Volume Of Cell Nuclei Research Articles

Functional state of mammary gland of sows dried off by different techniques

Sows were dried off by a traditional method (control − C, restricted feeding before, during and after weaning) or by a modified one (experimental − E, intensive feeding before, during and after weaning). On day 5−6 after weaning of the 3<sup or 6<sup>th</sup> litter, in the sows lactating for the period of 6 weeks (experiment I) or 4 weeks (experiment II), histomorphological and caryometric evaluation of mammary alveoli was carried out. The cellular infiltrations (plasmocytes, eosinophils, histiocytes and neutrophils) in the mammary gland showed no significant differences between groups dried off by different techniques. The alveolar epithelial cell DNA index (<i>DI</i>) and nucleus volume (<i>V<sub>N</sub></i>) were higher in sows lactating for 4 weeks than in those lactating for 6 weeks and in sows after 3<sup lactation than in those after 6<sup lactation. In experiment I, after weaning of the 3rd or 6th litter, absolute <i>DI</i> values in groups C and E were as follows: 2.092, 1.520, 1.409, 2.443, and <i>V<sub>N</sub></i> 42.679, 28.060, 38.064, 48.185. In experiment II, they were 2.072, 3.039, 2.890, 3.208, and <i>V<sub>N</sub></i> 52.274, 63.213, 57.980, 63.337, respectively. After weaning of the 3rd litter, the domination of group E compared to group C was found during 4-week lactation (<i>DI</i> − <i>P</i> ≤ 0.01, <i>V<sub>N</sub></i> − <i>P</i> ≤ 0.01). In 6-week lactation, more favourable conditions were obtained in group C compared to group E (<i>DI</i> − <i>P</i> ≤ 0.001, <i>V<sub>N</sub></i> − <i>P</i> ≤ 0.001). After weaning of the 6<sup>th</sup> litter, in 4-week lactation, the domination of group E in relation to group C was insignificant: <i>DI</i> + 11.0%, <i>V<sub>N</sub></i> + 9.24%, and during 6-week lactation, it was statistically confirmed (<i>DI</i> − <i>P</i> ≤ 0.01, <i>V<sub>N</sub></i> − <i>P</i> ≤ 0.01). The results justify the need of intensive feeding during the weaning time in sows with longer lactation compared to those with the shorter one, with the performance period prolonged till the 6th reproduction cycle.

Morphometric changes in the adrenal medulla of intact and ethane dimethanesulphonate (EDS)-injected rats subjected to chronic treatment with isoproterenol or propranolol

Morphometric characteristics of adrenal medulla were analysed stereologically in adult male rats injected with a single dose of ethane dimethanesulphonate (EDS), an agent that causes atrophy of the inner adrenocortical zone, or vehicle, and subjected to isoproterenol (ISO) or propranolol (PROP) treatment over the following 15 days. Compared with dimethylsulphoxide (DMSO) vehicle-injected controls, in EDS-administered rats the volume of chromaffin cell nuclei was decreased. ISO treatment in these rats increased the volumes of chromaffin cells and their nuclei. Furthermore, in both EDS- and vehicle-injected rats ISO significantly enlarged the total volume of medullary blood vessels, suggesting a vasodilatatory effect of β -adrenoceptor stimulation. However, unexpectedly, in EDS-injected rats PROP treatment also caused an increase in the volumes of chromaffin cells and their nuclei. This finding, most likely, may be related to a non- β -adrenoceptor-related action of PROP. Collectively, the present results suggest that the response of adrenomedullary chromaffin cells to chronic ISO-induced β -adrenoceptor stimulation is dependent on the functional status of adrenal cortex, so that the stereologically detectable changes were found only in rats previously exposed to the destructive action of EDS on the adrenal gland cortical cells. Moreover, they indicate that ISO treatment exerts a reversing effect on the morphometrical changes of chromaffine cells induced by EDS administration.

