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PubMed1975

[Ultrastructural-morphometric analysis of liver biopsies in patients with intrahepatic cholestasis. I. Correlations between morphometry of bile canaliculi and so-called "marker enzymes of cholestasis" (author's transl)].

Reports on correlations between the activity of so-called "marker enzymes of cholestasis" in serum and the ultrastructural changes of the liver are rare. Therefore studies of ultrastructural changes were carried out in 40 patients with intrahepatic cholestasis. In the patients' serum activity of alkaline phosphatase, bile duct alkaline phosphatase, leucine-aminopeptidase (LAP), and 5'-nucleotidase (5'-Nu) as well as the concentration of bilirubin were determined. The results showed a significant correlation between the morphometry of the bile canaliculi and the serum activity of LAP and 5'-Nu. In patients with elevated LAP, an enlargement of the bile canaliculi could be proved. An increased serum activity of 5'-Nu correlated with a higher incidence of bile canaliculi in the ultrastructural picture. The results suggest an investigation of the ultrastructure of bile canaliculi and the determination of marker enzymes of cholestasis in the serum may both contribute to the assessment of cholestatic liver disease.

Alkaline Phosphatase↗
PubMed1988

Ichthyosis congenita type III. Clinical and ultrastructural characteristics and distinction within the heterogeneous ichthyosis congenita group.

We describe one type of the heterogeneous ichthyosis congenita group, inherited autosomal-recessively, noting its clinical and ultrastructural features based on the findings in a female patient, aged 30 at the time of first clinical and ultrastructural investigation, and supplemented with those of eight further patients, aged 2 to 22 years. Clinically this keratinization disorder was characterized by a generalized congenital ichthyosis with a reticulate skin pattern pronounced in a variable degree of severity, also involving the large flexures and the face, palms, and soles. Typical ultrastructural criteria were membrane structures, abnormal vesicular keratinosomes, vesicular complexes, and membrane-bound vacuoles within the cytoplasm of the granular cells, partly retained in the horny layer. A successful therapy with retinoids resulted in a complete removal of the hyperkeratoses but left the striking skin pattern unchanged. The morphological peculiarities remained unaltered as well. They are independent of the localization of the biopsies, of age and sex of the patients, and of oral and local treatment. Based on the clinical and ultrastructural features, this scaling disorder can be delineated against all other inherited ichthyoses and was termed ichthyosis congenita type III. A new nomenclature contributing to a distinct classification within the heterogeneous ichthyosis congenita group is discussed.

Female↗
PubMed1978

[Ultrastructural morphometric changes in spiral ganglion cells of the rat after broad band noise (author's transl)].

The comparison of ultrastructural and ultrastructural-morphometric findings in spiral ganglion cells subsequent to broad noise with 105 dB SPL over a period of 40 min demonstrates that there are morphometric changes of the cytoarchitecture of granular ganglion cells even without evident ultrastructural changes. Morphometric analyses shows a significant extension of the volume proportion of mitochondria per unit volume cytoplasm. The volume and the surface of the rough endoplasmic reticulum, the volume of the free ribosomes and the average single volume of the nucleoli increase per granular ganglion cell. The physiologic significance of these changes is discussed. The results show that changes of the cytoarchitecture of granular spiral ganglion cells are earlier detected by morphometry than by ultrastructural description.

Acoustic Stimulation↗
PubMed1976

[Ultrastructural identification and immunocytochemical study of somatostatin cells in antral mucosa of the rabbit and the mouse (author's transl)].

In normal and L-Dopa treated rabbits and mice, combined immunochemical methods, photonic histological methods for endocrine cells and ultrastructural methods were used to elucidate ultrastructure and properties of somatostatin cells of the antral mucosa. In normal rabbits, immunoreactive cells giving no fluorescence with Falck's technic, they corresponded neither to serotonin cells nor gastrin cells; they were unreactive with Fontana, Hellerström-Hellmann, Sevier-Munger and Mac Conaill methods but very slightly stained with Grimelius methods. In L-Dopa treated animals somatostatin cells gave formaldehyde induced fluorescence (they were included in GIC cells, thus in Apud group), exhibited a good reaction with Grimelius and Sevier-Munger methods. In order to carry out the alternate semi-thin/thin section procedure (semi-thin sections for immunofluorescence or immunoenzymatic detection and serial thin sections counter-stained for conventional ultrastructure studies), immunological treatment were performed on M.F.F.--glutaraldehyde fixed small fragments of mucosa before inclusion in Epon 812 or, after inclusion, on semi-thin sections. We succeeded in identifying ultrastructurally somatostatin cells. They displayed round or ovoïd shaped secretory granules, and three constant typical structures: numerous microfilaments--light and homogenous granules, often seeming like lipids---granules made up by coarsely filamentous cores surrounded by a large empty halo. Somatostatin cells seemed different of X cells because of their predominant localisation in the antral mucosa (in the rabbit X cells were predominantly in the fundus) and because of the lack of nuclear microfilaments; they also seemed ultrastructuraly different of D1 cells.

