Biological evaluation and interaction of a newly designed anti-cancer Pd(II) complex and human serum albumin

The pharmacokinetics and pharmacodynamics of any drug will depend, largely, on the interaction that has with human serum albumin (HSA), the most abundant plasma protein. The interaction between newly synthesized Pd(II) complexe, 2,2'-bipyridin Butylglycinato Pd(II) nitrate, an anti-tumor component, with HSA was studied at different temperatures by fluorescence, far UV circular dichroism (CD), UV-visible spectrophotometry and theoretical approaches. The Pd(II) complex has a strong ability to quench the intrinsic fluorescence of HSA through a dynamic quenching procedure. The binding parameters and thermodynamic parameters, including δH°, δS° and δG° were calculated by fluorescence quenching method, indicated that hydrophobic forces play a major role in the interaction of Pd(II) complex with HSA. Based on Autodock, FRET (fluorescence resonance energy transfer) and fluorescence quenching data, it may be concluded that one of the binding sites in the complex of HSA is near the only one Trp of HSA (Trp214) in sub domain IIA of the protein. Far-UV-CD results indicated that Pd(II)-complex induced increase in the α-helical content of the protein. The anti-tumor property of the synthesized Pd(II) complex was studied by testing it on human tumor cell line K562. The 50% cytotoxic concentration (Cc??) of complex was determined using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay. Also, fluorescence staining with DAPI (4,6-diamidino-2-phenylindole) revealed some typical nuclear changes that are characteristic of apoptosis which is induced at Cc?? concentration of Pd(II) complex in K562 cell line after 24?h incubation. Our results suggest that Pd(II) complex is a promising anti-proliferative agent and should execute its biological effects by inducing apoptosis.     

Different doses of bone morphogenetic protein 4 promote the expression of early germ cell-specific gene in bone marrow mesenchymal stem cells

Bone morphogenetic protein (BMP)-4 has a crucial role on primordial germ cells (PGCs) development in vivo which can promote stem cell differentiation to PG-like cells. In this study, we investigated the expression of Mvh as one of the specific genes in primordial germ cells after treatment with different doses of BMP4 on bone mesenchymal stem cells (BMSCs)-derived PGCs. Following isolation of BMSCs from male mouse femur and tibia, cells were cultured in medium for 72 h. Passage 4 murine BMSCs were characterized by CD90, CD105, CD34, and CD45 markers and osteo-adipogenic differentiation. Different doses of BMP4 (0, 0.01, 0.1, 1, 5, 25, 50, and 100 ng/ml) were added to BMSCs for PGCs differentiation during 4-days culture. Viability percent, proliferation rates, and expression of Mvh gene were analyzed by RT-qPCR. Data analysis was done with ANOVA test. CD90⁺, CD105⁺, CD34⁻, and CD45⁻ BMSCs were able to differentiate to osteo-adipogenic lineages. The results revealed that proliferation rate and viability percent were raised significantly (p ≤ 0.05) by adding 1, 5, 25 ng/ml of BMP4 and there were decreased to the lowest rate after adding 100 ng/ml BMP4 (p ≤ 0.05). There were significant up regulation (p ≤ 0.05) in Mvh expression between 25, 50, and 100 ng/ml BMP4 with other doses. So the selective dose of BMP-4 for treatment during 4-day culture was 25 ng/ml. The results suggest that addition of 25 ng/ml BMP4 had the best effects based on gene-specific marker expression.     

Cytochrome CYP141: a new target for direct detection of Mycobacterium tuberculosis from clinical specimens

Cytochrome P450 CYP141 is an intermediary metabolic and respiratory protein that interferes with oxidation reduction in Mycobacterium tuberculosis. This conserved protein has also been debated as a hypothetical target for therapeutics. We used the sequences of CYP141 gene to develop a PCR for rapid detection of Mycobacterium tuberculosis from respiratory specimens. The sensitivity of this PCR for culture positive-smear positive and culture positive-smear negative samples were 92% and 62.5%, respectively. The overall sensitivity and specificity of this PCR was 85.7% and 97.8%. As compared with other studies, it appears that the CYP141 gene is a good target for direct detection of M. tuberculosis from respiratory specimens.     