ACTH-producing cells of 21-day-old rat fetuses after maternal dexamethasone exposure

Adrenocorticotrophic hormone (ACTH) is essential for developmental maturation of numerous organ systems during the fetal period and for adaptation to environmental challenges. Immunocytochemical and stereological methods were used in the present study to examine the effects of dexamethasone (Dx) administration during pregnancy on fetal rat pituitary ACTH-producing cells. Doses of 0.5, 0.5 and 1.0 mg Dx/kg body weight/day were given to the dams on 3 consecutive days starting on day 16 of gestation. Morphometric analysis of the ACTH-producing cells of fetuses at 21 days of gestation revealed significant inhibition by 24% and 27%, respectively, of cell volume and cell number after maternal Dx administration, whereas the volume of cell nuclei and volume density of ACTH-stained cells were insignificantly decreased. Immunocytochemical analysis showed reduced numbers, sizes and immunopositivity of ACTH cells of 21-day-old fetuses from Dx-treated dams as compared with the control group. Maternal Dx treatment in the period of intense differentiation of the hypothalamo–hypophyseal–adrenal system had an inhibitory effect on fetal function and proliferative activity of ACTH-producing cells at 21 days of gestation. Thus, inhibition of activity of fetal ACTH-producing cells may lead to adrenal suppression, modified activity of the hypothalamo–pituitary–adrenal axis and reduced body weight possibly causing lasting functional abnormalities.

The pesticide methoxychlor given orally during the perinatal/juvenile period, reduced the spermatogenic potential of males as adults by reducing their Sertoli cell number

Perinatal and juvenile oral treatment of rats with the insecticide, methoxychlor (MXC), reduced testicular size and other reproductive indices including the number of epididymal spermatozoa in those animals as adults 161. The objective was to determine if these males exposed during development had fewer Sertoli cells which might explain these testicular effects. Rat dams were gavaged with MXC at 0, 5, 50, or 150 mg x kg(-1) x day(-1) for the week before and after they gave birth. Resulting male pups (15/group) then were dosed directly from postnatal day 7 to 42. Testes were fixed in Bouin's and in OsO4, embedded in Epon and sectioned at 0.5 microm, stained with toluidine blue, and evaluated stereologically or cut at 20 microm to measure Sertoli cell nuclei with Nomarski optics. Sertoli cell number was calculated as the volume density of the nucleus times the parenchymal weight (90% of testicular weight) divided by the volume of a single Sertoli cell nucleus. Across dose groups, there were no changes in the nuclear volume density, the volume of a single nucleus, or the number of Sertoli cells per g parenchyma. There were highly significant dose-related changes in the volume of Sertoli cell nuclei per testis and the number of Sertoli cells per testis. Reduced testicular weight (r = 0.94) and reduced numbers of epididymal spermatozoa (r = 0.43) were significantly (p < 0.01) correlated to reduced number of Sertoli cells per testis. Hence, perinatal and juvenile oral exposure to MXC can reduce spermatogenic potential of males as adults by reducing their number of Sertoli cells.

Nuclear shrinkage in live mouse hippocampal slices.

Brain slices are used extensively for biochemical, electrophysiological and molecular investigations. However, only the time frame for electrophysiological and biochemical investigations has as yet been defined. The goal of the present study was to investigate the time course of nuclear structure in live brain slices. Hippocampal slices (300 microm) were prepared from male CD1 mice (25-30 g), stained with Hoechst 33342 (10 microM), calcein-AM (2 microM) and ethidium homodimer (4 microM), and imaged with single- and dual-photon microscopy. The volume of CA1 pyramidal cell nuclei decreased from 759+/-229 microm3 in 40-50 microm depth 25 min after preparation to 453+/-169 microm3 (P<0.001) after 60 min, 315+/-112 microm3 (P<0.001) after 120 min and 128+/-71 microm3 (P<0.001) after 8 h. Similar results were obtained on a prolonged time scale in 70-80 microm depth and with an accelerated time scale in 20-30 microm depth. Live-dead staining showed that cell damage is progressing from the surface to deeper layers of the slices in a time-dependent fashion. We conclude that nuclei of CA1 hippocampal pyramidal cells show a time- and depth-dependent shrinkage converging 8 h after slice preparation to a volume of 90-130 microm; in any depth between 20 and 80 microm. The nucleus in the superficial 80 microm of each side appears dysfunctional even at times suitable for electrophysiological and biochemical experimentation in hippocampal slices. Molecular analysis of cell regulation in brain slices may, therefore, be time-dependently distorted by progressing cell death in at least half of the tissue under investigation.

