The effect of thioacetamide on rat liver plasma membrane enzymes and its potentiation by fasting

Thioacetamide, given intraperitoneally (1.4 mmol/kg body mass) to male Wistar rats 24 h before sacrifice promoted a marked elevation of serum aminotransferases, loss of microsomal cytochrome P-450 content and a significant reduction (about 50%) of the liver plasma membrane enzymatic activities (5'-nucleotidase; K+, Na+- and Mg2+-adenosine triphosphatases; and gamma-glutamyl transferase). Previous starvation for 48 h, immediately prior to thioacetamide administration, strongly potentiated the effects of thioacetamide on the serum, microsomal and liver plasma membrane parameters, while fasting itself did not affect them. The liver plasma membrane damage may be one of the reasons for the cell death in thioacetamide-intoxicated rat livers.     

E-cadherin expression in upper urothelial carcinoma in Balkan Endemic Nephropathy and non-endemic regions

There is a high incidence of upper urothelial carcinoma (UUC) in regions affected by Balkan Endemic Nephropathy (BEN). The aim of this study was to compare E-cadherin expression in UUC, in regions affected by BEN, and in control rural and city populations free of BEN. Another aim was to determine the influence of some morphological parameters on the E-cadherin status. In the samples of 85 UUC patients, of whom 40 lived in BEN settlements and 45 served as control subjects, immunoreactions were performed using monoclonal anti-human E-cadherin antibody. Aberrant expression of E-cadherin was more frequent in BEN tumors than in control tumors (p<0.01). Decreased E-cadherin expression was linked to high grade and solid growth in control and BEN tumors (p<0.0001 and <0.05 versus p<0.05 and <0.05, respectively), and to the stage in control tumors (p<0.01). However, BEN low grade and low stage tumors showed aberrant expression more often than did control tumors (p<0.05 and <0.005, respectively). In control tumors, using univariate analysis, E-cadherin status was found to be influenced by grade, stage, and tumor growth (p=0.001, 0.017, 0.015, respectively). In the same group, only the grade was significant according to multistep logistic regression analysis (Wald=6.429 and p=0.011). The growth pattern had a predominant influence on E-cadherin expression in BEN tumors (p=0.005). A significant influence on normal membranous or abnormal cytoplasmic expression of E-cadherin in UUC is exerted by tumor grade, stage, growth, and metaplastic change (p=0.002, 0.048, 0.019, 0.011, respectively), but only by tumor grade in the multistep logistic regression model. These results suggest that decreased expression of E-cadherin in BEN tumors may be linked to tumor growth, while expression of E-cadherin in control tumors may be associated with tumor grade.     

Pharmacokinetic evaluation of olopatadine for the treatment of allergic rhinitis and conjunctivitis

INTRODUCTION: Olopatadine hydrochloride is an antihistamine and mast cell stabilizer available in three forms, including oral, intranasal and ocular preparations. Most of the practical applications focus on the use of olopatadine for the treatment of allergic rhinitis and conjunctivitis via intranasal and ocular routes. AREAS COVERED: This article was formed from a comprehensive literature search with information taken from meta-analyses, systematic reviews, treatment guidelines and clinical studies on children and adults. Articles that have been selected evaluate the use of intranasal and ocular antihistamines and their role in allergic rhinitis and conjunctivitis. EXPERT OPINION: Olopatadine is significantly more effective than placebos in alleviating the symptoms of allergic rhinitis and conjunctivitis. Olopatadine is a viable alternative and addition to the mainstay therapy of these conditions with intranasal steroids and oral antihistamines. The compliance of the patients would be improved if a once-per-day formulation of olopatadine was developed for intranasal application. The future treatments of allergic rhinitis will probably involve a combination of intranasal antihistamine and steroid because clinical trials have demonstrated an improved efficacy without a significant increase in adverse effects.     

Differential expression of neural-cadherin in pulmonary epithelial tumours

Aims:  Neural (N)-cadherin belongs to a group of transmembrane molecules with a crucial role in tissue morphogenesis and maintenance of an epithelioid phenotype and increased N-cadherin expression is implicated in tumour progression and dedifferentiation. The aim was to determine whether evaluation of N-cadherin in pulmonary tumours might assist in identifying lesions with more aggressive potential.
Methods and results:  One hundred and fifty-five pulmonary lesions were analysed for N-cadherin expression using immunohistochemistry, including neuroendocrine hyperplasia ( n  = 3), typical carcinoid ( n  = 59), atypical carcinoid ( n  = 12), small cell lung carcinoma ( n  = 11), large cell neuroendocrine carcinoma ( n  = 12), adenocarcinoma ( n  = 35) and squamous cell carcinoma ( n  = 23). Lymph node status was correlated with immunohistochemical expression. N-cadherin expression was demonstrated in all cases of neuroendocrine hyperplasia, 96% of typical carcinoids, 83% of atypical carcinoids, 63% of the small cell lung carcinomas and 32% of large cell neuroendocrine carcinomas. Over 90% of the adenocarcinomas and 100% of the squamous cell carcinomas were negative. Increased N-cadherin expression in typical carcinoids was associated with negative lymph node status ( P  < 0.001).
Discussion:  N-cadherin is differentially expressed in pulmonary tumours and is predominantly observed in neuroendocrine lung lesions with high expression in typical and atypical pulmonary carcinoids. The level of expression of N-cadherin between types of lung tumours does not appear to indicate malignant potential or aggressive behaviour.     

Plasma levels of 15 (S) 15-methyl-PGF 2 alpha-methyl ester following vaginal administration for induction of abortion in women

A single suppository containing 3.0 mg 15 (S)15-methyl-PGF2 alpha-methyl ester was administered vaginally in women to terminate mid-trimester pregnancy. Plasma levels of the drug (both methyl ester and free acid forms) were measured at different time intervals using deuterated carriers and gas chromatography-mass-spectrometry. 15(S)15-methyl PGF2 alpha (sum of methyl ester + free acid) was found to have a mean value of 1166 pg/ml plasma at 3 hrs after administration of the suppository. The mean levels were subsequently found to be maintained in the range of 1000 pg/ml. Preliminary studies showed that unlike the successfully aborted women, in those who did not abort within 30 hrs with this suppository, the plasma levels of the drug were not maintained for a sufficiently long time. The episodes of side effects, body surface area and the induction-abortion interval in relation to the plasma levels are discussed.