Level Of Potency Research Articles

Form and content of Jamaican cannabis edibles

BackgroundIn 2017, the Jamaican government banned the sale of cannabis-infused edibles after reports of over-intoxication in adults and children. There is a general lack of public awareness regarding the risk involved with edible dosage. Vandrey et al. in 2015 reported that random cannabis edibles sampled from dispensaries in California and Washington in the USA failed to meet the basic labeling standards for pharmaceuticals (Vandrey et al.; JAMA 2015). This study aims to measure the levels of THC and CBD in a variety of edibles available locally in order to establish current cannabinoid content and to report on safety and packaging. This study is deemed necessary as no such study has been done to measure the potency levels of edibles and to raise awareness of the potential risk to children.MethodsForty-five cannabis-infused edible items were collected as convenience samples over a 4-year period (2014–2018) and analyzed. The QuEChERS technique (modified) was used to extract cannabinoids from each item. The extracts were then derivatized with MSTFA prior to analysis by gas chromatography-mass spectrometry (GC-MS). The descriptive statistics were calculated using the Statistical Package for Social Sciences—SPSS Software. Descriptive statistics presented include the mean, median, standard deviation, and range for each product category. The distribution of data with a box and whisker plot and frequency of THC to CBD ratios with a histogram was also presented.ResultsEdibles on the Jamaican market comprise baked goods, candies, frozen foods, and beverages. Eighty-six percent of samples were poorly labeled and failed to meet basic labeling requirements. None of the packages were observed to be child-proof. THC levels ranged from 0.01 to 99.9 mg per product while CBD levels ranged from 0.001 to 69.2 mg per product. The highest THC and CBD levels were detected in cookies and brownies. Thirty percent of the samples had THC levels greater than the recommended 10 mg THC per serving.ConclusionThe lack of proper labeling and the wide range of THC levels in cannabis edibles raises public health concerns for all consumers including inexperienced persons who may be at a greater risk of overdosing. Concern must also be raised over the possibility that the attractive and tasty ways in which the drug is being presented might tempt young children and teens to take cannabis.Impact statementIt is hoped that this information will raise public awareness of the current potential danger these edibles pose to children and inexperienced users and that policymakers will see the need for the imposition of suitable regulations.

Potency and utilization of strawberry conch (Strombus luhuanus) in the rocky shore of Oma coastal waters, Central Maluku

The family of Strombidae is known as tropicopolitan species which is distributed in both tropical and subtropical areas. A coastal community in Maluku including people in Oma Village is always collected to the Strombid during low tide especially for Strombus luhuanus which is found in some areas shallow waters, rocky shore, sandy, muddy, rubble, and seagrass bed. Data needed for sustainable management for the species were potency and utilization level. Therefore, the objectives of the present study were to study the potency and utilization of Strombus luhuanus. The research was carried out from April to December 2018 by using the transects line method and interview. All of the individuals of the species found were counted and measured. The potency of Strombus luhuanus was estimated as many as 316,800 individuals and the size collected was 3.00-6.00 cm. Results showed that the utilization activity by coastal communities is known as “bameti” (collection of intertidal biota during low tide) and conducted by women, men, and children The utilization level was very high and has already overexploited. As a consequence, based on the size collected and the high level of utilization, the population of Strombus luhuanus would probably decrease in the future. Therefore, some management strategies are recommended to conserve the species sustainability in nature.

A hybrid NIR-soft sensor method for real time in-process control during continuous direct compression manufacturing operations

