarely been studied, and studies have shown conflicting results. We performed cardiovascular ANS assessment in 125 patients with autoimmune diseases in this case-control study, including 54 patients with systemic lupus erythematosus (SLE), 39 with rheumatoid arthritis (RA), 20 with primary Sjbgren syndrome (pSS), eight patients with polymyalgia rheumatica (PR), four patients with scleroderma (Ssc) and 35 healthy control subjects. The control group was formed to approximately match the mean age of SLE, RA and pSS patients; controls did not differ significantly by gender from the autoimmune pations. All patients with were in stable condition. Autonomic nervous system dysfunction was diagnosed by applying cardiovascular reflex tests according to Ewing, and was considered to exist if at least two tests were positive. Vagal dysfunction was established by applying three tests: Valsalva manoeuvre, deep breathing test, and heart rate response to standing. Sympathetic dysfunction was examined by applying two tests: blood pressure response to standing and handgrip test. In all cardiovascular reflex tests, frequencies of abnormal results were significantly higher among the patients than among the controls (P < 0.05). The difference between the autoimmune patients and the controls was particularly significant in sympathetic and parasympathetic tests, with P < 0.0001. No correlation was found between disease duration, clinical manifestations, cardiovascular risk factors and diseases activity on the one hand, and ANS dysfunction on the other hand. Cardiovascular autonomic dysfunction was revealed in the majority of autoimmune patients.

Ganglioside a/b ratio in different rat brain regions following chronic diazepam treatment.

Gangliosides are sialic acid-containing glycosphingolipids that play a variety of important functions in neurons. The main purpose of this study was to determine the a/b ratio of gangliosides in different rat brain regions (cerebral cortex, hypothalamus, caudate nucleus, hippocampus, thalamus and cerebellum) after prolonged diazepam treatment. Male Wistar rats were maintained on a nutritionally adequate diet and diazepam was administered in a dose of 10 mg/kg day for 180 days. Total gangliosides were extracted according to Harth and the total ganglioside-NeuAc content was determined by Svennerholm's resorcinol method, modified by Miettinen and Takki-Luukkainen. The a/b ratio remained unchanged in rat hypothalamus, thalamus and cerebellum. It was slightly decreased in the caudate nucleus and hippocampus, but this was not statistically significant. A drastic decrease ( p<0.01) in ganglioside content, compared to control animals, was found in rat cerebral cortex. Ganglioside a/b profile did not change significantly in most of the brain regions (except in cerebral cortex), which suggests that adaptive changes occurred upon prolonged exposure to diazepam, in order to maintain the physiological ratio of ganglioside a- and b-series in distinct brain areas.

Ganglioside content and composition in rat cerebellum after prolonged diazepam treatment.

The main purpose of this study was to determine the content and composition of cerebellar gangliosides after prolonged diazepam treatment and their possible recovery after diazepam withdrawal. Male Wistar rats were administered diazepam in a dose of 10 mg/kg/day in drinking water for 3, 5 or 6 months. A additional group of rats had a one-month recovery period after five months of diazepam treatment. Control animals were age-matched and pair-fed. At the end of the experiment, the animals were sacrificed and the total cerebellar contents of ganglioside-NeuAc as well as its content in particular ganglioside fractions were estimated. After three months of diazepam consumption, no changes of ganglioside-NeuAc in investigated fractions (G(Q1b), G(T1b), G(D1b), G(D1a), G(M1), G(M2), and G(M3)) were observed. Five months of diazepam treatment caused a significant decrease in the total amount of gangliosides, which was evident in most of the investigated fractions, with the exception of the monosialoganglioside G(M2). Six months of treatment induced a generalized decrease in all the investigated ganglioside fractions. The diazepam-induced ganglioside reduction found after five months of treatment was also present after a one-month recovery period. The only fraction, which recovered and reached its control value, was monosialoganglioside G(M3).

[Gamma aminobutyric acid--its function, disorders and their sequelae]. / Gama-aminobuterna kiselina--funkcija, poremecaji i posledice.

