•Additions of up to1.8 wt. % Ge in Zn-1.6 wt. % Al-1.6 wt. % Mg.•SVET and time lapse microscopy study of Zn-Al-Mg-Ge corroding in NaCl.•Ge additions result in formation of new Mg2Ge phase within the ...microstrusture.•Reduction in SVET derived mass loss and corroded area with increasing Ge levels.•Dissolving Mg2Ge acts as source of Mg2+ resulting in stabilisation of Zn surface.
In-situ scanning vibrating electrode technique and time-lapse microscopy are used to investigate the influence of germanium additions (0.19–1.8 wt.%) on the corrosion performance of zinc-aluminium-magnesium model alloys immersed in 0.17 mol.dm−3 NaCl. The addition of Ge results in the formation of Mg2Ge and a decrease in the fractional area of eutectic phase. A 58 % decrease in SVET derived mass loss is achieved at 1.8 wt.% Ge. It is proposed that Mg2Ge crystals are anodically attacked and behave as reservoirs of Mg2+ ions. Mg(OH)2 is precipitated and local electrolyte pH stabilises to values at which the zinc surface is passive.
Background & objectives: Search for novel compounds beneficial to the treatment of cancer attracts a great deal of attention. We earlier demonstrated the isolation of ...5,7-dihydroxy-2-4'-hydroxy-3'-(methoxymethyl)phenyl-6-C-β-glucopyranosyl flavone, a novel C-glycosyl flavone from Urginea indica bulb. The present study was undertaken to investigate the effect of this novel compound on human normal epithelial and breast, hepatic and colon cancer cell lines.
Methods: The maximum non-toxic concentration (MNTC) and cytotoxicity of C-glycosyl flavone were assayed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Cell cycle was analyzed by flow cytometry. Docking studies were performed to predict possible targets. Levels of cyclin-dependent kinase 1 (CDK1) and CDK6, Bcl2 and BAX and cytochrome c were quantified by specific ELISA. Mitochondrial membrane potential was determined using JC-1 dye. Apoptosis was quantified by Annexin V ELISA method.
Results: Flow cytometry analysis demonstrated G0/G1 arrest. In silico docking studies predicted CDK1 and CDK6 as a possible target of C-glycosyl flavone. In vitro study confirmed CDK6 as the main target in C-glycosyl flavone-treated cancer cell lines. C-glycosyl flavone treatment also induced membrane blebbing, chromatin fragmentation and nucleosome formation. C-glycosyl flavone treatment caused marked loss of mitochondrial membrane potential, decrease in Bcl2/BAX ratio and activation of caspase-3 and release of caspase-9 and cytochrome c. In addition, C-glycosyl flavone inhibited the tumour-induced angiogenesis and reduced the vascular endothelial growth factor levels. Similarly, CDK6 inhibitor significantly inhibited proliferation and angiogenesis and induced apoptosis in tested cell lines.
Interpretation & conclusions: The results indicate that C-glycosyl flavone may exert induction of apoptosis, cell cycle arrest and inhibition of angiogenesis via CDK6. Thus, targeting CDK6 using C-glycosyl flavone may serve as a novel therapeutic approach for the treatment of breast, hepatic and colon cancers.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Additions of 1 wt.% Ca were made to Zn (Zn-1Ca) to generate favourable chemical conditions during corrosion for enhanced performance of phosphate inhibitors. Zn-1Ca displayed a reduced corrosion rate ...in 0.17 M NaCl measured using the Scanning Vibrating Electrode Technique and polarisation. In-situ timelapse microscopy and SEM-EDS demonstrated that intermetallic CaZn13 preferentially corroded releasing Ca2+ that increased corrosion product precipitation, cathodically deactivating the system. 1 × 10−3 mol dm−3 phosphate additions to 0.17 M NaCl decreased the corrosion rate of Zn and Zn-1Ca. Inhibition was greater for Zn-1Ca where uniform precipitation of mixed metal phosphates produced anodic and cathodic inhibition.
•Addition of 1 wt.% Ca to Zn (Zn-1Ca) reduced its corrosion rate compared to Zn.•Distributed CaZn13 phases are preferentially corroded producing Ca2+ ions.•Zn-1Ca had increased corrosion products, cathodically deactivating the system.•Additions of phosphate ions inhibit the corrosion of both Zn and Zn-1Ca.•Inhibition is increased for Zn-1Ca due to precipitation of mixed metal phosphates.
C-glycosyl flavone, a phytochemical constituent in U.indica bulb, has been reported to possess cytotoxic activity.
