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PubMed2001

Ultrastructure of the rat duodenal endocrine cells after prolonged irradiation.

We propose classification of duodenal endocrine cells of intact rats based on ultrastructural signs of secretory granules and subdivided these cells into 10 basic types. The effect of long-term irradiation in a total dose of 2.5 Gy on ultrastructural organization of duodenal apudocytes was studied. Irradiation induced nonspecific changes of cell organelles in apudocytes. Differences in the ultrastructural disorganization were detected between different types of apudocyte populations and between different types of endocrine cells. Under conditions of adaptation to radiation apudocytes released the secretory product not only through molecular extrusion and exocytosis, but also via degranulation.

APUD Cells↗
PubMed1997

Spongiform degeneration of the gerbil cochlear nucleus: an ultrastructural and immunohistochemical evaluation.

Observations from ultrastructural and immunohistochemical studies suggest that spongiform lesions in the gerbil cochlear nucleus are derived principally from dendrites. Almost one-fifth of the lesion profiles examined ultrastructurally exhibited synaptic contacts with axon terminals. In addition, approximately 80% of lesions are immunopositive for the dendrite-specific microtubule associated protein, MAP2. Ultrastructural studies showed a small percentage (8%) of lesions were derived from myelinated axons, although none were immunohistochemically labelled with antibodies to the tau protein. Staining with the astrocyte-specific markers GFAP, S-100 and vimentin yielded equivocal results, but did not support a major role for astrocytes in lesion formation. The histological profile matches that seen in some other well characterized types of spongiform degeneration.

Animals↗
PubMed2003

Ultrastructure of the gingiva in cardiac patients treated with or without calcium channel blockers.

OBJECTIVES: In the last few years, several studies have suggested that periodontal diseases are related to the development of atherosclerosis and its complications. Our objective was to study the ultrastructural morphology of the gingiva from cardiac patients, some of whom were treated and some not with calcium channel blockers compared to a control group. MATERIAL AND METHODS: Fifty-five patients were studied and grouped in the following way: (a) healthy group (HG) (n=12) healthy patients with at least two pockets between 3 and 5 mm; (b) cardiac group (CG) (n=12) patients with cardiac disease untreated with calcium channel blockers; (c) diltiazem group (DG) (n=13) cardiac patients treated with diltiazem; (d) nifedipine group (NG) (n=18) cardiac patients treated with nifedipine. RESULTS: Ultrastructural studies in the CG showed inflammatory cells, collagen fibers disruption and a more extended morphologically compromised fibroblast mitochondria. Morphometric studies in CG showed mitochondria that were impaired in number but increased in volume, suggesting metabolic cell suffering. In DG and NG, morphometric data were similar to HG. The presence of myofibroblasts and collagen neosynthesis was detected in DG and NG. CONCLUSIONS: Our data showed differences in the ultrastructure of the gingival fibroblasts between the studied groups; the DG and NG showed features that could be interpreted as an attempt to restore the cellular metabolic function.

Calcium Channel Blockers↗
PubMed2000

Cutaneous epithelioid malignant nerve sheath tumor with rhabdoid features: a histologic, immunohistochemical, and ultrastructural study of three cases.

INTRODUCTION: Malignant rhabdoid tumors are morphologically defined as sheets of loosely cohesive cells with eccentric nuclei and hyaline, paranuclear inclusions. Although originally described as a distinctive renal neoplasm of childhood, these tumors have since been described in all age groups and in a variety of extrarenal sites. In the latter setting, it is thought that the rhabdoid phenotype is comprised of histogenetically unrelated tumors, that regardless of histogenesis, pursue a biologically aggressive behavior. METHODS: We report on the clinical, histologic, immunophenotypic, and ultrastructural characteristics of three cases of cutaneous malignant rhabdoid tumor. RESULTS: Each of the cases arose on the trunk or the extremity of elderly men. None of the patients had neurofibromatosis. All of the lesions histologically showed sheets of loosely cohesive polygonal cells with eccentric nuclei and hyaline paranuclear inclusions. Each of the cases showed the following immunophenotype: S-100 (+), synaptophysin(+), vimentin (+), alpha smooth muscle actin (-), CD-30 (-), HMB-45 (-), and pankeratin(-). Ultrastructure of two of the cases yielded similar results showing paranuclear filamentous aggregates of intermediate filaments, cell membrane dense plaques, and rudimentary cell junctions consistent with nerve sheath differentiation. Tonofilaments, dense bodies, microtubules, neurosecretory granules, and melanosomes were not identified. Each of the patients died of widely metastatic disease within 1 year of diagnosis. CONCLUSIONS: Cutaneous epithelioid malignant nerve sheath tumor is a potentially aggressive tumor capable of showing rhabdoid differentiation thus simulating a variety of neoplasms. Immunophenotyping and ultrastructural analysis reliably discriminates these lesions from melanoma, de-differentiated carcinoma, lymphoma, and rhabdomyosarcoma.