Size of neocortical neurons in control subjects and in Alzheimer's disease.

The aim of the present study was to estimate mean neuronal volume and absolute size distributions of the neocortical neurons in brains from controls and AD patients using stereological methods based on unbiased principles to determine whether changes in absolute cell size are part of the neuropathological pattern of Alzheimer's disease. The neocortex of 8 patients with Alzheimer's disease (AD), mean age 81.1 (68-94) y was compared with 9 nondemented controls, mean age 80.9 (65-101) y. The brains came from Johns Hopkins University Hospital (JHUH) in Baltimore, USA, the Netherlands Brain Bank (NBB), and from a large brain repository in Denmark. The rotator method was used to obtain an estimate of cell volumes providing absolute size distributions of the volume of both cell perikaryon and cell nuclei. The geometric mean volume of cell nuclei in neocortical neurons was 328 microm3 (interindividual CV = 0.15) in the Alzheimer group compared with 277 microm3 (interindividual CV = 0.17) in controls which was a statistically significant increase (P = 0.049). The perikaryal volume was 1117 microm3 in the Alzheimer group compared with 999 microm3 in controls which was a nonsignificant difference (P = 0.20). There was a highly significant correlation between the nuclear and perikaryal volumes in all individuals. The average slope of the regression lines was significantly higher in the Alzheimer patients than in the controls, illustrating that nuclear hypertrophy was more pronounced in the largest neurons.

Vasopressin and oxytocin neurons of the human supraoptic and paraventricular nucleus: size changes in relation to age and sex.

The hypothalamic supraoptic (SON) and paraventricular (PVN) nuclei consist of arginine vasopressin (AVP)- and oxytocin (OT)-synthesizing neurons that send projections to the neurohypophysis, whereas the PVN also projects to other brain areas. A growing body of evidence in animals suggests the presence of sex differences in the vasopressinergic and oxytocinergic systems. The present study was aimed at determining whether the sizes of AVP and OT neurons in the human SON and PVN show sex differences, as earlier studies demonstrated that a change in neuronal size is a sensitive parameter for activity. The minimal and maximal diameters were determined to estimate the volumes of cell somata and cell nuclei in AVP and OT neurons stained with an antibody against human glycoprotein-(22-39), a part of the AVP precursor, and a monoclonal anti-OT antibody in 15 men and 17 women ranging in age from 29-94 yr. The AVP neurons appeared to be larger in young men than in young women (< or =50 yr old). In elderly women (>50 yr old) AVP cell size considerably exceeded that in young women. In elderly men AVP neurons were larger than in young men and elderly women, although these differences were not significant. In addition, AVP cell size correlated positively with age in women but not in men. No significant differences were found in the AVP cell nucleus volumes among all four groups studied. Sex differences in the size of the PVN vasopressin neurons were pronounced at the left side (P = 0.048) and absent at the right side (P = 0.368), indicating the presence of functional lateralization in this nucleus. No difference was found in any morphometric parameter of OT neurons in the PVN among the 4 groups studied. Thus, our data demonstrate sex differences in the size of the AVP neurons, and thus in their function, that are age and probably also side dependent and the absence of such changes in OT neurons in the PVN. These data provide a basis for the reported higher AVP plasma levels in men compared to women.

Myocardial structure as a determinant of pre- and postoperative ventricular function and long-term prognosis after valve replacement for aortic stenosis.