The present study aims to investigate the toxicity and anticancer potentials of ...C-glycosyl flavone against Ehrlich ascites carcinoma mice model.
In present study, acute and chronic toxicity along with antitumor activity of C-glycosyl flavone isolated from U.indica bulb were Performed using in vitro and in vivo methods. Acute and chronic toxicity of C-glycosyl flavone was evaluated using Swiss albino mice. The effect of C-glycosyl flavone on proliferation of Ehrlich ascites carcinoma (EAC) cells was determined. Further, growth inhibition and dissemination were studied using EAC induced mice model.
C-glycosyl flavone showed significant therapeutic potency against EAC cells in terms of reduced viability, cell cycle arrest, induction of apoptosis, inhibition of capillary formation, reduced VEGF levels. Moreover, there was reduction in body weight, tumor volume, viable tumor cells, increased survival of EAC induced mice upon C-glycosyl flavone treatment. Treatment also reduced dissemination of EAC cells into heart, kidney, liver and brain and diminished the pathological alterations induced by EAC cells in mice. In addition, there was an improvement in hemoglobin levels and counts of RBC, neutrophils, lymphocytes and monocytes in C-glycosyl flavone-treated mice with tumor. An enhancement of antioxidant status in C-glycosyl flavone treated EAC-bearing mice which appeared in terms of decreased serum thiobarbituric acid reactive substance and lipid peroxidation, increased GSH, SOD, Catalase and GPX. These results were comparable to a standard 5- fluorouracil treatment. C-glycosyl flavone exhibited safety profile in toxicity studies.
Our study confirms the therapeutic potency of C-glycosyl flavone against EAC in inhibition of dissemination and growth of EAC in mice.
A chelating type ion exchange resin (Amberlite IRC-718), containing iminodiacetate groups as active sites, has been characterized regarding the sorption and subsequent elution of Cd, Zn and Pb, ...aiming to metal preconcentration from solution samples of different origins. The methodology developed is based on off-line operation employing mini columns made of the sorbent. The eluted metals were determined by flame atomic absorption spectrometry. The effect of column conditioning, influent pH and flow rate during the sorption step, and the nature of the acid medium employed for desorption of the retained metals were investigated. Working (breakthrough) and total capacities were measured under dynamic operating conditions and the results compared with those obtained with Chelex-100, a resin extensively employed for analytical preconcentration. Structural information on the complexation of metals by the chelating groups was obtained by Fourier Transform infrared spectrometry. The analytical response of the Amberlite sorbent was assessed for the analysis of water samples and digestates of marine sediments.
Part 2 of the guidelines on responsible opioid prescribing provides the following recommendations for initiating and maintaining chronic opioid therapy of 90 days or longer. 1. A) Comprehensive ...assessment and documentation is recommended before initiating opioid therapy, including documentation of comprehensive history, general medical condition, psychosocial history, psychiatric status, and substance use history. (
good) B) Despite limited evidence for reliability and accuracy, screening for opioid use is recommended, as it will identify opioid abusers and reduce opioid abuse. (
limited) C) Prescription monitoring programs must be implemented, as they provide data on patterns of prescription usage, reduce prescription drug abuse or doctor shopping. (
good to fair) D) Urine drug testing (UDT) must be implemented from initiation along with subsequent adherence monitoring to decrease prescription drug abuse or illicit drug use when patients are in chronic pain management therapy. (
good) 2. A) Establish appropriate physical diagnosis and psychological diagnosis if available prior to initiating opioid therapy. (
good) B) Caution must be exercised in ordering various imaging and other evaluations, interpretation and communication with the patient, to avoid increased fear, activity restriction, requests for increased opioids, and maladaptive behaviors. (
good) C) Stratify patients into one of the 3 risk categories - low, medium, or high risk. D) A pain management consultation, may assist non-pain physicians, if high-dose opioid therapy is utilized. (
fair) 3. Essential to establish medical necessity prior to initiation or maintenance of opioid therapy. (
good) 4. Establish treatment goals of opioid therapy with regard to pain relief and improvement in function. (
good) 5. A) Long-acting opioids in high doses are recommended only in specific circumstances with severe intractable pain that is not amenable to short-acting or moderate doses of long-acting opioids, as there is no significant difference between long-acting and short-acting opioids for their effectiveness or adverse effects. (
fair) B) The relative and absolute contraindications to opioid use in chronic non-cancer pain must be evaluated including respiratory instability, acute psychiatric instability, uncontrolled suicide risk, active or history of alcohol or substance abuse, confirmed allergy to opioid agents, coadministration of drugs capable of inducing life-limiting drug interaction, concomitant use of benzodiazepines, active diversion of controlled substances, and concomitant use of heavy doses of central nervous system depressants. (