Abdomen↗
PubMed2002

Immunohistochemical and ultrastructural observations of desmoplastic trichoepithelioma with a special reference to a morphological comparison with normal apocrine acrosyringeum.

BACKGROUND: Desmoplastic trichoepithelioma is a benign neoplasm considered to have follicular differentiation. Its sweat gland- or sebaceous-lines of differentiation have been also reported. There have been, however, only a few reports regarding extensive immunohistochemical and ultrastructural investigations of this neoplasm. METHODS: Histopathological and immunohistochemical studies were performed on three cases of desmoplastic trichoepithelioma, comparing it with normal skin. One of these cases was ultrastructurally investigated. RESULTS: The cord-like basaloid nests were reacted with the anti-cytokeratin (CK)1/5/10/14, -CK5/8, -CK14 and -CK15 antibodies, but not with the anti-CK6 antibody. Similar findings were observed in the outer layers of the normal follicular outer root sheath. Basaloid cell nests in one case, which showed ductal structures in the nests, also expressed CK7, CK8/18 and CK19. These keratins were also detected in the normal sweat glands. In addition, CK8/18 and CK19 were expressed in the basal cells of the outer root sheath. Keratinous cysts had inner reactions with the anti-CK10/11 and -CK6 antibodies, and outer reactions with anti-CK5/8 and -CK14 antibodies. Ultrastructurally, the cells in the cord-like nests were basically immature and basaloid in appearance. A few cells contained Odland bodies, which were also observed in the normal apocrine acrosyringeum. The ductal structure was lined by the cells which bore numerous microvilli in the luminal surface. CONCLUSION: The cells in desmoplastic trichoepithelioma are suggested to be in close association with the basal cells in the outer root sheath, which can differentiate into various parts of the folliculosebaceous apocrine unit.

Adolescent↗
PubMed1983

The effect of cerebral ischemia on the ultrastructure of the hypothalamo-neurohypophysial system of the mongolian gerbil. The neurohypophysial axons and pituicytes.

The results of ultrastructural studies of the neurohypophysial axons and pituicytes of male mongolian gerbils subjected to experimental cerebral ischemia induced by 10 min bilateral occlusion of the common carotids are reported. In gerbils with cerebral ischemia some neurohypophysial axons were well preserved and, as regards ultrastructural organization, did not differ from the control animals. Some axons showed ultrastructural changes. They were characterized by depletion of dense cored neurosecretory granules and the appearance of optically empty vesicles. These suggest the increased secretion of neurohypophysial hormones. Moreover, the findings of intra-axonal large multilamellar bodies and externally lying tightly arranged lamellar whorls (similar to myelin sheath) were linked with simultaneous obliteration of the primary structure of certain axons. The neurohypophysis of the animals subjected to cerebral ischemia revealed the presence of 'light' ('fibrillar') and 'dark' pituicytes. The 'light' cells were characterized by large Golgi complex and the presence of fine fibrilles or fibrillar bundles which occupied a large cytoplasmic area of the cell body or of the processes. The finding of accumulated fibrilles suggests the ischemia damage of the cells. The 'dark' cells revealed the presence of dense cytoplasmic ground and the lobulated nucleus. In these cells ribosomes were predominant. The mitochondria were swollen in both varieties of pituicytes, arbitrarily designated here as 'light' ('fibrillar') and 'dark'. The results of the present study, therefore, indicate a functional susceptibility of neurosecretory axons and pituicytes to haemodynamic disturbances associated with bilateral cerebral ischemia.

Animals↗
PubMed1991

The effect of bile salts on the permeability and ultrastructure of the perfused, energy-depleted, rat blood-brain barrier.

