Diethylstilbestrol and tetrahydrochrysenes are calcium channel blockers in human platelets: relationship to the stilbene pharmacophore

The effects of compounds with the stilbene pharmacophore [diethylstilbestrol (DES), DES derivatives, tetrahydrochrysene (THC), and THC derivatives] were examined for their ability to inhibit thrombin-induced Ca(2+) influx in human platelets. DES derivatives (DES dimethyl ether, DES dipropionate, dienestrol, and hexestrol) had lower inhibitory activity than DES. Esterification of DES with the bulky monobenzyl group eliminated inhibitory activity. Unsubstituted THC diol had the lowest inhibitory activity in the series of the THC derivatives bearing substituents in the 5,11 positions. These derivatives, either diethyl or dipropyl, cis or trans, were potent inhibitors of thrombin-induced [Ca(2+)](i) elevation (near 100% inhibition at 10 microM). Therefore, stilbene pharmacophore having bulk out of the plane of the double bond (from the twisting of the two aromatic rings or from addition of all substituents) seems to be requirement for the inhibitory activity. Free hydroxyl groups are also required for inhibitory activity, most likely for hydrogen bonding, since trans-diethyl tetrahydrochrysene dimethyl ether was inactive. Compounds bearing ethyl substituents (DES and THC derivatives) inhibited thrombin-induced release of calcium from the endoplasmic reticulum. These compounds also inhibited thapsigargin-induced Ca(2+) influx. This result implies that these compounds also block store-operated Ca(2+) influx directly, as well as internal Ca(2+) release. Compounds without ethyl substituents (trans-resveratrol, genistein, daidzein, and THC diol) only inhibited calcium influx into platelets.     

Human galectin-3 promotes Trypanosoma cruzi adhesion to human coronary artery smooth muscle cells

Human galectin-3 binds to the surface of Trypanosoma cruzi trypomastigotes and human coronary artery smooth muscle (CASM) cells. CASM cells express galectin-3 on their surface and secrete it. Exogenous galectin-3 increased the binding of T. cruzi to CASM cells. Trypanosome binding to CASM cells was enhanced when either T. cruzi or CASM cells were preincubated with galectin-3. Cells stably transfected with galectin-3 antisense show a dramatic decrease in galectin-3 expression and very little T. cruzi adhesion to cells. The addition of galectin-3 to these cells restores their initial capacity to bind to trypanosomes. Thus, host galectin-3 expression is required for T. cruzi adhesion to human cells and exogenous galectin-3 enhances this process, leading to parasite entry.     

Therapeutic effect of iodised serum milk protein,lycopene and their combination on benign prostatic hyperplasia induced in rats

Benign prostatic hyperplasia (BPH) is a common chronic disease in ageing men. Synthetic inhibitors of 5α-reductase commonly used in BPH treatment have limited effectiveness and may cause side effects. Evaluation of iodised serum milk protein and lycopene therapeutic effect in rat BPH model was the aim of the present study. BPH was induced in male Wistar rats by surgical castration and subsequent testosterone administrations (25 mg/kg, 7 injections). Rats with induced BPH received lycopene (5 mg/kg), iodised serum milk protein (200 µg/kg) or their combination for 1 month daily. The efficacy of the treatment was evaluated by the prostate weight, prostatic index and ventral lobe epithelium thickness. In lycopene and iodised serum milk protein-treated rats, prostate weight and prostatic index were significantly reduced compared to control group; and lycopene and iodised serum milk protein used in combination yielded an additive effect. Thus, further investigation of combined supplementation with micronutrients and plant-derived substances in BPH models may help to find new opportunities or its safe and effective treatment.     

Effect of structural factors on the physicochemical properties of functionalized polyanilines

This review discusses the physical and physicochemical properties of polyaniline (PANI) derivatives. The most important methods for the preparation of functionalized polyanilines are presented. The presence of various substituents in its structure changes the polymer characteristics significantly due to steric and electronic effects of the functional groups. This review describes the relationship between the properties of functionalized polyanilines depending on the nature, number and position of the substituents at the aromatic ring.

The review describes the relationship between the properties of functionalized polyanilines depending on the nature of the substituents at the aromatic ring.     

