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C Bertoni-Freddari

Publications and source records attributed to C Bertoni-Freddari.

At least 73 records · Page 4Linked to original sources
PubMed1983

Alterations of the synaptosomal membrane 'microviscosity' in the brain cortex of rats during aging and centrophenoxine treatment.

Synaptosomal and myelin fractions were isolated from the brain cortex of young, adult and old male CFY rats (2, 12 and 24 mth, respectively). The purity of the fractions was tested by transmission electron microscopy and marker enzyme assays. The cholesterol content of the fractions was also determined. Samples of the fractions were labelled with diphenylhexatriene (DPH) and the fluorescence anisotropy (r) of the label was measured at various optical densities. The values of r extrapolated to zero optical density were compared in the age groups and used for calculating the 'microviscosity' of the membranes. The 'microviscosity' of synaptosomal membranes displayed a significant age-dependent increase: from 2.3 +/- 0.02 (SD) in the young group it increased to 2.6 +/- 0.03 poise by the age of 24 mth at 37 degrees C. Most of this increase occurred between the adult and old age. The cholesterol content of the synaptosomes also increased significantly during aging. Centrophenoxine (CPH)-treatment with 100 mg/kg body weight daily dose for 2 mth was able to reverse the age-dependent alterations of both the membrane 'microviscosity' and the cholesterol content in the synaptosomes: the values returned nearly to the adult level. The results obtained are interpreted in terms of the membrane hypothesis of aging attributing to primary role to the free-radical induced membrane damage in cellular aging.

Aging↗
PubMed1983

X-ray microanalysis of monovalent electrolyte contents of quiescent, proliferating as well as tumor rat hepatocytes.

Energy-dispersive X-ray microanalysis was carried out on normal and regenerating liver as well as on 3924 A hepatoma cells. Specimens were quickly removed from the sacrificed animals, frozen in liquid isopentane, fractured still in the frozen state and freeze-dried under vacuum. The dried samples were examined in secondary electron image mode, and the X-ray spectra were recorded by means of an EDAX 707A system. Sodium and chlorine contents were higher both in nuclei and cytoplasms of regenerating and tumor hepatocytes than in normal liver. Moreover, hepatoma cells showed higher sodium and chlorine contents than did normal proliferating hepatocytes. Potassium contents did not show any differences among the experimental models. The increased sodium content and the resulting increased Na:K ratios of proliferating normal and tumor cells were not due to a generalized increase of these parameters in all the cells, but to the presence of new cell populations with high Na content and high Na:K ratios. Findings of present work are consistent with the hypothesis that high sodium content is associated with mitogenesis. Moreover, the much higher concentration of sodium in tumor cells as compared with normal proliferating hepatocytes supports the hypothesis that the concentration of this ion is related to oncogenesis of hepatocytes.

Animals↗
PubMed1982

Intracellular water and dry mass content as measured in bulk specimens by energy-dispersive X-ray microanalysis.

Intracellular water content (IWC) was measured in freeze-fractured biological bulk specimens by means of energy-dispersive X-ray microanalysis. The method is based on the concentration differences of certain elements (potassium and phosphorus) between frozen-hydrated and frozen-dried states of the tissues as applied formerly to sectioned material by others. A new mathematical formula has been derived giving rather precise figures for IWC. No elemental standards are necessary for the measurement: one has to obtain only the peak to background ratios in wet and dry states of the cells. the method is sensitive enough to reveal age-dependent as well as drug-induced changes of IWC in liver and brain cells. The values obtained are quite comparable with the theoretically expected one. Technical problems of the application of this method are discussed in detail.

Animals↗
PubMed1982

Age-dependence of the stimulatory effect of triiodothyronine on the DNA synthesis of rat hepatocytes.

