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1.
mBio ; 14(3): e0009823, 2023 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-37129484

RESUMO

Adaptive evolutionary processes are constrained by the availability of mutations which cause a fitness benefit and together make up the fitness landscape, which maps genotype space onto fitness under specified conditions. Experimentally derived fitness landscapes have demonstrated a predictability to evolution by identifying limited "mutational routes" that evolution by natural selection may take between low and high-fitness genotypes. However, such studies often utilize indirect measures to determine fitness. We estimated the competitive fitness of mutants relative to all single-mutation neighbors to describe the fitness landscape of three mutations in a ß-lactamase enzyme. Fitness assays were performed at sublethal concentrations of the antibiotic cefotaxime in a structured and unstructured environment. In the unstructured environment, the antibiotic selected for higher-resistance types-but with an equivalent fitness for a subset of mutants, despite substantial variation in resistance-resulting in a stratified fitness landscape. In contrast, in a structured environment with a low antibiotic concentration, antibiotic-susceptible genotypes had a relative fitness advantage, which was associated with antibiotic-induced filamentation. These results cast doubt that highly resistant genotypes have a unique selective advantage in environments with subinhibitory concentrations of antibiotics and demonstrate that direct fitness measures are required for meaningful predictions of the accessibility of evolutionary routes. IMPORTANCE The evolution of antibiotic-resistant bacterial populations underpins the ongoing antibiotic resistance crisis. We aim to understand how antibiotic-degrading enzymes can evolve to cause increased resistance, how this process is constrained, and whether it can be predictable. To this end, competition experiments were performed with a combinatorially complete set of mutants of a ß-lactamase gene subject to subinhibitory concentrations of the antibiotic cefotaxime. While some mutations confer on their hosts high resistance to cefotaxime, in competition these mutations do not always confer a selective advantage. Specifically, high-resistance mutants had equivalent fitnesses despite different resistance levels and even had selective disadvantages under conditions involving spatial structure. Together, our findings suggest that the relationship between resistance level and fitness at subinhibitory concentrations is complex; predicting the evolution of antibiotic resistance requires knowledge of the conditions that select for resistant genotypes and the selective advantage evolved types have over their predecessors.


Assuntos
Antibacterianos , beta-Lactamases , Antibacterianos/farmacologia , beta-Lactamases/genética , Cefotaxima/farmacologia , Resistência Microbiana a Medicamentos/genética , Seleção Genética , Mutação
2.
Chem Asian J ; 18(14): e202300352, 2023 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-37246486

RESUMO

The design of multifunctional materials is a challenging and important objective for a wide array of multidisciplinary applications. However, a multifunctional organic emitter exhibiting simultaneous aggregation-induced emission (AIE), multi-responsive polymorphs, mechanoluminescence and electroluminescence have been scarce. In this study, two anthracene based compounds, namely 10-(4-(9H-carbazol-9-yl)phenyl)anthracene-9-carbonitrile (CzPACN) and 10-(4-(di-p-tolylamino)phenyl)anthracene-9-carbonitrile (DTPACN) was designed and synthesized with rigid and flexible donors, respectively. The CzPACN shows the bright blue emission and DTPACN shows the bright green emission in solution. We have demonstrated an effective strategy to achieve three polymorphic phases such as DTPACN-α, DTPACN-ß and DTPACN-γ from DTPACN by controlling the temperature. Under mechanical stimuli, highly restricted and non-planar crystals of the structurally tuned polymorphs DTPACN-α, and DTPACN-ß exhibited red shifted emission and DTPACN-γ showed blue shifted emission. Conversely, CzPACN is not showing polymorphism and is not sensitive to external stimuli. In addition, blue and green OLEDs were fabricated using CzPACN and DTPACN, respectively, as an emitter and achieved a maximum external quantum efficiency (EQEmax ) of 5.5% and 5.7%, respectively, for blue and green OLEDs. Further, this study suggests designing multi-responsive smart materials via a simple modification by introducing a non-planar unit with a large twist.

