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Abstract: The antimicrobial and antiplasmid activities of essential oils (orange oil, eucalyptus oil, fennel oil, geranium oil, juniper oil, peppermint oil, rosemary oil, purified turpentine oil, thyme oil, Australian tea tree oil) and of menthol, the main component of peppermint oil, were investigated. The antimicrobial activities were determined on the Gram (+) Staphylococcus epidermidis and the Gram (−) Escherichia coli F''lac K12 LE140, and on two yeast Saccharomyces cerevisiae 0425 δ/1 and 0425 52C strains. The antiplasmid activities were investigated on E. coli F''lac bacterial strain. Each of the oils exhibited antimicrobial activity and three of them antiplasmid action. The interaction of peppermint oil and menthol with the antibiotics was studied on the same bacterial strain with the checkerboard method. Peppermint oil and menthol displayed additive synergy with oxytetracycline. A new mechanism of plasmid curing was established for one of the oil components. [Copyright &y& Elsevier]

Exposing a healthy wound bed for skin grafting is an important step during burn surgery to ensure graft take and maintain good functional outcomes. Currently, the removal of non-viable tissue in the burn wound bed during excision is determined by expert clinician judgment. Using a porcine model of tangential burn excision, we investigated the effectiveness of an intraoperative multispectral imaging device combined with artificial intelligence to aid clinician judgment for the excision of non-viable tissue. Multispectral imaging data was obtained from serial tangential excisions of thermal burn injuries and used to train a deep learning algorithm to identify the presence and location of non-viable tissue in the wound bed. Following algorithm development, we studied the ability of two surgeons to estimate wound bed viability, both unaided and aided by the imaging device. The deep learning algorithm was 87% accurate in identifying the viability of a burn wound bed. When paired with the surgeons, this device significantly improved their abilities to determine the viability of the wound bed by 25% (p = 0.03). Each time a surgeon changed their decision after seeing the AI model output, it was always a change from an incorrect decision to excise more tissue to a correct decision to stop excision. This study provides insight into the feasibility of image-guided burn excision, its effect on surgeon decision making, and suggests further investigation of a real-time imaging system for burn surgery could reduce over-excision of burn wounds. • Study demonstrates usefulness of an imaging device in providing surgical guidance to aid clinicians in burn excision. • Multispectral imaging and artificial intelligence correctly identified the viable and non-viable wound bed. • Multispectral imaging and artificial intelligence helped surgeons stop at the correct depth during burn excision surgery. • Multispectral imaging and artificial intelligence could eventually provide reliable guidance during burn surgery. [ABSTRACT FROM AUTHOR]

The ability as P-glycoprotein (P-gp, ABCB1) modulators of thirty ( 1 – 30 ) triterpenoids of the cucurbitane-type was evaluated on human L5178 mouse T-lymphoma cell line transfected with the human MDR1 gene, through the rhodamine-123 exclusion assay. Compounds ( 1 – 26 , and 29 , 30 ) were previously obtained from the African medicinal plant Momordica balsamina , through both isolation ( 1 – 15 ) and molecular derivatization ( 16 – 26 and 29 , 30 ). Compounds 27 – 28 are two new karavilagenin C ( 34 ) derivatives having succinic acid moieties. Apart from 4 , 6 , 8 , 10 and 11 , most of the isolated compounds ( 1 – 15 ) displayed strong MDR reversing activity in a dose-dependent mode, exhibiting a many-fold activity when compared with verapamil, used as positive control. At the lowest concentration tested, compounds 2 and 7 were the most active. However, a decrease of activity was found for the acyl derivatives ( 16 – 30 ). In a chemosensitivity assay, the MDR reversing activity of some of the most active compounds ( 1 – 3 , 5 , 7 , 12 – 15 ) was further assessed on the same cell model. All the tested compounds, excepting 15 , corroborated the results of the transport assay, revealing to synergistically interact with doxorubicin. Structure–activity relationship studies, taking into account previous results, showed that different substitution patterns, at both the tetracyclic nucleus and the side chain, play important role in ABCB1 reversal activity. An optimal lipophilicity was also recognized. [ABSTRACT FROM AUTHOR]

