Objectives : The present study was undertaken to determine whether an ethanol extract of Citri Pericarpium (CP-E), which is the pericarp of Citrus unshiu Markovich is efficacious against collagen-induced arthritis (CIA) in mice. Methods : CIA was induced in male DBA/1J mice by intradermal injection of bovine collagen-II in Freund's incomplete adjuvant (IFA). The mice in the onset of arthritis were treated daily with oral administration of CP-E ethanol extract at different doses (50 and 100 mg/kg/bw) for 28 days. Arthritis index, histopathologic changes and the levels of TNF-${\alpha}$ as well as anti-CII IgG in blood were evaluated to confirm the anti-arthritic effect of CP-E on CIA in rats. Results : The results showed that comparing with untreated CIA mice, treated with CP-E extract significantly decreased the arthritic scores and the pathological changes of knee joint tissues, and also reduced the serum levels of TNF-${\alpha}$ and anti-CII IgG in CIA-mice. These results indicate that CP-E extract may effectively alleviate inflammatory response on CIA, and its anti-inflammation can be attributed, at least partially, to the inhibition of proinflamamtory cytokine, TNF-${\alpha}$ in CIA. Conclusions : This study suggest that CP-E has a therapeutic potential in inflammatory joint diseases such as rheumatoid arthritis.
To know the effect of Ivermectin(IVM) toxicity in testis, histopathologic changes as well as clinical signs were observed in experimental animals including dogs by the subcutaneous injection with 3-50mg/kg of IVM. Clinically, it was observed to have depression and ataxia in all groups whereas tremor and coma in mice, rats and guinea pigs, coma in hamsters and rabbits, and tremor and salivation in dogs were shown. The clinical signs were different by the dosage of IVM, species and individuals in all animals. Susceptibility to IVM was most sensitive in dogs, especially in a Tosa dog and this was susceptible in mice, hamsters and rabbits, guinea pigs and rats in order. Microscopical observation revealed that the seminiferous tubules of testis had decreased thickness of germinal epithelium due to the necrosis and desquamation of the spermatids and spermatocytes. The progressive pattern by the times of administration showed vacuolar formation between the layer of spermatids and spermatogonia due to the marked necrosis of spermatocytes and the presence of multinucleated giant cells derived from spermatid throughout the seminiferous tubules of testis. Only a layer of spermatogonia, a few spermatogonia, and Sertoli cells wore observed with atrophied wavelike basement membrane in the seminiferous tubules of testis. Necrotic germinal cells, sloughed immature spermatids and spermatocytes were present in the lumen of epididymis and ductus deferens. Microscopical observation showed different susceptibility to IVM with clinical observation in which it was also most sensitive in dogs, especially in a Tosa dog and this was susceptible in rabbits and guinea pigs, hamsters, rats and mice in order. It was considered that IVM affects mainly spermatocyte or spermatid stage in the spermatogenesis and disturbs their developing beyond these stage.
In this study, the effect of verapamil (VER) on cyclosporin A (CsA)-induced nephrotoxicity was investigated in uninephrectomized rats. Male Wistar rats were administered CsA (50 mg/kg/day, p.o.) or VER (0.5 mg/kg/day, i.p.) with CsA (50 mg/kg/day, p.o.) for 20 days. The urinary N-acetyl-$\beta$-D-glucosaminidase (NAG) activity along with BUN, serum creatinine, creatinine clearance (CLcr), body weight, and 24 hr-urine output were measured and histopathologic changes of kidney were evaluated by light and electron microscopy. The results obtained from this study can be summarized as follows: While NAG activity, BUN and serum creatinine was progressively increased and CLcr significantly decreased in CsA group, VER almost signifi-cantly (p<0.05) suppressed and normalized CsA-induced changes in VER+CSA group. While urine output increased until 12th days and thereafter progressively decreased in CsA group, it gradually increased in control and VER+CSA group. While body weight progressively made a gain in control and VER+CSA groups, it significantly (p<0.05) lost in CsA group. On light microscopy, the glomerular hyperemia and proximal convoluted tubular (PCT) dilatation, focal tubular cell vacuolation and necrosis were clearly evident in CsA group, but, were not seen in other groups. Ultrastructural studies revealed thickened glomerular endothelium and basal lamina of capillary, irregular shaped pedicels of podocytes, indistinct slit pores and narrowed bowman's space. The large oval vacuoles with dense debris and phagosome were distributed in apical zone and deformed microvilli and mitochondria were seen in the PCT cell of CsA group. But, glomeruli and PCT cell were relatively preserved in normal apperance in other groups. In conclusion, it is suggested that verapamil has a protective effect on cyclosporine-induced nephrotoxicity in uninephrectomized rats.
