Investigating the Antiangiogenic,Anti-drug Resistance and Apoptotic Effects of Soy Isoflavone Extract Alone or in Combination with Docetaxel on Murine 4T1 Breast Tumor Model

Background: One major concern in the treatment of cancer patients during chemotherapy is drug resistance. Here we investigated the effects of soy isoflavone extracts alone or in combination with Docetaxel on the drug resistance, angiogenesis, apoptosis, and tumor volume in mouse 4T1 breast tumor model. Methods: Sixty female BALB/c mice were randomly divided into 4 groups: control, dietary soy isoflavone extract [Iso, 100 mg/kg diet (0.01%)], Docetaxel (10 mg/kg) injection, and the combination of dietary soy isoflavone extract and intravenous Docetaxel injection (Docetaxel + Iso). One week after the third injection, the breast tumors of eight mice from each group were excised to analyze NF-κBp65′ vascular endothelial growth factor receptor-2 (VEGFR2) and Pgp gene and protein expressions and the other seven mice were monitored for survival rate analysis until they died. Results: NF-κBp65 gene and protein expressions were significantly lower in the Docetaxel + Iso group in comparison with that of the Docetaxel group. VEGFR2 protein expression in the Docetaxel + Iso and Iso groups was significantly lower than that of the Docetaxel group. Conclusion: These findings may indicate that the combined use of isoflavone extracts together with chemotherapeutic agents has more efficient anti-carcinogenic effects than their individual use.     

Is the knowledge of contact force beneficial in pulmonary vein antrum isolation?

Objective: To investigate the effect of the operator knowing the real-time contact force (CF) on the efficacy of pulmonary vein antrum isolation (PVAI).

Methods: Fifty patients with paroxysmal atrial fibrillation (AF) or short lasting persistent AF were randomized to CF guided PVAI (n?=?25) or conventional PVAI (n?=?25). In the CF guided group, CF between 10 and 40?g was aimed at. Efficacy of PVAI was measured as reduction in AF burden (AFB) and time to AF recurrence detected by implantable cardiac monitor (ICM), inserted three months before PVAI. Blanking period was three months and follow-up 12 months.

Results: All pulmonary veins were isolated in the CF guided group and all but one in the conventional group. Mean CF was 25?g in the CF guided group and 24?g in the conventional group (p?=?0.75). Compared to pre-ablation, median [IQR] relative reduction in AFB 3–12 months after ablation was 100 [99–100]% in the CF guided group (p?p?p?=?0.09). Nine patients (36%) had AF recurrence in the CF guided group and 13 (52%) in the conventional group (p?=?0.21, log-rank test). CF differed between operators. When adjusted for operator by regression analysis, patients without recurrent AF had lower proportion of ablation time with CF <10?g than recurrent patients (p?=?0.034). No complications occurred.

Conclusions: Operator knowledge of real-time CF had no significant effect on AFB reduction or time to AF recurrence. Larger trials should be done to study benefit of real-time CF.     

Evaluation of a biosimilar recombinant alpha epoetin in the management of anemia in hemodialysis patients

Background: The efficacy of human recombinant erythropoietins (rHuEPOs) in the treatment of anemia with different etiologies is proven. Development of biosimilar rHuEPO products with lower cost and wider availability is important for the care of anemic patients. Objective: The aim of the present study was to determine the bioequivalence and safety of a biosimilar rHuEPO (Pastopoitin^®) and compare it with the innovator product Eprex^®, as a standard rHuEPO. Methods: One hundred and seven anemic patients on stable hemodialysis were recruited to this randomized double-blind comparative trial and assigned to either subcutaneous Pastopoitin (n = 50) or Eprex (n = 57). Each study group received rHuEPO at a dose of 80–120 IU/kg/week in 2–3 divided doses for a period of 3 months. Hematologic parameters including Hemoglobin, hematocrit, RBC, EBC, platelet, MCV, MCH and MCHC were checked every 2 weeks. Blood iron, ferritin, TIBC, creatinine, BUN and electrolytes (Na, K, Ca and P) were evaluated monthly over the 3 months. Results: A significant increase in hemoglobin, hematocrit and RBC was observed by the end of study in both Pastopoitin and Eprex groups (p < 0.001). However, these factors were not significantly different between the groups, neither at baseline nor at the end of study (p > 0.05). Likewise, the groups were comparable regarding MCV, MCH, MCHC, iron, ferritin, TIBC, creatinine, BUN and electrolytes at baseline as well as at the end of trial. Adverse events were not serious and occurred with the same frequency in the study groups. Conclusion: Pastopoitin showed comparable efficacy and safety profile with Eprex in anemic patients on hemodialysis. Hence, Pastopoitin may be considered as a rHuEPO with a lower cost and wider availability compared with the innovator product Eprex.     