Gama-Aminobutyric acid (GABA) is an important neurotransmitter that mediates inhibition in the central nervous system. Approximately 30-50% of all synapses are defined as GABA-ergic. GABA is a neurotransmitter in cortical and hippocampal interneurones. GABA-RECEPTORS: Till today, three receptor subtypes have been known: GABAA, GABAB and GABAC, which are pharmacologically different. GABAA receptor is postsynaptic and localized in central and peripheral sympathetic neurones. Its agonist is muscimol and is antagonized by bicucculline. GABAB is a presynaptic receptor of vegetative and central nerve terminals. Its agonist is baclofen. The main difference between these two subtypes is that the first one acts directly on Cl ionphore, while GABAB activity is mediated by Gi protein. GABAC receptors are the integral part of the membrane, which stabilise the resting potential of the cell by increasing conductivity for Cl. Their most effective agonist is TACA. GABA ACTIVITY ON SYNAPSES: GABA is the most powerful inhibitory neurotransmitter in CNS. Synaptic inhibition decreases cell's ability to communicate with other cells and it is realised by various inhibitory mechanism of GABA, such as preventing of stimuluss generation, dendritic inhibition and dendro-dendritic inhibition. GABA AND NEUROENDOCRINE REGULATION: Besides physiological significance in maintaining regular excitation and inhibition balance. GABA plays an important role in neuroendocrine regulation of the following hormones: LH, FSH, PRL, STH, SS, ACTH, TSH, TRH, MSH, VP and OX. GABA IN NEUROLOGICAL DISEASES: Increasing or decreasing of GABA-ergic tone, due to different reasons, may lead to numerous neurodegenerative disorders (epilepsy, hepatic encephalopathy, Huntington's chorea, spinocerebellar degeneration, dementia and psychosis).

Phospholipid content and fatty acid composition in the rat heart after chronic diazepam treatment.

The effects of chronic diazepam treatment (10 mg/kg/day for 180 days) on the fractional distribution and fatty acid composition of heart phospholipids were studied in male Wistar rats. It was found that diazepam treatment increased the content of phosphatidylcholine and cardiolipin in the heart and slightly increased its phosphatidylcholine fraction. There were no significant changes in fatty acid composition after diazepam treatment in heart phospholipids, with the exception of significant decrease of 20:3n-6 and 20:5n-3 fatty acids. Our findings suggest that diazepam, probably through peripheral benzodiazepine binding sites, altered the content of heart cardiolipin and caused changes in the flux of oxidative phosphorylation in the heart.

Liver, plasma and erythrocyte phospholipid content after chronic diazepam treatment in the rat.

Male Wistar rats were maintained on a nutritionally adequate diet and diazepam was administered in a dose of 10 mg/kg/day. Control animals were pair-fed an adequate diet. Feeding was continued for 180 days, and the effects on the liver, plasma and erythrocyte phospholipid content were studied. It was found that the contents of sphingophospholipids and phosphatidylinositol + phosphatidylserine were significantly reduced in the erythrocytes of diazepam-treated rats. There was a significantly increased content of phosphatidylcholine in the liver an erythrocytes after 180 days of diazepam treatment. Such treatment did not cause statistically significant changes in the plasma of diazepam-treated rats. These investigations are in agreement with the hypothesis that extended or chronic use of drugs such as diazepam may alter membrane-dependent processes.

[Gangliosides as neurobiochemical markers]. / Gangliozidi kao neurobiohemijski obelezivaci.

Gangliosides are primary brain membrane lipids which, due to their localization, present specific markers of certain nerve cells. Their structure and content is tightly connected with cytogenesis and histogenesis of brain in mammals. Their biologic function, at the surface of the neurons' membrane, is important for bioelectric neuronal activity and synaptic transmission. Apart from that, gangliosides are important as receptors of bacterial toxins. Effects that gangliosides may have on dendrites' and axons' growth have been studies and it can be concluded that they have a significant impact on recovery of ischemic brain lesions. They are also important therapeutic and diagnostic markers of certain malignant tumors. The most valuable results are expected in future by examination of gangliosides metabolism in neurologic diseases by application of cell cultures.