Chelation of Zinc with Biogenic Amino Acids: Description of Properties Using Balaban Index, Assessment of Biological Activity on Spirostomum Ambiguum Cellular Biosensor, Influence on Biofilms and Direct Antibacterial Action.

The complexation of biogenic molecules with metals is the widespread strategy in screening for new pharmaceuticals with improved therapeutic and physicochemical properties. This paper demonstrates the possibility of using simple QSAR modeling based on topological descriptors for chelates study. The presence of a relationship between the structure (J) and lipophilic properties (logP) of zinc complexes with amino acids, where two molecules coordinate the central atom through carboxyl oxygen and amino group nitrogen, and thus form a double ring structure, was predicted. Using a cellular biosensor model for Gly, Ala, Met, Val, Phe and their complexes Zn(AA)2, we experimentally confirmed the existence of a direct relationship between logP and biological activity (Ea). The results obtained using topological analysis, Spirotox method and microbiological testing allowed us to assume and prove that the chelate complex of zinc with methionine has the highest activity of inhibiting bacterial biofilms, while in aqueous solutions it does not reveal direct antibacterial effect.

Antibacterial Activity of Medicinal Plants against Uropathogenic Escherichia coli.

Urinary tract infections (UTIs) are one of the most common bacterial infections with uropathogenic Escherichia coli (UPEC) being the most prevalent causative agent in both complicated and uncomplicated UTIs. Antibiotic resistance among UPEC has been already demonstrated against a wide variety of antibiotics and the situation is continuing to deteriorate increasing the rate of recurrence and the difficulty of treatment and prophylaxis. Recently, a big attention has been paid to non-antibiotic approaches as an alternative to conventional antibiotics. Among many strategies, phytotherapy has gained a special attention worldwide. Herbal remedies have been used in traditional medicine since ancient times and they are well known for their effectiveness in treating many health conditions including UTIs. Researches are conducted continuously to validate the use of many medicinal plants against UPEC, investigate their mechanisms of action, and determine their active constituents. Our extensive review of the recent literature revealed that many phytochemicals are shown to target and inhibit a wide variety of bioprocesses in UPEC, such as adhesion, motility, biofilm formation, and quorum sensing. Such natural approaches are very promising in confronting the antibiotic resistance of UPEC and can be further used to develop plant-based strategies and pharmaceutical products to treat and prevent UTIs caused by UPEC.

A botanical from the antiproliferative Cameroonian spice, Imperata cylindrica is safe at lower doses, as demonstrated by oral acute and sub-chronic toxicity screenings.

BACKGROUND: The cytotoxicity of the root's methanol extract of Imperata cylindrica (ICR). was previously reported in a panel of human cancer cell lines, including multi-drug resistant phenotypes. The aim of this study was to assess the acute and sub-chronic oral toxicity of methanol root extract of Imperata cylindrica. METHODS: The acute toxicity was carried out according to the experimental protocol of OECD. The plant extract was administered orally to female rats at a single dose of 5000 mg/kg for 14 days and the animals were observed for any behavioral changes or mortality. For sub-chronic toxicity study, ICR was orally administered daily to male and female rats at different doses (250, 500 and 1000 mg/kg per b.w.) for 30 days. During these treatment days the animals were observed for any appearance of toxicity symptoms; following the treatment period, animals were sacrificed for hematological, biochemical and histopathology analysis. RESULTS: From the results of the acute oral toxicity assay, ICR was found to be non-toxic at the dose of 5000 mg/kg b.w. During the period of sub-chronic toxicity test, observation of signs, behavior and health status of the animals showed no abnormality in the groups of animals treated with ICR as compared to the controls. Significant variation of the relative body weights of heart and kidney were observed at dose a 1000 mg/kg b.w. Significant decrease of aspartate aminotransferase, creatinine level, low density lipoprotein concentration, triglyceride and total cholesterol were observed. In males, we noticed a significant decrease of the level of granulocytes with an increase of lymphocytes and mean corpuscular hemoglobin concentration levels. Histological examinations performed on kidney and liver showed a normal kidney architecture and liver also presented a normal hepatic architecture with slight degeneration at a dose 1000 mg/kg b.w. CONCLUSION: ICR is safe for acute oral administration; however, for long-term oral administration, safety measures should be taken. Thus, oral sub-chronic exposure of ICR at lower doses are recommended while higher doses around 1000 mg/kg b.w. should be discouraged.