Long-term results after aortic value replacement for aortic stenosis can be correlated to a cardiac-related pre-operative risk profile. This predictability indicates that there is a common basis in subtle or overt structural abnormalities of left ventricular myocardium. Forty-nine patients aged 24-82 (mean 61) years, with aortic stenosis had a full wall thickness transmural biopsy of the left ventricular antero-lateral free wall during aortic valve replacement. Echocardiography and radionuclide ventriculography were performed prior to, and 18 months (n = 41) after, the operation. Postoperative follow-up to a maximum of 7.7 years was 100% complete. Pre-operatively, all patients had an increase in both the left ventricular mass index (202 +/- 67 g.m-2) and the muscle cell diameter (41 +/- 8 microns); other morphological data included a muscle cell nucleus volume of 752 +/- 192 microns3, a muscle cell mass index of 163 +/- 54.m-2, and a fibrous tissue mass index of 39 +/- 16 g.m-2. Patients with a pre-operative episode of clinical left ventricular failure (n = 19) had significantly greater morphological variables than those without. Pre-operative ejection fraction and other measures of systolic function correlated inversely with the morphological data, except for the fibrous tissue mass index; diastolic function indices correlated inversely with all the morphological variables. At the 18-month re-study, the same general picture was noted, but with an underlying strengthening, especially of the muscle cell mass index. Overall, the mass index dropped to 152 +/- 51 g.m-2 (P < 0.0001), but in 17% of the patients it became normal; the mass index at 18 months was directly correlated to morphological variables. A high muscle cell nucleus volume was identified as an independent predictor of early and late mortality. Abnormalities of the hypertrophied left ventricular muscle cell and the degree of muscle hypertrophy are, to some degree, underlying determinants of pre-operative symptomatology, pre- and postoperative ventricular function, and early and late mortality after valve replacement for aortic stenosis. Incomplete hypertrophy impaired results, was related to pre-operative myocardial structural abnormalities.

Microgametophytic plastid nucleoid content and reproductive and life history traits of tribeTrifolieae (Fabaceae)

Microgametophytic plastid nucleoids were quantified for 18 species representing the four core genera of the tribeTrifolieae (Fabaceae),Medicago, Melilotus, Trigonella, andTrifolium. Generative cells of all taxa contained nucleoids, establishing that biparental plastid inheritance is common in theTrifolieae. Nucleoid number and volumes of pollen grains and generative cell nuclei differed among taxa. Nucleoid number was positively correlated with pollen grain and generative cell nuclear volumes, flower size and style length. These relationships disappeared after adjusting nucleoid number for pollen grain and generative cell nuclear volumes. Adjusted nucleoid numbers provided no evidence to support hypotheses that plastid content is associated with ploidy level, mating system, perenniality or size of the reproductive apparatus.

Cell number and distribution in human and rat airways.

Morphometric procedures were used to determine the number of cells, cell volume, cell diameter, and surface areas of the airways in human and rat lungs. Nuclear sizes of epithelial cells from human bronchi were significantly larger than other lung cell nuclei. The average volume of human ciliated cell nuclei was 310 +/- 30 microns 3 and 167 +/- 12 microns 3 in bronchi and bronchioles, respectively. The smaller nuclei of human bronchioles were comparable to those of alveolar cells. In the pseudostratified epithelium of human bronchi, basal cells had a large surface area in contact with the basement membrane (51.3 +/- 4.6 microns 2 per cell) when compared with ciliated (1.1 +/- 0.1 microns 2), goblet (7.6 +/- 1.2 microns 2), or other secretory cells (12.0 +/- 2.1 microns 2). In the first four airway generations distal to the trachea, basal cells account for 30% of the cells in human airway epithelium and 2% of the cells in rat airway epithelium. Total airway surface area from trachea to bronchioles was 2,471 +/- 320 and 27.2 +/- 1.7 cm2 in human and rat lungs, respectively. These direct measurements of airway surface area are less than half of the estimates based on current lung models. The total number of airway epithelial cells were 10.5 x 10(9) for human and 0.05 x 10(9) for rat lungs. For both species, there were 18 times more alveolar cells than bronchial epithelial cells.