Animals↗
PubMed1976

Influence of fasting and stimulation on the rat gastric endocrine cells. Histochemical and ultrastructural study.

The ultrastructure and certain cytochemical parameters of endocrine cells of the rat gastric mucosa during 168 h of fasting were investigated. To some of the fasting animals peroral food or alcohol was administered before decapitation. The EC (enterochromaffin cells) the ECL (enterochromaffin-like cells), D1 cells, AL (A-like cells) and G cells were identified by means of electron microscopy. Only the EC, ECL, and G cells could be identified by means of light microscopy by an adequate histochemical technique. The ultrastructural picture of the ECL and of the EC cells did not change markedly during the fasting. In the D1 cells there occurred an agglomeration of secretory granules. Some of them disintegrated and disappeared. In the AL cells an agglomeration of granules during the fasting was also observed. Granules engulfed in lysosomes were often found. The participation of lysosomes in the degradation of granules during the fasting was more marked in the AL cells than in the G cells. The participation of lysosomes was questionable in the EC and D1 cells, and in the ECL cells no lysosomes were observed. In contradistinction to the G cells of the non-fasting animals, where more than one half of the gastrin granules were "empty", the G cells during the fasting were filled with agglomerated dense granules and contained lysosomes with fragments of engulfed secretory granules. Following the administration of food (Larsen's diet) 3 h before sacrificing the dissolution of the content of granules with well preserved membranes was observed (emiocytosis did not take place). The administration of food did not lead to changes in the ultrastructural appearance of the EC cells. The peroral administration of alcohol did not lead to any changes in the ultrastructural appearance of the AL and G cells.

Animals↗
PubMed1976

Recovery of ultrastructural changes accompanying caffeine contractures in isolated muscle fibres of the crayfish.

Reversible caffeine contractures in isolated muscle fibres of the crayfish (Astacus fluviatilis; m. extensor carpopoditi) are accompanied by swelling of the diadic cisternae of the sarcoplasmic reticulum and by constriction of the T-system tubules. The membranes of the tubules may coalesce and form pentalaminar structures. These changes in the diadic region can be found already in fibres fixed 10 s after the sudden introduction of 4 mM or 6 mM caffeine solution. The changes are completely reversible. The recovery period after a 6 mM caffeine contracture lasts 20 min. The restitution of ultrastructural changes induced by caffeine correlates well with the recovery of responsiveness to a repeated application of caffeine. The pretreatment of fibres with procaine prevents both the generation of caffeine contractures and the occurrence of changes in the ultrastructure. No changes or a very slight enlargement of diadic cisternae were found during potassium contractures of comparable size and duration to caffeine contractures. The effect of procaine as well as the restitution of ultrastructural changes after the recovery of responsiveness to caffeine support the view that the cisternal swelling is a direct consequence of the calcium releasing action of caffeine. Isolated swelling of diadic cisternae and the absence of any changes in the remaining parts of the sarcoplasmic reticulum during reversible caffeine contractures could point to the existence of functional differentiation of the respective parts of the sarcoplasmic reticulum. The absence of ultrastructural changes during potassium contractures might indicate a different source of the activating calcium for contraction and/or a different mechanism of its release.

Animals↗
PubMed1983

Pituitary adenomas: immunohistology and ultrastructural analysis of 118 tumors.