3.
Proc Natl Acad Sci U S A ; 119(39): e2209373119, 2022 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-36122210

RESUMO

The extent of parallel evolution at the genotypic level is quantitatively linked to the distribution of beneficial fitness effects (DBFE) of mutations. The standard view, based on light-tailed distributions (i.e., distributions with finite moments), is that the probability of parallel evolution in duplicate populations is inversely proportional to the number of available mutations and, moreover, that the DBFE is sufficient to determine the probability when the number of available mutations is large. Here, we show that when the DBFE is heavy-tailed, as found in several recent experiments, these expectations are defied. The probability of parallel evolution decays anomalously slowly in the number of mutations or even becomes independent of it, implying higher repeatability of evolution. At the same time, the probability of parallel evolution is non-self-averaging-that is, it does not converge to its mean value, even when a large number of mutations are involved. This behavior arises because the evolutionary process is dominated by only a few mutations of high weight. Consequently, the probability varies widely across systems with the same DBFE. Contrary to the standard view, the DBFE is no longer sufficient to determine the extent of parallel evolution, making it much less predictable. We illustrate these ideas theoretically and through analysis of empirical data on antibiotic-resistance evolution.


Assuntos
Evolução Molecular , Bactérias/classificação , Bactérias/genética , Resistência Microbiana a Medicamentos/genética , Genótipo , Mutação , Probabilidade , Seleção Genética
4.
Proc Biol Sci ; 289(1974): 20212486, 2022 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-35506221

RESUMO

For antibiotic resistance to arise, new resistant mutants must establish in a bacterial population before they can spread via natural selection. Comprehending the stochastic factors that influence mutant establishment is crucial for a quantitative understanding of antibiotic resistance emergence. Here, we quantify the single-cell establishment probability of four Escherichia coli strains expressing ß-lactamase alleles with different activity against the antibiotic cefotaxime, as a function of antibiotic concentration in both unstructured (liquid) and structured (agar) environments. We show that concentrations well below the minimum inhibitory concentration (MIC) can substantially hamper establishment, particularly for highly resistant mutants. While the pattern of establishment suppression is comparable in both tested environments, we find greater variability in establishment probability on agar. Using a simple branching model, we investigate possible sources of this stochasticity, including environment-dependent lineage variability, but cannot reject other possible causes. Lastly, we use the single-cell establishment probability to predict each strain's MIC in the absence of social interactions. We observe substantially higher measured than predicted MIC values, particularly for highly resistant strains, which indicates cooperative effects among resistant cells at large cell numbers, such as in standard MIC assays.


Assuntos
Escherichia coli , beta-Lactamas , Ágar/farmacologia , Antibacterianos/farmacologia , Escherichia coli/genética , Testes de Sensibilidade Microbiana , beta-Lactamas/farmacologia
5.
Front Microbiol ; 12: 698970, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34489889

RESUMO

For a better understanding of the evolution of antibiotic resistance, it is imperative to study the factors that determine the initial establishment of mutant resistance alleles. In addition to the antibiotic concentration, the establishment of resistance alleles may be affected by interactions with the surrounding susceptible cells from which they derive, for instance via the release of nutrients or removal of the antibiotic. Here, we investigate the effects of social interactions with surrounding susceptible cells on the establishment of Escherichia coli mutants with increasing ß-lactamase activity (i.e., the capacity to hydrolyze ß-lactam antibiotics) from single cells under the exposure of the antibiotic cefotaxime (CTX) on agar plates. We find that relatively susceptible cells, expressing a ß-lactamase with very low antibiotic-hydrolyzing activity, increase the probability of mutant cells to survive and outgrow into colonies due to the active breakdown of the antibiotic. However, the rate of breakdown by the susceptible strain is much higher than expected based on its low enzymatic activity. A detailed theoretical model suggests that this observation may be explained by cell filamentation causing delayed lysis. While susceptible cells may hamper the spread of higher-resistant ß-lactamase mutants at relatively high frequencies, our findings show that they promote their initial establishment.

