Pharmacodynamic and Pharmacokinetic Studies on Tetracycline Hydrochloride in Rabbits

Tetracycline is one of the most important groups of antibiotics that have harmful effects on the consumers, therefore the public health safety against its residues represents a significant issue. This study aimed to estimate the effect of tetracycline hydrochloride on some hematological parameters, kidneys function tests as well as liver and breast muscle enzymes with special reference to the supposed withdrawal time of this drug in different rabbits’ tissues (kidney, liver and muscles), following oral dose of tetracycline using High Performance Liquid Chromatography. Tetracycline was administrated to eighteen rabbits directly into the stomach at a dose of 35 mg/kg BW once daily for five successive days. Samples were collected on the 1st, 3rd, 7th, 14th, 21st and 28th days after the last oral dose. The results revealed that, tetracycline caused a significant increase in the uric acid, urea, creatinine, alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatine phosphokinase (CPK) and lactate dehydrogenase (LDH) activities with no significant changes in the hematological parameters when compared with the control group. The residues remained in the liver and kidney for 7 days, while in muscles for 3 days only after the last oral dose of the drug. In conclusion, the disturbances in the biological parameters occurred by tetracycline administration in rabbits was transient and returned to normal after 7 days of last treatment. The withdrawal time of tetracycline was 14 days from the rabbit's tissues

ADSORBABILITY OF “TALPUS-RO” AND “TALPUS-KK” MOULD

The adsorption activity of the “Talpus-RO” and “Talpus-KK” mould for methylene blue, and its sorptive capacity for various metal cations is investigated. The possibility of further utilization of waste materials is shown

Amyloid fibril formation by macrophage migration inhibitory factor

We demonstrate herein that human macrophage migration inhibitory factor (MIF), a pro-inflammatory cytokine expressed in the brain and not previously considered to be amyloidogenic, forms amyloid fibrils similar to those derived from the disease associated amyloidogenic proteins beta-amyloid and alpha-synuclein. Acid denaturing conditions were found to readily induce MIF to undergo amyloid fibril formation. MIF aggregates to form amyloid-like structures with a morphology that is highly dependent on pH. The mechanism of MIF amyloid formation was probed by electron microscopy, turbidity, Thioflavin T binding, circular dichroism spectroscopy, and analytical ultracentrifugation. The fibrillar structures formed by MIF bind Congo red and exhibit the characteristic green birefringence under polarized light. These results are consistent with the notion that amyloid fibril formation is not an exclusive property of a select group of amyloidogenic proteins, and contribute to a better understanding of the factors which govern protein conformational changes and amyloid fibril formation in vivo

Structural and Functional Insights into the Pilotin-Secretin Complex of the Type II Secretion System

Gram-negative bacteria secrete virulence factors and assemble fibre structures on their cell surface using specialized secretion systems. Three of these, T2SS, T3SS and T4PS, are characterized by large outer membrane channels formed by proteins called secretins. Usually, a cognate lipoprotein pilot is essential for the assembly of the secretin in the outer membrane. The structures of the pilotins of the T3SS and T4PS have been described. However in the T2SS, the molecular mechanism of this process is poorly understood and its structural basis is unknown. Here we report the crystal structure of the pilotin of the T2SS that comprises an arrangement of four α-helices profoundly different from previously solved pilotins from the T3SS and T4P and known four α-helix bundles. The architecture can be described as the insertion of one α-helical hairpin into a second open α-helical hairpin with bent final helix. NMR, CD and fluorescence spectroscopy show that the pilotin binds tightly to 18 residues close to the C-terminus of the secretin. These residues, unstructured before binding to the pilotin, become helical on binding. Data collected from crystals of the complex suggests how the secretin peptide binds to the pilotin and further experiments confirm the importance of these C-terminal residues in vivo

Two-Photon Microscopy for Non-Invasive, Quantitative Monitoring of Stem Cell Differentiation

BACKGROUND: The engineering of functional tissues is a complex multi-stage process, the success of which depends on the careful control of culture conditions and ultimately tissue maturation. To enable the efficient optimization of tissue development protocols, techniques suitable for monitoring the effects of added stimuli and induced tissue changes are needed. METHODOLOGY/PRINCIPAL FINDINGS: Here, we present the quantitative use of two-photon excited fluorescence (TPEF) and second harmonic generation (SHG) as a noninvasive means to monitor the differentiation of human mesenchymal stem cells (hMSCs) using entirely endogenous sources of contrast. We demonstrate that the individual fluorescence contribution from the intrinsic cellular fluorophores NAD(P)H, flavoproteins and lipofuscin can be extracted from TPEF images and monitored dynamically from the same cell population over time. Using the redox ratio, calculated from the contributions of NAD(P)H and flavoproteins, we identify distinct patterns in the evolution of the metabolic activity of hMSCs maintained in either propagation, osteogenic or adipogenic differentiation media. The differentiation of these cells is mirrored by changes in cell morphology apparent in high resolution TPEF images and by the detection of collagen production via SHG imaging. Finally, we find dramatic increases in lipofuscin levels in hMSCs maintained at 20% oxygen vs. those in 5% oxygen, establishing the use of this chromophore as a potential biomarker for oxidative stress. CONCLUSIONS/SIGNIFICANCE: In this study we demonstrate that it is possible to monitor the metabolic activity, morphology, ECM production and oxidative stress of hMSCs in a non-invasive manner. This is accomplished using generally available multiphoton microscopy equipment and simple data analysis techniques, such that the method can widely adopted by laboratories with a diversity of comparable equipment. This method therefore represents a powerful tool, which enables researchers to monitor engineered tissues and optimize culture conditions in a near real time manner

