Weeks Of Ligation Research Articles

Active participation of apoptosis and mitosis in sublingual gland regeneration of the rat following release from duct ligation

This study was designed to establish how mitotic cell proliferation and apoptotic cell death participate in the regeneration of atrophied rat sublingual glands. To induce atrophy to the sublingual gland of rats, the excretory duct was ligated unilaterally near the hilum, and after 1 week of ligation (day 0) the duct ligation was released to enable gland regeneration. The regenerating glands were examined with routine histology, immunohistochemistry for proliferating cell nuclear antigen (PCNA) as a marker of proliferating cells, terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) as a marker of apoptotic cells, and transmission electron microscopy. At day 0, a few acini and many ducts remained in the atrophic sublingual glands, and newly formed immature acini were observed at day 3. Thereafter acinar cells progressively matured and increased in number, although the number of ducts decreased. Many PCNA- and some TUNEL-positive cells were seen in acini and ducts during regeneration. The labeling indices for both cell types were statistically significantly different from that of the control at several time points of the regeneration. Apoptotic and mitotic cells were also confirmed to be present in the experimental sublingual glands by electron microscopy. These observations suggest that apoptosis as well as mitosis of duct and acinar cells actively participate in and play important roles in sublingual gland regeneration.

Cell death and cell proliferation in the regeneration of atrophied rat submandibular glands after duct ligation.

The present study aimed to clarify the proliferation and apoptosis of parenchymal cells during regeneration of rat submandibular glands following atrophy. Atrophy of the right submandibular gland of rats was induced by excretory duct ligation at the hilum with metal clips, which were removed 1 week (day 0) after ligation. The right submandibular glands were collected from 0 to 14 days after removal of the clips and investigated using immunohistochemistry for proliferating cell nuclear antigen (PCNA) as a marker of proliferating cells, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick end labeling (TUNEL) as a marker of apoptotic cells, and transmission electron microscopy (TEM). After 1 week of ligation, there were many remaining ducts and a few acini in the atrophic glands. At day 3 after discontinuing the ligation, newly formed acini appeared and thereafter increased in number and maturity. Many residual and newly formed acinar cells showed positive reaction to PCNA especially at days 4 and 5. The PCNA-positive duct cells decreased in number with the regeneration. A few TUNEL-positive acinar and duct cells were identified during regeneration. Mitosis and apoptosis of parenchymal cells were also identified by TEM. During regeneration of the submandibular gland after atrophy, both residual and newly formed acinar cells proliferate actively. There is also apoptosis of parenchymal cells; however, the significance of apoptosis is low.

Streptozotocin-induced hyperglycemia exacerbates left ventricular remodeling and failure after experimental myocardial infarction

ObjectivesThe aim of the present study was to determine whether streptozotocin (STZ)-induced hyperglycemia exacerbates progressive left ventricular (LV) dilation and dysfunction after myocardial infarction (MI). BackgroundDiabetes mellitus (DM) adversely affects the outcomes in patients with MI. However, it is unknown whether DM can directly affect the development of post-MI LV remodeling and failure. MethodsMale mice were injected intraperitoneally with STZ (200 mg/kg; DM group) or vehicle only. At two weeks, MI was created in the STZ-injected (DM+MI group) or vehicle-injected mice (MI group) by left coronary artery ligation, and they were followed up for another four weeks. ResultsSurvival during six weeks was significantly lower in the DM+MI versus MI group (25% vs. 71%; p < 0.01), despite a similar infarct size (60 ± 2% vs. 61 ± 2%; p = NS). Echocardiography after two weeks of ligation showed LV dilation and dysfunction with MI, both of which were exaggerated in the DM+MI group. Likewise, LV end-diastolic pressure and lung weight were increased in mice with MI, and this increase was enhanced in the DM+MI group. The myocyte cross-sectional area in the non-infarcted LV increased to a similar degree in the DM+MI and MI groups, whereas the collagen volume fraction was greater in the DM+MI group. Deoxyribonucleic acid laddering was greater in the DM+MI group. ConclusionsHyperglycemia decreased survival and exaggerated LV remodeling and failure after MI by increasing interstitial fibrosis and myocyte apoptosis. Diabetes mellitus could be a risk factor for heart failure, independent of coronary artery lesions.