6.
Sci Rep ; 11(1): 6199, 2021 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-33739021

RESUMO

Elevated levels of radon and thoron in the indoor atmosphere may cause the deleterious effects on the mankind. Mining sites and their environs attract a special interest in radon studies as higher levels are frequently reported in the habitats. In the present study, radon and thoron levels were measured in the dwellings of Buddonithanda, a village in the environs of proposed uranium mining site, with pin-hole (SSNTDs) dosimeters for the period of a year. The measured radon and thoron levels were found to vary widely from 14 to 675 Bq m-3 (geometric mean = 94 Bq m-3) and from 21 to 704 Bq m-3 (geometric mean = 121 Bq m-3), respectively. An attempt was made to understand the large spatial variation of these levels. The seasonal and diurnal variation studies were used in unraveling the behavior of the radioactive isotopes in indoor environment and the same was explained with the help of a simplified mathematical model. Quantification of inhalation dose due to radon and thoron was done with suitable occupancy factors.

7.
Elife ; 92020 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-32423531

RESUMO

Fitness effects of mutations depend on environmental parameters. For example, mutations that increase fitness of bacteria at high antibiotic concentration often decrease fitness in the absence of antibiotic, exemplifying a tradeoff between adaptation to environmental extremes. We develop a mathematical model for fitness landscapes generated by such tradeoffs, based on experiments that determine the antibiotic dose-response curves of Escherichia coli strains, and previous observations on antibiotic resistance mutations. Our model generates a succession of landscapes with predictable properties as antibiotic concentration is varied. The landscape is nearly smooth at low and high concentrations, but the tradeoff induces a high ruggedness at intermediate antibiotic concentrations. Despite this high ruggedness, however, all the fitness maxima in the landscapes are evolutionarily accessible from the wild type. This implies that selection for antibiotic resistance in multiple mutational steps is relatively facile despite the complexity of the underlying landscape.


Drug resistant bacteria pose a major threat to public health systems all over the world. Darwinian evolution is at the heart of this drug resistance: a mutation that allows bacteria to divide in the presence of a drug appears initially in a single cell. This mutation makes this cell and its descendants more likely to survive, so they can end up taking over the population. The evolution of resistance can be thought of in terms of 'bacterial fitness landscapes'. These landscapes visualise the relationship between the mutations present in a population of bacteria and how quickly the bacteria divide or reproduce. They are called landscapes because they can be represented as a series of mountains and valleys. The peaks of this landscape represent combinations of mutations that give bacteria the greatest chance of dividing (the greatest fitness). In a landscape with multiple peaks, some peaks will be higher than others. If the landscape is smooth, bacteria can easily acquire mutations for drug resistance. However, in a rugged landscape, bacteria may get stuck at sub-optimal peaks, because the mutations that would enable them to reach a higher peak would first lead them to losing fitness. Several studies on the evolution of antibiotic resistance exist for specific bacteria and specific drugs, but relatively little is known about the general properties of the underlying fitness landscapes. Do these landscapes have features that can help explain the rapid evolution of high levels of resistance? Antibiotic resistance often comes at a cost ­ more resistant strains of bacteria tend to grow more slowly when the drug is absent. To build a model of antibiotic resistance landscapes, Das et al. performed growth experiments on several strains of Escherichia coli exposed to a drug called ciprofloxacin. They measured how the rate at which the bacteria divided changed at different antibiotic concentrations, and combined this with the observation about resistant strains growing slower to formulate a mathematical model of antibiotic resistance landscapes. The landscapes that resulted were found to be very rugged, but unexpectedly, the bacteria could still evolve to access all fitness peaks. This means that landscape ruggedness does not constrain the evolution of resistance. Understanding how and when resistance evolves is important both for the design of new drugs and the development of treatment protocols. A specific prediction of the model is that resistance evolution in fitness landscapes where resistant strains divide more slowly is reversible. This implies that the bacteria could regain their susceptibility to treatment when the drug concentration decreases, but this would depend on the specific bacteria and drug in question. More broadly, the model provides a framework for addressing the evolution of resistance in clinical and environmental settings, where drug concentrations vary widely in time and space.