The effect of a single subcutaneous injection of triiodothyronine (T3) on DNA synthesis rate and liver growth was studied in young and old female Wistar rats. The hormonal treatment was effective in stimulating DNA synthesis, resulting in an increase of the specific liver volume as well as volume and numerical density of nuclei/100 g body wt. in young animals. In the old animals T3 injection induced a reduced and delayed synthesis of DNA, which did not affect the morphometric parameters of liver/100 g body wt.

Aging↗
PubMed1982

The effect of acute and chronic centrophenoxine treatment on the synaptic plasticity of old rats.

The cerebellar glomerulus was studied by electron microscopic morphometry in female Wistar rats. Age-dependent alterations have been revealed from 3 to 28 mth of age, and the effect of centrophenoxine (CPH) was analyzed in two different patterns of administration. First, 27-mth-old rats were treated daily for 6 wk (acute treatment), and second, 18-mth-old rats were treated 3 times per week for 5 months (chronic treatment). The dose was 100 mg CPH/kg body weight, injected intraperitoneally. The surface density (SV), the numerical density (NV) and the average length (L) of the synaptic junctions were calculated from data obtained on ethanol-phosphotungstic acid stained ultrathin sections. An age-dependent reduction of SV and NV of the synaptic contact zones was found, and the L increased in the oldest animals. CPH-treatment resulted in a marked increase of SV in both types of application, whereas the other two parameters behaved differently in the two groups. The chronic treatment resulted in a significant slowing down of the decrease of NV, whereas L remained invariate. On the contrary, the acute treatment increased L but did not alter significantly NV. The results and the differences between the treatment types are discussed in terms of synaptic plasticity and are interpreted as different manifestations of the same reactive synaptogenetic process.

Aging↗
PubMed1981

In vivo effects of vitamin E deficiency on the intracellular monovalent electrolyte concentrations in brain and liver of rat. An energy dispersive X-ray microanalytic study.

Vitamin E is known to play a protective role for cell membranes against free-radical attacks. Vitamin E deficiency causes a rapid macroscopic ageing of rats. On the other hand, during normal ageing, cell membranes undergo functional alterations resulting in an increased intracellular potassium concentration in brain and liver cells. Therefore, is was of interest to study whether vitamin E deficiency produces similar alterations in young rats. Female Wistar rats were fed with a vitamin E deficient diet from 1 month of age for 10 months. The parietal brain cortex and the liver were analyzed by means of a quantitative energy dispersive X-ray microanalytic method using a JEOL JSM-35C-EDAX-711-NOVA-3 system. Monovalent electrolyte contents as well as the water content of the cells were determined in 5 treated and 5 control animals. Water content was measured by analyzing the potassium content in aqueous, frozen state, and again in the dry mass of the cells. On the basis of these data, a computer program calculated the water proportions. Average values for 200 or more cells of each organ per group revealed a significant increase in the intracellular potassium content of the brain cells, whereas the sodium and chloride contents increased to a much lower extent. There was a 2.6% loss of intracellular water in the brain cells in the vitamin E deficient group. The liver monovalent ions and water content remained unchanged. The results obtained are discussed in terms of the membrane hypothesis of ageing.

Aging↗
PubMed1981

Intracellular Na+:K+ ratios in human cancer cells as revealed by energy dispersive x-ray microanalysis.

Intranuclear sodium, potassium, and chloride contents were measured by energy-dispersive x-ray microanalysis in freeze-fractured, freeze-dried, bulk-tumor samples taken from 10 patients suffering from invasive urogenital cancers. Human biopsies were carried out during the first diagnostic interventions before any cytostatic treatment had been applied. Pathohistological diagnosis established the malignancy in each case. The cancers were classified in three types: keratinizing, transitional cell, and hypernephroid carcinoma. More than 250 cell nuclei were measured from each type of cancer. The results were compared with those obtained in intact human urothelium taken from patients having no malignant processes. Proximal and distal tubular epithelial cell nuclei representing the origin of human hypernephroid cancer were also measured in rat kidney because corresponding healthy human material cannot be obtained. The analyses revealed, in all three types of cancer cells, that the average intranuclear sodium content increased more than three-fold, the potassium content decreased 32, 16, and 13%, respectively; meanwhile the chloride content increased, but to a lesser extent than did the sodium. The intranuclear Na+:K+ ratios were more than five-fold higher in the cancer cells on the average, and their distribution histograms were much broader than in the normal human urothelium and in the tubular cell nuclei of the rat kidney. The results obtained fit well with the theory of Cone, C. D., Jr. 1971. J. Theor. Biol. 30: 151-181 according to which the sustained depolarization of the cell membrane may be of mitogenic effect.