To investigate additive effects of endocrine disruptors, we have histopathologically studied the exchanges of the reproductive organ to ovariectomized ICR mice. Female ICR mice were ovariectomized and then treated with endocrine disruptors after two weeks. Macroscopic exchanges, which were body weight, feed and water intake, of all groups were not seen during experiment period. Histopathological changes of uterine epithelial cells, vaginal epithelial cells, mammary glands and the diameter in uterine tubles were observed. In the results, the histopathological sensitivity to endocrine disruptors effect was more seen to the vaginal epithelial cell height than others. The additive estrogenic effects of endocrine disruptors, which were combinations of DEHP, DBP and BPA, were seen with E2 and BPA treatments. These results offers a sysmatic and mechanistically informative approach to assessing estrogenicity. It provides a useful profile of activity using a reasonable amount of resources and is compatible with the study of individual chemicals as well as the investigation of interactions among combinations of chemicals.
We investigated the anti-inflammatory effect of Pyunkang-tang extract (PGT), a complex herbal extract based on traditional Chinese medicine that is used in Korea for controlling diverse pulmonary diseases, on cigarette smoke-induced pulmonary pathology in a rat model of chronic obstructive pulmonary disease (COPD). The constituents of PGT were Lonicerae japonica, Liriope platyphylla, Adenophora triphilla, Xantium strumarinum, Selaginella tamariscina and Rehmannia glutinosa. Rats were exposed by inhalation to a mixture of cigarette smoke extract (CSE) and sulfur dioxide for three weeks to induce COPD-like pulmonary inflammation. PGT was administered orally to rats and pathological changes to the pulmonary system were examined in each group of animals through measurement of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and interleukin-6 (IL-6) levels in bronchoalveolar lavage fluid (BALF) at 21 days post-CSE treatment. The effect of PGT on the hypersecretion of pulmonary mucin in rats was assessed by quantification of the amount of mucus secreted and by examining histopathologic changes in tracheal epithelium. Confluent NCI-H292 cells were pretreated with PGT for 30 min and then stimulated with CSE plus PMA (phorbol 12-myristate 13-acetate), for 24 h. The MUC5AC mucin gene expression was measured by RT-PCR. Production of MUC5AC mucin protein was measured by ELISA. The results were as follows: (1) PGT inhibited CSE-induced pulmonary inflammation as shown by decreased TNF-${\alpha}$ and IL-6 levels in BALF; (2) PGT inhibited the hypersecretion of pulmonary mucin and normalized the increased amount of mucosubstances in goblet cells of the CSE-induced COPD rat model; (3) PGT inhibited CSE-induced MUC5AC mucin production and gene expression in vitro in NCI-H292 cells, a human airway epithelial cell line. These results suggest that PGT might regulate the inflammatory aspects of COPD in a rat model.