Assuntos
Farmacorresistência Bacteriana/genética , Escherichia coli/genética , Aptidão Genética , Modelos Genéticos , Mutação , Antibacterianos/farmacologia , Relação Dose-Resposta a Droga , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento
8.
Radiat Prot Dosimetry ; 189(2): 205-212, 2020 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-32195551

RESUMO

Studies are being conducted for the past few decades in and around the uranium mining sites across the globe to identify environmental nuclear radiation risk to the common public. The area near Dasarlapally village was identified for uranium exploration by the AMDER, Hyderabad. The present study was carried out to measure the indoor radon and thoron activity concentrations in the dwellings of Dasarlapally village. For this purpose different types of dwellings were chosen randomly across the village. The measured annual average concentration of radon and thoron in dwellings were found to be 141 ± 42 and 139 ± 77 Bqm-3, respectively, and the calculated annual effective inhalation dose due to radon was determined to be 3.5 mSv. Seasonal variation and diurnal variation of radon and thoron activity concentration were investigated. The variation of radon and thoron activity concentration in different types of dwellings was also studied, and the variation was found to be statistically insignificant. The uncertainty propagated in the effective inhalation dose due to thoron was discussed.


Assuntos
Poluentes Radioativos do Ar , Poluição do Ar em Ambientes Fechados , Monitoramento de Radiação , Radônio , Urânio , Poluentes Radioativos do Ar/análise , Poluição do Ar em Ambientes Fechados/análise , Habitação , Índia , Mineração , Radônio/análise , Produtos de Decaimento de Radônio/análise , Urânio/análise
9.
Phys Rev E ; 95(6-1): 062410, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28709258

RESUMO

The living cell uses a variety of molecular receptors to read and process chemical signals that vary in space and time. We model the dynamics of such molecular level measurements as Markov processes in steady state, with a coupling between the receptor and the signal. We prove exactly that, when the signal dynamics is not perturbed by the receptors, the free energy consumed by the measurement process is lower bounded by a quantity proportional to the mutual information. Our result is completely independent of the receptor architecture and dependent on signal properties alone, and therefore holds as a general principle for molecular information processing.

10.
Biol Trace Elem Res ; 169(1): 22-6, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26066526

RESUMO

In India, endemic goitre is present in sub-Himalayan region and in pockets in states of Andhra Pradesh, Karnataka and Gujarat. Being a public health problem amenable for prevention, the assessment of prevalence of endemic goitre in an area helps in understanding whether the preventive strategies under National Iodine Deficiency Disorder Control Program (NIDDCP) have any impact on the control of endemic goitre. Hence, the current study was carried out to determine the prevalence, distribution and factors associated with iodine deficiency goitre among 6-12-year-old children in a rural area in south Karnataka. A cross-sectional study was conducted among 838 children, using a questionnaire adopted from Iodized Salt Program Assessment Tool and the tools prescribed by WHO for goitre survey. The prevalence of goitre in the study area was 21.9% (95% CI 19.2-24.8). There was higher prevalence of goitre among those having salt iodine <15 ppm than those with >15 ppm (P = 0.01; OR 1.59; 95% CI 1.10-2.29). In 10% of the children, urinary iodine excretion (UIE) was assessed and prevalence was higher among those with <100 µg/l of UIE than those with normal UIE, which was not statistically significant (P = 0.8, OR 1.36; 95% CI 0.62-2.96). Multiple logistic regression revealed that gender (P = 0.002; OR 1.7; 95% CI 1.21-2.35) was an independent variable associated with goitre. The study area was found to be moderately endemic for goitre based on the WHO criteria. Higher prevalence of goitre was found to be still associated with consumption of low iodized salt (<15 ppm) necessitating emphasis on monitoring of salt iodine levels in the study area. Though NIDDCP is being implemented since five decades in India, the burden of iodine deficiency disorders (IDDs) is still high demanding further impetus to the monitoring systems of the programme.