Core needle biopsy is a safe and accurate initial diagnostic procedure for suspected lymphoma

Background

Excisional biopsy is currently recommended for the analysis of lymphadenopathy suspicious for lymphoma. This study aims to evaluate the efficacy and safety of image-guided core needle biopsy (IGCNB) for the diagnosis of lymphoma using a standard protocol for tissue acquisition and analysis.

Methods

All IGCNBs from 2008 to 2014 performed under the study protocol were included in analysis. Demographics, pathology results, additional studies, and follow-up information were recorded.

Results

Seventy-three IGCNBs were performed in 71 consecutive patients. Lymphoma was diagnosed in 37 patients (51%). All 37 patients (100%) were subtyped and treated based on IGCNB results. The remaining 36 IGCNBs in 34 patients did not have subsequent diagnosis of lymphoma in a mean follow-up of 15 months (range, 0 to 54 months). There were no complications.

Conclusions

IGCNB performed under a standard protocol is effective and safe and should be considered as an initial diagnostic tool for the evaluation of lymphadenopathy suspicious for lymphoma.     

Palliative chemotherapy for malignant ascites secondary to ovarian cancer

Although research has shown that palliative chemotherapy is beneficial compared to lack of treatment (Schorge JO, Schaffer JI, Halvorson LM, et al. ed. Williams Gynecology. New York, NY: McGraw Hill Medical; 2008.), other studies show aggressive end-of-life treatment adversely affects quality of life and shortens life span (Arriba L, Fader A, Frasure H, von Gruenigen V. A review of issues surrounding quality of life among women with ovarian cancer. Gynecol Oncol. 2010;119(2):390-396.). Without a consensus on palliative chemotherapy, underutilization during end of life prevails, and likely will continue without additional research (Barbera L, Elit L, Krzyzanowska M, et al. End of life care for women with gynecologic cancers. Gynecol Oncol. 2010;118(2):196-201.). This article aims to evaluate and examine existing chemotherapy for palliation of malignant ascites secondary to ovarian cancer and compare commonly used regimens. Agents will be evaluated by their modes of administration. Oral agents include cyclophosphamide and thalidomide, and intraperitoneal vehicles include taxane-based agents, platinum-based agents, antibiotics, and biologic agents. In addition, cost, ethics, and quality of life discussions factor into this review. Palliative care's goal is to find a balance between life expectancy and symptom relief with minimal adverse effects.     

Elevated levels of the small GTPase Cdc42 induces senescence in male rat mesenchymal stem cells

Mesenchymal stem cells (MSCs) represent a promising cell source for cellular therapy and tissue engineering and are currently being tested in a number of clinical trials for various diseases. However, like other somatic cells, MSCs age, and this senescence is accompanied by a progressive decline in stem cell function. Several lines of evidence suggest a role for the Rho family GTPase Cdc42 activity in cellular senescence processes. In the present study, we have examined aging-associated Cdc42 activity in rat adipose-derived mesenchymal stem cells (ADMSCs) and the consequences of pharmacological inhibition of Cdc42 in ADMSCs from aged rats. We demonstrate that ADMSCs show a decreased rate of cell growth and a decreased ability to differentiate into chrodrogenic, osteogenic and adipogenic cell lineages as a function of rat age. This is accompanied with an increased staining for SA-β-Gal activity and increased levels of Cdc42 bound to GTP. Treatment of ADMSCs from 24-month old rats with three Cdc42 inhibitors significantly increased proliferation rates, decreased SA-β-Gal staining, and reduced Cdc42-GTP. The Cdc42 inhibitor CASIN increased adipogenic and osteogenic differentiation potential in ADMSCs from 24-month old rats, and decreased the levels of radical oxygen species (ROS), p16^INK4a levels, F-actin, and the activity of the ERK1/2 and JNK signaling pathways that were all elevated in these cells. These data suggest that ADMSCs show increased rates of senescence as rats age that appear to be due to elevated Cdc42 activity. Thus, Cdc42 plays important roles in MSC senescence and differentiation potential, and pharmacological reduction of Cdc42 activity can, at least partially, rejuvenate aged MSCs.