An analysis is presented of the immunohistological and ultrastructural features in a series of 118 surgically removed pituitary adenomas all of which were studied immunohistologically using antisera to growth hormone (GH), prolactin (PRL) ACTH, beta FSH, beta LH and beta TSH, and 75 of which were studied ultrastructurally. Results were analysed according to the mode of presentation of patients. Forty-one (35%) of the tumours were from patients with acromegaly or gigantism, ten (9%) from patients with Cushing's syndrome or Nelson's syndrome, 19 (16%) from patients with clinical features associated with hyperprolactinaemia and 48 (40%) from patients with space occupying lesions which appeared clinically to be overtly endocrinologically functionless. By light microscopy, using the immunoperoxidase (PAP) technique, immunoreactive GH was demonstrated in all the tumours from patients with acromegaly or gigantism, immunoreactive ACTH in all tumours from patients with Cushing's syndrome or Nelson's syndrome and immunoreactive PRL in 95% of tumours associated with effects of hyperprolactinaemia. Forty-five percent of the tumours from acromegalic patients contained some PRL-positive cells as well as GH-positive cells. Among the tumours which appeared clinically to be endocrinologically functionless were three tumours (from males) uniformly stained for immunoreactive PRL. Of the remainder, 60% were negative for immunoreactive hormones and 40% contained small numbers of cells which were positive for a variety of immunoreactive hormones. ACTH-cell and PRL-cell tumours had ultrastructural features as described in previous studies. Fifty percent of GH-cell tumours examined at the EM level contained fibrous bodies, while in the remainder these structures were not identified. Tumours with fibrous bodies were more likely to contain PRL as well as GH with immunoperoxidase. All tumours that were endocrinologically functionless and which were examined at the EM level contained secretory granules. Oncocytic change was common in these tumours. No ultrastructural differences were observed between those which contained immunoreactive hormones by light microscopy and those which did not.

Acromegaly↗
PubMed1981

Distribution and ultrastructure of Alzheimer's neurofibrillary tangles in postencephalitic Parkinsonism of Economo type.

The distribution and ultrastructure of Alzheimer's neurofibrillary tangles (ANT) in the brain stem, hypothalamus, and Ammon's horn were studied in four patients with postencephalitic parkinsonism of Economo type (PEPE). The distribution of ANT was as previously reported; the pattern of distribution resembled to that of amine-containing nerve cells. Ultrastructurally, ANT revealed twisted tubules (TT), but straight tubules (ST) of 150 A width were also found in the locus ceruleus of three cases; sometimes, TT and ST were mixed in a single neuron. Whether the coexistence of TT and ST in the locus ceruleus is a characteristic ultrastructural feature of ANT in PEPE or a regional peculiarity could not be determined. Ultrastructurally, ANT in PEPE were identical to those found in the brains of patients with Alzheimer's disease or senile dementia.

Aged↗
PubMed1993

An immunogold electron microscopic analysis of FMRFamide-like immunoreactive neurons in the CNS of Helix pomatia: ultrastructure and synaptic connections.

The ultrastructure and synaptic connections of FMRFamide-like immunoreactive neurons were investigated in the CNS of the snail Helix pomatia, following the application of a post-embedding immunogold method. For comparison, first, we analyzed the ultrastructure and granule content of the identified FMRFamide-containing C3 neuron in the cerebral ganglion. Three types of unidentified immunoreactive neuronal perikarya, and five types of varicosities could be distinguished on the basis of granule content. The different granule types revealed a highly selective accumulation of gold particles. One granule type contained by one FMRFamide-like immunoreactive neuron type (N1) and by one varicosity type (T2) showed similar ultrastructure to that of the granules seen in the C3 cell. In the neuropil, the majority of FMRFamide-like immunoreactive varicosities (four of the five varicosity types) established specialized synaptic contacts with unidentified postsynaptic profiles. In the connective tissue sheath around the ganglia, three types of FMRFamide-like immunoreactive varicosities were found to establish unspecialized contacts with smooth muscle fibres or to be free in the mass of collagen fibres. On the basis of these observations, we suggest (1) an extensive diversity of the localization of FMRFamide (and related substances) at the ultrastructural level; (2) the involvement of FMRFamide-like immunoreactive varicosities in synaptic, modulatory and neurohormonal regulatory processes in the Helix nervous system.

Amino Acid Sequence↗
PubMed1990

Development of the ultrastructural features of neuropeptide Y-immunoreactive neurons in the rat visual cortex.