Experimental Model of Obstructive, Chronic Pancreatitis in Pigs

Background: We aimed to develop a reproducible, experimental model of obstructive pancreatitis for future analysis of surgical interventions, and characterized this model using functional, histological and biochemical parameters. Animals and Methods: In 10 female pigs the pancreatic duct (PD) was ligated. After 4, 6 or 8 weeks the animals were sacrificed. Before and after ligation, glucose tolerance and intraductal pressure were measured, and pancreatic juice was collected after stimulation with cholecystokinin and secretin. Amylase and lipase activities were analyzed in plasma and juice. Pancreatic tissue was collected for histochemical analysis. Results: Within 4 weeks of ligation, the pancreas appeared atrophic. Intraductal pressure had risen significantly. Acinar-to-ductal metaplasia was accompanied by strong proliferation of stellate cells and increased collagen deposition. Islets of Langerhans appeared smaller and more numerous. Blood amylase and lipase levels were normal and glucose tolerance was unaffected. Pancreatic juice volume and amylase and lipase activities were significantly lower. Conclusion: Ligation of the PD in pigs resulted in a marked fibrosing obstructive pancreatitis within 4 weeks, similar to human chronic pancreatitis in regard to clinical, functional, histological and biochemical parameters.

Protective effect of posterior cerebral circulation on carotid body ischemia.

Carotid Bodies (CB) are fed mainly by External Carotid Artery (ECA) and rarely by Internal Carotid Artery (ICA). We aimed to investigate the effect of Bilateral Common Carotid Artery ligation and BCCAL plus bilateral external carotid artery ligation on CB. This study has been conducted on 30 hybrid male rabbits. Normal CB analyses were made in six of these animals and others divided into two groups. BCCAL has been applied to the 1st group, and the 2nd group has undergone bilateral ECA ligation in addition to BCCAL. After sacrificing the animals, both sides CB were histopathologically observed. Normal and ischemic cells were counted. Bilateral Common Carotid Artery ligation did not cause total atrophy in CB. Partial reversible atrophy of CB was seen in group I, but that atrophy was found to be irreversible and all animals died within one week after ligation in group II. Retrograde blood flow mechanisms and collateral circulation impede the oligemic CB atrophy after BCCAL. But bilateral ECA ligation, in addition to BCCAL, causes both sides irreversible CB atrophy and death of animals within one week of ligation. The CB are parasympathetic paraganglia. They are chemoreceptors and located at the bifurcation zone of common carotid arteries. They are fed mainly by ECA or by its branches and rarely by ICA. As a consequence of this, BCCAL and/or ligation of external branches of common carotid artery may lead to an ischemic impairment of CB. In order to analyse the effect of carotid stenosis on CB, CB were directly examined in 6 of 30 hybrid rabbits. BCCAL was applied to twelve rabbits (group I) with ligation of both ECA in addition to BCCAL were made to the others (group II). Animals were followed up four months in group I; but all of the animals in group II died within one week. From both sides the CB were taken including the carotid bifurcation and histopathological changes were evaluated. As a result, it has been observed that incomplete ischemic lesions have developed in the CB because of retrograde blood flow from posterior circulation to the ECA providing blood for the CB. But in the second group these changes were irreversible and on both sides CB complete atrophy developed in those whose ECA were also ligated bilaterally.

Chronic cerebral hypoperfusion induces transient reversible monoaminergic changes in the rat brain.