Clinical governance implementation in a selected teaching emergency department: a systems approach

ABSTRACT: BACKGROUND: Clinical governance (CG) is among the different frameworks proposed to improve the quality of healthcare. Iran, like many other countries, has put healthcare quality improvement in its top health policy priorities. In November 2009, implementation of CG became a task for all hospitals across the country. However, it has been a challenge to clarify the notion of CG and the way to implement it in Iran. The purpose of this action research study is to understand how CG can be defined and implemented in a selected teaching emergency department (ED).Methods/designWe will use Soft Systems Methodology for both designing the study and inquiring into its content. As we considered a complex problem situation regarding the quality of care in the selected ED, we initially conceptualized CG as a cyclic set of purposeful activities designed to explore the situation and find relevant changes to improve the quality of care. Then, implementation of CG will conceptually be to carry out that set of purposeful activities. The activities will be about: understanding the situation and finding out relevant issues concerning the quality of care; exploring different stakeholders' views and ideas about the situation and how it can be improved; and defining actions to improve the quality of care through structured debates and development of accommodations among stakeholders. We will flexibly use qualitative methods of data collection and analysis in the course of the study. To ensure the study rigor, we will use different strategies. DISCUSSION: Successful implementation of CG, like other quality improvement frameworks, requires special consideration of underlying complexities. We believe that addressing the complex situation and reflections on involvement in this action research will make it possible to understand the concept of CG and its implementation in the selected setting. By describing the context and executed flexible methods of implementation, the results of this study would contribute to the development of implementation science and be employed by boards and executives governing other clinical settings to facilitate CG implementation.     

Antimicrobial Activity of Artemisia absinthium Against Surgical Wounds Infected by Staphylococcus aureus in a Rat Model

The wound infection is one of the frequent complications in patients undergoing surgical operations. Staphylococcus aureus is the most common cause of surgical wounds. Artemisia absinthium has been shown to bear strong antimicrobial activity, especially against Gram-positive pathogens. This study was designed to investigate the antimicrobial effects of A. absinthium against surgical wounds infected by S. aureus in a rat model. Twenty male Sprague–Dawley rats were divided randomly into two equal groups of treated and control rats. A circular incision was created on the dorsal inter-scapular region of each rat. After skin wounding, rats were inoculated locally with 1 × 10⁴ CFU of S. aureus at sites of skin wounds. The extract was applied topically twice a day throughout the experiment. Animals of the control group were left untreated. Results have revealed that topical application of A. absinthium extract on the infected wound sites produced significant antibacterial activity against S. aureus.     

Biocontrol of Rhizoctonia solani damping-off of sugar beet with native Streptomyces strains under field conditions

A 3-year study was conducted to evaluate the effectiveness of two disease-suppressive Streptomyces spp. to control sugar beet Rhizoctonia solani damping off under field conditions. Streptomyces seed treatments reduced seedling damping off in naturally (2005) and artificially (2006 and 2007) infested soils. All biocontrol agents provided better efficacy than Vitavax to control seedling damping-off. There were no significant differences among Streptomyces isolates. Isolate C increased plant stand by 19.5, 50.5 and 53.75% in 2005, 2006 and 2007, respectively. Evaluation of final harvest revealed that the root yield of the biocontrol agents increased compared to untreated control in these years.     

A Comparative Study to Evaluate Myogenic Differentiation Potential of Human Chorion versus Umbilical Cord Blood-derived Mesenchymal Stem Cells

Objective

Musculodegenerative diseases threaten the life of many patients in the world. Since drug administration is not efficient in regeneration of damaged tissues, stem cell therapy is considered as a good strategy to restore the lost cells. Since the efficiency of myogenic differentiation potential of human Chorion- derived Mesenchymal Stem Cells (C-MSCs) has not been addressed so far; we set out to evaluate myogenic differentiation property of these cells in comparison with Umbilical Cord Blood- derived Mesenchymal Stem Cells (UCB-MSCs) in the presence of 5-azacytidine.

