Phenformin as prophylaxis and therapy in breast cancer xenografts.

BACKGROUND: Observations that diabetics treated with biguanide drugs have a reduced risk of developing cancer have prompted an enthusiasm for these agents as anti-cancer therapies. We sought to determine the efficacy of the biguanide phenformin in the chemoprophylaxis and in the treatment of oestrogen receptor (ER)-positive MCF7 and receptor triple-negative MDAMB231 xenografts in immunocompromised mice. We also compared the efficacy of phenformin and metformin in the treatment of MDAMB231. METHODS: Immunocompromised mice were divided into groups: (1) phenformin administered for 2 weeks prior to cell injection; (2) established tumours treated with phenformin; (3) established tumours treated with metformin (only for MDAMB231 tumours); (4) untreated controls. Post-treatment tumours, liver and spleen were harvested for further analysis. RESULTS: Phenformin significantly inhibited both the development and growth of MCF7 and MDAMB231 tumours, and for MDAMB231 at greater efficacy than metformin without murine toxicity. The number of mitotic figures was significantly fewer in xenografts treated with phenformin compared with controls. Results suggested that the mechanism of action of phenformin in vivo is consistent with AMPK activation. CONCLUSION: Phenformin has clinical potential as an antineoplastic agent and should be considered for clinical trials both in ER-positive and triple-negative breast cancer.

An objective analysis of quality and readability of online information on COVID-19.

High quality, readable health information is vital to mitigate the impact of the COVID-19 pandemic. The aim of this study was to assess the quality and readability of online COVID-19 information using 6 validated tools. This is a cross-sectional study. "COVID-19" was searched across the three most popular English language search engines. Quality was evaluated using the DISCERN score, Journal of the American Medical Association benchmark criteria and Health On the Net Foundation Code of Conduct. Readability was assessed using the Flesch Reading Ease Score, Flesch-Kincaid Grade Level and Gunning-Fog Index. 41 websites were suitable for analysis. 9.8% fulfilled all JAMA criteria. Only one website was HONCode certified. Mean DISCERN score was 47.8/80 ("fair"). This was highest in websites published by a professional society/medical journal/healthcare provider. Readability varied from an 8th to 12th grade level. The overall quality of online COVID-19 information was "fair". Much of this information was above the recommended 5th to 6th grade level, impeding access for many.

Sorption behavior of a synthetic antioxidant, polycyclic musk, and an organophosphate insecticide in wastewater sludge.

Emerging contaminants (ECs) are chemicals that are currently unregulated due to limited understanding of health effects and limited data regarding occurrence. Wastewater treatment plants (WWTP) receive many ECs as components of influent waste and the removal of organic contaminants, such as ECs, occurs primarily by sorption to sludge. Therefore, it is important to develop measures of sorption behavior by ECs to sludge. This study evaluates sorption of three ECs: 3-tert-butyl-4-hydroxyanisole (BHA) a synthetic antioxidant, 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethyl-cyclopenta(g)-2-benzopyrane (HHCB) a polycyclic musk, and chlorpyrifos a organophosphate insecticide. Twenty-four hour laboratory-scale sorption experiments were conducted for each compound individually and then in combination, which allowed the quantification of sorption onto wastewater sludge and the affects of multiple compounds. ECs in both the liquid and solid phases were analyzed using a gas chromatograph with flame ionization detector (GC/FID). Isotherms of individual sorption behavior followed a linear trend (R2 > 0.9) for individual ECs, while K(d) averaged 2,689 L kg(-1), 27,786 L kg(-1) and 31,402 L kg(-1) for BHA, chlorpyrifos and HHCB, respectively. Sorption behavior for BHA was linear during combined studies with K(d) of 1,766 L kg(-1) or a decrease of 34%, while HHCB and chlorpyrifos followed non-linear isotherm models. Synergistic effects were observed with spike concentrations > or =25 mg L(-1) for HHCB and > or =20 mg L(-1) for chlorpyrifos. K(d) values ranged from 16,984-6,000,000 L kg(-1) for HHCB and 19,536-3,000,000 L kg(-1) for chlorpyrifos. These distribution coefficients differed substantially from previously published values, mainly because few studies used sludge as the sorption media. Results suggest that HHCB and chlorpyrifos may be contained in the sludge unlike BHA, which is more available in the aqueous phase. Future investigations should evaluate WWTP processes for degrading ECs to harmless products and releases of ECs from sludge.

Awareness and knowledge of Human papillomavirus (HPV) among ethnically diverse women varying in generation status.

