Increase In Volume Density Research Articles

EFFECT OF BILE DUCT OBSTRUCTION ON HEPATIC UPTAKE OF 1-METHYL-4-PHENYLPYRIDINIUM IN THE RAT

Previous studies have demonstrated that the organic cation 1-methyl-4-phenylpyridinium (MPP+) is avidly taken up by rat freshly isolated hepatocytes through at least two distinct transport mechanisms: the type I hepatic transporter of organic cations and P-glycoprotein. In this study, the effects of extrahepatic cholestasis induced by bile duct ligation for 4 days on the uptake of [3H]MPP+by rat freshly isolated hepatocytes and liver slices were determined. Bile duct ligation produced no significant alterations in the characteristics of [3H]MPP+uptake by freshly isolated hepatocytes. The strong correlation found between the effect of various drugs on [3H]MPP+uptake by hepatocytes from control and treated rats (r=0.958;P<0.0001;n=15) suggests that neither the type I hepatic transporter of organic cations nor P-glycoprotein were affected by bile duct ligation. On the contrary, uptake of [3H]MPP+by liver slices was markedly changed after bile duct ligation: (1) there was a significant increase (≅40%) in the amount of [3H]MPP+taken up by liver slices from bile duct-ligated rats; (2) there was no correlation between the effect of various drugs on [3H]MPP+uptake by liver slices from control and treated rats (r=0.772;P=0.072;n=6). On the basis of (1) the lack of effect of bile duct ligation on [3H]MPP+uptake by isolated hepatocytes; and (2) the profound morphological alterations of liver tissue observed 4 days after bile duct ligation (increase in volume density of bile ductules, ductular cells and infiltration of inflammatory cells), we suggest that non-parenchymal liver cells have an important participation in the hepatic uptake of [3H]MPP+after bile duct ligation in the rat.

Histological alterations following short‐term smokeless tobacco exposure in humans

The purpose of this study was to investigate the histological changes following short‐term smokeless tobacco application in humans. Sixteen smokeless tobacco‐using subjects participated in this trial. Each subject had used at least 3 cans of snuff per week for the previous 2 yr and had an existing lesion at the site of habitual snuff placement. The experimental design included subject placement of moist snuff (University of Kentucky reference tobacco brand 1S3) at a new site in the mandibular arch. At either 2 or 7 d, biopsies were taken from the new lesions and from a non‐placement site in the opposing arch. The volume density of inflammatory cells was determined by point counting. Keratin and epithelial thickness were evaluated by digitizing morphometry. Data were analyzed by repeated measures analysis of variance. In 7‐d lesions, increased keratin thickness was observed at the new sites compared to the non‐placement sites (p =0.05). Increased volume density of fibroblasts (p =0.027) and decreased volume densities of macrophages (p = 0.0083) and mast cells (p = 0.05) were observed at 2 d in new versus nonplacement sites. Clinically, the new sites showed erythema, erythema plus ulceration, or white striations. This study demonstrated histological and clinical changes at new snuff placement sites in as few as 2‐7 d, underscoring the rapidity of tissue alterations following snuff use.

Effect of antenatal tracheal occlusion on lung development in the sheep model of congenital diaphragmatic hernia: a morphometric analysis of pulmonary structure and maturity.