Radioprotective Effect of Achillea millefolium L Against Genotoxicity Induced by Ionizing Radiation in Human Normal Lymphocytes

The radioprotective effect of Achillea millefolium L (ACM) extract was investigated against genotoxicity induced by ionizing radiation (IR) in human lymphocytes. Peripheral blood samples were collected from human volunteers and incubated with the methanolic extract of ACM at different concentrations (10, 50, 100, and 200 μg/mL) for 2 hours. At each dose point, the whole blood was exposed in vitro to 2.5 Gy of X-ray and then the lymphocytes were cultured with mitogenic stimulation to determine the micronuclei in cytokinesis-blocked binucleated cell. Antioxidant capacity of the extract was determined using free radical-scavenging method. The treatment of lymphocytes with the extract showed a significant decrease in the incidence of micronuclei binucleated cells, as compared with similarly irradiated lymphocytes without any extract treatment. The maximum protection and decrease in frequency of micronuclei were observed at 200 μg/mL of ACM extract which completely protected genotoxicity induced by IR in human lymphocytes. Achillea millefolium extract exhibited concentration-dependent radical-scavenging activity on 1,1-diphenyl-2-picryl hydrazyl free radicals. These data suggest that the methanolic extract of ACM may play an important role in the protection of normal tissues against genetic damage induced by IR.     

Inhibition of microglial activity alters spinal wide dynamic range neuron discharge and reduces microglial Toll‐like receptor 4 expression in neuropathic rats

It is believed that neuropathic pain results from aberrant neuronal discharges although some evidence suggests that the activation of glia cells contributes to pain after an injury to the nervous system. This study aimed to evaluate the role of microglial activation on the hyper‐responsiveness of wide dynamic range neurons (WDR) and Toll‐like receptor 4 (TLR4) expressions in a chronic constriction injury (CCI) model of neuropathic pain in rats. Adult male Wistar rats (230 ± 30 g) underwent surgery for induction of CCI neuropathy. Six days after surgery, administration of minocycline (10, 20, and 40 mg/kg, i.p.) was initiated and continued until day 14. After administration of the last dose of minocycline or saline, a behavioral test was conducted, then animals were sacrificed and lumbar segments of the spinal cord were collected for Western blot analysis of TLR4 expression. The electrophysiological properties of WDR neurons were investigated by single unit recordings in separate groups. The findings showed that after CCI, in parallel with thermal hyperalgesia, the expression of TLR4 in the spinal cord and the evoked response of the WDR neurons to electrical, mechanical, and thermal stimulation significantly increased. Post‐injury administration of minocycline effectively decreased thermal hyperalgesia, TLR4 expression, and hyper‐responsiveness of WDR neurons in CCI rats. The results of this study indicate that post‐injury, repeated administration of minocycline attenuated neuropathic pain by suppressing microglia activation and reducing WDR neuron hyper‐responsiveness. This study confirms that post‐injury modulation of microglial activity is a new strategy for treating neuropathic pain.     

Loving‐Kindness in the Treatment of Traumatized Refugees and Minority Groups: A Typology of Mindfulness and the Nodal Network Model of Affect and Affect Regulation

This article discusses how loving‐kindness can be used to treat traumatized refugees and minority groups, focusing on examples from our treatment, culturally adapted cognitive‐behavioral therapy (CA‐CBT). To show how we integrate loving‐kindness with other mindfulness interventions and why loving‐kindness should be an effective therapeutic technique, we present a typology of mindfulness states and the Nodal Network Model (NNM) of Affect and Affect Regulation. We argue that mindfulness techniques such as loving‐kindness are therapeutic for refugees and minority populations because of their potential for increasing emotional flexibility, decreasing rumination, serving as emotional regulation techniques, and forming part of a new adaptive processing mode centered on psychological flexibility. We present a case to illustrate the clinical use of loving‐kindness within the context of CA‐CBT.     

Elder abuse among Spanish and Iranian people: new methodological approach to the same old story

International Journal of Legal Medicine - Elder abuse continues to be a taboo, mostly underestimated, ignored by societies across the world. Recent systematic reviews and meta-analyses have...