An Anomalous Type IV Secretion System in Rickettsia Is Evolutionarily Conserved

Bacterial type IV secretion systems (T4SSs) comprise a diverse transporter family functioning in conjugation, competence, and effector molecule (DNA and/or protein) translocation. Thirteen genome sequences from Rickettsia, obligate intracellular symbionts/pathogens of a wide range of eukaryotes, have revealed a reduced T4SS relative to the Agrobacterium tumefaciens archetype (vir). However, the Rickettsia T4SS has not been functionally characterized for its role in symbiosis/virulence, and none of its substrates are known.Superimposition of T4SS structural/functional information over previously identified Rickettsia components implicate a functional Rickettsia T4SS. virB4, virB8 and virB9 are duplicated, yet only one copy of each has the conserved features of similar genes in other T4SSs. An extraordinarily duplicated VirB6 gene encodes five hydrophobic proteins conserved only in a short region known to be involved in DNA transfer in A. tumefaciens. virB1, virB2 and virB7 are newly identified, revealing a Rickettsia T4SS lacking only virB5 relative to the vir archetype. Phylogeny estimation suggests vertical inheritance of all components, despite gene rearrangements into an archipelago of five islets. Similarities of Rickettsia VirB7/VirB9 to ComB7/ComB9 proteins of epsilon-proteobacteria, as well as phylogenetic affinities to the Legionella lvh T4SS, imply the Rickettsiales ancestor acquired a vir-like locus from distantly related bacteria, perhaps while residing in a protozoan host. Modern modifications of these systems likely reflect diversification with various eukaryotic host cells.We present the rvh (Rickettsiales vir homolog) T4SS, an evolutionary conserved transporter with an unknown role in rickettsial biology. This work lays the foundation for future laboratory characterization of this system, and also identifies the Legionella lvh T4SS as a suitable genetic model

Coronary Artery Bypass Grafting (CABG) versus Percutaneous Coronary Intervention (PCI) in treatment of left main coronary artery disease

BackgroundCoronary artery bypass graft surgery (CABG) has been widely used for left main coronary artery disease (LMCAD). Percutaneous coronary intervention (PCI) has become an option for this condition.AimsTo summarize the current evidence that compare between CABG vs. PCI in regards to ‎cardiac death, stroke, and myocardial infarction.‎Methods We searched randomized trials of treatment of LMCAD with PubMed, Google Scholar, and EBSCO.Results Five randomized studies were retrieved, which compared the efficacy between CABG vs. PCI in treatment of LMCAD.ConclusionPCI may be reasonable management of patients with LM stenosis involving distal bifurcation or with coexisting multivessel disease

Gender Awareness in Healthcare: Contextualization of an Arabic Version of the Nijmegen Gender Awareness in Medicine Scale (N-GAMS)

Gender is one of the important social determinants of health known to be highly associated with health status. Despite the importance of gender awareness, it has not been addressed and researched in the Arab region, including Palestine. This study aimed to contextualize an Arabic version of the Nijmegen Gender Awareness in Medicine Scale (N-GAMS) and to assess the level of gender awareness and its associated factors among primary health care providers. The N-GAMS tool was translated and adapted through a gender expert consultation and a focus group discussion. Then, it was administered online to a sample of primary health care general physicians and nurses of all health care providing actors in Ramallah and al-Bireh Governorate. The reliability of the N-GAMS subscales using Cronbach’s alpha (α) was 0.681 for the gender sensitivity (GS) scale (9 items), 0.658 for the gender role ideology towards co-workers (GRIC) scale (6 items), and α = 0.848 for the gender role ideology towards patients (GRIP) scale (11 items). The results showed that participants had scored near the midpoint of the gender sensitivity subscale (M = 2.84, SD = 0.486). They also expressed moderate gender stereotypes towards patients (M = 3.11, SD = 0.624), where females held lower stereotypical thinking. Participants also expressed low to moderate stereotypes towards co-workers (M = 2.72, SD = 0.660) and females expressed less stereotypical thinking compared to males. Furthermore, the participant’s age had some effect on the outcome, specifically on the GRIP subscale, while gender was associated with both GRIP and GRID subscales. The rest of the social and other variables showed no association with the gender awareness subscales. This study adds to our understanding of gender awareness. Further tests are required to confirm the psychometric qualities of the instrument