The incidence of congenital diaphragmatic hernia (CDH) is 1:1,207-5,000, and the condition is associated with high mortality and morbidity, attributed principally to associated pulmonary hypoplasia. Repairing the diaphragmatic defect by antenatal surgery has high mortality, mainly due to premature labor. Antenatal tracheal occlusion, which is achievable by less invasive methods, stimulates lung growth (weight and DNA). However, its effectiveness in reversing structural and maturational abnormalities and its optimal timing requires further investigation. We hypothesized that (1) antenatal tracheal occlusion performed in the lamb model of congenital diaphragmatic hernia will stimulate lung growth and structural development and restore lung structure and maturity toward normal levels by term gestation; (2) effects will be detectable by morphometric measurements of the following parameters: lung volume, ratio of parenchyma to nonparenchyma, volume density of connective tissue within nonparenchyma, ratio of gas exchange tissue to airspace in parenchyma, gas exchange surface area, capillary loading, alveolar/airspace density and alveolar perimeter; (3) effects will be seen in all lobes of the lung; and (4) a greater effect will be observed when tracheal occlusion is performed early rather than late in gestation. Fourteen lambs underwent CDH creation at gestation day 72-74 followed by tracheal occlusion at day 101 (n = 7) or 129 (n = 7). They were delivered by Cesarean section at 143 days (term = 145-149). Lungs were obtained at autopsy, inflation fixed, divided into lobes, and sampled; morphometric analysis was performed. Comparisons were made with previously reported results from control lungs of normal lambs and lambs with untreated CDH. In comparison with untreated lungs, antenatal tracheal occlusion at both times resulted in increased volumes for total lung and lobes, increased volume density of parenchyma and of airspace within parenchyma, and increased gas exchange surface areas. Normal values for gas exchange surface area density, and alveolar density and perimeter were attained and the lungs appeared more mature than non-occluded lungs. Tracheal occlusion earlier in gestation produced a greater effect, achieving greater than normal values for lung volumes and volume densities, whereas the capillary loading value was similar to normal lung. Later occlusion achieved less than normal values for lung volumes and volume densities, with a reduced capillary loading value. We conclude that antenatal tracheal occlusion is capable of reversing structural total lung and lobar hypoplasia and immaturity caused by CDH as determined by morphometrically determined parameters. The effect is greater when tracheal occlusion is performed early rather than late in gestation. The results are encouraging for development of treatment methods for humans with antenatally diagnosed CDH.

Age-related effects on the zona glomerulosa cells of the rat adrenal cortex

Zona glomerulosa cells of the rat adrenal cortex were studied at 2, 6, 12, 18 and 24 months. Adrenals from unstimulated rats were processed for light and electron microscopy and trunk blood was obtained for the assay of plasma renin activity and aldosterone. Similar assays were made in rats stimulated with adrenocorticotropic hormone (ACTH), 30 min before sacrifice. At light microscopy, no major structural changes were observed; the ultrastructure of most organelles was well preserved and the presence of lipofuscin granules in older animals was remarkable. Acid phosphatase activity was observed in lysosomes and some lipofuscin granules. The quantitative study showed an age-related decrease in cell and nuclear volume (p < 0.01 and p < 0.001 respectively) and an increase in volume density of lipid droplets, lipofuscin granules (p < 0.001), lysosomes and Golgi complex; a decrease in volume density of mitochondria and smooth endoplasmic reticulum (p = 0.052) was also observed. Plasma renin activity and aldosterone level were both reduced (p < 0.001). In stimulated animals, an enhanced aldosterone level was obtained which was higher at 12 months and decreased thereafter. These results show an age-related decrease of aldosterone secretion, consistent with structural and ultrastructural data and related to plasma renin decrement. They also show a decline in the response to aldosterone stimulation by ACTH, indicating a lesser functional ability of zona glomerulosa cells in old animals.

Morphological investigations of the myocardium ofcardiomyopathic hamsters during the postnatal development and experimental hypoxia. A quantitative ultrastructural study

