G2/M-Phase-Inhibitory Mitochondrial-Depolarizing Re(I)/Ru(II)/Ir(III)-2,2'-Bipyrimidine-Based Heterobimetallic Luminescent Complexes: An Assessment of In Vitro Antiproliferative Activity and Bioimaging for Targeted Therapy toward Human TNBC Cells.

Triple-negative breast cancer (TNBC) is an extremely vicious subtype of human breast cancer having the worst prognosis along with strong invasive and metastatic competency. Hence, it can easily invade into blood vessels, and presently, no targeted therapeutic approach is available to annihilate this type of cancer. Metal complexes have successfully stepped into the anticancer research and are now being applauded due to their anticancer potency after the discovery of cisplatin. Many of these metal complexes are also well recognized for their activity toward breast cancer. As the TNBC is a very dangerous subtype and has long been a challenging ailment to treat, we have intended to develop a few brand new mixed metallic Ru(II)/Ir(III)/Re(I)-2,2'-bipyrimidine complexes [L'Re2], [L'RuRe], and [L'IrRe] to abate the unbridled proliferation of TNBC cells. The potency of the complexes against TNBC cells has been justified using MDA-MB-468 TNBC cell lines where complex [L'IrRe] has displayed significant potency among all the three complexes with an IC50 value of 24.12 µM. The complex [L'IrRe] has been competent to cause apoptosis of TNBC cells through inhibition of the G2/M phase in the cell cycle in association with a profuse amount of ROS generation and mitochondrial depolarization.

Human umbilical cord and its vessels: a histomorphometric study in difference severity of hypertensive disorders of pregnancy.

The umbilical cord (UC) is a platform for fetal nourishment and growth. The fetus, mother and placenta with UC form a triad, which contributes to pregnancy outcome. When pregnancy is complicated by a medical condition like hypertension, affects both maternal and fetal health. Being a fetal structure it can be used as a window to know the maternal dysfunctions and their impacts on fetal wellbeing. The present study is to explore the histomorphometric changes of the UC and its vessels involved in the development of hypertension during pregnancy. Sixty UCs were used and the following parameters, total UC area; total vessel area; jelly area; wall area, luminal area and wall thickness of umbilical arteries 1 and 2 and vein were studied using ImageJ software. From the results, the mean differences of above parameters of hypertensive UCs were found to be lesser than control and it was significantly higher in cases of severe preeclampsia (P≤0.05). From the present study, we conclude hypertensive cords and its vessels are associated with significant structural changes. Since it is a global health issue it is important to know the factors contributing it to diagnose and prevent.

Evaluation of the sub-acute toxicity of Acacia catechu Willd seed extract in a Wistar albino rat model.

Acacia catechu (A. catechu) or Khair (Hindi) is used in several herbal preparations in the Ayurvedic system of medicine in India. Traditionally, this drug is beneficial against several gastrointestinal and stomach related ailments, and leprosy. The present investigation was carried out to evaluate the sub-acute oral toxicity of the ethanolic extract of A. catechu seeds in Wistar albino rats. Results obtained from the quantitative chemical analysis of A. catechu seed extract were compared with commercially available standards. A. catechu seed extract was administered orally at the doses of 250, 500 and 1000 mg/kg b.w. daily for 28 days. General behavior, bodyweight and mortality were examined during the entire study period. At the end of 28 days, hematological and biochemical parameters along with the relative organ weights were determined. It was observed that the extract did not induce death or any significant changes in the body weight, relative weight of vital organs and in hematological parameters for up to a dose of 1000 mg/kg. The oral administration of the plant extract did not produce any significant changes in the levels of glucose. In addition, there were no significant changes in the activity of both hepatotoxic and nephrotoxic marker enzymes in the serum. Oral administration of A. catechu also did not produce any significant changes in the levels of oxidative markers. Furthermore, the findings from the biochemical studies were, well corroborated with the histological findings.

Synthesis of manganese doped ß-FeOOH and MnFe2O4 nanorods for enhanced drug delivery and hyperthermia application.

Preparation of manganese ferrite (MnFe2O4) nanorods by the reduction of akaganeite seeds in the presence of oleylamine is reported. The Mn-doped ß-FeOOH akaganeite seeds have been processed by the hydrolysis of metal-chloride salts in the presence of polyethylenimine (PEI) surfactant. The hydrophobic oleylamine capped nanorods are made hydrophilic using trisodium citrate as a phase transferring agent. The nanorods form with an aspect ratio of 5.47 and possess a high magnetisation value of 69 emu/g at an applied magnetic field of 1.5 T. The colloidal water dispersion of nanorods exhibits superior heating efficiency by the application of alternating magnetic field (AMF). A specific absorption rate value of 798 W/g is achieved at an applied AMF of field strength 500 Oe and frequency 316 kHz. Further, the citrate functionalised nanorods are capable of attaching with doxorubicin (DOX) electrostatically with a loading efficiency of 97% and the drug release is pH responsive. The DOX loaded nanorods show a promising effect on the apoptosis of MCF-7 as experimented in vitro.

Safety Evaluation of Various Vector Repellents in Combination with Deltamethrin in Wistar Rats.