Although Human papillomavirus (HPV) is a common sexually transmitted infection, there is limited knowledge of HPV with ethnic/racial minorities experiencing the greatest disparities. This cross-sectional study used the most recent available data from the California Health Interview Survey to assess disparities in awareness and knowledge of HPV among ethnically/racially diverse women varying in generation status (N = 19,928). Generation status emerged as a significant predictor of HPV awareness across ethnic/racial groups, with 1st generation Asian-Americans and 1st and 2nd generation Latinas reporting the least awareness when compared to same-generation White counterparts. Also, generation status was a significant predictor of HPV knowledge, but only for Asian-Americans. Regardless of ethnicity/race, 1st generation women reported lowest HPV knowledge when compared to 2nd and 3rd generation women. These findings underscore the importance of looking at differences within and across ethnic/racial groups to identify sub-groups at greatest risk for poor health outcomes. In particular, we found generation status to be an important yet often overlooked factor in the identification of health disparities.

The reaction of methyl sterculate and malvalate with silver nitrate-silica gel and its use as a basis for the estimation of cyclopropene fatty acids.

When in contact with silver nitratesilica gel, methyl esters of cyclopropene fatty acids undergo ring opening to yield pairs of isomers with methylene, hydroxymethyl, or nitratomethyl side-chains at the original ring positions. Thus the main products from methyl sterculate were the methyl 9 (or 10)-methylene octadec-10 (or 8)-enoates, and, in lesser quantities, the methyl 9 (or 10)-(nitratomethyl)-octadec-9-enoates and the methyl 9 (or 10)-(hydroxymethyl)-octadec-9-enoates. Hydrogenation quantitatively converted this mixture of isomeric pairs to a mixture of methyl 9- and methyl 10-methyloctadecanoates.Chromatography on silver nitrate-silica gel, followed by gas chromatography of the hydrogenated products, has been used as the basis of a new method for estimating individual cyclopropene and cyclopropane acids in lipids.

Does usnic acid affect microtubules in human cancer cells?

Usnic acid, a lichen metabolite, is known to exert antimitotic and antiproliferative activities against normal and malignant human cells. Many chemotherapy agents exert their activities by blocking cell cycle progression, inducing cell death through apoptosis. Microtubules, protein structure involved in the segregation of chromosomes during mitosis, serve as chemotherapeutical targets due to their key role in cellular division as well as apoptosis. The aim of this work was to investigate whether usnic acid affects the formation and/or stabilisation of microtubules by visualising microtubules and determining mitotic indices after treatment. The breast cancer cell line MCF7 and the lung cancer cell line H1299 were treated with usnic acid 29 microM for 24 hours and two positive controls: vincristine (which prevents the formation of microtubules) or taxol (which stabilizes microtubules). Treatment of MCF7 and H1299 cells with usnic acid did not result in any morphological changes in microtubules or increase in the mitotic index. These results suggest that the antineoplastic activity of usnic acid is not related to alterations in the formation and/or stabilisation of microtubules.

Does usnic acid affect microtubules in human cancer cells? / O ácido úsnico pode afetar microtúbulos em células cancerosas humanas?

Usnic acid, a lichen metabolite, is known to exert antimitotic and antiproliferative activities against normal and malignant human cells. Many chemotherapy agents exert their activities by blocking cell cycle progression, inducing cell death through apoptosis. Microtubules, protein structure involved in the segregation of chromosomes during mitosis, serve as chemotherapeutical targets due to their key role in cellular division as well as apoptosis. The aim of this work was to investigate whether usnic acid affects the formation and/or stabilisation of microtubules by visualising microtubules and determining mitotic indices after treatment. The breast cancer cell line MCF7 and the lung cancer cell line H1299 were treated with usnic acid 29 µM for 24 hours and two positive controls: vincristine (which prevents the formation of microtubules) or taxol (which stabilizes microtubules). Treatment of MCF7 and H1299 cells with usnic acid did not result in any morphological changes in microtubules or increase in the mitotic index. These results suggest that the antineoplastic activity of usnic acid is not related to alterations in the formation and/or stabilisation of microtubules.

O ácido úsnico, um metabólito de liquens, é conhecido por sua atividade antimitótica e antiproliferativa em células humanas normais e malignas. Muitos quimioterápicos exercem suas atividades bloqueando a progressão do ciclo celular e induzindo morte celular por apoptose. Os microtúbulos, estruturas protéicas envolvidas na segregação dos cromossomos durante a mitose, servem como alvo quimioterapêutico devido ao seu importante papel tanto na divisão celular quanto nos mecanismos de morte celular por apoptose. O objetivo deste trabalho foi investigar se o ácido úsnico afeta a formação e/ou estabilização dos microtúbulos, a partir da visualização de microtúbulos e determinação de índices mitóticos após o tratamento. Células de câncer de mama MCF7 e de câncer de pulmão H1299 foram tratadas por 24 horas com 29 µM de ácido úsnico e dois controles positivos: vincristina (que impede a formação de microtúbulos) e taxol (que estabiliza microtúbulos). O tratamento das células MCF7 e H1299 com o ácido úsnico não resultou em aumento do índice mitótico. Os resultados sugerem que a atividade antineoplásica do ácido úsnico não está relacionada a alterações na formação e/ou estabilização de microtúbulos.