The hereditary cardiomyopathy of the Syrian hamster (strain BIO 8262) as a model of human cardiomyopathy was investigated during postnatal development using ultrastructural morphometric analysis. The aim of the study was to establish basic ultrastructural morphometric data of cardiomyocytes of this model during all stages of the disease in comparison to corresponding stages of normal development, and to compare the ultrastructural resistance of normal and myopathic myocardium against acute hypoxic stress. The postnatal development of this cardiomyopathy is characterized by focal myolytic lesions already in the first postnatal days, extended myofibrillic and mitochondrial damage developing after the 1st month, and features of hypertrophy, disarray of myofibrils, thickening, and clumping of z-lines after the 4th month. Morphometric parameters of myopathic cardiomyocytes differing from those of the control are diminished volume density of myofibrils by about 10% of the control values in middle age, slightly increased volume density of sarcoplasmic reticulum and t-tubules in the 1st months, significant increase of them after the 3rd month, and significant alterations of many mitochondrial parameters indicating degenerations (numeric density, volume density, average volume, volume density of cristae, and of destroyed areas, and ratio of surface to volume density of mitochondrial cristae). Acute isobaric hypoxia was applied to myopathic and healthy hamsters of corresponding age (at day 100). Evaluation of ultrastructural morphometric parameters of cardiomyocytes revealed that especially mitochondria were more affected by hypoxia in the myopathic animals. The average mitochondrial volume was significantly more increased in the myopathic condition, the ratio of surface to volume density of cristae significantly diminished. Our ultrastructural - morphometric study has shown, that morphometric parameters in general can be assigned to the stages of cardiomyopathy, and that the ultrastructural differences are best expressed about the 4th month.

Four-week repeated inhalation study of HCFC 225ca and HCFC 225cb in the common marmoset

Four male and three female marmosets in each group were exposed to air only, 1000 ppm of HCFC 225ca or 5000 ppm of HCFC 225cb, for 6 h per day for 28 consecutive days. HCFC 225ca caused a slight reduction in body weight. HCPC 225cb occasionally caused somnolence during exposure and vomiting on the first day of exposure. Clinical chemistry findings included a mild reduction of triglyceride, cholesterol and phospholipid levels and increased GOT level m the HCFC 225ca exposure group. HCFC 225cb also caused a reduction of triglyceride levels in some animals. HCFC 225ca caused a slight increase of hepatic carnitine palmitoyltransferase (CPT) activity while HCFC 225cb slightly increased cyanide-insensitive palmitoyl CoA β-oxidation (FAOS) activity. In the HCFC 225cb exposure group, an increase in cytochrome P-450 content was also observed. HCFC 225ca caused a fatty change in the hepatic cells. Increased incidence of lipid droplets in the hepatic cells and myelin-like bodies in hepatic cells, Kupffer's cells and hepatic blood vessels were observed electron microscopically in the HCFC 225ca exposure group. A proliferation of smooth endoplasmic reticulum was observed in the HCFC 225cb exposure group. Decreased peroxisome volume density in the HCFC 225ca group, and increased volume density m the HCFC 225cb exposed females were seen. However, organ weight measurement and histopathological examination did not reveal hepatomegaly or hypertrophy with either substance. Although slight changes were noticed in peroxisome volume density and in some of the peroxisomal enzyme; activities, the changes related to peroxisome proliferation with HCFC 225ca and 225cb were minimal in marmosets compared to those seen in rats. Histopathological examination and hormonal analysis did not reveal any abnormalities in the pancreas or testes.

The human striatum in schizophrenia. I. Increase in overall relative striatal volume in schizophrenics

Postmortem volumetry of the human striatum and its subdvisions (putamen, n.caudatus, n.accumbens) was performed on serial coronal sections of complete hemispheres. Both hemispheres of 9 male schizophrenic patients younger than 65 years were closely matched in age with the hemispheres of 9 male control individuals. All obtained values were corrected with individual and region-specific shrinkage factors; the intrarater reliability was 1% difference in volume. The absolute striatal volume was significantly correlated with the volume of the hemisphere ( r = 0.931; P = 0.0003 ∗∗∗). Reflecting differences in the hemispheric volumes of the schizophrenic and the control group, the absolute striatal volume consequently did not differ both groups ( P > 0.55). However, we found a clear increase in the volume density (i.e. the relative striatal portion of the hemisphere; the relative striatal volume) in the schizophrenic group, highly significant on both sides ( P = 0.003 ∗∗ for the right striatum, P = 0.002 ∗∗ for the left striatum). The increase in volume density concerned both the putamen ( P = 0.003 ∗∗ for the right side) and the n.caudatus/n.accumbens ( P = 0.01 ∗ for the right side). Discrepant volumetric results of previous authors who compared only absolute volume values in samples not matched for identical hemispheric volume could thus be explained by this high positive correlation with the hemispheric volume. Since exact matching for identical hemispheric volume is not feasible and examined groups will never be large enough to rule out the influence of the hemispheric volume, the determination of relative volumes (i.e. volume densities) seems to be advantageous for future volumetric studies.