The action of bile salts upon the rat blood-brain barrier (BBB) was assessed in the absence of energy-yielding metabolism. Brains were perfused in situ with a Ringer solution for 5 min followed by a 1 min perfusion containing either sodium deoxycholate (DOC), taurochenodeoxycholate (TCDC), or Ringer/DNP. The integrity of the BBB was then determined by perfusing with the radiotracer [14C]mannitol for 2.5 min. Alternatively, the brains were perfusion fixed for ultrastructural assessment. At 0.2 mM DOC, the BBB remained intact and the cerebral ultrastructure was similar to the controls. At 1 mM and above, disruption of the BBB became evident. At 2 mM, the cerebral cortex became severely vacuolated, with damaged endothelium and collapsed capillaries. With TCDC, BBB disruption occurred at 0.2 mM without any apparent ultrastructural damage to the microvasculature. Following 2 mM TCDC, similar, but less widespread, structural changes to the 2 mM DOC-perfused animals was apparent. Opening of the BBB occurred at a concentration lower than that required to cause lysis of either red blood cells or cultured cerebral endothelial cells. It is proposed that the effect of bile salts at concentrations of 1.5 mM and above is largely due to their lytic action as strong detergents on endothelial cell membranes, but that at lower concentrations a more subtle modification of the BBB occurs.

Animals↗
PubMed2002

Infantile dilated X-linked cardiomyopathy, G4.5 mutations, altered lipids, and ultrastructural malformations of mitochondria in heart, liver, and skeletal muscle.

Mutations in the Xq28 gene G4.5 lead to dilated cardiomyopathy (DCM). Differential splicing of G4.5 results in a family of proteins called "tafazzins" with homology to acyltransferases. These enzymes assemble fatty acids into membrane lipids. We sequenced G4.5 in two kindreds with X-linked DCM and in two unrelated men, one with idiopathic DCM and the other with DCM of arrhythmogenic right ventricular dysplasia. We examined the ultrastructure of heart, liver, and muscle biopsy specimens in these three DCM types; we used gas chromatography to compare fatty acid composition in heart, liver, and muscle autopsy specimens of two patients of kindred 1 with that of controls. In X-linked DCM, G4.5 had a stop codon (E188X), a nonsense mutation, in kindred 1 and an amino acid substitution (G240R), a missense mutation, in kindred 2. In the two men with isolated DCM, G4.5 was not mutated. Ultrastructural mitochondrial malformations were present in the biopsy tissues of the patients with DCM. Cardiac biopsy specimens of both kindreds with X-linked DCM exhibited greatly enlarged mitochondria with large bundles of stacked, compacted, disarrayed cristae that differed from those of the two types of isolated DCM. Autopsy tissue of patients with X-linked DCM had decreased unsaturated and increased saturated fatty acid concentrations. Seven of 13 published G4.5 missense mutations, including the one presented here, occur in acyltransferase motifs. Impaired acyltransferase function could result in increased fatty acid saturation that would decrease membrane fluidity. Mitochondrial membrane proliferation may be an attempt to compensate for impaired function of acyltransferase. Cardiac ultrastructure separates X-linked DCM with G4.5 mutations from the two types of isolated DCM without G4.5 mutations. Electron microscopy of promptly fixed myocardial biopsy specimens has a role in defining the differential diagnosis of DCM. Mutational analysis of the G4.5 gene also serves this purpose.

Acyltransferases↗
PubMed1985

Protection of rats by clofibrate against the hypoglycaemic and toxic effects of hypoglycin and pent-4-enoate. An ultrastructural and biochemical study.

An ultrastructural and biochemical study of the toxic and hypoglycaemic effects of hypoglycin and pent-4-enoate was made on the livers of normal and clofibrate-fed rats. Injection of hypoglycin to rats doubles (from 22% to 44%) the volume fraction of mitochondria and decreases (from 1.05% to 0.26%) the volume fraction of peroxisomes in hepatocytes. The fast-acting toxin pent-4-enoate causes few ultrastructural changes except for the accumulation of lipids. In male adult rats fed with 0.5% clofibrate in their diet for 1-2 months, the volume fraction occupied by peroxisomes and mitochondria in hepatocytes rose to 6.26% and 29.5% respectively. Clofibrate feeding apparently protected the animals against the toxic, hypoglycaemic and hypothermic effects of hypoglycin and of pent-4-enoate, and completely prevented the ultrastructural damage caused by hypoglycin. After hypoglycin administration, hepatic mitochondrial butyryl-CoA dehydrogenase activity was inhibited by more than 90% and, surprisingly, the activity of the peroxisomal enzymes studied was largely preserved. When hypoglycin was given to rats fed on a clofibrate-containing diet, the oxidation of decanoylcarnitine, which was incomplete after hypoglycin treatment alone, remained incomplete with uncoupled mitochondria, but became apparently complete with coupled mitochondria. In the latter condition, there was a slowing of the rate during the last quarter of the pulse of oxygen uptake. Further, butyryl-CoA dehydrogenase activity was much less affected by hypoglycin in clofibrate-fed animals. Pent-4-enoate does not inhibit beta-oxidation in coupled mitochondria from clofibrate-treated rats.