Concentration of headspace, airborne and aqueous volatiles on Chromosorb 105 for examination by gas chromatography and gas chromatography-mass spectrometry.

Techniques are described for the collection of volatile material from headspace vapours and the atmosphere and for the direct extraction of volatiles from aqueous solution by traps containing the porous polymer Chromosorb 105. The traps are inserted through a valve into a gas chromatograph which facilitates the desorption and transfer of the volatiles to high-resolution capillary columns. Selected applications of the technique are described.

Flash-lamp-pumped Ho:Tm:Cr:YAG and Ho:Tm:Er:YLF lasers: experimental results of a single, long pulse length comparison.

Flash-lamp-pumped, room-temperature Ho:Tm:Cr:YAG and Ho:Tm:Er:YLF are compared for single but long pulse operation, with pulse lengths of approximately 1.0 mus. Under similar operating conditions in normal-mode operation, a slope efficiency of 0.0331 was observed for Ho:Tm:Er:YLF compared with 0.0047 for Ho:Tm:Cr:YAG. For Q-switched operation, Ho:Tm:Er:YLF yielded a slope efficiency of 0.0075. In comparison, a slope efficiency of 0.0012 was obtained for Ho:Tm:Cr:YAG. Two methods of producing long pulse lengths are compared: pulse selection of normal-mode relaxation oscillations and Q-switching in a long resonator. Theoretical models developed in a companion paper for normal-mode relaxation oscillations and Q-switching in quasi-four-level solid-state lasers are in agreement with the experimental results.

Flash-lamp-pumped Ho:Tm:Cr:YAG and Ho:Tm:Er:YLF lasers: modeling of a single, long pulse length comparison.

Two methods of producing the long pulse lengths that promote efficient extraction of energy from low-gain, quasi-four-level lasers are analyzed. A long pulse length output can mitigate laser-induced damage effects and can be generated in quasi-four-level lasers by two disparate methods. One method utilizes Q-switching techniques in resonators designed to extend the pulse length and another utilizes the first pulse in a relaxation oscillation pulse train. Models for quasi-four-level lasers are derived here taking into account the nonnegligible thermal population of the lower laser level. Closed-form expressions are derived for both modes of operation of quasi-four-level laser systems so the parametric dependencies of both forms of operation become obvious, allowing facile comparison. In addition, a combined absorption and quantum efficiency, germane for flash-lamp pumping, is calculated for both Cr and Er sensitizers. Although the former has the advantage of broad absorption bands, the latter has the advantage of a quantum efficiency approaching 3.

Poly(rC) binding proteins mediate poliovirus mRNA stability.

The 5'-terminal 88 nt of poliovirus RNA fold into a cloverleaf RNA structure and form ribonucleoprotein complexes with poly(rC) binding proteins (PCBPs; AV Gamarnik, R Andino, RNA, 1997, 3:882-892; TB Parsley, JS Towner, LB Blyn, E Ehrenfeld, BL Semler, RNA, 1997, 3:1124-1134). To determine the functional role of these ribonucleoprotein complexes in poliovirus replication, HeLa S10 translation-replication reactions were used to quantitatively assay poliovirus mRNA stability, poliovirus mRNA translation, and poliovirus negative-strand RNA synthesis. Ribohomopoly(C) RNA competitor rendered wild-type poliovirus mRNA unstable in these reactions. A 5'-terminal 7-methylguanosine cap prevented the degradation of wild-type poliovirus mRNA in the presence of ribohomopoly(C) competitor. Ribohomopoly(A), -(G), and -(U) did not adversely affect poliovirus mRNA stability. Ribohomopoly(C) competitor RNA inhibited the translation of poliovirus mRNA but did not inhibit poliovirus negative-strand RNA synthesis when poliovirus replication proteins were provided in trans using a chimeric helper mRNA possessing the hepatitis C virus IRES. A C24A mutation prevented UV crosslinking of PCBPs to 5' cloverleaf RNA and rendered poliovirus mRNA unstable. A 5'-terminal 7-methylguanosine cap blocked the degradation of C24A mutant poliovirus mRNA. The C24A mutation did not inhibit the translation of poliovirus mRNA nor diminish viral negative-strand RNA synthesis relative to wild-type RNA. These data support the conclusion that poly(rC) binding protein(s) mediate the stability of poliovirus mRNA by binding to the 5'-terminal cloverleaf structure of poliovirus mRNA. Because of the general conservation of 5' cloverleaf RNA sequences among picornaviruses, including C24 in loop b of the cloverleaf, we suggest that viral mRNA stability of polioviruses, coxsackieviruses, echoviruses, and rhinoviruses is mediated by interactions between PCBPs and 5' cloverleaf RNA.