Near Infrared (NIR) spectroscopy is commonly utilized for continuous manufacturing as Process Analytical Technology (PAT) tool. This paper focus on a continuous direct compression manufacturing process, in which an NIR PAT probe is integrated into the tablet press feed frame and into the tablet diversion control system to ensure continuous monitoring of the potency and homogeneity of the blend within the process line. The quantification of NIR spectra is achieved through Partial Least-Squares (PLS) modeling, calibrated with offline analyzed tablet cores at different potency levels. Because the NIR measurements are often sensitive to sample physical properties caused by raw materials or process conditions, etc., adopting a data-driven approach will require a large amount of representative data throughout the method lifecycle. During the early stages of process development, whenever new uncaptured source of variability in the model space are encountered, the chemometric predictions can deviate from the offline reference, requiring frequent model updates. These deviations can be reduced by integrating process and physico-chemical knowledge in the on-line potency estimation. This paper presents a novel hybrid method combining the online NIR PLS and a potency soft sensor estimation, enabling a robust potency prediction whilst minimizing maintenance downtimes and facilitating cross-site method transfer.

Benchtop NIR method development for continuous manufacturing scale to enable efficient PAT application for solid oral dosage form

A Near Infrared (NIR) method was developed using a small benchtop feed frame system to quantify Saccharin potency in a powder blend during continuous manufacturing process. A 15-point Design of Experiments (DoE) was created based on the NIR spectral response and compositions of the formulation to develop a calibration set. The calibration set was designed to create compositional and raw material lots variation using minimum resources. The calibration experiments utilized around 0.5 kg Saccharin (Active Pharmaceutical Ingredient (API) surrogate) and 1.8 kg of excipients. Partial Least Square (PLS) modeling was used to develop a quantitative NIR method from the calibration data. The NIR method was implemented during 5 test batches in two different manufacturing sites across different potency levels at a continuous manufacturing platform for direction compression. Acceptable prediction performance was achieved from the NIR method at both sites. The NIR method was robust against changes in process scale and NIR instruments. The variance information built into the calibration set was found to be critical to successful model performance. This study shows a benchtop feed frame can be used for material sparing calibration method development without operating at a full-scale process line and applied across multiple sites, instruments at different potency levels.

Effects of Homeopathic Preparations of Mercurius corrosivus on the Growth Rate of Moderately Mercury-Stressed Duckweed Lemna gibba L.

Background A bioassay with severely mercury-stressed duckweed ( Lemna gibba L.) had revealed growth-inhibiting effects of homeopathically potentised mercury(II) chloride ( Mercurius corrosivus, Merc-c. ). We hypothesised that effects of potentised preparations are dependent on the stress level of the organisms used in the bioassay. The aim of the present investigation was to examine the response of duckweed to potentised Merc-c. at a lower stress level. Methods Duckweed was moderately stressed with 2.5 mg/L mercury(II) chloride for 48 hours. Afterwards plants grew in either Merc-c. (seven different potency levels, 24x–30x) or water controls (unsuccussed or succussed water) for 7 days. Growth rates of the frond (leaf) area were determined using a computerised image-analysis system for day 0–3 and 3–7. Three independent experiments with potentised Merc-c. and three systematic negative control experiments were performed. All experiments were randomised and blinded. Results Unsuccussed and succussed water did not significantly differ in their effects on duckweed growth rate. The systematic negative control experiments did not yield any significant effects, thus providing evidence for the stability of the experimental system. Data from the two control groups and the seven treatment groups ( Merc-c. 24x–30x) were each pooled to increase statistical power. Duckweed growth rates for day 3–7 were enhanced ( p < 0.05) after application of Merc-c. compared with the controls. Growth rates for day 0–3 were not influenced by the homeopathic preparations. Conclusions Moderately mercury-stressed Lemna gibba L. yielded evidence of growth-enhancing specific effects of Merc-c. 24x–30x in the second observation period (day 3–7). This observation is complementary to previous experiments with severely mercury-stressed duckweed, in which a decrease in growth was observed in the first observation period (day 0–3). We hypothesise that the differing results are associated with the level of stress intensity (moderate vs. severe).

Corticosteroid delivery using oral mucosa equivalents for the treatment of inflammatory mucosal diseases.