BACKGROUND: Vector repellents are used globally to avoid insect bites and control transmission of diseases. It is important to ensure safety levels of these compounds, although they are noxious to insects. Vector repellents when used in combination are known to bring additional benefits in getting rid of the harmful insects. Unfortunately, the safety levels of various vector repellents such as Deet (N,N-diethyl-m-toluamide), Depa (N,N-diethyl phenylacetamide), and Deb (N,N-diethylbenzamide) are not studied in combination with the widely used pyrethroid deltamethrin (Del). MATERIALS AND METHODS: In this study, safety evaluation of various vector repellents by oral route in combination with Del was studied by assessing body weight and organ weight changes, hematological parameters, and biochemical parameters in Wistar rats. RESULTS: The results revealed significant changes in liver marker enzymes in Del, Deb, Del + Depa, and Del + Deet groups. Urea levels were significantly altered after treatment with various repellents and in combination with Del, except Deb-alone group. Hematological and rest of the biochemical parameters were found to be unaltered in all the treatment groups. Significant changes in the liver weight were found in Deb, Depa, Deet, Del + Deb, and Del + Deet groups. CONCLUSIONS: Taken together, the overall results of this study indicate that single, high oral dose of various insect repellents did not show any additive toxicity.

A New Synergetic Nanocomposite for Dye Degradation in Dark and Light.

Environmental hazard caused due to the release of dyes in effluents is a concern in many countries. Among the various methods to combat this problem, Advanced Oxidation Process, in which semiconductor photocatalysts are used, is considered the most effective one. These materials release Reactive Oxygen Species (ROS) such as hydroxyl radical and superoxide in suspension that degrade the dyes into non-toxic minerals. However, this process requires visible or UV light for activation. Hence, there is a need to develop materials that release ROS, both in the absence and in the presence of light, so that the efficiency of dye removal is enhanced. Towards this objective, we have designed and synthesized a new nanocomposite ZnO2/polypyrrole which releases ROS even in the dark. The ROS released in the dark and in light were estimated by standard methods. It is to be noted that ZnO2 degrades the dye only under UV light but not in dark or in the presence of visible light. We propose the mechanism of dye degradation in dark and light. The synergically coupled nanocomposite of ZnO2/ppy is the first example that degrades dyes in the dark, through advanced oxidation process without employing additional reagents.

Therapeutic effect of bone marrow mesenchymal stem cells on cold stress induced changes in the hippocampus of rats.

The present study aims to evaluate the effect of bone marrow mesenchymal stem cells on cold stress induced neuronal changes in hippocampal CA1 region of Wistar rats. Bone marrow mesenchymal stem cells were isolated from a 6-week-old Wistar rat. Bone marrow from adult femora and tibia was collected and mesenchymal stem cells were cultured in minimal essential medium containing 10% heat-inactivated fetal bovine serum and were sub-cultured. Passage 3 cells were analyzed by flow cytometry for positive expression of CD44 and CD90 and negative expression of CD45. Once CD44 and CD90 positive expression was achieved, the cells were cultured again to 90% confluence for later experiments. Twenty-four rats aged 8 weeks old were randomly and evenly divided into normal control, cold water swim stress (cold stress), cold stress + PBS (intravenous infusion), and cold stress + bone marrow mesenchymal stem cells (1 × 10(6); intravenous infusion) groups. The total period of study was 60 days which included 1 month stress period followed by 1 month treatment. Behavioral functional test was performed during the entire study period. After treatment, rats were sacrificed for histological studies. Treatment with bone marrow mesenchymal stem cells significantly increased the number of neuronal cells in hippocampal CA1 region. Adult bone marrow mesenchymal stem cells injected by intravenous administration show potential therapeutic effects in cognitive decline associated with stress-related lesions.

Preclinical investigation of the pharmacokinetics, metabolism, and protein and red blood cell binding of DRDE-07: a prophylactic agent against sulphur mustard

DRDE-07, a newly synthesized amifostine analog currently under clinical investigation in a phase I trial, is a potent antidote against sulfur mustard toxicity. The purpose of this research was to evaluate the pharmacokinetic profile of DRDE-07 in female Swiss Albino mice after a single oral dose of 400 or 600 mg/kg. The physicochemical properties of DRDE-07, including solubility, pK a, Log P, plasma protein binding and plasma/blood partitioning, were determined to support the pharmacokinetic characterization. DRDE-07 concentration was determined by an HPLC-UV method. The profile of plasma concentration versus time was analyzed using a non-compartmental model. Plasma protein binding was assessed using ultrafiltration. DRDE-07 appeared rapidly in plasma after oral administration with peak plasma levels (C max) observed in less than 15 min. There was a rapid decline in the plasma levels followed by a smaller second peak about 90 min after dosing. The plasma protein binding of DRDE-07 was found to be less than 25% at all concentrations studied. Plasma clearance of DRDE-07 is expected to be ~1.5 fold higher than the blood clearance of DRDE-07. The probable metabolite of DRDE-07 was identified as phenyl-S-ethyl amine.

Fatal small bowel ischaemia following laparoscopic cholecystectomy: report of a case.

Veress needle, trocar insertion, pneumoperitoneum-related complications, biliary injuries apart from haemorrhage, intestinal injuries and lateral thermal injuries are all well described entities following laparoscopic cholecystectomy. The development of intestinal ischaemia following laparoscopic cholecystectomy is rare; this report describes a case of fatal small bowel ischaemia following laparoscopic cholecystectomy and discusses the various possibilities that led to this event.