Adult↗
PubMed1977

Alterations in the numerical density of perichromatin granules in different tissues during ageing and cell differentiation.

Perichromatin granules (PG) were counted on electron micrographs of different tissues taken from young and old female Wistar rats as well as in the basal and spinous layers of adult human epidermis. A significant age-dependent decrease was observed in the following cell types: large brain cortical cells, cerebellar granular cells, hepatocytes, parotid gland cells. No significant decrease was found in the heart muscle nuclei and in the erythroblasts of identical maturation level. The number of PG decreased during the erythroblast maturation almost to zero, and increased in the cells of spinous layer of human epidermis as compared to the basal cells. There is a very wide variation in the number of PG per nucleus between the different tissues. The correlation between the transcriptional activity, the protein synthesis, ageing and cell differentiation is discussed.

Adult↗
PubMed1977

Age-dependent increase of intranuclear monovalent electrolytes as revealed by quantitative energy dispersive x-ray microanalysis.

The concentration of univalent electrolytes in the cell nucleus and cytoplasm of the big neurons of the brain and in hepatocytes was established in young, mature and old rats by means of microanalysis with X-rays. It was demonstrated that the Na+ and Cl-- content increases with aging in both tissues, while K+ increases in the neurons but not in the nuclei of the hepatocytes, At the same time some ions in the cytoplasm increase, while others decrease or remain stable. If a possible loss of water during aging is taken into consideration the result is a considerable increase in ion concentration in the nucleus. This may be regarded as one of the principal reasons for the increased density which accompanies aging and possibly as one of the cause of the aging process.

Aging↗
PubMed1977

On the relationship between the perichromatin granules and cellular ageing as well as cell differentiation.

Current hypotheses ascribe the role of pre-RNA storage or transport structures to the perichromatin granules. Their numerical density is directly related to the transcription activity of the nucleus. The perichromatin granules (P.K.) can be demonstrated in ultrathin sections with the stain used by Bernhard (1969) for ribonucleo-proteins. We have established the numerical density per unit of area in nuclear cross-sections of cells in young rats (1-2 months), old rats (26-29 months) and in relation to various cell function types. Cell aging causes a reduction in the numerical density of perichomatin granules in the big neurons of the cerebral cortex, the cerebellar granulocytes, the hepatocytes and the parotid cells. No age-related changes were found in the myocardial cells and erythroblasts of the same maturity. However, at the end of maturation, the number of perichromatin granules both in young and old erythroblasts was nil. (1) There is a quantitative reduction of perichromatin granules primarily in postmitotic and relatively postmitotic cells; (2) cell types showing no age-related reduction in perichromatin granules maintain high synthetic activity throughout their life; (3) the results confirm that relationships exist between numerical density of the perichromatin granules and cell activity; (4) the big fluctuations in the numbers of perichromatin granules in various cell types are probably connected with cell function.

Aging↗
PubMedDate not supplied

Morphometric studies on synapses of the cerebellar glomerulus: the effect of centrophenoxine treatment in old rats.

