DNA-binding activity and cytotoxicity of Pt-berenil compounds in MDA-MB-231 and MCF-7 breast cancer cells

The compounds of formula [Pt2Cl4(berenil)2]Cl4 and [Pt2Cl2(NH3)2(berenil)2]Cl4 were examined for cytotoxicity in breast cancer cell cultures and for inhibition of topoisomerases I and II. Evaluation of the cytotoxicity of these compounds employing a MTT assay and inhibition of [3H]thymidine incorporation into DNA in both MDA-MB-231 and MCF-7 breast cancer cells demonstrated that these compounds were more active than cisplatin. The DNA-binding ability of these compounds was evaluated by an ultrafiltration method using calf thymus DNA, poly(dA-dT)2 and poly(dG-dC)2, indicated that these compounds show strong specificity for AT base pairs. Binding studies indicate that these compounds bind more tightly to double-stranded DNA than cisplatin. The degree to which these compounds inhibited cell growth breast cancer cells was generally consistent with their relative DNA binding affinity. Mechanistic studies revealed that these compounds act as topoisomerase II (topo II) inhibitors in plasmid relaxation assays.     

The correlations between endogenous dehydroepiandrosterone sulfate and some atherosclerosis risk factors in premenopausal women.

BACKGROUND: Dehydroepiandrosterone (DHEA) is postulated to have antiatherogenic properties, but the possible mechanism of this action is unclear. The aim of this study was to determine the influence of endogenous DHEA-S on the levels of some factors playing significant roles in atherogenesis. MATERIAL/METHODS: In a group of 40 premenopausal women, relationships between endogenous DHEA-S and serum lipids and the apolipoproteins A1 (apoA1) and B (apoB), serum lipid peroxide (LPO), and total antioxidant system (TAS) concentrations as markers of the serum antioxidant-prooxidant balance were measured as well as clinical and biochemical parameters playing roles in atheromatosis such as the type of obesity and the serum glucose, insulin, insulin-like growth factor (IGF-1) and homocysteine (HCY) concentrations. RESULTS: Statistical analysis revealed significant correlation (p<0.05) between serum DHEA-S level and the serum concentrations of: HDL(2)-C (r=0.53), HDL(2)-C/HDL(3)-C (r=0.58), TG (r=0.35), IGF-1 (r=0.39), and HCY (r=-0.44). There was no statistically significant correlation between DHEA-S level and other biochemical and clinical parameters (age, BMI, WHR) found in this study. CONCLUSIONS: Despite unfavorable correlation between DHEA-S and TG concentration, the results of this study indicate a potential antiatherogenic action of DHEA which may occur through various mechanisms: by increasing HDL(2)-C and the HDL(2)-C/HDL(3)-C ratio, which has an atheroprotective effect, by elevating the serum IGF-1 concentration, or by decreasing the HCY level. These preliminary results, however, require further investigation.     

Permeability of Ibuprofen in the Form of Free Acid and Salts of L-Valine Alkyl Esters from a Hydrogel Formulation through Strat-M™ Membrane and Human Skin

This paper aimed to evaluate the effect of vehicle and chemical modifications of the structure of active compounds on the skin permeation and accumulation of ibuprofen [IBU]. In vitro permeation experiments were performed using human abdominal skin and Strat-M™ membrane. The HPLC method was used for quantitative determinations. The formulations tested were hydrogels containing IBU and its derivatives and commercial gel with ibuprofen. The results obtained indicate that Celugel^® had an enhancing effect on the skin penetration of IBU. The average cumulative mass of [IBU] after 24 h permeation test from Celugel^® formulation through human skin was over 3 times higher than for the commercial product. Three ibuprofen derivatives containing [ValOiPr][IBU], [ValOPr][IBU], and [ValOBu][IBU] cation were evaluated as chemical penetration enhancers. The cumulative mass after 24 h of penetration was 790.526 ± 41.426, 682.201 ± 29.910, and 684.538 ± 5.599 μg IBU cm⁻², respectively, compared to the formulation containing unmodified IBU-429.672 ± 60.151 μg IBU cm⁻². This study demonstrates the perspective of the transdermal hydrogel vehicle in conjunction with the modification of the drug as a potential faster drug delivery system.     