Oral lichen planus (OLP) is an immune‐mediated disease of the oral mucosa with idiopathic aetiology. It is frequently treated with topical corticosteroids (applied as gels, mouthwashes, or sprays); however, the mucosal exposure times of topical corticosteroids are short because of removal by the constant flow of saliva and mechanical forces. In this study we used cell monolayers, as well as oral mucosal equivalents (OMEs) containing activated T‐cells, to examine corticosteroid potency and delivery of clobetasol‐17‐propionate from a novel electrospun mucoadhesive patch. The OMEs displayed tight junctions, desmosomes, hemidesmosomes, and an efficient permeability barrier. Following application of corticosteroids to cells cultured as monolayers, the degree of cytotoxicity measured correlated to the level of potency recognized for each corticosteroid; by contrast, OMEs were largely unaffected by corticosteroid treatment. Permeation of clobetasol‐17‐propionate into and through the OMEs was time‐ and dose‐dependent, regardless of whether this corticosteroid was delivered in liquid form or from a mucoadhesive patch, and both liquid‐ and patch‐delivered clobetasol‐17‐propionate significantly reduced the secretion of interleukin‐2 by activated T‐cells. This study confirms that OMEs are more suitable models than cell monolayers for evaluating toxicity and drug delivery. After topical exposure, clobetasol‐17‐propionate accumulated in OMEs at a higher level than betamethasone‐17‐valerate and hydrocortisone‐17‐valerate, and exerted its immunosuppressive actions following application via the patch delivery system, highlighting the efficacy of this mode of drug delivery to treat OLP.

The Plasticity and Developmental Potential of Termites

Phenotypic plasticity provides organisms with the potential to adapt to their environment and can drive evolutionary innovations. Developmental plasticity is environmentally induced variation in phenotypes during development that arise from a shared genomic background. Social insects are useful models for studying the mechanisms of developmental plasticity, due to the phenotypic diversity they display in the form of castes. However, the literature has been biased toward the study of developmental plasticity in the holometabolous social insects (i.e., bees, wasps, and ants); the hemimetabolous social insects (i.e., the termites) have received less attention. Here, we review the phenotypic complexity and diversity of termites as models for studying developmental plasticity. We argue that the current terminology used to define plastic phenotypes in social insects does not capture the diversity and complexity of these hemimetabolous social insects. We suggest that terminology used to describe levels of cellular potency could be helpful in describing the many levels of phenotypic plasticity in termites. Accordingly, we propose a conceptual framework for categorizing the changes in potential of individuals to express alternative phenotypes through the developmental life stages of termites. We compile from the literature an exemplar dataset on the phenotypic potencies expressed within and between species across the phylogeny of the termites and use this to illustrate how the potencies of different life stages of different species can be described using this framework. We highlight how this conceptual framework can help exploit the rich phenotypic diversity of termites to address fundamental questions about the evolution and mechanisms of developmental plasticity. This conceptual contribution is likely to have wider relevance to the study of other hemimetabolous insects, such as aphids and gall-forming thrips, and may even prove useful for some holometabolous social insects which have high caste polyphenism.

Royal jelly alleviates the detrimental effects of aging on immune functions by enhancing the in vitro cellular proliferation, cytokines, and nitric oxide release in aged human PBMCS

Aging strongly delays the immunity. Our research aims to assess the in vitro effects of royal jelly (RJ) on the immune function of aged PBMCs. PBMCs were obtained from 10 healthy aged and young donors by the gradient density centrifugation method and further cultured in RPMI-1640 medium supplemented with or without RJ in the presence of Con A. Cell proliferation was assessed by MTT assay along with the measurement of interleukins, Nitric oxide (NO), Glutathione (GSH), and Malondialdehydes (MDA). Our results showed that RJ improved PBMCs proliferation significantly in the elderly subjects, accompanied by the increase in NO (p=.001) and the release of IL-2, IL-4, and IL-6 cytokines. RJ also increased the intracellular GSH (p= .001) and MDA (p=.001) levels in aged PBMCs. In young subjects, RJ enhanced PBMCs proliferation potency, IL-4, IL-6, GSH, and intracellular MDA levels but with a concomitant decrease in NO and IL-2 cytokine secretion as compared with non RJ-treated cells. In conclusion, RJ restored functions of the aged PBMCs as well as the young control subjects, indicating a beneficial effect on immune status during the aging process. PRACTICAL APPLICATIONS: Royal jelly is a well-known edible dietary compound, used traditionally to treat many diseases throughout the world. Since antiquity, it was shown to have medicinal importance. The immuno-enhancing potential of this food was largely and scientifically established by the lipid and protein fractions. The present study illustrates the anti-aging and stimulatory effects of the fresh RJ whole extract, from local Algerian honey bee: Apis mellifera intermissa, on the immunity of aged men. This study provides the experimental evidence supporting anti-immunosenesence effects of royal jelly. RJ supplementation can be used in the old age management and human age-related complications, especially, associated with the weaknesses of the immune response.