Animals↗
PubMed2005

Dietary iron deficiency induces ventricular dilation, mitochondrial ultrastructural aberrations and cytochrome c release: involvement of nitric oxide synthase and protein tyrosine nitration.

Iron deficiency is associated with multiple health problems, including the cardiovascular system. However, the mechanism of action of iron-deficiency-induced cardiovascular damage is unclear. The aim of the present study was to examine the effect of dietary iron deficiency on cardiac ultrastructure, mitochondrial cytochrome c release, NOS (nitric oxide synthase) and several stress-related protein molecules, including protein nitrotyrosine, the p47phox subunit of NADPH oxidase, caveolin-1 and RhoA. Male weanling rats were fed with either control or iron-deficient diets for 12 weeks. Cardiac ultrastructure was examined by transmission electron microscopy. Western blot analysis was used to evaluate cytochrome c, endothelial and inducible NOS, NADPH oxidase, caveolin-1 and RhoA. Protein nitrotyrosine formation was measured by ELISA. Rats fed an iron-deficient diet exhibited increased heart weight and size compared with the control group. Heart width, length and ventricular free wall thickness were similar between the two groups. However, the left ventricular dimension and chamber volume were significantly enhanced in the iron-deficient group compared with controls. Ultrastructural examination revealed mitochondrial swelling and abnormal sarcomere structure in iron-deficient ventricular tissues. Cytochrome c release was significantly enhanced in iron-deficient rats. Protein expression of eNOS (endothelial NOS) and iNOS (inducible NOS), and protein nitrotyrosine formation were significantly elevated in cardiac tissue or mitochondrial extraction from the iron-deficient group. Significantly up-regulated NADPH oxidase, caveolin-1 and RhoA expression were also detected in ventricular tissue of the iron-deficient group. Taken together, these results suggest that dietary iron deficiency may have induced cardiac hypertrophy characterized by aberrant mitochondrial and irregular sarcomere organization, which was accompanied by increased reactive nitrogen species and RhoA expression.

Animals↗
PubMed1996

The ultrastructure of mantle cell lymphoma and other B-cell disorders with translocation t(11;14)(q13;q32).

We conducted an ultrastructural study in 22 cases of B-lymphoproliferative disorders in leukaemic phase bearing the t(11;14) translocation. The features of peripheral blood leukaemic cells in nine cases of mantle cell lymphoma (MCL) were compared to those diagnosed as B-prolymphocytic leukaemia (B-PLL) (five cases), splenic lymphoma with villous lymphocytes (SLVL) (four cases), lymphoplasmocytic lymphoma (LPL) (one case), chronic lymphocytic leukaemia with > 10% prolymphocytes (CLL/ PL) (one case) and unclassified B-non Hodgkin's lymphoma (B-NHL) (two cases). The ultrastructural characteristics were also compared to those present in B-NHL without t(11;14), including cases of follicular centre lymphoma (FCL). This study shows that MCL has distinct ultrastructural features including a cleaved or indented nucleus with an even heterochromatin distribution, an absent or inconspicuous nucleolus, low N/C ratio, abundant mitochondria, a well developed Golgi zone, profiles of endoplasmic reticulum and centrioles. This pattern clearly differs from that found in FCL cells. The nuclear pattern of MCL cells also differed from the cells in the other disorders with t(11;14), but shared an organelle-rich cytoplasm, and features which were not apparent in cases without t(11;14). The cytoplasmic changes observed in cells bearing t(11;14) suggest increased cellular activity which may relate to the chromosome translocation and the resulting over-expression of bcl-1.

B-Lymphocytes↗
PubMed2002

Ultrastructural and immunohistochemical characterization of the so-called giant multinucleate cells in cutaneous collagenomas.