The relationships between housing quality and occupant health in Uganda.

The Government of Uganda created in 2010 a strategic plan to invest in public health as part of its broader national development goals. The health plan recognizes housing and urbanization as a determinant of health, but has not yet formulated policy to address the relationship. This study can help guide health policy development as it relates to housing. It estimates relationships between housing quality and occupant health using "count outcome" regression models. An economic model of optimal household labor allocation in poor countries provides the foundation for the regression modeling. The data used to estimate the regressions are a stratified random sample of 7096 households surveyed in the 2005-06 Uganda National Household Survey. They provide, among other things, detailed information on physical housing attributes as well as the health status of its occupants. Consistent with the economic model and other empirical work, the results show that exposure to burning of biomass for cooking has the largest adverse health effect. Different definitions of illness yield results consistent with expectations, and a separate specification test suggests that the findings are reasonably robust.

The G1 phase Cdks regulate the centrosome cycle and mediate oncogene-dependent centrosome amplification.

Because centrosome amplification generates aneuploidy and since centrosome amplification is ubiquitous in human tumors, a strong case is made for centrosome amplification being a major force in tumor biogenesis. Various evidence showing that oncogenes and altered tumor suppressors lead to centrosome amplification and aneuploidy suggests that oncogenes and altered tumor suppressors are a major source of genomic instability in tumors, and that they generate those abnormal processes to initiate and sustain tumorigenesis. We discuss how altered tumor suppressors and oncogenes utilize the cell cycle regulatory machinery to signal centrosome amplification and aneuploidy.

Cdk2 and Cdk4 regulate the centrosome cycle and are critical mediators of centrosome amplification in p53-null cells.

The two mitotic centrosomes direct spindle bipolarity to maintain euploidy. Centrosome amplification-the acquisition of > or =3 centrosomes-generates multipolar mitoses, aneuploidy, and chromosome instability to promote cancer biogenesis. While much evidence suggests that Cdk2 is the major conductor of the centrosome cycle and that it mediates centrosome amplification induced by various altered tumor suppressors, the role played by Cdk4 in a normal or deregulated centrosome cycle is unknown. Using a gene knockout approach, we report that Cdk2 and Cdk4 are critical to the centrosome cycle, since centrosome separation and duplication are premature in Cdk2(-)(/)(-) mouse embryonic fibroblasts (MEFs) and are compromised in Cdk4(-)(/)(-) MEFs. Additionally, ablation of Cdk4 or Cdk2 abrogates centrosome amplification and chromosome instability in p53-null MEFs. Absence of Cdk2 or Cdk4 prevents centrosome amplification by abrogating excessive centriole duplication. Furthermore, hyperactive Cdk2 and Cdk4 deregulate the licensing of the centrosome duplication cycle in p53-null cells by hyperphosphorylating nucleophosmin (NPM) at Thr199, as evidenced by observations that ablation of Cdk2, Cdk4, or both Cdk2 and Cdk4 abrogates that excessive phosphorylation. Since a mutant form of NPM lacking the G(1) Cdk phosphorylation site (NPM(T199A)) prevents centrosome amplification to the same extent as ablation of Cdk2 or Cdk4, we conclude that the Cdk2/Cdk4/NPM pathway is a major guardian of centrosome dysfunction and genomic integrity.

Comparison of ceftazidime degradation in glass bottles and plastic bags under various conditions.

OBJECTIVE: To study the effect of type of container on ceftazidime stability in intravenous solutions. METHODS: One hundred millilitre polypropylene (PP) and polyvinyl chloride (PVC) bags and 100-mL glass bottles were filled with 5% dextrose or 0.9% sodium chloride solutions containing ceftazidime (Fortumset) at 40 mg/mL. Three containers of each solution were stored at 20 and 35 degrees C. One millilitre samples were drawn from each container at 0 and 20 h and assayed. Pyridine concentrations, the main degradation product of ceftazidime, were determined by high-pressure liquid chromatography. RESULTS: Pyridine levels increased during storage and were higher in PVC and PP bags than in glass bottles in both diluents. Solutions stored in PP bags showed better stability than in PVC bags. CONCLUSION: This study shows that ceftazidime undergoes slower degradation in PP than PVC containers although the difference is small. Glass bottles seems to be the better container for storing ceftazidime solutions, whatever storage temperature and diluent used.