Effect of ethnomedicinal plants used in folklore medicine in Jordan as antibiotic resistant inhibitors on Escherichia coli

<p>Abstract</p> <p>Background</p> <p><it>Escherichia coli </it>occurs naturally in the human gut; however, certain strains that can cause infections, are becoming resistant to antibiotics. Multidrug-resistant <it>E. coli </it>that produce extended-spectrum β lactamases (ESBLs), such as the CTX-M enzymes, have emerged within the community setting as an important cause of urinary tract infections (UTIs) and bloodstream infections may be associated with these community-onsets. This is the first report testing the antibiotic resistance-modifying activity of nineteen Jordanian plants against multidrug-resistant <it>E. coli</it>.</p> <p>Methods</p> <p>The susceptibility of bacterial isolates to antibiotics was tested by determining their minimum inhibitory concentrations (MICs) using a broth microdilution method. Nineteen Jordanian plant extracts (<it>Capparis spinosa </it>L., <it>Artemisia herba-alba Asso, Echinops polyceras </it>Boiss., <it>Gundelia tournefortii </it>L, <it>Varthemia iphionoides </it>Boiss. & Blanche, <it>Eruca sativa Mill</it>., <it>Euphorbia macroclada </it>L., <it>Hypericum trequetrifolium </it>Turra, <it>Achillea santolina </it>L., <it>Mentha longifolia </it>Host, <it>Origanum syriacum </it>L., <it>Phlomis brachydo</it>(Boiss.) Zohary, <it>Teucrium polium </it>L., <it>Anagyris foetida </it>L., <it>Trigonella foenum-graecum </it>L., <it>Thea sinensis </it>L., <it>Hibiscus sabdariffa </it>L., <it>Lepidium sativum </it>L., <it>Pimpinella anisum </it>L.) were combined with antibiotics, from different classes, and the inhibitory effect of the combinations was estimated.</p> <p>Results</p> <p>Methanolic extracts of the plant materials enhanced the inhibitory effects of chloramphenicol, neomycin, doxycycline, cephalexin and nalidixic acid against both the standard strain and to a lesser extent the resistant strain of <it>E. coli</it>. Two edible plant extracts (<it>Gundelia tournefortii L</it>. and <it>Pimpinella anisum L</it>.) generally enhanced activity against resistant strain. Some of the plant extracts like <it>Origanum syriacum </it>L.(Labiateae), <it>Trigonella foenum- graecum </it>L.(Leguminosae), <it>Euphorbia macroclada </it>(Euphorbiaceae) and <it>Hibiscus sabdariffa </it>(Malvaceae) did not enhance the activity of amoxicillin against both standard and resistant <it>E. coli</it>. On the other hand combinations of amoxicillin with other plant extracts used showed variable effect between standard and resistant strains. Plant extracts like <it>Anagyris foetida </it>(Leguminosae) and <it>Lepidium sativum </it>(Umbelliferae) reduced the activity of amoxicillin against the standard strain but enhanced the activity against resistant strains. Three edible plants; Gundelia <it>tournefortii </it>L. (Compositae) <it>Eruca sativa </it>Mill. (Cruciferae), and <it>Origanum syriacum </it>L. (Labiateae), enhanced activity of clarithromycin against the resistant <it>E. coli </it>strain.</p> <p>Conclusion</p> <p>This study probably suggests possibility of concurrent use of these antibiotics and plant extracts in treating infections caused by <it>E. coli </it>or at least the concomitant administration may not impair the antimicrobial activity of these antibiotics.</p

Assessing Susceptibility from Early-Life Exposure to Carcinogens

Cancer risk assessment methods currently assume that children and adults are equally susceptible to exposure to chemicals. We reviewed available scientific literature to determine whether this was scientifically supported. We identified more than 50 chemicals causing cancer after perinatal exposure. Human data are extremely limited, with radiation exposures showing increased early susceptibility at some tumor sites. Twenty-seven rodent studies for 18 chemicals had sufficient data after postnatal and adult exposures to quantitatively estimate potential increased susceptibility from early-life exposure, calculated as the ratio of juvenile to adult cancer potencies for three study types: acute dosing, repeated dosing, and lifetime dosing. Twelve of the chemicals act through a mutagenic mode of action. For these, the geometric mean ratio was 11 for lifetime exposures and 8.7 for repeat exposures, with a ratio of 10 for these studies combined. The geometric mean ratio for acute studies is 1.5, which was influenced by tissue-specific results [geometric mean ratios for kidney, leukemia, liver, lymph, mammary, nerve, reticular tissue, thymic lymphoma, and uterus/vagina > 1 (range, 1.6–8.1); forestomach, harderian gland, ovaries, and thyroid < 1 (range, 0.033–0.45)]. Chemicals causing cancer through other modes of action indicate some increased susceptibility from postnatal exposure (geometric mean ratio is 3.4 for lifetime exposure, 2.2 for repeat exposure). Early exposures to compounds with endocrine activity sometimes produce different tumors after exposures at different ages. These analyses suggest increased susceptibility to cancer from early-life exposure, particularly for chemicals acting through a mutagenic mode of action