AIMS: This study was undertaken to compare the histopathological, immunohistochemical and ultrastructural features of the so-called giant multi nucleate cells in cutaneous collagenomas: giant-cell collagenoma and solitary sclerotic fibroma. METHODS AND RESULTS: We studied four collagenomas: one giant-cell collagenoma and three solitary sclerotic fibromas. All the cases showed an indolent clinical presentation and were histologically constituted by a well-demarcated dome-shaped proliferation of coarse collagen bundles with a varying number of interspersed giant multinucleate cells and stellate mononuclear cells. The immunohistochemical study on paraffin sections revealed that neoplastic cells in both collagenomas were vimentin and CD34-positive, whereas FXIIIa was only expressed in solitary sclerotic fibromas. In regard to the so-called giant multinucleate cells, we have ultrastructurally found that these cells were 'real' multinucleate cells in giant-cell collagenoma, whereas in solitary sclerotic fibromas they consisted of closely packed aggregates of individual stellate mononuclear cells. Moreover, perinuclear cisternae focally containing finely textured material of moderate density were unexpectedly found in giant cells of giant-cell collagenoma, a finding which was not observed in solitary sclerotic fibromas. Additionally, a characteristic cell-cell interaction between tumour cells and mast cells was encountered in all collagenomas. CONCLUSIONS: This study supports a distinctive immunohistochemical and overall ultrastructural profile of giant multinucleate cells in giant-cell collagenoma and solitary sclerotic fibroma, which suggests a different pattern of differentiation for these two related cutaneous lesions.

Adult↗
PubMed1997

Improved preservation of ultrastructural morphology in human spermatozoa using betaine in the primary fixative.

Improved preservation of the ultrastructural morphology of human spermatozoa was obtained by filtration onto a Millipore filter (0.45 micron pore size) followed by fixation for 1 h in a fixative containing 3% glutaraldehyde, 1% formaldehyde and 21 mM betaine in Hepes or cacodylate buffer. Betaine raised fixative osmolality only slightly but markedly improved the ultrastructural appearance of the spermatozoa; it is known to function as an osmoprotectant in other situations, and may protect the cells from osmotic damage during the initial stages of fixation. The method is suitable for oligozoospermic samples as they are concentrated when the seminal plasma passes through the filter. Utilizing fixation after swim-up, it is suitable also for highly viscous semen. The fixative gave equally good preservation of sperm heads and tails and can be stored prior to use. The Millipore filter did not dissolve until placed in acetone prior to embedding, simplifying the exchange of solutions during processing. Improved preservation of rat epididymal ultrastructure was obtained by addition of betaine to the fixative of Ito & Karnovsky (1968), using immersion fixation.

Animals↗
PubMed1999

Biological ultrastructure as revealed by high resolution cryo-SEM of block faces after cryo-sectioning.

Ultrastructural information was obtained by imaging the block face of high-pressure-frozen cryo-sectioned biological samples in a high-resolution cryo-SEM. Cryo-sectioning leads to a well-defined flat artificial surface in contrast to cryo-fracturing. Typical artefacts of cryo-sections such as compression and crevasses were not visible on the block face. The ultrastructural features known from resin sections and from freeze-fractures could also be found on the block faces. The cytoplasms show particles of different size which most likely represent proteins. The effects of radiation damage could be reduced considerably by applying the double layer coating technique and backscattered electron imaging. High quality cryo-sections are only obtained from vitrified material. Reasonably flat block faces were, however, also obtained from adequately frozen microcrystalline samples, thereby facilitating ultrastructural studies in the frozen hydrated state.

Animals↗
PubMed1999

A comparison of the ultrastructure and metabolic response of the skeletal muscle of horses performing intense treadmill exercise at 20 and 35 degrees C.

The aim of this study was to determine whether the metabolic response and ultrastructure of muscle differed when horses performed intense exercise at different ambient temperatures. Four Standardbred geldings performed treadmill exercise, including an intensive trot of 2600 m on two different occasions, either at a high ambient temperature of 35 degrees C or at a temperature of 20 degrees C. The horses had a warm-up period of 23.5 min of submaximal exercise, followed by 2 h of box rest before the intensive exercise. Muscle biopsy data of adenine nucleotides, creatine phosphate, lactate and glycogen concentrations measured before the warm-up period were similar to those measured before the period of intensive exercise. Muscle lactate concentrations did not differ between the two temperatures, but increased significantly after intense exercise to levels of 34.7 +/- 8.3 mmol/kg d.w. at 20 degrees C, and to 41.7 +/- 12.5 mmol/kg d.w. at 35 degrees C. Muscle glycogen and creatine phosphate concentrations did not differ between the two ambient temperatures, but decreased significantly by 122 +/- 82 mmol/kg d.w. and 25.2 +/- 17.4 mmol/kg d.w., respectively, after the intensive exercise. No changes were seen in adenosine triphosphate, adenosine diphosphate and adenosine monophosphate concentrations. The muscle biopsies were investigated by electron microscopy, and showed no marked changes in the ultrastructure of the muscle due to exercise at the two different ambient temperatures. In conclusion, no marked changes were seen in the muscle metabolic response or in the ultrastructure of the muscle when the horses performed intense exercise at 35 degrees C compared to 20 degrees C.