Objective : Chiari II malformation (CM II) is still the main cause of severe morbidity and mortality in children with open neural tube defects (ONTDs). The goal of this study was to validate a CM II model in late-stage chick embryos with surgically induced ONTDs. Methods : To make the chick embryo model of ONTD, their neural tubes were opened for a length of 5-6 somites at the thoracic level in Hamburger and Hamilton stage 18 chick embryos (n=150). They were reincubated in ovo up to a total age of 17-21 days. A total of 19 embryos survived and were assigned to either the postoperative day (POD) 14-15 group (n=6) or the POD 17-18 group (n=13). Magnetic resonance imaging (MRI) and histopathologic findings of embryo heads with spinal ONTDs were compared with age-matched normal chick embryos. Results : The chick embryos with ONTDs demonstrated definite and constant structural changes, such as downward displacement of the cerebellum to just above the foramen magnum and narrow and small cerebrospinal fluid spaces in the crowded small posterior fossa. These morphologic features were more prominent in the POD 17-18 group than in the POD 14-15 group. Conclusion : This is the first description of CM II with spinal ONTD in a late-stage chick embryo model with MRI and histopathological analysis. The morphological changes of the posterior fossa in this study mimic those of CM II associated with spinal ONTD in humans. This model will facilitate investigation of the pathogenesis of CM II.
This study was undertaken to observe the histopathologic changes in submandibular glands of the white rats when exposed to megavoltage fractionated dose of CLINAC 2100 C-D 6 MV X-RAY irradiation and 42 female white rats, weighing approximately 100gm, were divided into control and 2 experimental groups. At sacrifice, submandibular glands were excised and examined microscopically and electromicroscopically. The results were as follows : 1. The acinar cells of submandibular gland showed damage varied with dose, 12 Gy resulted in very mild injury while 24 Gy caused extensive injury. 2. The acinar cells of sumandibular gland showed similar ultrastructual alterations, appeared as pleomorphic nucleus, decreased numbers and pleomorpgism of secretory granules, distention of rough endoplasmic reticulum, expansion and pallor appearance of mitochondria, and hypertrophy of Golgi complex. 3. A serous cells were the most sensitive components, displaying morphological alterations of radiation damage as early as 3 hours, followed by submandibular seromucinous cells and secretory tubular cells. 4. The mucous cells, as well as the whole ductal lining cells, displayed no significant alterations. 5. No evidence of microvascular injury through whole experimental groups indicated that microvascular impairment dose not contribute to early. salivary gland injury.
Global cerebral ischemia occurs commonly in patients who have a variety of clinical conditions including cardiac arrest and shock. Cerebral ischemia results in a rapid depletion of energy stores that triggers resulting in excitotoxic death. Imaging studies of the brain with computed tomography(CT) or magnetic resonance imaging(MRI) are necessary to confirm the clinical neurolocalization, identify any associated mass effect, and rule out other causes of focal brain disorders. Cardiopulmonary arrest was occurred by propofol anesthesia in a 1 year old, intact female Beagle dog. After successful cardiopulmonary resuscitation was performed within 5 minutes, clinical signs such as vocalization, paddling, opisthotonus and seizure were represented. At the 12th day, CT and MRI examinations of the brain were performed to evaluate the brain. After euthanasia, histopathologic examination was performed. On transverse image of CT, lesions appeared as a hypodense in the right dorsal surface of the frontal lobe and level of optic canal, and dorsomedial surface of occipital lobe of cerebrum. No contrast enhancement was represented following intravenous contrast administration. On MR images of brain, the lesions were seen as a hyperintense on T2-weighted(T2W) images and a isointense or mild hypointense on T1-weighted(T1W) images. Hyperintense lesions both T2W and T1W images were observed at the surrounding cerebral sulcus. There was no significant signal changes on contrast T1WI. Histopathologic examination after euthanasia revealed that the lesion was necrosis of the cerebral cortex caused by cerebral ischemia.