Immunohistochemical studies have localized neuropeptide Y into a small population of non-pyramidal neurons in the mammalian cerebral cortex. In the rat, these cells are distributed in layers II-VI and are characterized at the ultrastructural level by an abundance of cytoplasm containing a plethora or organelles, most conspicuous of which are cisternae of granular endoplasmic reticulum stacked in parallel arrays. In the present study, we used electron microscopic immunocytochemistry to examine the ultrastructural development of neuropeptide Y-labelled neurons in the rat visual cortex from birth, when they first appear in this cortical area, until postnatal day 32. At birth and in the subsequent few days, neuropeptide Y neurons, found exclusively in layers V and VI, often show a deeply infolded nucleus and little cytoplasm containing few organelles. At the end of the first postnatal week, labelled cells are still restricted to layers V and VI and display immature features. However, at this stage, cells often show irregularly enlarged proximal dendrites filled with organelles. During the second postnatal week, neuropeptide Y-immunoreactive cell bodies appear for the first time in layers II and III, and at the end of this week they have a distribution similar to that observed in the adult. Labelled cells are overall more differentiated than at earlier ages showing some of the ultrastructural features which distinguish them in the adult. No differences in maturation are evident between immunoreactive neurons located in the superficial layers and those in the deep layers, suggesting that the neuropeptide Y neurons in the more superficial layers express the peptide after having completed their migration and have acquired their characteristic ultrastructural features. Maturation proceeds during the third postnatal week. At the end of this stage, neuropeptide Y-containing cells acquired their mature nuclear and cytoplasmic features and an adult complement of synapses.

Animals↗
PubMed1976

Ultrastructural findings after microsurgical interventions on the carotid artery of the rat.

For 10 years, it has been known that operations on vessels 1 mm in diameter are possible. The application of microvascular techniques to neurosurgery demands microscopic and ultrastructural examinations of the effects of such interventions on small vessels. Histological examinations can help to provide answers to questions concerning operating technique, ultrastructural examinations give information on the indications for operation. Since these questions have not been studied previously, preliminary examinations on easily accessible vessels are necessary. For this purpose, the common carotid artery of the rat was chosen. Histological and ultrastructural examinations were carried out on end-to-end anastomoses of these vessels. The ultrastructural findings are described and compared with anatomical findings in normal and abnormal vessels in the rat.

Animals↗
PubMed1996

The effects of the pretreatment of intravenous high dose methylprednisolone on Na(+)-K(+)/Mg(+2) ATPase and lipid peroxidation and early ultrastructural findings following middle cerebral artery occlusion in the rat.

The sodium-potassium activated and magnesium dependent adenosine-5'-triphosphatase (Na(+)-K(+)/Mg(+2) ATPase EC.3.6.1.3.) activity and lipid peroxidation and early ultrastructural findings were determined in rat brain at the acute stage of ischaemia produced by permanent unilateral occlusion of the middle cerebral artery (MCA). The effects of the pretreatment with intravenous high-dose methylprednisolone (MP) on these biochemical indices and ultrastructural findings were also evaluated in the same model. The rats were divided into four groups. In group I, 10 rats were used to determine Na(+)-K(+)/Mg(+2) ATPase activity and the extent of lipid peroxidation by measuring the malondialdehyde (MDA) content and normal ultrastructural findings. In group II on 20 rats, only subtemporal craniectomy was done in order to determine the effects of the surgical procedure on these indices and findings. This group was treated intravenously with saline solution before occlusion. In group III with MCA occlusion, saline solution was administered intravenously to 20 rats in the same amount of methylprednisolone used in group IV, ten minutes before the occlusion. In Group IV, a single high-dose (30 mg/kg) of methylprednisolone was administered intravenously, ten minutes before occlusion in 20 rats. After occlusion of the middle cerebral artery, Na(+)-K(+)/Mg(+2) ATPase activity was decreased promptly in the first ten minutes in the ischaemic hemisphere and remained at a lower level than the contralateral hemispheres in the same group and the normal levels in group I, during 120 minutes of ischaemia. A single dose methylprednisolone pretreatment prohibited the inactivation of Na(+)-K(+)/Mg(+2) ATPase. On the other hand, there was significant difference in malondialdehyde content between group I and group III. Malondialdehyde levels were significantly increased following ischaemia and a non-significant increase was observed in the contralateral hemisphere. Methylprednisolone treatment significantly decreased malondialdehyde content on the side of the ischaemic hemisphere. We conclude that there is a positive relationship between membrane-bound enzyme Na(+)-K(+)/Mg(+2) ATPase activity, malondialdehyde content and early ultrastructural changes in the treated group with MP. These data suggest that the pretreatment injection of high doses (30 mg/kg) methylprednisolone contribute to the protection of the brain from ischaemia with stabilization of the cell membrane by effecting the lipid peroxidation and the activation of Na(+)-K(+)/Mg(+2) ATPase.