Characterization of a candidate multi-pole molecular switch using computational techniques

An organic molecule, designed in this study, is proposed as a candidate molecular switch and characterized using the B3LYP/6-31G* computational method. Structural and electronic properties of this molecular switch (M) and its singly charged (M⁺ and M⁻) species in their lowest and the first higher spin states are calculated and analyzed. Molecular volume and electronic spatial extent (ESE) of this nanoswitch undergo negligibly small changes (<2%) upon charging. Furthermore, the small difference between the calculated dipole moments of the M⁺ and M⁻ species shows that switching between negative and positive poles does not significantly affect the charge transfer performance of this molecular switch. Natural bond orbital (NBO) and spin density distributions are also calculated and analyzed. A preliminary study on the response of the proposed molecular switch to the external electric field approves its function as a multi-pole nanoswitch controlled by a bias voltage. Figure Electron transfer scheme and arrangement of the π-electrons in the turn-on state of the candidate multi-pole molecular switch.     

First report of vaginal prolapse in a bitch treated with oestrogen

Vaginal prolapse is the protrusion of edematous vaginal tissue into and through the opening of the vulva occurring during the pro-oestrus and oestrus stages of the sexual cycle. True vaginal prolapse may occur near parturition, as the concentration of serum progesterone declines and the concentration of serum oestrogen increases. In a bitch, true vaginal prolapse is a very rare condition. This case report describes an 18-month-old crossbreed bitch, weighing 40 kg presented with type III vaginal prolapse. The patient had developed vaginal prolapse after receiving oestrogen in order to oestrus induction. Subsequent to unsuccessful attempts for repositioning, ovariohysterectomy (OHE), circumferential excision of the prolapsed tissue and finally vulvoplasty were performed. There was no evidence of recurrence of the prolapse during 30 days after surgery. This case report describes type III vaginal prolapse as an unusual side effect of oestrus induction hormonal therapy in the bitch.     

Altered frequency of CD8+CD11c+ T cells and expression of immunosuppressive molecules in lymphoid organs of mouse model of colorectal cancer

CD11c is a member of the β2-integrin family typically used to define myeloid dendritic cells (DCs). Recent reports identify CD11c-expressing CD8⁺ T cells as a new subset of CD8⁺ regulatory T cells (Treg). Evidence exists that CD11c⁺CD8⁺ T cells may exert their effector or regulatory functions under different conditions. To date, no studies have addressed the frequency of CD11c⁺ T cells in cancer. Limited evidence exists in terms of expression of immune-checkpoint receptors, programmed cell death protein 1 (PD-1) and T-lymphocyte-associated antigen 4 (CTLA-4), as well as forkhead box P3 (Foxp3) in mouse lymphoid organs. Here, we have assessed CD11c⁺CD8⁺ and CD11c⁺CD4⁺ T cells, Foxp3, PD-1, and CTLA-4 expressing CD4⁺ T cells and CD8⁺ T cells in different tissues from three groups of male BALB/c mice—young, mature, and those with colorectal cancer (CRC). Analysis of CD3⁺CD11c⁺ T cells in the bone marrow (BM), spleen, and lymph nodes (LN) in each group showed a higher percentage of CD3⁺CD11c⁺ T cells in the BM from all groups and in the lymphoid organs of the cancer group compared with the young and mature groups. CD4^low and CD4^high cell fractions in mice BM have different expression patterns for Foxp3 and CTLA-4. We have observed a higher frequency of CD8⁺PD-1⁺ T cells in the BM, spleen, and LN of CRC mice compared with normal mice. T-cell exhaustion is associated with inhibitory receptor PD-1. According to the regulatory roles of CD11c expression in CD8⁺ T cells, we have proposed that the elevated percentage of CD11c, Foxp3, CTLA-4, and PD-1 expressing T cells were associated with immune response dysregulation in CRC.