Fatty acids profile and antiinflammatory activity of Nonea setosa R. et S

In order to verify the antiinflammatory properties of Nonea setosa R. et S. (Fam. Boraginaceae) and to identify the relevant active principles, aerial parts of this plant were extracted with increasing polarity solvents. The antiinflammatory activity was investigated by a bioassay-oriented fractionation using the inhibition of the croton oil-induced ear oedema in mice as an experimental model of inflammation. GC-MS analysis of the most active fraction revealed the presence of high amounts of polyunsaturated fatty acids.     

Little effects of Insulin-like Growth Factor-I on testicular atrophy induced by hypoxia

Background

Insulin-like Growth Factor-I (IGF-I) supplementation restores testicular atrophy associated with advanced liver cirrhosis that is a condition of IGF-I deficiency. The aim of this work was to evaluate the effect of IGF-I in rats with ischemia-induced testicular atrophy (AT) without liver disease and consequently with normal serum level of IGF-I.

Methods

Testicular atrophy was induced by epinephrine (1, 2 mg/Kg intra-scrotal injection five times per week) during 11 weeks. Then, rats with testicular atrophy (AT) were divided into two groups (n = 10 each): untreated rats (AT) receiving saline sc, and AT+IGF, which were treated with IGF-I (2 μg.100 g b.w.^-1.day^-1, sc.) for 28d. Healthy controls (CO, n = 10) were studied in parallel. Animals were sacrificed on day 29^th. Hypophyso-gonadal axis, IGF-I and IGFBPs levels, testicular morphometry and histopathology, immuno-histochemical studies and antioxidant enzyme activity phospholipid hydroperoxide glutathione peroxidase (PHGPx) were assessed.

Results

Compared to controls, AT rats displayed a reduction in testicular size and weight, with histological testicular atrophy, decreased cellular proliferation and transferrin expression, and all of these alterations were slightly improved by IGF-I at low doses. IGF-I therapy increased signifincantly steroidogenesis and PHGPx activity (p < 0.05). Interestingly, plasma IGF-I did not augment in rats with testicular atrophy treated with IGF-I, while IGFBP3 levels, that reduces IGF-I availability, was increased in this group (p < 0.05).

Conclusion

In testicular atrophy by hypoxia, condition without IGF-I deficiency, IGF-treatment induces only partial effects. These findings suggest that IGF-I therapy appears as an appropriate treatment in hypogonadism only when this is associated to conditions of IGF-I deficiency (such as Laron Syndrom or liver cirrhosis).     

Development of the "Cell Chip": a new in vitro alternative technique for immunotoxicity testing

Predictive testing of immunotoxicity associated with chemical compounds is complicated and cannot be accomplished with a single test. As most of the existing tests for immunotoxicity employ experimental animals, there is an increasing need for alternative tests in vitro. We have developed a new system for in vitro immunotoxicity testing, which employs changes in cytokine expression observed in vitro as an endpoint indicating potential for perturbation of the immune system in vivo. This system named "fluorescent cell chip" (FCC) is based on a number of genetically modified cell lines that regulate the expression of a transgene coding for fluorescent protein enhanced green fluorescent protein (EGFP) in a similar way as they regulate expression of IL-1beta, IL-2, IL-4, IFN-gamma, IL-10, TNF-alpha, and beta-actin. Morphological and functional features of selected cell lines expressing EGFP under the control of cytokine promotors were compared with maternal cell lines and this comparison showed that critical functional features of the maternal cell lines were preserved in EGFP expressing cells. Two chemicals with known immunotoxic activities, cyclosporine A and potassium tetrachloro-platinate(II), mediated compound-specific pattern of inhibition and activation of reporter gene expression. Thus, the "fluorescent cell chip" has demonstrated potential for application as a predictive screening test for immunomodulatory activities of chemicals. The major advantage of this approach is the possibility to apply this test in high throughput screening of high number of compounds for their well defined biological activity.     