fair to limited) 6. A robust agreement which is followed by all parties is essential in initiating and maintaining opioid therapy as such agreements reduce overuse, misuse, abuse, and diversion. (
fair) 7. A) Once medical necessity is established, opioid therapy may be initiated with low doses and short-acting drugs with appropriate monitoring to provide effective relief and avoid side effects. (
fair for short-term effectiveness, limited for long-term effectiveness) B) Up to 40 mg of morphine equivalent is considered as low dose, 41 to 90 mg of morphine equivalent as a moderate dose, and greater than 91 mg of morphine equivalence as high dose. (
fair) C) In reference to long-acting opioids, titration must be carried out with caution and overdose and misuse must be avoided. (
good) 8. A) Methadone is recommended for use in late stages after failure of other opioid therapy and only by clinicians with specific training in the risks and uses. (
limited) B) Monitoring recommendation for methadone prescription is that an electrocardiogram should be obtained prior to initiation, at 30 days and yearly thereafter. (
fair) 9. In order to reduce prescription drug abuse and doctor shopping, adherence monitoring by UDT and PMDPs provide evidence that is essential to the identification of those patients who are non-compliant or abusing prescription drugs or illicit drugs. (
fair) 10. Constipation must be closely monitored and a bowel regimen be initiated as soon as deemed necessary. (
good) 11. Chronic opioid therapy may be continued, with continuous adherence monitoring, in well-selected populations, in conjunction with or after failure of other modalities of treatments with improvement in physical and functional status and minimal adverse effects. (
fair).
The guidelines are based on the best available evidence and do not constitute inflexible treatment recommendations. Due to the changing body of evidence, this document is not intended to be a "standard of care."
Opioid abuse has continued to increase at an alarming rate since the 1990 s. As documented by different medical specialties, medical boards, advocacy groups, and the Drug Enforcement Administration, ...available evidence suggests a wide variance in chronic opioid therapy of 90 days or longer in chronic non-cancer pain. Part 1 describes evidence assessment.
The objectives of opioid guidelines as issued by the American Society of Interventional Pain Physicians (ASIPP) are to provide guidance for the use of opioids for the treatment of chronic non-cancer pain, to produce consistency in the application of an opioid philosophy among the many diverse groups involved, to improve the treatment of chronic non-cancer pain, and to reduce the incidence of abuse and drug diversion. The focus of these guidelines is to curtail the abuse of opioids without jeopardizing non-cancer pain management with opioids.
1) There is good evidence that non-medical use of opioids is extensive; one-third of chronic pain patients may not use prescribed opioids as prescribed or may abuse them, and illicit drug use is significantly higher in these patients. 2) There is good evidence that opioid prescriptions are increasing rapidly, as the majority of prescriptions are from non-pain physicians, many patients are on long-acting opioids, and many patients are provided with combinations of long-acting and short-acting opioids. 3) There is good evidence that the increased supply of opioids, use of high dose opioids, doctor shoppers, and patients with multiple comorbid factors contribute to the majority of the fatalities. 4) There is fair evidence that long-acting opioids and a combination of long-acting and short-acting opioids contribute to increasing fatalities and that even low-doses of 40 mg or 50 mg of daily morphine equivalent doses may be responsible for emergency room admissions with overdoses and deaths. 5) There is good evidence that approximately 60% of fatalities originate from opioids prescribed within the guidelines, with approximately 40% of fatalities occurring in 10% of drug abusers. 6) The short-term effectiveness of opioids is fair, whereas the long-term effectiveness of opioids is limited due to a lack of long-term (> 3 months) high quality studies, with fair evidence with no significant difference between long-acting and short-acting opioids. 7) Among the individual drugs, most opioids have fair evidence for short-term and limited evidence for long-term due to a lack of quality studies. 8) The evidence for the effectiveness and safety of chronic opioid therapy in the elderly for chronic non-cancer pain is fair for short-term and limited for long-term due to lack of high quality studies; limited in children and adolescents and patients with comorbid psychological disorders due to lack of quality studies; and the evidence is poor in pregnant women. 9) There is limited evidence for reliability and accuracy of screening tests for opioid abuse due to lack of high quality studies. 10) There is fair evidence to support the identification of patients who are non-compliant or abusing prescription drugs or illicit drugs through urine drug testing and prescription drug monitoring programs, both of which can reduce prescription drug abuse or doctor shopping.
The guidelines are based on the best available evidence and do not constitute inflexible treatment recommendations. Due to the changing body of evidence, this document is not intended to be a "standard of care."