Morphometric evaluation of bronchial glands of beagle dogs

Using lung tissues of beagle dogs, we developed a method for objective estimation of bronchial glands. Defined generations (5th, 10th, 15th and 20th) of bronchi were collected according to the microdissection method by Plopper et al. (1983) [1]. Transverse sections were prepared for both light microscopic and electron microscopic studies. The point counting using prints made by a video copy processor was performed for estimation of the volume density of bronchial glands. Bronchial glands were observed throughout the canine bronchial tree. Moreover, a distinct difference was found in the volume density of bronchial glands depending on the lobe examined and the generation number. Recently, we performed a long-term inhalation study using beagle dogs in order to elucidate toxic effects of sulfur(IV) and acidic sulfate aerosols (Heyder et al., 1994) [2]. In addition to the quantitative analysis of surface epithelia, the volume density of submucosal glands in the bronchial wall was measured according to the method described above. As preliminary result, there was a tendency to an increased volume density of glands in the exposure group. Detailed quantitative evaluation of bronchial glands may enable detection of finite changes induced by low level concentrations of air pollutants.

Endothelin-1 causes sequential trapping of platelets and neutrophils in pulmonary microcirculation in rats.

We previously showed that endothelin-1 (ET-1) causes accumulation of leukocytes in the pulmonary microvasculature and increases vascular permeability in isolated rat lungs provided the presence of leukocytes in the perfusate. In the present study, we examined the time sequence for morphological changes induced by ET-1 in rat alveolar tissue. For this purpose we used morphometric analysis based on lung transmission electron micrographs. Morphometry was performed by point counting, and data were expressed as relative volume density. ET-1 (0.06, 0.6, and 6 nmol/kg) was infused into the internal jugular vein, and the animals were killed at certain points of time. The lungs were fixed by endotracheal instillation of McDowell's fixative. Infusion of ET-1 (0.06 or 0.6 nmol/kg) caused no significant morphological changes in the rat alveolar tissue as assessed by morphometric examination. A sevenfold increase in volume density of platelets was seen 5 min after infusion of ET-1 6 nmol/kg. The platelets were loosely aggregated, adhered partly to the endothelium, and some of them had a spherical shape with vacuoles, indicating activation. The volume density of erythrocytes increased threefold, lasting 30 min. At 120 min, the volume density of polymorphonuclear leukocytes (PMN) increased 10-fold. The PMN adhered closely to the endothelium and partly occluded the capillary lumen. Simultaneously, the endothelial cell surface showed morphological signs of injury. No significant changes were observed in the volume density of alveolar macrophages or monocytes. No significant changes were seen in lung volumes or the volume of the alveolar tissue compartment. The results showed that ET-1 causes a time- and dose-dependent sequential entrapment of platelets and neutrophils in the pulmonary circulation.

Renal expression of a transforming growth factor-α transgene accelerates the progression of inherited, slowly progressive polycystic kidney disease in the mouse