Effect of milrinone on echocardiographic parameters after single dose in Beagle dogs and relationship with drug-induced cardiotoxicity

The aim of this study was to further investigate the mechanism of development of cardiac lesions occurring under treatment with milrinone in dogs, by using echocardiography for assessing the effects of this drug on cardiac function. Milrinone is a cAMP phosphodiesterase 3 inhibitor having positive inotropic and vasodilatory effects. We treated groups of three dogs with milrinone at a single dose of 0.5 or 1 mg/kg and recorded M-mode and Doppler parameters at different time points before and after treatment. The hearts of the high-dose animals were histopathologically examined. The treatment with milrinone at 1 mg/kg produced mild cardiac lesions at two different locations. In the left ventricle, haemorrhages in the subendocardium and myocardium occurred in all three dogs. In the right atrium, subepicardial haemorrhages occurred in one dog and inflammation of the epicardium was observed in two dogs. These lesions were considered to be related to changes in the cardiac function, which were investigated by echocardiography. Milrinone treatment produced a moderate tachycardia and changes in M-mode parameters indicating an increase in contractility, in particular, a decrease in end-systolic volume, an increase in ejection fraction and an increase in the rate of circumferential fiber shortening. In addition, there was an increase in the maximal aortic flow velocity evaluated by Doppler measurements, which is thought to represent a haemodynamic correlate of an increase in left ventricular contractility. This increase in myocardial work is considered to play a key role in the development of the lesions observed in the left ventricle. Doppler measurements also revealed changes in the right atrioventricular flow, probably resulting from cardiac stimulation produced by milrinone. In particular, there was an increase in the Vmax of the A-wave of the tricuspid flow, suggesting an increase in contractility of the right atrium. This change, by increasing blood flow in atrial wall, may be involved in the induction of the lesions observed in the right atrium. In conclusion, Doppler and M-mode echocardiography are useful tools to assess haemodynamic changes occurring upon treatment with vasodilators or cardiac stimulants in order to further understand the mechanism of development of cardiac lesions produced by such compounds.     

Synthesis and biological evaluation of a new class of acyl derivatives of 3-amino-1-phenyl-4,5-dihydro-1H-pyrazol-5-one as potential dual cyclooxygenase (COX-1 and COX-2) and human lipoxygenase (5-LOX) inhibitors

A series of acyl derivatives of 3-amino-1-phenyl-4,5-dihydro-1H-pyrazol-5-one as potential human 5-LOX and COX 1 and COX-2 inhibitors structurally related to the 1-phenyl-3-pyrazolidinone (phenidone, 1) have been synthesized and the activity against COX-1, COX-2 and human 5-LOX enzymes has been evaluated. All the derivatives showed poor activity against enzymes. These data, together with our previous studies, indicated that phenidone and related compounds are not suitable as human 5-LOX inhibitors and that pyrazoline nucleus should not be considered a good scaffold for inhibitors of human 5-LOX enzyme, suggesting the necessity to revisit the proposed mechanism of action of phenidone (1) in human models.     

Compound heterozygosity for two new mutations in the beta-globin gene [codon 9 (+TA) and polyadenylation site (AATAAA-->AAAAAA)] leads to thalassemia intermedia in a Tunisian patient

More than 200 mutations that are associated with beta-thalassemia (thal) have been found. In most cases, studies to detect a mutation in a patient is made easier because of the existence of geographical sets of mutations that allow the use of a dedicated mutation detection kit. We describe here a patient who originated from Tunisia, in whom we found two as yet unreported mutations, showing that even in a well-studied population a full gene study might be needed to characterize mutation(s).     

Overexpression of cyclooxygenase-2 in human prostate carcinoma and prostatic intraepithelial neoplasia-association with increased expression of Polo-like kinase-1

BACKGROUND: Cyclooxygenases (COX) as well as Polo-like kinases (PLK) are involved in proliferation and cell cycle regulation and have been suggested for preventive and therapeutic approaches in prostate carcinoma. METHODS: In this study, we studied expression and prognostic impact of COX-2 in invasive prostate carcinoma, prostatic intraepithelial neoplasia (PIN), atrophic glands, and normal prostatic glands, and investigated the association between COX-2 and PLK-1. RESULTS: We observed a positivity for COX-2 in 72.1% of PIN and in 44.7% of prostate carcinomas with an overexpression of COX-2 in prostate cancer and PIN compared to benign prostatic tissue (P < 0.0005). Furthermore, we observed a strong correlation between expression of PLK-1 and COX-2 (P < 0.0005). CONCLUSIONS: To our knowledge, this is the first report of a correlation between COX-2 and PLK-1 in a malignant tumor. COX-2 and PLK-1 may be interesting targets for new molecular therapies in prostate cancer.