Two existing sequential chemical extraction schemes, involving respectively five and six leaching steps with solutions of increasing dissolving power, were compared. The methods have been applied to ...surface sediment samples collected in a marine estuary zone potentially exposed to contamination arising from nearby industrial activities. A certified reference material (MURST-ISS-A1) consisting of an Antarctic bottom sediment for which no information regarding phase dependent concentration is available, was also analyzed. In order to evaluate the partition of metals among different geochemical forms, the concentrations of cadmium, chromium, lead and zinc were measured in the liquid extracts by Zeeman-corrected flame atomic absorption and by inductively coupled plasma-atomic emission spectrometry. The total metal concentrations were determined after strong acid attack, and the adequacy of this total digestion/dissolution technique was verified by its application to the reference material. Comparison of total metal concentrations with the sum of concentrations associated with the individual phases was employed to assess possible analyte losses or contaminations. Precisions for both sequential procedures were comparable, but some inconsistencies in mass balances were found in one of the samples for the distribution of Zn in the soluble/exchangeable fractions and for Cd in the bound to carbonates form. In addition, the six steps procedure produced lower concentration values in the case of elements associated to the residual fraction. For the five steps method mass balances showed acceptable agreement, with average recoveries in the 87 to 106% range. On the whole, differences in metal distributions were observed, being more marked for the bottom sediment. Significant proportions of the studied elements, with the exception of Cr, were found as easily extractable forms. X-ray diffraction and petrographic observation of the surface sediments allowed qualitative correlation between the leaching results obtained and the presence of defined geochemical phases.
Decisions about the use of killed oral cholera vaccines, which confer moderate levels of direct protection to vaccinees, can depend on whether the vaccines also provide indirect (herd) protection ...when high levels of vaccine coverage are attained. We reanalysed data from a field trial in Bangladesh to ascertain whether there is evidence of indirect protection from killed oral cholera vaccines.
We analysed the first year of surveillance data from a placebo-controlled trial of B subunit-killed whole-cell and killed whole-cell-only oral cholera vaccines in children and adult women in Bangladesh. We calculated whether there was an inverse, monotonic trend for the relation between the level of vaccine coverage in a residential cluster and the incidence of cholera in individual vaccine recipients or placebo recipients residing in the cluster after controlling for potential confounding variables.
Vaccine coverage of the targeted population ranged from 4% to 65%. Incidence rates of cholera among placebo recipients were inversely related to levels of vaccine coverage (7·01 cases per 1000 in the lowest quintile of coverage
vs 1·47 cases per 1000 in the highest quintile; p<0·0001 for trend). Receipt of vaccine by an individual and the level of vaccine coverage of the individual's cluster were independently related to a reduced risk of cholera. Moreover, after adjustment for the level of vaccine coverage of the cluster, vaccine protective efficacy remained significant (55% 95% CI 41–66, p<0·0001).
In addition to providing direct protection to vaccine recipients, killed oral cholera vaccines confer significant herd protection to neighbouring non-vaccinated individuals. Use of these vaccines could have a major effect on the burden of cholera in endemic settings.
Background Hydrogen peroxide is continuously generated in living cells through metabolic pathways and serves as a source of reactive oxygen species. Beyond the threshold level, it damages cells and ...causes several human disorders, including cancer. Methods Effect of isolated 3-O-methyl quercetin and kaempferol on H.sub.2O.sub.2 induced cytotoxicity, ROS formation, plasma membrane damage, loss of mitochondrial membrane potential, DNA damage was evaluated in normal liver and lung cells. The RT-PCR analysis used to determine Nrf 2 gene expression. Calorimetric ELISA was used to determine Nrf2 and p-38 levels. Expression of SOD and catalase was analyzed by Western blot analysis. Results The present study isolated 3-O-methyl quercetin and kaempferol from the stem bark. They protected normal lung and liver cells from H.sub.2O.sub.2 induced cytotoxicity, ROS formation, membrane damage and DNA damage. Pre-treatment with 3-O-methyl quercetin and kaempferol caused translocation of Nrf2 from cytosol to nucleus. It also increased expression of p-p38, Nrf2, SOD and catalase in H.sub.2O.sub.2 treated lung and liver cells. Conclusion The flavonoids isolated from S. anacardium significantly reduced H.sub.2O.sub.2 induced stress and increased expression of Nrf2, catalase and superoxide dismutase-2 indicating cytoprotective nature of 3-O-methylquercetin and kaempferol. Keywords: Hydrogen peroxide, Flavonoids, Lung cells, Liver cells
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