Animals↗
PubMed2002

Effects of anabolic implants of oestradiol alone or in combination with trenbolone acetate on the ultrastructure of mammary glands in female lambs regarding their interference in prolactin secretion.

The side-effects of anabolic steroid implants on mammary gland ultrastructure were evaluated in female lambs treated with oestradiol (n = 10) and with oestradiol plus trenbolone acetate (n = 10). Ten non-implanted lambs were used as controls. Apart from the ultrastructural study of the mammary gland, an assessment of the prolactin pituitary cell population was carried out by immunological methods. Our results showed that oestrogenic implants exert stimulating effects on mammary gland development, both by activating the synthesis process at mammary gland cell levels and by increasing prolactin pituitary production. Nevertheless, there was no evidence of secretory products in the lumen of the gland. Implants containing trenbolone acetate counteracted the mammary stimulus of oestrogens showing ultrastructural images of cell autolysis and necrosis.

Anabolic Agents↗
PubMed1999

Ultrastructural studies on the centrosome-attracting body: electron-dense matrix and its role in unequal cleavages in ascidian embryos.

In ascidian embryos, three successive unequal cleavages occur at the posterior pole, generating a specific cleavage pattern. A recently reported novel structure designated the centrosome-attracting body (CAB) has been suggested to play essential roles in the unequal cleavages attracting centrosomes and the nucleus towards the posterior pole. To examine the morphological features of the CAB, the ultrastructure of the CAB of two ascidian species, Halocynthia roretzi and Ciona intestinalis was observed by transmission electron microscopy. Detailed observations clarified that the electron-dense matrix (EDM) was a CAB-specific component that was commonly observed in the CAB of both species but was not found in other areas of the embryo. Further observations of the CAB in various staged embryos revealed that the ultrastructure was quite stable, with no difference between points of a cell cycle or between each stage from the 8- to 64-cell stage when unequal cleavage occurred. Observations of extracted embryos implied that the EDM was the extraction-resistant component of the CAB and was tightly anchored to the plasma membrane. It has been proposed that the EDM functions as a physical attachment site at the cell cortex for microtubules emanating from centrosomes and provides a scaffold for the centrosome-attracting machinery. Interestingly, the ultrastructure of the CAB resembled germ plasm reported in other animals, raising the possibility that the CAB-containing posterior-most blastomeres are germline precursors.

Animals↗
PubMed1998

Histological and ultrastructural alterations in an animal model of Peyronie's disease.

OBJECTIVE: To determine the role of transforming growth factor beta (TGF-beta), one of the cytokines known to induce tissue fibrosis, in the induction of a Peyronie's-like condition, and to produce an animal model for the further study of Peyronie's disease. MATERIALS AND METHODS: Twenty-four adult male Sprague-Dawley rats were divided into two groups: in group 1, different concentrations of cytomodulin, a synthetic heptapeptide with TGF-beta-like activity, were injected into the tunica of each of 18 rats and six rats group 2 received saline injections as a control. The tunical tissues were taken after 3 days, 2 and 6 weeks and were examined histologically using Hart and trichrome stains. Electron microscopy was used to examine the ultrastructural changes in the same tissue samples. RESULTS: There were histological and ultrastructural alterations in 15 of 18 rats in group 1 (cytomodulin-injected), especially in tissue examined after 6 weeks. The most prominent histological changes were chronic inflammatory cellular infiltration, focal and diffuse elastosis, thickening, disorganization and clumping of the collagen bundles. The ultrastructural changes were in the form of densely packed collagen, fragmented and scarce elastic fibres, separation of neuronal fibres by interposing clumps of packed collagen, and perivascular collagen deposition as a part of the reorganization of the interstitial matrix. CONCLUSION: Cytomodulin can induce a Peyronie's-like condition in the rat penis, which may explain the role of TGF-beta in the pathogenesis of Peyronie's disease. With further refinement, such rats may be used as an experimental model for studies of Peyronie's disease.

Animals↗