In vitro antiplasmodial activity of Phyllanthus amarus against Plasmodium falciparum and evaluation of its acute toxicity effect in mouse model.

Background:The emergence of widespread resistance of Plasmodium species to most antimalarial drugs has led to a more vigorous and concerted research on traditional medicinal plants for the treatment of malaria.Objective of Study:The study was aimed to investigate the in vitro antiplasmodial activity of crude ethanolic and aqueous extracts of Phyllanthus amarus against clinical isolates of Plasmodium falciparum in Northwestern Nigeria.Materials and Methods:The plant was extracted using two solvents, water and ethanol, where a high yield was obtained from the aqueous extracts (11.9%) as compared to the ethanolic extract (9.64%). The extracts were evaluated in vitro at concentrations of 6.25, 12.5, 25, 50, and 100 μg/ml, and the level of potency in each case was expressed as the concentration of the extract that exhibited a 50% reduction of the parasites relative to control (100%) parasitemia. Artemether-lumefantrine was used as a positive standard in the assay.Results:All extracts showed a significant reduction in parasite growth relative to control (P ≤ 0.05). Ethanolic extract exhibited a higher antiplasmodial activity of 76.8%, half-maximal inhibitory concentration (IC50) of 5.80 μg/ml, and aqueous extract had an activity of 75.3%, IC50 of 7.94 μg/ml. Both extracts exhibited very active antiplasmodial activity. Oral acute toxicity test in the doses of 500, 1000, and 1500 mg/kg showed no sign of toxicity on albino mice after 48 h.Conclusion:Although there was an increase in appetite after 24 and 48 h, the findings from this study show that P. amarus possesses a promising antimalarial activity which can be exploited for malaria therapy and justifies the traditional use of the plant in malaria treatment.

Evaluation of the Impact of Hydrocarbon-Generated Soot on Antibiotics Susceptibility of &amp;lt;i&amp;gt;Staphylococcus aureus&amp;lt;/i&amp;gt; and &amp;lt;i&amp;gt;Escherichia coli&amp;lt;/i&amp;gt; Isolates

Background: The antibiotic susceptibility of bacterial interaction with soot, a by-product of incomplete combustion of fossil fuel, has not been established. Aim: The study aimed to establish the antibiotics susceptibility of Staphylococcus aureus and Escherichia coli exposed to soot. Method: The bacteria were exposed to 12.5%, 25%, and 50% concentrations of soot at different time intervals. Control bacterial cultures without exposure to soot were also carried out. These cultures were incubated for 24 hrs. The numbers of surviving bacteria were determined by analyzing 10 μL of the incubated cultures at 6 hrs and 24 hrs on tryptone soy agar. Again, the bacteria were inoculated on Mueller Hinton agar and subjected to antibiotics susceptibility testing using the disk diffusion method. Results: After 6 hrs of exposure, the number of E. coli in the absence of soot was 102.50 ± 3.54 × 103 CFU/mL while at 12.5%, 25%, and 50% of soot, the surviving E. coli were 26.00 ± 1.41 (p = 0.0012), 21.00 ± 1.41 (p = 0.0011) and 5.50 ± 2.12 (p = 0.0009) × 103 CFU/mL respectively. Similarly, the population of S. aureus without soot was 122.5 ± 3.53 × 104 CFU/mL while at 12.5%, 25.0% and 50.0% of soot, the surviving S. aureus 46.00 ± 2.83 (p = 0.0017), 23.00 ± 1.41 (p = 0.0007) and 11.50 ± 2.12 (p = 0.0007) × 104 CFU/mL respectively. Similar results were obtained after 24 hrs of exposure. The soot shows some level of potency in reducing the number of E. coli and S. aureus significantly (p S. aureus), there was resistance to all the antibiotics while at 0 hr there was sensitivity to these drugs. Conclusion: These results suggest that while soot has some potency on E. coli and S. aureus, their exposure to soot could induce resistance.