Polycystic kidney disease (PKD) is a prevalent inherited disease in human beings. The pathogenesis of PKD is as yet unclear. The epidermal growth factor family of proteins has been implicated in PKD based largely on in vitro data. To determine whether these growth factors contribute to the progression of inherited PKD in vivo, we crossed mice with a transgene for human transforming growth factor-α (TGF-α, a member of the epidermal growth factor (EGF) family) and mice with the pcy gene (which causes a slowly progressive form of PKD very similar to human autosomal dominant PKD). Renal expression of the TGF-α transgene in cystic mice (homozygous for the pcy gene) accelerated the development of PKD as shown by an increased kidney weight as a percent of body weight and an increased volume density of renal cysts at 8.5 weeks of age. However, renal expression of the TGF-α transgene did not appear to precociously initiate cyst development (at 6.5 weeks), nor did it cause an increase in the final degree of renal enlargement (at 29 weeks). Thus TGF-α accelerated the enlargement of cysts once initiated. At 8.5 weeks of age, renal expression of the TGF-α mRNA correlated positively with the amount of renal enlargement. At all time points studied, cystic kidneys exhibited increased expression of c-myc mRNA as compared with phenotypic normal kidneys, consistent with PKD being a hyperplastic disease of renal tubules. However, the renal expression of c-myc in 8.5 week cystic kidneys, with or without the transgene, did not correlate with the degree of renal enlargement. The results of this study suggest that EGF-like proteins may accelerate the progression of inherited renal cystic disease. However, the final degree of cystic change is dictated by the primary disease process rather than by the continued presence of growth factor.

The morphology of valves and valve-like structures in the canine and feline thoracic duct.

The microanatomy and ultrastructure of the feline and canine thoracic duct and afferent lymphatics were studied by scanning and transmission electron microscopy. We found that the lymphatic vessels were always terminated by ostial valves of two shapes, crescent- and navicular-like, in a ratio of 4:1. Specific regulatory structures along the free edges of the valves, including marginal thickenings and buttresses, are described. The tissue and cellular organization of the valve endothelium showed distinct peculiarities, particularly in the orientation and shape of the cells and their microrelief. We found that valvular endothelial cells, especially ¿tip cells¿, which are situated in unfavourable lymphodynamic conditions, were characterized by an increased volume density of intermediate (probably vimentin-based) filaments, suggesting an accommodative mechanism involving such filaments.

Approach to Estimation of Pesticide Occupational Hazard

In the present work, mussels (Mytilus edulis) were transplanted into a copper (Cu) gradient in Visnes (Norway) for a period of 3 weeks during November 2003. Sites 1 and 2 showed similar low levels of Cu, site 3 had intermediate Cu levels and site 4 was the most polluted with Cu as confirmed by AAS of digestive gland tissue. Values of lysosomal membrane labilization period were significantly lower at sites 3 and 4 compared to sites 1 and 2. The volume density and size of lysosomes was significantly decreased at site 4. The volume density of neutral lipids was also significantly lower at site 4 compared with the rest of sites. The volume density of lipofuscins showed significantly higher values at sites 2 and 3 compared to the reference site 1. Similar results were obtained regarding bioavailable metal levels measured by autometallography. All together, results are indicative of exocytosis of metal-containing lysosomes and lipofuscins to the digestive tubule lumen in mussels from site 4. In fact, autometallographic metal deposits were detected in digestive tubule lumen, brown cells and stomach in site 4 mussels. In agreement, there was a loss of digestive cells in mussels from site 4 (atrophy of the digestive epithelium) and cell type replacement (diminished volume density of digestive cells and increased volume density of basophilic cells). In conclusion, selected biomarkers indicated that mussels transplanted to sites closest to the Cu mine showed significant differences in metal accumulation pattern and in organization of the digestive gland tissue. Finally, female mussels closest to the Cu mine showed advanced gametogenesis with higher gonad index and vitellogenin-like protein levels than mussels at sites 1 and 2.