Animals↗
PubMed1988

Effects of intrauterine devices on the surface ultrastructure of human endometrium before and after removal.

The effects of copper-releasing IUDs on the endometrial ultrastructure were evaluated in 101 women. Endometrial samples were obtained in the secretory phase of the menstrual cycle, both during and after IUD use, and were evaluated using both scanning and electron microscopy. The degree and extent of changes to the surface ultrastructure of the endometrium were found to be related to the copper surface area of the IUD. Regardless of the duration of IUD use, by one month after IUD removal the endometrial ultrastructure had returned to its normal state. The results of this study show that the effects of copper-releasing IUDs on the endometrial ultrastructure are essentially limited to the time the IUD is in utero.

Adult↗
PubMedDate not supplied

Ultrastructure of electrophysiologically identified human sinoatrial nodes.

The ultrastructure of freshly excised human sinus node tissue was studied. In three female patients (ages 20, 30, and 36 years) medically refractory disabling episodes of inappropriate sinus tachycardia were surgically treated by extirpation of the sinus node. Each patient underwent intraoperative electrophysiological mapping to determine the area of earliest atrial activation. This area corresponded anatomically to the region of the sinoatrial node and was excised in each patient, the defect repaired using a pericardial patch. The freshly excised SA nodes underwent ultrastructural study. Three types of myocardial cells were identified: pacemaker or polygonal cells with clear cytoplasm, few mitochondria and sparse numbers of contractile elements (P cells); a transitional cell with slightly increased numbers of myofibrils (T cells); and typical atrial myocardial cells with normal numbers of contractile elements. These cell types have previously been identified in post-mortem studies of presumed SA node. The current study confirms the cell types in electrophysiologically documented SA nodes. The one abnormal finding observed in transitional cells in all patients was an increased number of lipofuscin-laden vacuoles. These vacuoles are considered a sign of cell degeneration and their occurrence was totally unexpected in these young adults. In summary, ultrastructural study of electrophysiologically documented human SA nodes confirmed the cell types identified in post-mortem studies. Furthermore, lipofuscin-laden vacuoles were increased in these three patients and this finding may serve as an ultrastructural marker associated with the syndrome of inappropriate sinus tachycardia.

Adult↗
PubMed1996

Ultrastructural localization of activity of phosphatases by low temperature incubation of unfixed cryostat sections.

In the present study, we demonstrate the activity of several phosphatases ultrastructurally in long-term (up to 24 months) cold-stored (-80 degrees C) rat tissues. Phosphatase activity was histochemically studied with the use of unfixed cryostat sections in combination with low temperature (4 degrees C) incubation conditions in order to prevent inactivation of enzyme activity and to limit the loss of ultrastructure. 5'-Nucleotidase activity was observed at plasma membranes, mainly at bile canalicular membranes of hepatocytes in liver. Thiamine pyrophosphatase activity was detected not only in trans side cisternae but also in medial and cis side cisternae of Golgi complexes in the parotid gland. Glucose-6-phosphatase activity was localized in endoplasmic reticulum as well as at the outer membrane of the nuclear envelope. Acid phosphatase reaction product was found in lysosomes. Furthermore, the localization patterns of 5'-nucleotidase and thiamine pyrophosphatase activity were compared with those obtained after different fixation procedures such as immediate chemical fixation of tissues or fixation of tissues after freezing and thawing. The results showed similar localization patterns of these enzymes after the different pretreatments. However, with respect to the ultrastructural morphology, some damage was observed in unfixed material after incubation. It can be concluded that the procedure described here enables ultrastructural localization of activity of phosphatases in long-term cold-stored tissues. This procedure will be useful for a retrospective study on archival material when histochemical parameters are needed.

5'-Nucleotidase↗
PubMed1995

Ultrastructural analysis of the development of human basophils and mast cells in vitro.

