Cyclosporine A-induced acute hepatotoxicity in guinea pigs is associated with endothelin-mediated decrease in local hepatic blood flow.

AIMS: To bring further insight into the mechanism of cyclosporine A (CsA)-induced hepatotoxicity, the acute effect of CsA on local hepatic blood flow (LHBF) and its association with systemic hemodynamics, histopathological and biochemical indicators of liver toxicity were studied in guinea pigs in vivo. The association of endothelin (ET) and/or Cremophor-EL (C-EL, vehicle in parenteral CsA preparation) with CsA effects was also investigated. MAIN METHODS: Animals were assigned into five groups; control, CsA, C-EL, Bosentan (non-selective ET receptor antagonist)+CsA, and BQ-123 (ET(A) receptor antagonist)+CsA. CsA was infused intravenously (i.v.) at 20 and 10mg/kg doses by 15 min interval. Antagonists were administered 15 min before CsA infusion. LHBF and mean arterial blood pressure (MAP) changes were simultaneously recorded. Blood and liver samples were collected for biochemical and histopathological examinations. KEY FINDINGS: CsA, but not C-EL, decreased LHBF by 53.3% at the end of 30 min. Although being non-significant, CsA slightly increased MAP suggesting that, CsA-induced acute decrease in LHBF was likely independent of MAP changes. Bosentan (5mg/kg, i.v.) and BQ-123 (1mg/kg, i.v.) pre-treatments prevented the CsA-induced decrease in LHBF suggesting that CsA decreases LHBF through an ET-related mechanism. Additionally, CsA, but not its vehicle C-EL, caused marked acute pathological changes in the liver morphology. SIGNIFICANCE: CsA-induced findings of acute hepatotoxicity were prevented by bosentan and BQ-123 pre-treatments. Thus, CsA seems to exert acute hepatotoxic effect through ET-related mechanisms.

An animal study on cartilage healing using auricular cartilage as a model.

We investigated the effect of different surgical procedures on cartilage healing, using auricular cartilage as a model, which would be useful to create a rationale for septal cartilage surgery. Different kinds of manipulations were performed on the auricular cartilage of six female New Zealand white rabbits. Histopathological investigations were performed under light microscopy 4 months postoperatively. The autologous cartilage grafts survived well under the forehead skin regardless of the presence of the perichondrium. The response of perichondrium to either incomplete or complete trauma was not only new cartilage formation but also ossification. When incomplete incisions were made on the non-perichondrial side, new cartilage formation was stimulated whereas ossification was induced when there was perichondrium on the cartilage. If the cartilage with perichondrium was sliced into small pieces and planted back in its original place, many ossification areas occurred. The crushed cartilage was usually absorbed but sometimes replaced by bony plates. The traumatized cartilage with perichondrium undergoes ossification. This finding may be important clinically in that surgeons should not traumatize septal cartilage with perichondrium and work under the perichondrium. This ossification of traumatized cartilage may later result in thickening of the septal cartilage which we sometimes face in revision surgery.

Effects of topotecan treatment on nasal, buccal, and lingual mucosa in the rabbit: light and transmission electron microscopic evaluation.

Anticancer agents may cause side effects and some of which may be dose dependant. It is important for clinicians to see the effects on tissues histopathologically. The aim of this study was to investigate the effects of topotecan (hycamtin), a topoisomerase I inhibiting anticancer agent, on nasal, buccal, and lingual mucosa of rabbits. The study was carried out in two groups each consisting of 20 rabbits. Rabbits in group I received i.v. topotecan (0.5 mg/kg once daily) for 3 days. Rabbits in group II received i.v. topotecan (0.25 mg/kg once daily) for 3 days. In group I and II, biopsies from the nasal, buccal, and lingual mucosa were taken on the fourth (1 day after the 3-day topotecan treatment) and 15th day (12 days after the 3-day topotecan treatment). Light and transmission electron microscopic (TEM) observations have shown that nasal mucosa was not affected by topotecan administration. Topotecan treatment resulted in the formation of some ulcerative lesions in the lingual mucosa especially on the lower surface of the tongue. On the dorsal surface, the epithelium showed highly edematous and degenerating cells and separations in the stratum granulosum. In the buccal mucosa, effects were similar. In lingual and buccal mucosa, healing was observed on the 15th day. The oral (lingual and buccal) mucosal side effects of topotecan were observed as reversible and not dose dependent. It was concluded that these side effects are not severe, and topotecan may be used safely in cancer treatment.

Activation antigens during the proliferative and secretory phases of endometrium and early-pregnancy decidua.