Geospatial approach to determining potential of springs at the Palu Groundwater Basin for post disaster water supply in Central Sulawesi Province

The disaster that occurred on 28 September 2018 in Palu City, Sigi and Donggala regencies had an impact on damage to a number of water resource. This study aims to determine the quantitative potential of springs with using a geospatial approach and hydrogeomorphological mapping. Based on the results of the field survey, the springs in Palu Groundwater Basin amounted to + 104 springs with divisions in the east and west. The results showed that in Palu Groundwater Basin the appearance of springs was not only caused by geomorphological conditions but also influenced by geological conditions. Based on the type of springs, it is dominated by the type of artesian, fracture and contact. The quantitative potency level of springs ranges from small (< 5.0 liters/second) to large (> 10.0 liters/second) quantitative potency levels. Small quantitative potential levels (< 5.0 liters/second) in the eastern part include the districts: East Palu, South Palu, Dolo and Biromaru. The western part of Palu Groundawter Basin includes the sub-districts: West Palu and South Palu. Based on the results of the study, it can be concluded that the quantitative potential of springs is very potential to meet the needs of clean water in post-disaster areas.

Combating A36 mild steel corrosion in 1 M H&lt;sub&gt;2&lt;/sub&gt;SO&lt;sub&gt;4&lt;/sub&gt; medium using watermelon seed oil inhibitor

<abstract> Corrosion inhibitive performance of the extracted watermelon seed oil on A36 mild steel in 1 M H₂SO₄ medium, at 305 and 319 K corrosion reaction temperatures, was investigated. Weight loss and inhibition efficiency were determined using gravimetric method while corrosion rate and inhibitoion efficiency were evaluated using potentiodynamic tests. Gravimetric tests showed that watermelon seed oil inhibitor attained a better corrosion inhibition efficiency of 50% at the operating temperature of 305 K compared to an efficiency of 48% obtained at the operating temperature of 319 K. Electrochemical potentiodynamic polarization tests showed that 3 vol/vol% inhibitor concentration gave the most promising corrosion inhibiting results at the operating temperature of 305 K, while 4 vol/vol% inhibitor concentration gave the most reliable corrosion resisting one at the operating temperature of 319 K. Langmuir adsorption isotherm correctly predicted the adsorption behaviour of the watermelon seed oil on A36 mild steel surface in 1 M H₂SO₄ medium. the negative values of ∆G_ads revealed the spontaneous adsorption nature of the inhibitor on the mild steel surface and the electrochemical potentiodynamic polarization results showed that the watermelon seed oil acted as a mixed-type corrosion inhibitor. The optical image analysis revealed both the potency level of watermelon seed oil as an inhibitor as well as the optimum inhibitor concentrations of 3 vol/vol% (at 305 K) and 4 vol/vol% (at 319 K). </abstract>

1254. In vitro activity of sulbactam-durlobactam against recent global clinical Acinetobacter baumannii-calcoaceticus complex isolates