Assuntos
Bócio Endêmico/epidemiologia , Criança , Estudos Transversais , Feminino , Humanos , Índia/epidemiologia , Iodo , Masculino , Prevalência , Saúde Pública , Fatores de Risco , Cloreto de Sódio na Dieta
11.
Ayu ; 37(1): 62-66, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28827957

RESUMO

BACKGROUND: Cissampelos pareira Linn. is considered as an established source of Patha, whereas Cyclea peltata (Lam.) Hook. F. & Thomas is used as a source plant of Patha in the southern part of India. In classical texts, two different varieties of Patha, i.e. Rajpatha (C. peltata) and Laghupatha (C. pareira), are mentioned which possess almost similar properties. OBJECTIVE: To compare antipyretic and analgesic activities of C. pareira and C. peltata in suitable experimental model. MATERIALS AND METHODS: Powder (540 mg/kg) and ethanolic extract (200 mg/kg) of both the test drugs (C. pareira and C. peltata) were evaluated for antipyretic activity in Brewer's yeast-induced pyrexia model in rats. Analgesic activity was evaluated by radiant heat model in rats and acetic acid-induced writhing syndrome in mice. RESULTS AND DISCUSSION: Result of the present study had shown that powder of C. pareira (540 mg/kg) has moderate antipyretic activity as compared to the powder of C. peltata and extract of both test drugs. C. pareira powder showed better analgesic effect than ethanolic extract (200 mg/kg) of both the test drugs in radiant heat model in rats, while in acetic acid-induced writhing syndrome, ethanolic extract (280 mg/kg) of both drugs showed pronounced effect as compared to powder form (780 mg/kg) in mice. CONCLUSION: Both C. pareira and C. peltata exhibited analgesic effects in experimental animals. The effect is more significant in C. peltata treated group compared to C. pareira. Antipyretic effect was observed with the pretreatment of C. pareira.

12.
Luminescence ; 30(5): 611-8, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25352277

RESUMO

The effect of solvents of varying polarity on the absorption and fluorescence emission of the Schiff base, 2-{[3-(1H-benzimidazole-2-yl) phenyl]carbonoimidoyl}phenol, was studied using Lippert-Mataga bulk polarity function, Reichardt's microscopic solvent polarity parameter and Kamlet's multiple linear regression approach. The spectral properties follow Reichardt's microscopic solvent polarity parameter better than Lippert-Mataga bulk polarity parameter, indicating the presence of both general solute-solvent interactions and specific interactions. Catalan's multiple linear regression approach indicates the major role of solvent polarizability/dipolarity influence compared with solvent acidity or basicity. The solvatochromic effect was utilized to calculate the dipole moments of ground and excited states of the Schiff base using different methods. Bathochromic shift in the emission spectrum and the increase in dipole moment in the excited state signifies the intramolecular charge transfer character in the emitting singlet state. Fluorescence quenching by aniline was also studied in 1,4-dioxane and n-butanol, and the results were analyzed using sphere of action static quenching and finite sink approximation models.


Assuntos
Benzimidazóis/química , Bases de Schiff/química , Solventes/química , Espectrometria de Fluorescência/métodos , 1-Butanol/química , Compostos de Anilina/química , Dioxanos/química , Modelos Lineares
13.
Artigo em Inglês | MEDLINE | ID: mdl-25122268

RESUMO

Recent work has developed a nonlinear hydrodynamic fluctuation theory for a chain of coupled anharmonic oscillators governing the conserved fields, namely, stretch, momentum, and energy. The linear theory yields two propagating sound modes and one diffusing heat mode, all three with diffusive broadening. In contrast, the nonlinear theory predicts that, at long times, the sound mode correlations satisfy Kardar-Parisi-Zhang scaling, while the heat mode correlations have Lévy-walk scaling. In the present contribution we report on molecular dynamics simulations of Fermi-Pasta-Ulam chains to compute various spatiotemporal correlation functions and compare them with the predictions of the theory. We obtain very good agreement in many cases, but also some deviations.