The influence of tissue processing on quantitative histopathology in breast cancer

Objective grading of breast cancer by morphometry has been suggested for improving the precision of the prognostic prediction. However, the tissue components evaluated might be influenced by variations in the processing, reducing the clinical value. In the present study, the impact of the period of fixation, of the acidity of the fixative and of the embedding medium was investigated by allocating tissue samples from 27 surgical breast cancer specimens systematically randomly to different modes of processing. The volume-weighted mean volume of cancer cell nuclei, vu v(nuc), was estimated using the method of point-sampled intercepts on vertical sections. In addition, estimates of the mean nuclear profile area, alpha H(nuc), the nuclear volume fraction, Vv(nuc), the nuclear profile density, ND, and the mitotic profile frequency, MF, were obtained. The quantitative histopathological estimates were stable with respect to the investigated variables of the tissue processing. No significant differences were found when comparing the estimates obtained in samples from five tumours fixed in formalin at pH 5.0, 6.0, 7.0, 7.4 and 8.0, respectively. Similarly, no significant correlations between the estimates and the period of formalin fixation (24 h, 3 days and 3 months) were found in samples from five other tumours. However, the nu v(nuc) was 13% larger (2p = 0.004) and the mean ND 17% smaller (2p = 0.04) in hydroxyethyl-methacrylate-embedded samples from 17 tumours as compared to paraffin-embedded samples. Thus, the shrinkage observed in paraffin seems to affect nuclei less than tissue.

Role of H+ ions in volume and voltage of epithelial cell nuclei.

Condensation of chromatin depends upon the ion composition in the cell nucleus. We tested in isolated nuclei of Madin-Darby canine kidney cells the influence of various ions on nuclear volume (i. e. DNA packing) and intranuclear voltage. After isolation, nuclei were superfused with cytosolic solutions in which Na+, K+, Ca2+ and H+ ions were varied. With video-imaging and microelectrode techniques nuclear volume and intranuclear potential were measured in response to the various ions. In control cytosolic solution, isolated nuclei exhibited an intranuclear electrical potential of -6.5 +/- 0.5 mV (relative to a reference electrode in the cytosolic solution) corresponding to a nuclear volume of 250 +/- 10 fl (n = 104). Changing the Na+, K+ or free Ca2+ concentration in the superfusate in the physiological range resulted in minor changes of volume and intranuclear potential whereas pH altered both parameters dramatically. Nuclear swelling and intranuclear negative voltage increased with alkalinization and decreased when pH was reduced. An intact nuclear envelope was found to be no prerequisite for maintaining intranuclear negativity, indicating that the composition and functional state of nuclear chromatin rather than specific ion permeabilities of the nuclear envelope determine nuclear electrical potential. We present a model that explains nuclear volume and voltage on the basis of interaction between negatively charged DNA and positively charged histones of the nuclear chromatin.

Morphometric and stereological study of the glandular epithelium of the seminal vesicle of castrated guinea pigs treated with 17 beta-oestradiol benzoate.

Morphometric and stereological data are presented showing that the average thickness of the glandular epithelium (including secretory and basal cells together with intercellular spaces) of the seminal vesicle of the guinea pig increased significantly after oestradiol administration when compared with castrated controls. The increase in thickness was accompanied by a significant increase in the volume density of intercellular spaces. There were significant decreases in volume, surface and numerical densities of the secretory cell nuclei with respect to the glandular epithelium. The increase in the volume and surface densities of the secretory cell nuclei with respect to the average secretory cell was due to the significant increase in the average volume of the secretory cell. The increase in the mean volume of secretory cells was the result of a significant increase in the average cytoplasmic volume. In comparison with castrated controls, the structural data of cytoplasmic organelles also showed significant increases in total volume and surface area of granular endoplasmic reticulum per average secretory cell following oestradiol administration. This was accompanied by a significant increase in the total volume of Golgi cisternae per cell. The increase in the cytoplasmic volume of secretory cells after oestradiol treatment may be the result of an increase in number of organelles responsible for protein synthesis. The present study has provided quantitative evidence that the secretory function of the seminal vesicle of castrated guinea pigs may have been stimulated after oestradiol administration, which cannot be easily detected in a qualitative manner.