Background Acinetobacter baumannii-calcoaceticus complex (ABC) causes severe infections that are difficult to treat due to increasing resistance to antibacterial therapy. Sulbactam (SUL) has intrinsic antibacterial activity against ABC, but its clinical utility has been compromised by the prevalence of serine β-lactamases. Durlobactam (DUR, previously ETX2514) is a diazabicyclooctenone β-lactamase inhibitor with potent activity against Ambler classes A, C and D serine β-lactamases that effectively restores SUL activity against ABC isolates. SUL-DUR is an antibiotic designed to treat serious infections caused by Acinetobacter, including multidrug-resistant strains, which is currently in Phase 3 clinical testing. The potency of SUL-DUR against geographically diverse ABC isolates collected in 2018 was measured.Methods929 ABC isolates, including 698 A. baumannii, 13 A. calcoaceticus, 54 A. nosocomialis, and 164 A. pittii, were collected in 2018 from geographically diverse medical centers in the United States, Europe, Latin America, Israel and the Asia-Pacific region. Susceptibility testing was performed according to CLSI guidelines. Data analysis was performed using CLSI and EUCAST breakpoint criteria where available. Select isolates were subjected to whole genome sequencing with an Illumina MiSeq V2 instrument and analysis using CLCBio Genomics Workbench v6.5.ResultsIn surveillance of 929 global isolates from 2018, the SUL-DUR MIC90 was 2 mg/L compared with 64 mg/L for SUL alone. This level of potency was consistent across species, regions, source of infection and subsets of resistance phenotypes. Fifty percent of the isolates were non-susceptible to carbapenems. Only 7 isolates (0.75%) had SUL-DUR MIC values >4 mg/L. Whole genome sequencing of these 7 isolates revealed that they either encoded the metallo-β-lactamase NDM-1, which DUR does not inhibit, or single amino acid substitutions near the active site of PBP3, the primary target of SUL.ConclusionSUL-DUR demonstrated potent antibacterial activity against recent, geographically diverse clinical isolates of ABC, including MDR isolates. These data support the potential utility of SUL-DUR for the treatment of antibiotic-resistant infections caused by ABC.DisclosuresSarah McLeod, PhD, Entasis Therapeutics (Employee) Samir Moussa, PhD, Entasis Therapeutics (Employee) Alita Miller, PhD, Entasis Therapeutics (Employee)

Study of the venom proteome of Vipera ammodytes ammodytes (Linnaeus, 1758): A qualitative overview, biochemical and biological profiling

Vipera ammodytes (Va), is the European venomous snake of the greatest medical importance. We analyzed whole venom proteome of the subspecies V. ammodytes ammodytes (Vaa) from Serbia for the first time using the shotgun proteomics approach and identified 99 proteins belonging to four enzymatic families: serine protease (SVSPs), L-amino acid oxidase (LAAOs), metalloproteinases (SVMPs), group II phospholipase (PLA2s), and five nonenzymatic families: cysteine-rich secretory proteins (CRISPs), C-type lectins (snaclecs), growth factors -nerve (NGFs) and vascular endothelium (VEGFs), and Kunitz-type protease inhibitors (SPIs). Considerable enzymatic activity of LAAO, SVSPs, and SVMPs and a high acidic PLA2 activity was measured implying potential of Vaa to produce haemotoxic, myotoxic, neuro and cardiotoxic effects. Moreover, significant antimicrobial activity of Vaa venom against Gram-negative (Klebsiella pneumoniae, Pseudomonas aeruginosa) and Gram-positive bacteria (Staphylococcus aureus) was found. The crude venom shows considerable potential cytotoxic activity on the C6 and HL60 and a moderate level of potency on B16 cell lines. HeLa cells showed the same sensitivity, while DU 145 and PC-3 are less sensitive than as normal cell line. Our data demonstrated a high complexity of Vaa and considerable enzymatic, antibacterial and cytotoxic activity, implying a great medical potential of Vaa venom as a promising source for new antibacterial and cytostatic agents.