Background: In many parts of the world, hydrotherapy plays an important role in the management of patients with wounds including burns. Different centers practice hydrotherapy differently. At the University Teaching Hospital in Lusaka, Zambia, burn patients use a common bathtub for cleaning their wounds which theoretically increases the risk of cross-infection, an important source of morbidity and mortality. There is currently no evidence that hydrotherapy as practiced at our institution leads to cross infection among patients with burns.Objective: The objective was to determine if our hydrotherapy practice and water plays a role in cross-infection and what organisms cause this infection.Methods: This was a prospective analytical study. Patients meeting the selection criteria were recruited. Swabs from the burn wounds were collected on admission (day 0), day 4 and day 7. Weekly swabs of the bathtub were also collected, after the tub had been cleaned and declared ready for the next patient. Weekly water samples were also collected. Selected results, for Staphylococcus aureus and Klebsiella pneumoniae, were subjected to further analysis and PCR. Results were analyzed using statistics software, SPSS version 23.Results: In this study, there were 96 participants of which 51 (53.1%) were males and 45 (46.9%) were females. Age distribution ranged from 5months to 91 years. The modal age range was 1 to 2 years. The modal burn percentage was 6%-10%, followed by 11%-15%. Hot water was the cause of burns in 65.6%. S. aureus and K. pneumoniae were the most common organisms isolated. Others were enteric organisms. In terms of readily available antibiotics, there was more sensitivity to Amikacin and Chloramphenicol than Ciprofloxacin (our commonly used antibiotic). The bathtub also had S. aureus and K. pneumoniae, besides enteric organisms. Sixty five point four percent (65.4%) of the Klebsiella were ESBL (Extended Spectrum Beta Lactamase) producers. The tub had samples that were both ESBL producers as well as widely resistant Klebsiella by other means. No growth was obtained from the water samples. Seventy-two point nine percent (72.9%) of the patients were discharged, 19.8% died, while 7.3% left against medical advice.Conclusion: Hydrotherapy as currently practiced at the University Teaching Hospital does contribute significantly to cross-infection among burn patients with widely resistant organisms. The main ones are S. aureus and K. pneumoniae. Switching care to a shower mechanism might help eliminate this problem as the study demonstrates that no bacteria were found in the water samples. [ABSTRACT FROM AUTHOR]

Aiming at overcoming multidrug resistance (MDR) in cancer, we have been studying Momordica balsamina, a vegetable known as African pumpkin. Five undescribed cucurbitane-type triterpenoids (balsaminaepoxide, balsaminatriol, balsaminoic acid, balsaminal, and balsaminol G) along with five known cucurbitacins were isolated from the methanol extract of Momordica balsamina aerial parts, whose structures were elucidated by spectroscopic data, mainly 1D and 2D NMR experiments. Compounds were evaluated for their ability as P-glycoprotein (P-gp/ABCB1) inhibitors in multidrug resistant human ABCB1 -transfected mouse lymphoma cells (L5178Y, MDR) and resistant human colon adenocarcinoma cells (COLO 320), using the rhodamine-123 exclusion test, by flow cytometry. Several compounds, which were found to be non-cytotoxic, strongly inhibited P-gp efflux activity in a dose-dependent manner in both cell models. In MRD mouse lymphoma cells, balsaminol G and karavilagenin B were the most active, while in resistant colon adenocarcinoma cells, the strongest inhibitory activity was found for balsaminaepoxide, balsaminatriol and karavilagenin C, being several-fold more active than the positive control verapamil. In chemosensitivity assays, in a model of combination chemotherapy, selected compounds showed to interact synergistically with doxorubicin, thus substantiating their potential as MDR reversers. The strongest synergistic interaction was found for balsaminal and balsaminol G. Five undescribed cucurbitane-type triterpenoids along with five known cucurbitacins were isolated from Momordica balsamina. Some compounds strongly inhibited P-gp efflux activity and interacted synergistically with doxorubicin. [Display omitted] • Ten cucurbitacins, including five undescribed, were isolated from Momordica balsamina. • Their structures were elucidated mainly by 1D and 2D NMR experiments. • They were evaluated as MDR reversers, by transport and chemosensitivity assays. • Some compounds strongly inhibited P-gp efflux activity, in a dose-dependent manner. • Selected compounds interacted synergistically with the anticancer drug doxorubicin. [ABSTRACT FROM AUTHOR]