Chronic restriction of cerebral blood flow in hypoperfused Wistar rats has been proposed as a new model of cerebrovascular-type dementia. Using this model, we have investigated central monoaminergic neuronal systems that are closely related to higher brain function. Monoamine and monoamine-metabolite levels were determined, as relative monoaminergic markers, at 1 day and 1,3,6 and 12 weeks after the bilateral occlusion of common carotid arteries. Dopaminergic changes in the frontal cortex and striatum were observed in hypoperfused rats at 1-3 weeks following occlusion. Serotonergic changes were recognized at four brain regions examined (frontal cortex, hippocampus, striatum and thalamus+midbrain). In particular, the immediate enhancement of serotonin turnover in the striatum appeared to influence the reaction to the acute ischemic attack such as vasoconstriction produced by hypoperfusion. Our findings suggest that chronic cerebral hypoperfusion induces transient reversible changes in central monoaminergic neuronal function within three weeks of ligation of carotid arteries. This time interval seems to represent a turning point in the process of chronic cerebral hypoperfusion-induced progressive brain injury.

Fate of the type II pneumocyte following tracheal occlusion in utero: a time-course study in fetal sheep.

Tracheal occlusion in utero has been shown to cause accelerated fetal lung growth and is now being considered as a therapeutic modality for pulmonary hypoplasia. We report the effects of tracheal ligation on the surfactant-producing type II pneumocyte population. Three groups of fetal lambs underwent tracheal ligation of 2 weeks', 4 weeks' and 6 weeks' duration, respectively, and all were sacrificed at 136 days' gestation (9 days pre-term). Nonoperated twins served as controls. The type II pneumocyte population was studied morphometrically using a combination of anti-surfactant protein B immunohistochemistry and computer-assisted stereologic morphometry at light and electron microscopic levels. Single-factor ANOVA was used for statistical analysis. Two weeks of tracheal ligation resulted in doubling of the total lung volume as a result of airspace distension and, to lesser extent, growth of the tissue compartment. With increasing duration of tracheal ligation, there was no additional lung growth. However, more prolonged tracheal occlusion was found to result in significant reduction of the surfactant system, as reflected in the marked decrease of total pneumocyte type II volume (3.14 cm3, 0.95 cm3, and 0.46 cm3, after 2, 4, and 6 weeks of ligation, compared with 5.96 cm3 for controls) and total pneumocyte type II number (13.9 x 10(9), 3.8 x 10(9), and 2.4 x 10(9), compared with 53.2 x 10(9) for controls). Ultrastructural analysis of the type II cells in obstructed lungs showed vacuolar degenerative changes that, after 6 weeks of ligation, were apparently irreversible. In utero tracheal ligation causes fetal lung hyperplasia, but results in reduction of and injury to the surfactant-producing cell population. Before tracheal occlusion can find wide-spread clinical application, its pathophysiology needs to be further elucidated.

The response of rabbit spermatozoa to artificial cryptorchidism and ligation of the epididymis.

SUMMARY By means of unilateral ligation of the epididymis and experimental cryptorchidism in twenty-one adult male rabbits, the reaction of spermatozoa in proximal regions of the epididymis to the effects of retention in the abdomen was investigated. Combined estimates of eosinophilic spermatozoa and decapitated spermatozoa in smears stained with aqueous nigrosin eosin were used to indicate the response in different samples. Examination of spermatozoa withdrawn from four levels of the tubule showed that those in the caput epididymidis and the initial segment reacted rapidly to the effects of artificial cryptorchidism, whilst the response of spermatozoa from the corpus epididymidis appeared to be delayed. Contralateral testes and ligated epididymides were maintained in the scrotum to serve as controls, and under these circumstances spermatogenesis continued for at least 3 weeks although, shortly after ligation, the epididymides were tightly packed with spermatozoa and fluid. Examination of the tubular contents in these specimens by means of the nigrosin eosin technique revealed a progressive degeneration of spermatozoa above the site of ligation. However, microscopical observations of motility indicated enhanced activity in samples collected during the first 3 weeks of ligation of the epididymis.