The impact of team potency and leadership member exchange on expatriate creative work involvement

PurposeThe purpose of this study is to examine whether team potency moderates the effect of the leader member exchange (LMX) on the expatriate's creative work involvement such that the effect of leader member exchange on creative work involvement becomes less when team potency is high.Design/methodology/approachData were gathered via a printed survey instrument, using a purposive sampling approach and administered directly to 150 expatriate (non-Emirate nationals) employees located in the Jabal Ali Dubai Free Zone of the United Arab Emirates (UAE).FindingsOur findings indicate that the higher the level of team potency the less the effect of LMX on expatriate creative work involvement.Practical implicationsThe findings suggest that, team potency, which is an asset in certain situations, can be a liability suppressing the effect of LMX on the expatriate employees creative work involvement. Expatriate employees experiencing satisfaction and fulfillment through the leadership exchange feel sufficiently empowered in their abilities to engage in creative work behaviors.Originality/valueTesting a theoretical model within the intranational cultural diversity of an expatriate workforce may be a stronger source of diversity than other sources, providing for an original theoretical contribution to the extant literature. Moreover, the UAE, with its prominent network of expatriate employment integrated within the national economy presents a highly relevant contextual environment in which to study expatriate behavior.

Effective degradation of tetracycline by manganese peroxidase producing Bacillus velezensis strain Al-Dhabi 140 from Saudi Arabia using fibrous-bed reactor

A tetracycline degrading bacterial strains was characterized from the municipal sludge and detected its ability to produce manganese peroxidase. The molecular weight of manganese peroxidase was determined as 46 kDa after Biogel P-100 gel filtration column chromatography purification. Maximum tetracycline degradation was observed with the manganese peroxidase from the strain Bacillus velezensis Al-Dhabi 140 and the optimum degradation process was studied. Optimization revealed the maximum removal efficacy was obtained as 87 mg/L at initial tetracycline concentration 143.75 mg/L, pH 6.94 and 8.04% inoculum. Consequently, fibrous bed reactor containing the culture of B. velezensis Al-Dhabi 140 in fibrous matrix was formed to transform tetracycline in synthetic wastewater. The transformed product of tetracycline from the fibrous bed reactor was evident by the activity of ligninolytic enzymes produced by B. velezensis Al-Dhabi 140 in reactor. The decreased level of antibacterial potency was obtained after 10 days. The zone of inhibition was 24 ± 1 mm after 1 day and it decreased as 9 ± 1 mm after 10 days. Based on the findings, fibrous bed B. velezensis Al-Dhabi 140 could be an efficient strain for tetracycline removal from artificial wastewater, even from natural wastewater.

Combining kinase inhibitors for optimally co-targeting cancer and drug escape by exploitation of drug target promiscuities.

Cancers resist targeted therapeutics by drug-escape signaling. Multitarget drugs co-targeting cancer and drug-escape mediators (DEMs) are clinically advantageous. DEM coverage may be expanded by drug combinations. This work evaluated to what extent the kinase DEMs (KDEMs) can be optimally co-targeted by drug combinations based on target promiscuities of individual drugs. We focused on 41 approved and 28 clinical trial small molecule kinase inhibitor drugs with available experimental kinome and clinical pharmacokinetic data. From the kinome inhibitory profiles of these drugs, drug combinations were assembled for optimally co-targeting an established cancer target (EGFR, HER2, ABL1, or MEK1) and 9-16 target-associated KDEMs at comparable potency levels as that against the cancer target. Each set of two-, three-, and four-drug combinations co-target 36-71%, 44-89%, 50-88%, and 27-55% KDEMs of EGFR, HER2, ABL1, and MEK1, respectively, compared with the 36, 33, 38, and 18% KDEMs maximally co-targeted by an existing drug or drug combination approved or clinically tested for the respective cancer. Some co-targeted KDEMs are not covered by any existing drug or drug combination. Our work suggested that novel drug combinations may be constructed for optimally co-targeting cancer and drug escape by the exploitation of drug target promiscuities.

Erectile dysfunction and cancer: current perspective.