PRISMA for abstracts: best practice for reporting abstracts of systematic reviews in Endodontology

An abstract is a brief overview of a scientific, clinical or review manuscript as well as a stand‐alone summary of a conference abstract. Scientists, clinician–scientists and clinicians rely on the summary information provided in the abstracts of systematic reviews to assist in subsequent clinical decision‐making. The Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) for Abstracts checklist was developed to improve the quality, accuracy and completeness of abstracts associated with systematic reviews and meta‐analyses. The PRISMA for Abstracts checklist provides a framework for authors to follow, which helps them provide in the abstract the key information from the systematic review that is required by stakeholders. The PRISMA for Abstracts checklist contains 12 items (title, objectives, eligibility criteria, information sources, risk of bias, included studies, synthesis of results, description of the effect, strength and limitations, interpretation, funding and systematic review registration) under six sections (title, background, methods, results, discussion, other). The current article highlights the relevance and importance of the items in the PRISMA for Abstracts checklist to the specialty of Endodontology, while offering explanations and specific examples to assist authors when writing abstracts for systematic reviews when reported in manuscripts or submitted to conferences. Strict adherence to the PRISMA for Abstracts checklist by authors, reviewers and journal editors will result in the consistent publication of high‐quality abstracts within Endodontology

An Analysis of Enzyme Kinetics Data for Mitochondrial DNA Strand Termination by Nucleoside Reverse Transcription Inhibitors

Nucleoside analogs used in antiretroviral treatment have been associated with mitochondrial toxicity. The polymerase-γ hypothesis states that this toxicity stems from the analogs' inhibition of the mitochondrial DNA polymerase (polymerase-γ) leading to mitochondrial DNA (mtDNA) depletion. We have constructed a computational model of the interaction of polymerase-γ with activated nucleoside and nucleotide analog drugs, based on experimentally measured reaction rates and base excision rates, together with the mtDNA genome size, the human mtDNA sequence, and mitochondrial dNTP concentrations. The model predicts an approximately 1000-fold difference in the activated drug concentration required for a 50% probability of mtDNA strand termination between the activated di-deoxy analogs d4T, ddC, and ddI (activated to ddA) and the activated forms of the analogs 3TC, TDF, AZT, FTC, and ABC. These predictions are supported by experimental and clinical data showing significantly greater mtDNA depletion in cell culture and patient samples caused by the di-deoxy analog drugs. For zidovudine (AZT) we calculated a very low mtDNA replication termination probability, in contrast to its reported mitochondrial toxicity in vitro and clinically. Therefore AZT mitochondrial toxicity is likely due to a mechanism that does not involve strand termination of mtDNA replication

Cancer Biomarker Discovery: The Entropic Hallmark

Background: It is a commonly accepted belief that cancer cells modify their transcriptional state during the progression of the disease. We propose that the progression of cancer cells towards malignant phenotypes can be efficiently tracked using high-throughput technologies that follow the gradual changes observed in the gene expression profiles by employing Shannon's mathematical theory of communication. Methods based on Information Theory can then quantify the divergence of cancer cells' transcriptional profiles from those of normally appearing cells of the originating tissues. The relevance of the proposed methods can be evaluated using microarray datasets available in the public domain but the method is in principle applicable to other high-throughput methods. Methodology/Principal Findings: Using melanoma and prostate cancer datasets we illustrate how it is possible to employ Shannon Entropy and the Jensen-Shannon divergence to trace the transcriptional changes progression of the disease. We establish how the variations of these two measures correlate with established biomarkers of cancer progression. The Information Theory measures allow us to identify novel biomarkers for both progressive and relatively more sudden transcriptional changes leading to malignant phenotypes. At the same time, the methodology was able to validate a large number of genes and processes that seem to be implicated in the progression of melanoma and prostate cancer. Conclusions/Significance: We thus present a quantitative guiding rule, a new unifying hallmark of cancer: the cancer cell's transcriptome changes lead to measurable observed transitions of Normalized Shannon Entropy values (as measured by high-throughput technologies). At the same time, tumor cells increment their divergence from the normal tissue profile increasing their disorder via creation of states that we might not directly measure. This unifying hallmark allows, via the the Jensen-Shannon divergence, to identify the arrow of time of the processes from the gene expression profiles, and helps to map the phenotypical and molecular hallmarks of specific cancer subtypes. The deep mathematical basis of the approach allows us to suggest that this principle is, hopefully, of general applicability for other diseases