Effect of diltiazem isomers and thiamine on piglet liver microsomal peroxidation using dichlorofluorescein.

PURPOSE: We investigated a potential hepatoprotective role of d-cis diltiazem, l-cis diltiazem, thiamine and the combination d-cis diltiazem and thiamine against lipid peroxidation in a piglet liver microsomal model. A modified in vitro dichlorofluorescein assay was developed to assess the extent of peroxidative damage induced by reactive oxygen species in the piglet liver microsomal fraction. METHODS: Microsomal membrane fraction, obtained from 3 week old female piglets, was treated with either the biologically vasoactive d-cis diltiazem or the non-vasoactive stereoisomer l-cis diltiazem (5-1000 microM) for 1 hour at 37 degrees C followed by one hour incubation with the free radical generator AAPH (2,2'-azobis-(2-amidinopropane) dihydrochloride; 1 mM) to initiate lipid peroxidation. In a separate study, piglet liver microsomes were pre-treated with d-cis diltiazem (50 or 500 microM) and thiamine (10-100 microM) to assess the antioxidant activity of the combination. RESULTS: A dose dependant inhibition of membrane lipid peroxidation was observed with d-cis diltiazem (p<0.05) but not with l-cis diltiazem, suggesting that diltiazem is stereospecific in protecting against microsomal lipid peroxidation. Combining diltiazem with thiamine further protected microsomes against lipid peroxidation compared to use of individual drugs. CONCLUSION: We conclude that diltiazem and the combination of diltiazem and thiamine offers a hepatoprotective effect against free radicals.     

(226)Ra, (232)Th and (40)K contents in soil samples from Garhwal Himalaya, India, and its radiological implications

The exposure of human beings to ionising radiation from natural sources is a continuing and inescapable feature of life on earth. Natural radionuclides are widely distributed in various geological formations and ecosystems such as rocks, soil groundwater and foodstuffs. In the present study, the distribution of (226)Ra, (232)Th and (40)K was measured in soil samples collected from different lithological units of the Thauldhar and Budhakedar regions of Garhwal Himalaya, India. The collected soil samples were analysed using gamma ray spectrometry. The activity concentrations of the naturally occurring radionuclides (226)Ra, (232)Th and (40)K in these soil samples were found to vary from below detection level (BDL) to 131 +/- 18 Bq kg(-1), 9 +/- 6 to 384 +/- 53 Bq kg(-1) and 471 +/- 96 to 1406 +/- 175 Bq kg(-1), respectively. The distribution of radionuclides depends upon the rock formation and chemical properties within the earth. The activity concentrations vary widely depending on the sample origin. The external absorbed gamma dose rates due to (226)Ra, (232)Th and (40)K were found to vary from 49 to 306 nGy h(-1). The average radium equivalent activity from these soil samples was 300 Bq kg(-1).     

Undifferentiated Tumors: An Immunohistochemical Analysis on Biopsies

Immunohistochemical staining was performed on 145 biopsies with a diagnosis of undifferentiated or poorly differentiated tumor in order to classify them into lymphoid, epithelial, or mesenchymal in origin. It was possible to arrive at a histogenetic diagnosis on immunostaining in 85.5% of cases. Immunostaining confirmed the diagnosis in 32.4% and contributed to diagnosis in 53.1%. Malignant lymphoma was the most common diagnosis (35.9%), followed by carcinoma (23.4%). A panel of antibodies consisting of anti-common leucocyte antigen (LCA), anti-epithelial membrane antigen (EMA), anti-cytokeratin (CK), anti-low to intermediate molecular weight cytokeratin (CAM 5.2), anti-S-100 protein (S-100), and anti-vimentin (VM) may resolve, to a large extent, some of the common diagnostic problems. © 1994 Wiley-Liss, Inc.     

Comparison of ticarcillin plus clavulanic acid with clindamycin and gentamicin in the treatment of postcesarean endomyometritis

The efficacy of a single antibiotic--Timentin (ticarcillin with clavulanic acid)--was compared with a standard two antibiotic regimen (clindamycin and gentamicin) for the treatment of endomyometritis after cesarean delivery. The regimens were 3 grams of ticarcillin plus 100 milligrams of clavulanic acid given intravenously every four hours, or 600 milligrams of clindamycin given intravenously every six hours plus 3 to 5 milligrams per kilogram per day of gentamicin given intramuscularly. The diagnosis of endomyometritis was based upon an oral temperature of 100.4 degrees F. or higher on any two occasions, excluding the first 24 hours post partum, uterine tenderness and the absence of another focus of infection. Ninety-one patients were treated. Treatment failure rates were three of 49 in the clindamycin and gentamicin group and four of 42 of the ticarcillin plus clavulanic acid group. Treatment failures did not appear to be different from successes demographically or in risk factors for endomyometritis. The results of this study suggest that ticarcillin with clavulanic acid is as effective in the treatment of postcesarean endomyometritis as the standard regimen of clindamycin and gentamicin.     

Effect of nortriptyline and paroxetine on measures of chaos of heart rate time series in patients with panic disorder

Tricyclic antidepressants have notable cardiac side effects, and this issue has become important due to the recent reports of increased cardiovascular mortality in patients with depression and anxiety. Several previous studies indicate that serotonin reuptake inhibitors (SRIs) do not appear to have such adverse effects. Apart from the effects of these drugs on routine 12-lead ECG, the effects on beat-to-beat heart rate (HR) and QT interval time series provide more information on the side effects related to cardiac autonomic function. In this study, we evaluated the effects of two antidepressants, nortriptyline (n=13), a tricyclic, and paroxetine (n=16), an SRI inhibitor, on HR variability in patients with panic disorder, using a measure of chaos, the largest Lyapunov exponent (LLE) using pre- and posttreatment HR time series. Our results show that nortriptyline is associated with a decrease in LLE of high frequency (HF: 0.15–0.5 Hz) filtered series, which is most likely due to its anticholinergic effect, while paroxetine had no such effect. Paroxetine significantly decreased sympathovagal ratios as measured by a decrease in LLE of LF/HF. These results suggest that paroxetine appears to be safer in regards to cardiovascular effects compared to nortriptyline in this group of patients.     

Monoclonal antibody therapy for genitourinary oncology: promise for the future

PURPOSE: Metastatic or recurrent cancer continues to be the bane of the urological oncologist. Despite recent improvements in therapeutic strategies and outcomes for clinically localized disease overall survival in patients with the majority of metastatic and recurrent genitourinary malignancies remains relatively unchanged. Modern advances in the field of immunotherapy hold the promise of providing the clinical urologist/oncologist with new tools to fight urological cancer. In this review we discuss the various mAb based strategies currently under investigation for urological oncology as well as the lessons learned from similar approaches in other fields. MATERIALS AND METHODS: We reviewed the literature on mAb based immunotherapy with a particular emphasis on target antigens, mAb design and potential applications in the field of urology. RESULTS: Early trials with mAb therapy for solid tumor oncology met with limited success due to difficulty with mAb design and production, the development of host immunological responses against murine monoclonal antibodies (that is human anti-mouse antibodies), suboptimal target antigen selection, and poor monoclonal antibody pharmacokinetics and tumor tissue penetration. Recent advances in the fields of immunology and oncology have sought to circumvent these obstacles. Today several preliminary studies have shown the effectiveness and usefulness of mAb based strategies for urological oncology. CONCLUSIONS: The field of mAb based immunotherapy continues to evolve. New discoveries in this burgeoning area of cancer therapy show promise for the future.