The study of present study was to determine the valuable laboratory tests for the differential diagnosis of lead poisoning in dogs. Sixteen mongrel dogs were divided into 2 experimental groups (A and B) and a control group (C). The A and B groups were administered orally 2 mg and 20 mg of lead per kilogram of body weight for 49 days, respectively. In addition to clinical observation, blood, urine and hair samples were collected on appointed day and examined for hematological changes, lead content of serum, whole blood and hair, and urinary $\delta$-aminolevulinic acid concentrations. All dogs were necropside on 49th day and examined for the lead content and histological changes of organs. The results obtained were summarized as follows: The group B showed digestive and nervous signs, and weight loss. The group A showed no significant hematological changes except polychromatophilla on the 7th day. But group B showed polychromatophilia as well as mild anemia and nucleated erythrocyte on the 7th and 35th day. Basophlic stippling erythrocytes were observed in some of the group B on the 14th day. The lead content of whole blood was increased significantly in both A and B groups on the 21the day. The urinary $\delta$-aminolevulinic acid content was increased in both A and B groups on the 7th day. The hair lead content of A and B groups was increased significantly on the 49th and 21th day, respectively. The lead contents of organs including liver, kidney, spleen, muscle and bone were increased significantly in group B. Histopathologic changes were characterized by hemorrhages, necrosis and intranuclear inclusion body in the epithelial cells of convoluted tubles of kidney, cloudy swelling and degeneration and/or necrosis of liver, enlargement of Virchow-Robin space, and swelling of endothelial cells and hyperplasia of the pericytes of brain. From these results it may be concluded that examination of nucleated erythrocyte/polychromatophilia, urinary $\delta$ -aminolevulinic acid, and whole blood and hair lead contents is a reliable clinico-pathological diagnostic methods, and that examination of the Virchow-Robin space, endothelial cells and pericytes of brain as well as intranuclear inclusion body in the epithelial cells of convoluted tubles of kidney is valualble postmortem diagnostic methods for lead poisoning in dogs.
Purpose : It was reported that Captopril (angiotensin converting enzyme inhibitor) had an effect to reduce the pneumonitis and pulmonary fibrosis induced by radiation in rat. We peformed this study to investigate the radioprotective effect and mechanism of Captopril. Methods and Materials : The comparison was made between the radiation only group and the combined Captopril and radiation group by examining histopathologic findings and immunohistochemical stains $(TNF\alpha\;and\;TGF\beta1)$ at 2 and 8 weeks after irradiation. Each group has 8 to 10 rats (Sprague-Dawley). 12.5 Gy of X-ray was irradiated to the left hemithorax in a single fraction. Captopril (50 mg/kg/d) mixed with water was given per oral and continuously from 1 week prior to irradiation up to 8th week of the experiment. Result : In the combined Captopril and radiation group, the histopathologic changes which were hemorrhage into alveolar space, changes of alveolar epithelium, bronchial epithelium and blood vessels, and perivascular edema were less severe than in the radisation only group at 2 weeks. At 8 weeks, the alveolar epithelial changes and perivascular edema were less prominant in the combined Captopril and radiation group. At 2 weeks, the $TNF\alpha$ expression of the combined Captopril and radiation group was markedly decreased at the alveolar epithelium (p<0.01), lymphoid tissue (p=0.06) and the macrophage of alveolar space (p<0.01) compared with the radiation only group. Furthermore the $TGF\beta1$ expression was significantly prominant at the alveolar epithelium (p<0.02) and the macrophage in alveolar space (p<0.02). At 8 weeks, the expression of $TNF\alpha\;and\;TGF\beta1$ of most sites, except $TGF\beta1$ of the macrophage of alveolar space (p=0.09), showed no significant difference between 2 groups. Conclusion : This study revealed that early lung damage induced by irradiation was reduced with the addition of Captopril in the latent and early pneumonitis phase. The expression of $TNF\alpha\;and\;TGF\beta1$ at 2 weeks and $TGF\beta1$ at 8 weeks was further decreased in the combined Captopril and radiation group than the radiation only group. From these results, it may be concluded that the proinflammatoy cytokine $(TNF\alpha)$ and fibrogenic cytokine $(TGF\beta1)$ probably play the role of the radioprotective mechanism in Captopril.
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