Distribution of lung cell numbers and volumes between alveolar and nonalveolar tissue.

Although total cell number has been determined for the alveolar region of the lungs of many species, it has not been calculated for the nonalveolar lung tissues. The oriented structure of airways and vessels makes the numerical assessment of cells in nonalveolar tissues difficult. This has led many investigators to use the number of cells in the alveolar region as a direct estimate of total lung cell number. To determine the number of cells in the nonalveolar lung tissues, the lungs of eight rats weighing 230 to 380 g were inflation-fixed and embedded in araldite, and 1.5-microns serial sections of the entire left lobe were cut and stained with methylene blue for light microscopy. The sections were then uniformly point-counted using computer-controlled distances between the fields to determine the fraction of points falling on air, blood, cellular tissue, and noncellular tissue for both the alveolar and the nonalveolar regions. The total volume of cell nuclei in each compartment was determined, and the total number of cells was calculated by dividing the total nuclear volume by the mean cell nuclear volume. It was found that 87% of the lung volume was alveolar, of which 6% was tissue and contained 725 x 10(6) cells. The nonalveolar region constituted 13% of the lung volume, of which 23% was tissue and contained 250 x 10(6) cells. The average rat lung therefore contains 975,000,000 cells, of which 74% was in alveolar tissues and 26% in nonalveolar tissues. On the basis of assays of isolated lung cells, there is an average of 7 pg DNA/cell.(ABSTRACT TRUNCATED AT 250 WORDS)

Development of an automatic program for the stereological estimation of the volume weighted mean volume of cell nuclei

A stereological method was recently developed for the estimation of the volume weighted mean volume of particles from 2D sections. Several authors successfully applied this manual method to paraffin sections of bladder cancers and malignant melanomas and found a good correlation between the mean nuclear volume and the histological grading and prognosis of these tumors. The implementation of this measuring method on an automatic image analyser, devoted to routine work in tumor pathology, is presented. The accuracy of the automatic measurement has been evaluated together with the first results obtained from human esophageal cancers.

Trophic doses of E2 prostaglandins do not influence the exocrine and endocrine pancreas in the presence of high levels of plasma somatostatin.

The aim of the present investigation was to study the effect of a long-term and a short-term treatment regimen with 15-R-15-methyl prostaglandin E2 and natural prostaglandin E2 (PGE2) on the endocrine cell populations of the rat pancreas. Graded oral doses of the analogue (5 and 50 micrograms/kg) and PGE2 (5000 micrograms/kg) were given twice daily for 4 weeks. The pancreas was carefully excised and weighed. Sections from randomly taken pancreatic biopsy specimens were processed for immunohistochemistry or hematoxylin and eosin staining before quantitative estimations were made, using stereologic methods. The total pancreatic volumes of insulin-, glucagon-, polypeptide P-, somatostatin-, and chromogranin A-immunoreactive cells were not affected by E2 prostaglandins. Neither the total volume of the islets of Langerhans nor that of the pancreatic cell nuclei was affected. The size of pancreatic cell nuclei was the same in the groups. The plasma levels of the antitrophic peptide somatostatin were significantly increased in rats treated with doses of both the analogue and PGE2 (p less than 0.05). In an additional short-term study rats were given oral placebo or 5000 micrograms/kg PGE2 twice daily for 5 days. The total endocrine pancreatic volume was not affected by PGE2. As in the long-term study, natural PGE2 did not affect the total pancreas volume or the total volume of pancreatic cell nuclei. These findings indicate that E2 prostaglandins produce no changes in the exocrine or endocrine pancreas in a dose range known to induce hyperplasia in the gastrointestinal epithelium.(ABSTRACT TRUNCATED AT 250 WORDS)