Young, adult and old female Wistar rats (3, 18 and 28 months of age, respectively), were studied using electron-microscopic stereology. Synaptic parameters of the cerebellar glomerulus were calculated and compared with similar data obtained from old Wistar rats of the same breed treated with centrophenoxine (CPH; HelferginR, Promonta, Hamburg) in the form of intraperitoneal injections (100 mg/kg body weight) for 40 days. This treatment resulted in a sort of "rejuvenation" of synaptic structures. Namely, the surface density and the total length of synaptic contact zones were markedly reduced in the untreated old group, but in the treated animals these parameters returned to the values found in the young and adult animals. At the same time the numerical density of synapses remained unaltered in the treated group, while the average synaptic length displayed some further increase. The results are interpreted in terms of the age-dependent decrease in reactive synaptogenesis, suggesting that CPH stimulates the metabolism of the nervous elements persisting in old brain. The possible mechanism of CPH effect is also discussed.

Aging↗
PubMedDate not supplied

Muscle involvement in rheumatoid arthritis: an ultrastructural study.

An electron microscopic investigation has been carried out on muscle bioptic samples from patients affected by rheumatoid arthritis (RA). This study was undertaken to seek further ultrastructural alterations affecting striated muscles in RA pathology. Bioptic samples were collected on a total of 30 surgical interventions of hip (10), knee (8), and foot (12). This yielded three muscle types: gluteus maximus, vastus lateralis, and extensor digitorum communis. Muscle samples from 12 patients with no RA stigmata, selected to match RA patients by age and gender, constituted the control group. Tissue samples were prepared both for conventional histochemical methods and according to conventional electron microscopic procedures, including morphometric analysis. Although to a different extent in each sample, in muscles from RA vs. controls the authors observed the simultaneous presence of discrete muscular alterations such as wider separation of myofibrils, myelin figures, dilated sarcotubular system, pleomorphic mitochondria, myofibril flaking, and lipofuscin deposition in the subsarcolemmal region. In addition to a progressive atrophy, the above findings are suggestive of rheumatoid myositis and lend further support to the still poorly documented presence of an idiopathic inflammatory myopathy and inclusion body myositis associated with RA.

Adult↗
PubMedDate not supplied

Mitochondrial genome lesions in the pathogenesis of sporadic Alzheimer's disease.

BACKGROUND: The recent, magnificent results of molecular biology concerning beta-amyloid (betaA) metabolism in early onset Alzheimer's disease (AD) have generated a series of new findings and, in turn, a new etiological concept. Attention on the early events in the pathogenesis of AD has been shifted from the chromosomal abnormalities in the nucleus of nerve cells onto genetic changes in the mitochondrial genome. This offers a new pathogenetic approach which also opens new pharmacological challenges particularly for the episodic forms of AD. OBJECTIVE: Alterations occurring at the mitochondrial genome result in major consequences of oxidative phosphorylation and, if a specific threshold is exceeded, they may constitute important causative events in the apoptosis of selected nerve cells. The fact that the main source of mitochondrial metabolism is its glucose turnover allows monitoring brain changes in glucose metabolism by 18F-2 deoxyglucose positron emission tomography. In the demented brain, a low glucose turnover causes a cholinergic deficit by decreasing the synthetic rate of acetyl coenzyme A (AcCoA). AcCoA represents the key substrate for the acetylation of choline to acetylcholine by choline acetyltransferase. The consistent energy need for AcCoA synthesis appears obvious when considering that 1 molecule of glucose generates just 2 molecules of AcCoA, but 38 molecules of ATP. In the brain, AcCoA is exclusively synthesized in the glycolitic pathway. Generation of betaA is increased if the synthetic rate of ATP drops below a critical threshold: under these conditions, the betaA precursor protein (betaAPP) is inserted only in part into synaptic membranes which have the highest betaAPP turnover. In conditions of short ATP supply, betaAPP is not split at the beta region by an ATP-activated protease and this results in a substantial increase in uncleaved betaA molecules. CONCLUSION: Peroxidative alterations in mitochondrial DNA are of importance in degenerative diseases of postmitotic tissues, particularly in degenerative diseases. This offers a new pharmacological approach for the treatment of AD. Neurotrophic factors and estrogen seem to be the first pharmacological leads.

Aging↗