Studies of the free faecal amines of infants with gastroenteritis and of healthy infants.

The free primary amines present in the faeces of 44 infants (1-18 months) with gastroenteritis have been examined by field desorption mass spectrometry of the lactone form of their fluorescamine derivatives without their prior separation. p-Tyramine, 2-phenylethylamine, the diamines, putrescine and cadaverine and several of their acyl derivatives were common constituents, but a number of other amines were also characterised. Using thin layer chromatography and field desorption mass spectrometry of the amine dansyl derivatives a comparative study was made of the faecal amines of 13 selected infants with gastroenteritis (diarrhoea) and of 13 healthy infants. p-Tyramine, the most abundant amine, was significantly higher (p = 0.02) in the sick infants. The overall presence of p-tyramine was more significantly related to the diet of the infants. Faecal tyramine was low in breast fed infants but significantly higher (p = 0.01) in infants fed cow's milk.

Poliovirus 5'-terminal cloverleaf RNA is required in cis for VPg uridylylation and the initiation of negative-strand RNA synthesis.

Chimeric poliovirus RNAs, possessing the 5' nontranslated region (NTR) of hepatitis C virus in place of the 5' NTR of poliovirus, were used to examine the role of the poliovirus 5' NTR in viral replication. The chimeric viral RNAs were incubated in cell-free reaction mixtures capable of supporting the sequential translation and replication of poliovirus RNA. Using preinitiation RNA replication complexes formed in these reactions, we demonstrated that the 3' NTR of poliovirus RNA was insufficient, by itself, to recruit the viral replication proteins required for negative-strand RNA synthesis. The 5'-terminal cloverleaf of poliovirus RNA was required in cis to form functional preinitiation RNA replication complexes capable of uridylylating VPg and initiating the synthesis of negative-strand RNA. These results are consistent with a model in which the 5'-terminal cloverleaf and 3' NTRs of poliovirus RNA interact via temporally dynamic ribonucleoprotein complexes to coordinately mediate and regulate the sequential translation and replication of poliovirus RNA.

Presence of N-acyl and acetoxy derivatives of putrescine and cadaverine in the human gut.

N-acyl and acetoxy derivatives of putrescine and cadaverine have been found in the faeces of children and in cultures of isolates of gut bacteria. The evidence was accumulated from two dimensional, thin layer chromatography, field desorption mass spectrometry, and accurate mass measurement of the DANS derivatives of the amines. The acetoxy compounds of putrescine and cadaverine have not previously been reported.

Diode-pumped long-pulse-length Ho:Tm:YLiF(4) laser at 10 Hz.

An optical efficiency of 0.052 under normal mode operation for diode-pumped Ho:Tm:YLiF(4) at a pulse repetition frequency of 10 Hz has been achieved. Laser output energy of 30 mJ in single Q-switched pulses with 600-ns pulse length were obtained for an input energy of 3 J. A diffusion-bonded birefringent laser rod consisting of Ho:Tm-doped and undoped pieces of YLF was utilized for 10-Hz operation.

TPO1, a member of a novel protein family, is developmentally regulated in cultured oligodendrocytes.

Although the myelin membrane contains only a small set of major proteins, more sensitive assays indicate the presence of a plethora of uncharacterized proteins. We have used an antibody perturbation approach to reversibly block the differentiation of prooligodendroblasts into myelinating cells, and, in combination with a differential screening procedure, identified novel mRNAs that are activated during this period. One cDNA, TPO1, recognizes a 5.5-kb mRNA that is strongly up-regulated in oligodendrocytes after release of the differentiation block and that is expressed at high levels in brain tissue during active myelination. This cDNA represents at least two mRNAs differing from each other in their 5'-termini. The TPO1 cDNA contains an open reading frame of 1,380 bp, encoding a protein of 51.8 kDa with a predicted pI of 9.1 that contains two regions homologous to nonclassic zinc finger motifs. Subcellular localization studies suggest the enriched presence of TPO1 in spherical structures along the major cytoplasmic processes of oligodendrocytes. TPO1, along with homologues expressed in testis, placenta, and PC12 cells, form a novel family of proteins with multiple hydrophobic domains possibly serving as membrane spanning regions. We postulate that in oligodendrocytes, TPO1 encodes a protein factor involved in myelin biogenesis.