Circadian Rhythmicity in the Rat Exocrine Pancreas: Chronomorphological Patterns

Circadian rhythmicity of the structural morphometric model of rat endocrine pancreas has been studied in 24 Wistar female rats, four months old, kept in LD 12:12. The following parameters were evaluated: the volume fractions of nucleus and cytoplasm of exocrine cells, the size distribution and number in unit tissue volume of acinar cell nuclei, the mean nuclear diameter, the shape coefficient of glandular acini (that is the ratio acinar area/perimeter2 which indicates the shifting of structures from circularity). A statistically significant circadian rhythm was demonstrated for the shape coefficient of glandular acini. Results obtained in the present experiment are compared with data recorded in a previous study.

The volumes of rat and human lung cells as measured by an image analyser.

Previous studies of the morphometry of lung cells have required long and tedious measurements involving serial sectioning and the reconstruction of models. However the advent of computer-based image analysers offers a more straightforward, although less direct, method of making such measurements. In the present study a Magiscan has been used to investigate the shapes and sizes of the nuclei from the lung cells of three mammalian species. Associated cellular volumes have also been derived. Based on the measurements of about two hundred cells the mean volumes of rat, beagle and human lung cell nuclei were estimated to be 67 microns 3, 41 microns 3 and 78 microns 3 respectively. Cell volumes were estimated to be about 500 microns 3. It was also confirmed that a sphere is a very poor approximation for the shape of a nucleus, spheroids representing the observations much more closely.

Myocardial interstitial fibrosis in experimental uremia—Implications for cardiac compliance

Experimental uremia is known to cause cardiac hypertrophy. In the present study we examined the effect of uremia with or without concomitant treatment of hypertension by the converting enzyme Ramipril (125 micrograms/day) on micromorphometric indices of cardiac interstitium at the light microscopical and ultrastructural level. In male SD rats, 21 days of uremia caused an increase of total heart weight (1040 +/- 73 mg wet wt vs. 871 +/- 81 in controls, P less than 0.05) with an increase of both right and left ventricular weight. This was accompanied by reduction of capillary cross-sectional area despite unchanged capillary length. The volume density (cm3/cm3) of cardiomyocytes was unchanged (0.881 +/- 0.01 vs. 0.871 +/- 0.016 in controls), but volume density of interstitial tissue (excluding capillary lumen) was significantly increased (0.042 +/- 0.011 cm3 interstitial tissue/cm3 total heart tissue vs. 0.019 +/- 0.007 in controls). This was associated with signs of activation of interstitial cells, that is, increased volume of interstitial cell nuclei and interstitial cell cytoplasm. Concomitantly, a significant increase of volume density of non-cellular interstitial ground substance was found which was not normalized by antihypertensive treatment using Ramipril. After three months of uremia, electron microscopy showed collagen fiber deposition in the interstitium. Comparable interstitial fibrosis was not observed in hearts of rats with renovascular (one clip-two kidney) hypertension. It is concluded that uremia increases myocardial interstitial ground substance by mechanisms independent of hypertension. The data may be relevant for recent findings of diastolic heart malfunction secondary to impaired compliance in uremic patients.

The influence of some antidepressant drugs on the nuclear volume of rat cingular cortex cells in culture

The changes in the volume of cell nuclei of the rat angular cortex were investigated in culture after incubation with some antidepressant drugs. Two-week incubation of the cingular cortex culture with both tricyclic (desipramine, imipramine, amitryptyline) and non-tricyclic (mianserin) antidepressants in concentration of 3 × 10 −6M resulted in a decrease of the volume of the cell nuclei. Because the size of the nucleus is regarded as a criterion of the cell metabolic activity, our results may point to a diminished activity of metabolic processes of the cells.