A series of amine derivatives of 5-aromatic imidazolidine-4-ones ( 7–19 ), representing three subgroups: piperazine derivatives of 5-arylideneimidazolones ( 7 – 13 ), piperazine derivatives of 5-arylideneimidazolidine-2,4-dione ( 14 – 16 ) and primary amines of 5-naphthyl-5-methylimidazolidine-2,4-diones ( 17 – 19 ), was evaluated for their ability to improve antibiotics effectiveness in two strains of Gram-positive Staphylococcus aureus : ATCC 25923 (a reference strain) and MRSA (methicillin resistant S. aureus ) HEMSA 5 (a resistant clinical isolate). The latter compounds ( 17–19 ) were obtained by 4-step synthesis using Bucherer-Bergs condensation, two-phase bromoalkylation and Gabriel reactions. The naphthalen derivative: (Z)-5-(naphthalen-2-ylmethylene)-2-(piperazin-1-yl)-3H-imidazol-4(5H)-one ( 10 ) was the most potent in combination with β-lactam antibiotics and ciprofloxacin against the resistant strain. The high potency to increase efficacy of oxacillin was noted for (Z)-5-(anthracen-10-ylmethylene)-2-(piperazin-1-yl)-3H-imidazol-4(5H)one ( 12 ) too. In order to explain the mechanism of action of the compounds 10 and 12 , docking studies with the use of crystal structures of a penicillin binding protein (PBP2a) and MecR1 were carried out. Their outcomes suggested that the most probable mechanism of action of the active compounds is the interaction with MecR1. Molecular dynamic experiments performed for the active compounds and compound 13 (structurally similar to 12 ) supported this hypothesis and provided possible explanation of activity dependencies of the tested compounds in terms of the restoration of antibiotic efficacy in S. aureus MRSA HEMSA 5. [ABSTRACT FROM AUTHOR]

Following the identification of a novel polycyclic scaffold, leading to the previously reported potent P-gp modulator 1 , a small series of easily affordable derivatives bearing a properly selected nitrogen-containing but-2-ynyl side chain was now synthesized and tested to evaluate the MDR reverting activity on two different experimental models. All compounds proved not to be cytotoxic when tested alone and more potent chemosensitizers than the reference verapamil. Some of them showed remarkable effects in combination with doxorubicin, being able to induce apoptotic cell death due to their reverting activity. In particular, 2a and 2c could be regarded as non-toxic new potential chemosensitizers, being able to interfere with different ABC proteins. Moreover, the intrinsic cytotoxicity of compound 1 could broaden its employment as MDR modulator. These results also seem to confirm the polycyclic core of these compounds as a potential new pharmacophoric carrier in medicinal chemistry. [ABSTRACT FROM AUTHOR]

Abstract: Alkaloids comprise one of the largest groups of plant secondary metabolites including vinca alkaloids. The ability of six alkaloids from Veratrum lobelianum, one from Veratrum nigrum and three from Peganum nigellastrum to modify transport activity of MDR1 was studied. Flow-cytometry in a multidrug-resistant human MDR1-gene-transfected mouse lymphoma cells (L5178Y) was applied. The inhibition of multidrug resistance was investigated by measuring the accumulation of rhodamine-123 in cancer cells. Veralosinine and veranigrine were the most effective resistance modifiers. In a checkerboard method veralosinine and veranigrine enhanced the antiproliferative effects of doxorubicin on MDR cells in combination. The structure–activity relationships were discussed. [Copyright &y& Elsevier]