Increased volume density of somatostatin- and decreased volume density of serotonin- and motilin-immunoreactive cells associated with changed gastroduodenal fasting motility in obese subjects

Increased volume density of somatostatin- and decreased volume density of serotonin- and motilin-immunoreactive cells associated with changed gastroduodenal fasting motility in obese subjects

Are enterochromaffinlike cell tumours reversible? An experimental study on gastric carcinoids induced in Mastomys by histamine 2-receptor blockade

A rapid induction of enterochromaffinlike (ECL) cell tumours has been shown in Praomys (Mastomys) natalensis subjected to histamine 2-receptor blockade. In the present study the reversibility of ECL cell proliferation induced by acid inhibition was investigated. Short-term treatment (8 weeks) with the histamine 2-receptor antagonist loxtidine caused a moderate hypergastrinemia, accompanied by a minor increase in histamine contents and a 2-fold increased volume density of the endocrine cells in gastric oxyntic mucosa. Eight weeks after withdrawal of treatment the volume density of endocrine cells was normalised as were the tissue levels of histamine, indicating a total reversibility of ECL cell hyperplasia. Long-term treatment (24 weeks) caused severe changes in the endocrine cell population of the oxyntic mucosa with neoplasia ( 5 21 ), dysplasia ( 11 21 ) and nodular hyperplasia ( 5 21 ). The endocrine cell density increased twofold and tissue histamine levels fourfold. 24 weeks after cessation of treatment, the endocrine cell density had decreased to 136% of controls, while histamine concentrations were normalised. The frequency of invasive carcinoids after recovery ( 4 23 ) differed only slightly from that seen after treatment for 24 weeks ( 5 21 ). Dysplastic lesions were only seen in 1 23 and hyperplastic lesions were of less severe type after recovery. The results demonstrate that ECL cell hyperplasia and dysplasia, induced by acid inhibition, are reversible after cessation of treatment. However, ECL cell tumours did not disappear, within the given observation period. One may therefore speculate that ECL cell proliferation is no longer reversible once the neoplastic (transformed) phenotype has developed.

Induction of age pigment accumulation in the brain cells of young male rats through iron-injection into the cerebrospinal fluid.

The OH free radical formation can be increased in the brain by intralumbar iron injections into the cerebrospinal fluid (CSF) through the Fenton reaction. Ferrous ammonium sulphate was injected to male CFY rats of 3 months of age. The animals survived a single dose of 4 mumoles, and this treatment was repeated daily for 3 or 6 days. The total iron contents of the large brain and the cerebellum were measured by atomic absorption spectroscopy; 3 days of iron administration resulted in significant increases of iron contents only in the cerebellum, whereas after 6 days, both parts of the brain showed considerably higher iron contents. Electron microscopic point-counting morphometric analysis revealed a 65% increase of volume density of the lipofuscin in the large cells of parietal cortex after 6 days of iron-treatment. The Purkinje cells displayed a particularly frequent occurrence of an "apoptosis"-like structural alteration under the effect of iron. This kind of experimental approach is complicated by the facts that (i) the increase of OH radical flux above a certain level is lethal, and (ii) the young animals have a very active elimination mechanism of the waste products. Nevertheless, the enhancement of OH radical yield by an increased availability of iron for Fenton reaction resulted in an accumulation of lipofuscin even in young rats.

Effects of cis-Diamminedichloroplatinum II (Cisplatin) on the Splenic Tissue of Rats: A Histoquantitative Study

Histoquantitative methods were applied to study the changes of splenic structure and proportions of splenic tissue compartments in cisplatin-treated (6 mg/kg body wt) male Wistar rats. Six days after treatment the significant reduction of volume density of white pulp was observed, which was due to the very prominent decrease of volume density of follicles. The volume density of periarteriolar lymphatic sheaths did not change substantially. Volume density of the marginal zone was also significantly reduced. A significant increase of volume density of connective tissue was observed. Morphometrical parameters of the follicles were also markedly altered: the number of follicles per mm 2 of spleen section area, the numerical density of the follicles in the spleen, and the total number of the follicles were significantly reduced.