BACKGROUND: Clarifying the normal distribution of activation antigens will contribute to database construction studies of monoclonal-antibody-based therapies in endometrial disorders. METHODS: In this study, endometrial tissue samples obtained during proliferative and secretory phases and decidual samples of early pregnancies were immunostained by the monoclonal antibodies anti-CD26, anti-CD30, anti-CD70, anti-CD71, and anti-CD98 using the indirect immunoperoxidase method. RESULTS: CD26 is expressed on the glandular epithelium in the endometrium and decidua. Endothelial CD26 is expressed less in the decidua when compared to the endometrium. CD30 is strongly expressed by decidual cells. It is only weakly expressed on endometrial and decidual vessels. Glandular and endothelial CD70 expression is mainly seen in the proliferative phase of the menstrual cycle. Glandular CD71 expression is less in the decidua when compared to the endometrium. Its expression on stromal cells is more in the secretory phase of the menstrual cycle and in early pregnancy deciduae. It is expressed on endometrial vessels but not on decidual vessels. Glandular CD98 is expressed more in the decidua when compared to the endometrium. This antigen exists on endometrial lymphocytes. It is strongly expressed on the endothelium in the endometrium and decidua. CONCLUSION: It seems that CD26 and CD70 are not involved in the functions of endometrial and decidual stromal cells. CD30 and CD71 are thought to be involved in decidualization. Absence of activation antigens other than CD98 on lymphocytes indicated an antigenic profile for large granular lymphocytes that is different from regular lymphocytes.

Expression of adhesion and extracellular matrix molecules in the developing human brain.

Cell adhesion molecules and extracellular matrix molecules have important roles in cell migration and connection. Their developmental expression has not been fully described in humans. In this report, these molecules were examined by immunohistochemistry in frontal tissue samples from 14- to 28-week-old fetuses aborted for obstetric reasons (n = 20) and four fetuses with nervous system abnormalities. Neural cell adhesion molecule (NCAM), tenascin, and laminin were expressed after 17 weeks. Neural cell adhesion molecule was observed in the neuropil, whereas tenascin and laminin also had cellular and vascular expression. Thrombospondin and fibronectin, apparent after 14 weeks, showed a redistribution from periventricular to outer cortical layers after midgestation. N-cadherin and integrin were observed in mid- and late gestation. Maternal or environmental conditions seemed to influence the pattern of expression. Fetuses with nervous system abnormalities had altered expression of several molecules. The descriptive data obtained in this study might constitute a basis for further studies investigating the role of these molecules in developmental abnormalities of the brain.

Evaluation of the analgesic and anti-inflammatory activities of some thiazolo[4,5-d]pyrimidines.

Some thiazolo[4,5-d]pyrimidine-7(6H)-one derivatives were evaluated in vivo for their analgesic and anti-inflammatory activities. The results were compared with that of acetyl salicylic acid and phenylbutazone. Compounds 3b and 3h were the most active in the anti-inflammatory paw edema inhibition test. In terms of the analgesic activity (acetic acid writhing test), the most active compound was 2a followed by 31. The most active members of the series were investigated for their ED50 values and ulcerogenic potential.

Effects of electrohydraulic extracorporeal shock wave lithotripsy on submandibular gland in the rat: electron microscopic evaluation.

OBJECTIVES: Extracorporeal shockwave lithotripsy (ESWL) has been applied in sialolithiasis as a new treatment modality. The aim of this experimental study is to investigate the local effects of electrohydraulic ESWL applied to the right submandibular gland of the rats. METHODS: This prospective study was conveyed in four groups; groups I, II, III and IV; each group consisting of 20, 20, 18 and 9 rats, respectively, with a randomized distribution. Groups I, II, III and IV received 250, 500, 1000 and 2000 shock waves at 14-16 kV (average 15.1 kV), respectively, to the right submandibular glands on the 0th day. In groups I, II, III, right submandibular glands of the rats were removed on the 0th, 1st, 7th and 15th days; in group IV, this procedure could be managed only on the 0th and 7th days. Light and electron microscopic evaluation were assessed. Using the light microscopic changes, severity of damage score of the glands (SDS) was found. Statistical analysis was done using SDSs. RESULTS: Light and electron microscopic observations have shown that the damage produced by the shock waves were confined to focal areas in the acinar cells (AC), granulated convoluted tubule (GCT) cells and blood vessels at all doses applied. Vacuolization in the cytoplasms of the AC and GCT cells, disintegration of membranes, alteration in the cytoplasmic organization, swelling of the mitochondria and loss of the features were observed on electron microscopy. Increase in the secretion rate; stasis and dilatation in the blood vessels; blebbing and loss of features in the cytoplasm of the endothelial cells were observed. According to the result of the statistical analysis using SDSs; at 250 shock wave dose, a statistically significant difference between the SDSs of the days (0th, 1st, 7th and 15th) was found (P<0.05). The SDS on the 0th day was found to have the lowest value among the other days. And also a statistically significant difference was found on the 0th day between the SDSs at doses of 250, 500, 1000 and 2000 shock waves (P<0.05). The SDS at 250 and 500 shock waves was found to have the lower value than the SDS at the 2000 shock wave. It was observed that produced damage was less prominent by small doses (250, 500 doses) initially (0th day). Electrohydraulic ESWL caused a "patchy type" generalized pathology on submandibular glands of the rats and damaged focal areas were widespread all through the gland from the 1st day on. CONCLUSION: Formation of the damage was concluded to be related to the direct effect of the shock waves rather than the dose used. Electrohydraulic lithotripters are not suitable for sialolithiasis because of the focus problems, local tissue damage and the risk of the damage to the adjacent structures.