Abstract: Multidrug-resistant and extensively drug-resistant tuberculosis (MDR/XDR-TB) are problematic to manage, especially in patients with acquired immune deficiency syndrome (AIDS). There is therefore a dire need for effective anti-MDR/XDR-TB agents. We have previously shown that agents that inhibit the efflux pumps of MDR bacteria and cancer cells also enhance killing of intracellular mycobacteria, possibly by increasing the availability of K+ and Ca2+ needed for the activation of lysosomal enzymes of the phagolysosomal unit. In this study, the newly synthesised and recently patented SILA 409 and 421 were tested for in vitro and ex vivo activity against XDR-TB. The minimum inhibitory concentration (MIC) of SILA compounds was determined by the BACTEC 460 TB system. The effect of each compound on the killing activity of human macrophages infected with XDR-TB was determined by exposing the macrophage that had phagocytosed the bacterium to the compounds and assessing the killing activity by colony-forming unit counting. Amongst the two compounds tested, SILA 421 was shown to have in vitro activity against XDR-TB (MIC<3.5mg/L) and to transform non-killing macrophages into effective killers of phagocytosed bacteria, without any cytotoxic activity. Because SILA 421 revealed good in vitro and ex vivo activities and is devoid of any cytotoxic activity, it is a potential candidate as an anti-MDR/XDR-TB drug. [Copyright &y& Elsevier]

Abstract: The levee pond is by far the most popular pond type for fish production. The specific object of this study was to develop a tool enabling extension, nongovernmental organization (NGO) agents, contractors and engineers in developing countries for computing levee pond excavation costs. We developed a spreadsheet-based computational tool in English and Spanish on the Microsoft Excel® platform. Knowing the original land slope and desired pond volume, one may compute excavation amounts that provide an acceptable cut-fill estimates based on a comparison with AutoCAD Civil 3-d®. The model computes projected costs in user-selected currency. Guidelines are provided for establishing pond bottom elevations and achieving the desired water depth. The model is relevant for small to medium sized levee ponds customarily used in aquacultural production in developing countries. [Copyright &y& Elsevier]

Abstract: Multidrug resistance in Gram-negative bacteria is now known to be primarily caused by overexpression of efflux pumps that extrude unrelated antibiotics from the periplasm or cytoplasm of the bacterium prior to their reaching their intended target. This review focuses on a variety of agents that have been shown to be efflux pump inhibitors (EPIs) and which, if used as ‘helper compounds’ in combination with antibiotics to which the organism is initially resistant, may produce the required cure. Although not all of the EPIs may serve a helper role owing to their toxicity, they may nevertheless serve as lead compounds. [Copyright &y& Elsevier]

Abstract: Diclofenac sodium (Dc), an anti-inflammatory agent, has remarkable inhibitory action both against drug-sensitive and drug-resistant clinical isolates of various Gram-positive and Gram-negative bacteria. The aim of this study was to determine the ability of Dc to protect mice from a virulent Salmonella infection. Dc injected at 1.5μg/g and 3.0μg/g mouse body weight significantly protected animals from the lethality of Salmonella infection. As was the case for the in vitro interaction, Dc in combination with streptomycin was even more effective. The non-antibiotic drug Dc has potential for the management of problematic antibiotic-resistant bacterial infections. [Copyright &y& Elsevier]

Abstract: Deoxynivalenol (DON) or Vomitoxin is the dominant toxin produced by Fusarium fungi, and is a tetracyclic sesquiterpenoid compound (C15H20O6). The structure of DON, containing seven stereo centers, is fully characterized. The molecule contains six oxygen atoms consisting of three alcoholic OH groups, a carbonyl, a cyclic ether and an epoxide which would allow for multiple hydrogen bondings. These possibilities were investigated quantum mechanically at the Density Functional [B3LYP/6-31G(d)] level of theory. Two functional groups of DON, a conjugated carbonyl and an epoxide may be related to its toxic effects. [Copyright &y& Elsevier]