Toxic effects of solanum malacoxylon on sheep bone

Solanum malacoxylon (Sm), a calcinogenic plant that contains 1,25-(OH) 2D 3 glycoside, was administered orally to sheep. Fifty milligrams of air-dried leaves three times a week caused an increased volume density of cancellous bone within lumbar vertebrae and an increased trabecular thickness. There was little remodeling activity at the end of a 180-day treatment period, and few trabecular bone surfaces had let-racycline double labels at this time. Bone biopsies taken at the end of a 1-month treatment demonstrated increased extent of bone-forming surfaces and osteoid volume. Sm caused a mineralization defect that was transitory but resulted in unmineralized lines and foci in osteones. These remaining foci of unmineralized bone were associated with the deposition of acid mucopolysaccharide, and acid mucopolysaccharide accumulation could be identified on all bone envelopes in 30-day biopsy specimens. A similar hyperostosis in the metaphyses of rats was produced by parenteral administration of 1,25-(OH) 2D 3 for 10 days.

Effects of training in normoxia and normobaric hypoxia on human muscle ultrastructure.

The adaptive response of skeletal muscle to training in normoxia and in severe normobaric hypoxia was studied. The first group of five male subjects trained for 3 weeks on a bicycle (2 h/day, 6 days/week) in normoxia (Control training, Con T). A second group of five subjects trained in an ambient FIO2 decreasing progressively from 12.7% to a final level of 10.0% (hypoxic training, Hyp T). Fourteen months later, these subjects trained in normoxia at the same absolute power (normoxic training, Nor T). Peak oxygen consumption (VO2 max) was measured in normoxic and hypoxic conditions. Biopsies from the vastus lateralis muscle were analysed for fibre size, capillary and ultrastructural composition. Nor T had no effect on muscle tissue or VO2 max. Con T increased volume density of total mitochondria and lipids by 36 and 135% respectively (P < 0.05). Hyp T induced a 10% increase (P < 0.05) in peak VO2 max measured in hypoxia. Mean fibre cross-sectional area, interfibrillar mitochondrial volume density and capillary-to-fibre ratio were increased (P < 0.05) by 10, 42 and 13% respectively in the Hyp T group. These results suggest that training at the same relative workload in normoxia and hypoxia have similar, but not identical, effects on muscle tissue. If training in normoxia is carried out at the same absolute workload as in severe hypoxia, no significant effects are observed.

Toxic effects of solanum malacoxylon on sheep bone

Solanum malacoxylon (Sm), a calcinogenic plant that contains 1,25-(OH) 2D 3 glycoside, was administered orally to sheep. Fifty milligrams of air-dried leaves three times a week caused an increased volume density of cancellous bone within lumbar vertebrae and an increased trabecular thickness. There was little remodeling activity at the end of a 180-day treatment period, and few trabecular bone surfaces had tetracycline double labels at this time. Bone biopsies taken at the end of a 1-month treatment demonstrated increased extent of bone-forming surfaces and osteoid volume. Sm caused a mineralization defect that was transitory but resulted in unmineralized lines and foci in osteones. These remaining foci of unmineralized bone were associated with the deposition of acid mucopolysaccharide, and acid mucopolysaccharide accumulation could be identified on all bone envelopes in 30-day biopsy specimens. A similar hyperostosis in the metaphyses of rats was produced by parenteral administration of 1,25-(OH) 2D 3 for 10 days.

Structure of the Bursa of Fabricius and immune response to Bruceila abortus in the chicken after neonatal gonadectomy

The structure of the bursa of Fabricius and the immune response to Brucella abortus in Prelux chickens were studied three and six months after neonatal gonadectomy. The different structural changes and immune response were revealed in male and female chickens. In six-months-old gonadectomized males an increased volume density of lymphoid follicles and follicular medulla was found. The follicular number and the follicular diameter were increased. In three- and six-months-old orchidectomized animals, the immune response exceeded that of the nonoperated males of the same age. In ovariectomized chickens, antibody levels were lower than (three months) or equivalent to (six months) to those of nonoperated females. Histoquantitative analysis showed that the volume density of lymphoid follicles and follicular cortex decreased. The follicular number and the mean follicular diameter also decreased. Our results demonstrate that sex steroids have an immunomodulatory role and influence the size and structure of the bursa.