Assessment of the Effect of Structural Modification of Ibuprofen on the Penetration of Ibuprofen from Pentravan® (Semisolid) Formulation Using Human Skin and a Transdermal Diffusion Test Model

The effect of transdermal vehicle (Pentravan^®) on skin permeability was examined for unmodified ibuprofen (IBU) and ion pairs of ibuprofen with new L-valine alkyl esters [ValOR][IBU]. The percutaneous permeation across the human skin and transdermal diffusion test model (Strat-M^® membranes) of ibuprofen and its structural modification were measured and compared using Franz diffusion cells. For comparison, the penetration of ibuprofen from a commercial product was also investigated. The cumulative amount of drug permeated through human skin at the end of the 24 h study was highest for ibuprofen derivatives containing propyl (C3), isopropyl (C3), ethyl (C2), and butyl (C4) esters. For Strat-M^®, the best results were obtained with the alkyl chain length of the ester from C2 to C5. The permeation profiles and parameters were appointed, such as steady-state flux, lag time, and permeability coefficient. It has been shown that L-valine alkyl ester ibuprofenates, with the propyl, butyl, and amyl chain, exhibit a higher permeation rate than ibuprofen. The diffusion parameters of analyzed drugs through human skin and Strat-M^® were similar and with good correlation. The resulting Pentravan-based creams with ibuprofen in the form of an ionic pair represent a potential alternative to other forms of the drug-containing analgesics administered transdermally. Furthermore, the Strat-M^® membranes can be used to assess the permeation of transdermal preparations containing anti-inflammatory drugs.     

Atypical beta-adrenoceptors,different from beta 3-adrenoceptors and probably from the low-affinity state of beta 1-adrenoceptors,relax the rat isolated mesenteric artery

(1) We examined whether beta3- and/or atypical beta-adrenoceptors relax the rat isolated mesenteric artery. (2) Mesenteric arteries precontracted with phenylephrine were relaxed by beta-agonists with the following potencies (pD2): nonselective agonist isoprenaline (6.00)>nonconventional partial agonist cyanopindolol (5.45)>beta2-agonist fenoterol (4.98)>nonconventional partial agonist CGP 12177 (4.19)>beta3-agonist ZD 2079 (3.72). The beta3-agonist CL 316243 1 mm relaxed the vessel only marginally. (3) The concentration-response curves (CRCs) for cyanopindolol, CGP 12177 and ZD 2079 were not affected by the nonselective beta-antagonist propranolol 0.3 microm, the beta2-antagonist ICI 118551 1 microm and by CL 316243 60 microm, but shifted to the right by bupranolol (pA2 5.3-5.7), CGP 20712 (5.4) and SR 59230A (6.5-6.7) (the latter three drugs block atypical and/or beta3-adrenoceptors at high concentrations). (4) The CRC for isoprenaline was shifted to the right by propranolol (pA2 7.0) but, in the presence of propranolol 0.3 microm, not affected by SR 59230A 1 microm. The CRC for fenoterol was shifted to the right by propranolol (pA2 6.9) and ICI 118551 (6.8). (5) Removal of endothelium diminished the vasorelaxant effects of cyanopindolol, CGP 12177 and ZD 2079. (6) Fenoterol and cyanopindolol also relaxed (endothelium-intact) mesenteric arteries precontracted with serotonin. The relaxant effect of cyanopindolol was antagonized by bupranolol to about the same degree as in phenylephrine-contracted vessels. (7) In conclusion, beta2- and atypical beta-adrenoceptors (but not beta3-adrenoceptors) relax the rat mesenteric artery. The atypical beta-adrenoceptor, which is partially located endothelially, may differ from the low-affinity state of the beta1-adrenoceptor.     