Abstract: The Carpobrotus edulis methanol extract, inactive against the methicillin-resistant-Staphylococcus aureus or the multidrug-resistant Mycobacterium tuberculosis, does inhibit the growth of these two bacteria once they are phagocytosed by monocyte derived human macrophages. [Copyright &y& Elsevier]

Variable rainfall distribution and terrain make surface water harvesting and storage a challenge in many developing countries. The overall goal of this study is to collect and develop information required to equip extension, non-governmental organization (NGO) agents, contractors and engineers for surface water development and aquaculture enterprise development in Honduras and Latin America. A pond water balance for the levee production pond enabling determination of water flow required to balance seepage, evaporation and direct rainfall was developed in English and Spanish on the Microsoft Excel® platform. The pump-in flow rate can also be determined for reaching a volume change per month target. A second model was formulated for evaluating surface water capture by watershed and/or hillside ponds for meeting the levee pond demand. Using hillside ponds that fill by impounding a fraction of total runoff (e.g., diverting water upstream) from streams appears to have promise for meeting water needs. A systematic approach using both models to reach a sustainable water supply target emerged from this work. Both the levee pond model and the water harvest model are based on balancing inputs and outputs given monthly rainfall patterns. A simple approach to mechanical spillways preliminary design was developed. The models are adaptable to any location if key input data is available, particularly average monthly rainfall and storm frequency–duration data. The models do not address water quality issues. The software is intended for watershed sizes not larger than 500 ha and storage ponds of less than 5 ha surface area—4 m depth due to relationship limitations and safety concerns. Coupling with other cooperative development concerns such as marketing association provides a platform for helping groups of people in a watershed to realize further the potential of enlightened self-interest in developing common solutions to water problems. [Copyright &y& Elsevier]

Abstract: Thioridazine (TZ) has previously been shown by us to have in vitro and ex vivo activity against antibiotic-susceptible and multidrug-resistant Mycobacterium tuberculosis (MDRTB). Because current therapy of MDRTB is highly problematic even when all five ‘first line of defence’ drugs are employed, there is a need for effective antituberculosis drugs. New derivatives of TZ were synthesised and their in vitro activity against a reference strain of M. tuberculosis was evaluated with the aid of the BACTEC 460 system. Derivatives that presented significant activity were evaluated by ex vivo studies and were shown to enhance the killing of intracellular M. tuberculosis. [Copyright &y& Elsevier]

We previously reported that a trifluoromethyl ketone derivative, 1-(2-benzoxazolyl)-3,3,3-trifluoro-2-propanone (TF18), exhibited the potent antibacterial activity against Helicobacter pylori, but had no urease activity. In order to clarify the mechanism of anti-H. pylori action of TF18, we evaluated the growth and motility of TF18 on clarithromycin-susceptible H. pylori (CSHP) and -resistant H. pylori (CRHP). An effective proton pump inhibitor (TF18) had remarkable dose-dependent antibacterial activity and was able to inhibit the flagellar motor of both CSHP and CRHP isolates. The antimotility effect of TF18 was more pronounced at subinhibitory concentration in CRHP than in CSHP. The swimming (the forward motion) was more sensitive to the inhibition than the tumbling. Based on the results, it is supposed that TF18 works as an uncoupler similar to the ‘clutch’ in a biological motor, in which counterclockwise rotation is more sensitive to the effect of TF18 than the clockwise rotation. [Copyright &y& Elsevier]

Tannerite(®) is a proprietary blend of an oxidizer, ammonium nitrate, and aluminum powder catalyst used to make homemade exploding targets. While it is currently approved for unrestricted sale in the United States, it can be used to form devices capable of inflicting major blast injury. We present here a case of close proximity exposure to detonation of the mixed Tannerite(®) blend. In our patient, the exposure lead to injuries typical of blast injury, such as tympanic membrane rupture, globe injury, and severe burns. We review here the sequelae of blast injuries that one must consider when treating a patient with close proximity exposure to Tannerite, with considerations unique to this product. [ABSTRACT FROM AUTHOR]