The ultrastructural analysis of a variety of culture systems of human cord blood mononuclear cells (spanning a 10-year research effort) is reviewed. Human basophils, eosinophils and mast cells reliably developed from their agranular precursors that are present in human cord blood. Suspension cultures and cocultures with fibroblasts were used to examine the effects on differentiation and maturation of full (fibroblast), interleukin-2-depleted (human T cells), and murine inducer T cell culture supernatants, partially purified mouse fibroblast factor(s), recombinant human interleukins 3 and 5, and recombinant human and murine c-kit ligands (stem cell factor, mast cell growth factor). Together, these studies allowed us to define the differentiation and full maturation of the basophil and eosinophil lineages and provided evidence for the induction of a form of secretion (termed piecemeal degranulation) of the basophil and eosinophil lineages in interleukin-3- or -5-supplemented cultures. Mast cells were absent from interleukin-3- or -5-containing cultures. The development of fully mature mast cells occurred regularly in fibroblast-containing cocultures; partially mature mast cells developed in fibroblast culture supernatant-, partially purified mouse fibroblast factor(s)-, and either recombinant human or murine c-kit ligand-supplemented suspension cultures. Small numbers of basophils and eosinophils were present in the suspension cultures that received c-kit ligand in its recombinant or naturally occurring forms. Ultrastructural immunogold analyses confirmed that basophils and eosinophils contained the Charcot-Leyden crystal protein (in different subcellular locations) but that mast cells did not. In both cocultures and suspension cultures, the primary event recorded for mast cells was that of differentiation and maturation, with the ultrastructural correlates of synthetic activity and granule building prevailing. Spontaneous secretory events, recognizable by ultrastructural analysis, were not evident in either mature or partially mature mast cells developing in these cultures.

Basophils↗
PubMed1991

Ultrastructural analysis of the midaxial extracellular matrix in spinal dysraphism.

Ultrastructural aspects of the extracellular matrix (ECM) in the midaxial region of dysraphic embryos of the loop-tail (Lp) mutant mouse were analyzed by means of electron microscopy. In 17-23 somite embryos, ultrastructural differences in the ECM occurred with respect to the presence of a pair of long trailing basal laminar strands extending continuously from the ventral notochordal cells to the gut in abnormal (Lp/Lp) embryos, in contrast to short, ragged, discontinuous strands in normal (+/+; Lp/+) embryos. The ultrastructural localization and configuration of fibronectin (FN) and laminin (L) associated with these strands, however, were similar in normals and abnormals. In addition, FN occurred over interstitial bodies, fibrils, and sporadically along the basal laminae of the neural tube (or folds), notochord, gut, and vessels, whereas L was largely confined to the basal laminae. The results indicate that although the ultrastructural pattern of FN and L reactivity are similar in normal and abnormal embryos, a disturbance in the manner whereby the notochord detaches from the gut in dysraphic embryos may be of causal significance in the etiology of dysraphism in this mutant.

Animals↗
PubMed1999

Metabolic and ultrastructural effects of cyclosporin A on pancreatic islets.

We investigated the effect of different doses of cyclosporin A (CyA) on glucose and insulin levels, as well as its residual effects on pancreatic islets ultrastructure after discontinuation of the drug. We studied four groups of Wistar rats. One control- (n = 5) and three experimental groups, n = 10 each, were treated with different doses of CyA i.m. for 14 days: group I, 5 mg/Kg; group II, 15 mg/Kg; and group III, 25 mg/Kg. Five animals of each group were sacrificed after 14 days, and the remaining five after 21 days to assess residual CyA effects. On the day of sacrifice, the rats underwent maltose absorption test, and glucose and insulin levels were measured. Pancreatic biopsies were obtained on day 21 to evaluate islets ultrastructure by electron microscopy. As a result, statistically significant, dose dependent (P < 0.05) increases in glucose and insulin levels were observed in CyA-treated groups. Groups II and III showed insulin levels significantly higher after fasting (P < 0.05) on day 14 comparing to the controls, while in groups I and II values returned to normal after CyA discontinuation. Group III showed persistently increased insulin levels on day 21. Pancreatic ultrastructural changes were observed only in group III. We can conclude that CyA effects on glucose and insulin levels were temporary and reversible at low doses. Ultrastructural changes in the pancreatic islets may occur with high doses of CyA.

Animals↗