Relationship between tumour necrosis factor‐related apoptosis inducing ligand (TRAIL) and vascular endothelial growth factor in human multiple myeloma patients

Tumour necrosis factor‐alfa (TNF‐α) is an inflammatory cytokine with a wide spectrum of biological activity, including angiogenesis. Tumour necrosis factor‐related apoptosis inducing ligand (TRAIL), which belongs to the TNF family of proteins, plays a role in the regulation of vascular responses, but its effect on the formation of new blood vessels (angiogenesis) is unclear. We analysed TRAIL concentrations in parallel with pro‐angiogenic cytokines in serum and their expression in trephine biopsy (TB) in 56 patients with newly diagnosed IgG MM and 24 healthy volunteers. The study showed statistically higher concentrations of TRAIL and TNF‐α, as well as of VEGF and its receptor, in MM patients compared to healthy volunteers and patients in advanced stages of the disease. Furthermore, we observed a significant decrease in all studied pro‐angiogenic cytokines and significant increase of TRAIL concentration after anti‐angiogenic therapy, with meaningful differences between responders (at least partial remission) and patients with progression during the induction treatment. It was also established that TRAIL correlated statistically and negatively with pro‐angiogenic cytokines such as VEGF with its receptor and expression of VEGF and syndecan‐1 in TB. In summary, our data indicate that in MM patients, both clinical course and treatment responsiveness are associated with dynamic yet corresponding changes of levels of TRAIL parallel pro‐angiogenic mediators such as VEGF with its receptor and expression of VEGF and syndecan‐1 in TB. Copyright © 2014 John Wiley & Sons, Ltd.     

Add-on treatment with nebulized hypertonic saline in a child with plastic bronchitis after the Glenn procedure,

Plastic bronchitis (PB), although a rare cause of airway obstruction, has mortalityrates up to 50% in children after Fontan-type cardiac surgery. We present the case ofan 18-month-old female patient with PB following pneumonia. At 6 months of age, thepatient underwent the Glenn procedure due to functionally univentricular heart.Fiberoptic bronchoscopy revealed complete blockage of the left bronchus by mucoidcasts. Pharmacotherapy consisted of glucocorticosteroids, azithromycin, and enalaprilmaleate. The child also received nebulized 3% NaCl solution, which proved to bebeneficial. In children submitted to Fontan-type procedures, physicians must be alertfor PB, which can be triggered by respiratory tract infection.     

Analysis of Quality of Life Subjective Perception by Patients Treated for Prostate Cancer with the EORTC QLQ-C30 Questionnaire and QLQ-PR25 Module

Prostate cancer in men is the second most occurring cancer in Poland and represents approximately 13.2 % of all cancers. At the same time, it is the third largest cause of death in men, being responsible for approximately 8 % of deaths. The study was conducted among patients of Oncological Hospital in Wieliszew. The study included 83 men diagnosed with prostate cancer at the age of 51–84 years. The patients gave their written consent to participate in the study, to which the overall standardized questionnaires EORTC QLQ-C30 and QLQ-PR25 for patients with prostate cancer was applied. Significant deterioration of the state of health due to cancer was indicated by a total of 10.84 % of patients. At the same time, it was found that although there are differences between quality of life in various age groups of respondents, they are statistically insignificant (Chi2?=?59.96; p?=?0.00734; R?=?0.09; p?>?0.05). Subjective QoL did not depend on the stage of cancer treatment, type of therapy, or significant deterioration in the patient’s state of health in the last stage of disease. Both disease and therapy have impact on quality of life in all its dimensions, in particular as regards the patient’s physical functioning and his frequent fatigue. There is a strong relationship between a patient’s subjective assessment of quality of life and pain that significantly hampers everyday activities. This demonstrates the need for continuous monitoring and relieving pain directly associated with cancer and methods of its treatment.