Erectile dysfunction (ED) is one of the major but underreported concerns in cancer patients and survivors. It can lead to depression, lack of intimacy between the couple, and impaired quality of life. The causes of erectile dysfunction are psychological distress and endocrinal dysfunction caused by cancer itself or side effect of anticancer treatment like surgery, radiotherapy, chemotherapy and hormonal therapy. The degree of ED depends on age, pre-cancer or pre-treatment potency level, comorbidities, type of cancer and its treatment. Treatment options available for ED are various pharmacotherapies, mechanical devices, penile implants, or reconstructive surgeries. A complete evaluation of sexual functioning should be done before starting anticancer therapy. Management should be individualized and couple counseling should be an integral part of the anticancer treatment.

Bacteriophages and the One Health Approach to Combat Multidrug Resistance: Is This the Way?

Antimicrobial resistance necessitates action to reduce and eliminate infectious disease, ensure animal and human health, and combat emerging diseases. Species such as Acinetobacter baumanniii, vancomycin resistant Enterococcus, methicillin resistance Staphylococcus aureus, and Pseudomonas aeruginosa, as well as other WHO priority pathogens, are becoming extremely difficult to treat. In 2017, the EU adopted the “One Health” approach to combat antibiotic resistance in animal and human medicine and to prevent the transmission of zoonotic disease. As the current therapeutic agents become increasingly inadequate, there is a dire need to establish novel methods of treatment under this One Health Framework. Bacteriophages (phages), viruses infecting bacterial species, demonstrate clear antimicrobial activity against an array of resistant species, with high levels of specificity and potency. Bacteriophages play key roles in bacterial evolution and are essential components of all ecosystems, including the human microbiome. Factors such are their specificity, potency, biocompatibility, and bactericidal activity make them desirable options as therapeutics. Issues remain, however, relating to their large-scale production, formulation, stability, and bacterial resistance, limiting their implementation globally. Phages used in therapy must be virulent, purified, and well characterized before administration. Clinical studies are warranted to assess the in vivo pharmacokinetics and pharmacodynamic characteristics of phages to fully establish their therapeutic potential.

Developmental, behavioral and endocrine alterations in male rats at early and late postnatal life following in utero exposure to low dose di-n-butylphthalate.

Environmental chemical pollutants that interfere with hormonal homeostasis or hormone signaling are the relevant agents inducing congenital or postnatally developed reproductive abnormalities in human beings, wild and domestic animals. In this study, we are examining reproductive effects of prenatal exposure of male rats to a low dose di-n-butylphthalate (DBP). Wistar female rats were given intragastrically DBP at a daily dose of 100mg/kg b.w. during 15th-21st days of pregnancy. Anogenital distance(AGD) in male offspring decreased on postnatal day (PND) 2 followed by its normalization on PND 7 and 10. There were no other visible teratogenic lesions in the newborns. The testicle descent into scrotum of control males occurred on PND 38.5 ± 0.1, while in DBP group it accelerated by 5.3days on the average. At the age of 6months, DBP-exposed animals exhibited double increase of blood plasma testosterone level as compared to controls, and hyperactive male sexual behavior in the presence of receptive female. The duration of latent periods of the first mount and the first intromission, as well as post-ejaculatory refractory period, have been shortened; the number of mounts with intromission and the number of ejaculations increased significantly. Histological examination of the testes indicated activation of Leydig cells. The female-type sexual behavior as evaluated by appearance of lordosis of orchidectomized and primed with estradiol and progesterone 10-month-old males in response to mount or approach of sexually active normal male was enhanced in DBP-group. Both 10-month-old and aging males (18months), castrated and hormone-primed, displayed homosexual type of behavior. Prenatal low dose DBP caused in 18-month-old males premature atrophy of the testes and accessory sexual glands, increased number of Leydig cell adenomas, a twice decrease of plasma testosterone level and exhausting of sexual potency. We concluded that prenatal exposition of male rats to low dose DBP determines epigenetic alterations of programming of sex brain differentiation and regulation of testicular steroidogenesis that leads to reproductive disorders and accelerated aging of reproductive system.