Assuntos
Hidrodinâmica , Simulação de Dinâmica Molecular , Temperatura Alta
14.
Asian Pac J Cancer Prev ; 15(15): 6095-8, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25124579

RESUMO

BACKGROUND: Cervical cancer is potentially the most preventable and treatable cancer. Despite the known efficacy of cervical screening, a significant number of women do not avail themselves of the procedure due to lack of awareness. OBJECTIVES: This study was conducted to elicit information on the knowledge, attitude and practice (KAP) regarding screening (Pap test) and vaccination for carcinoma cervix among female doctors and nurses in a tertiary care hospital in Bangalore and to assess barriers to acceptance of the Pap test. MATERIALS AND METHODS: A cross-sectional, descriptive study was conducted with semi-structured, self-administered questionnaire among female health professionals. The study subjects were interviewed for KAP regarding risk factors for cancer cervix, Pap test and HPV vaccination for protection against carcinoma cervix. RESULTS: Higher proportion of doctors 45 (78.9%) had very good knowledge as compared to only 13 (13.3%) of the nurses, about risk factors for cancer cervix and Pap test (p=0.001). As many as 138(89.6%) of the study subjects had favorable attitude towards Pap test and vaccination, but 114 (73.6%) of the study subjects never had a Pap test and the most common reason 35 (31%) for not practicing was absence of disease symptoms. CONCLUSIONS: In spite of good knowledge and attitudes towards cancer cervix and Pap test being good, practice remained low among the study subjects and most common reasons for not undergoing Pap test was absence of disease symptoms. The independent predictors of ever having a Pap test done was found to be the occupation and duration of married life above 9 yrs. Hence there is a strong need to improve uptake of Pap test by health professionals by demystifying the barriers.


Assuntos
Atitude do Pessoal de Saúde , Pessoal de Saúde/psicologia , Programas de Rastreamento/estatística & dados numéricos , Percepção , Padrões de Prática Médica/estatística & dados numéricos , Neoplasias do Colo do Útero/prevenção & controle , Vacinação/estatística & dados numéricos , Adulto , Colo do Útero/patologia , Estudos Transversais , Feminino , Seguimentos , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Índia , Teste de Papanicolaou , Prognóstico , Inquéritos e Questionários , Atenção Terciária à Saúde , Neoplasias do Colo do Útero/diagnóstico , Esfregaço Vaginal
15.
Mymensingh Med J ; 20(2): 303-7, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21522105

RESUMO

Four pregnancies were exposed to gonadotrophin-releasing hormone agonist (GnRHa) during early pregnancy and the patients were followed up to find out the outcome of their pregnancies. In three patients long-acting GnRHa (triptorelin acetate 3.75 mg) once monthly was used for severe pelvic endometriosis as part of preparation for undergoing assisted reproductive technology (ART) cycle, and in one patient daily injections of short-acting GnRHa (buserelin 0.05 mg) was given for down-regulation for ART cycle. The age of the patients ranged from 29 to 38 years and duration of infertility was 3 to 13 years. In patients prescribed long-acting GnRHa, diagnosis of pregnancy was done late at around 5-8 weeks by ultrasonography, whereas in patients using short-acting GnRHa diagnosis of pregnancy was made with blood beta human chorionic gonadotropin (HCG) level after the 26th day of injections. Three pregnancies were delivered around term and the babies had no apparent complication or any congenital anomaly. One of the pregnancies ended up into spontaneous abortion at 14 weeks of pregnancy. The children were regularly examined by pediatricians regarding physical and mental development and for any abnormal behavioral problems. All of them are normal till now.


Assuntos
Hormônio Liberador de Gonadotropina/agonistas , Infertilidade Feminina/tratamento farmacológico , Resultado da Gravidez , Adulto , Busserrelina/uso terapêutico , Feminino , Fármacos para a Fertilidade Feminina/uso terapêutico , Humanos , Gravidez
16.
Phys Rev E Stat Nonlin Soft Matter Phys ; 82(4 Pt 1): 041910, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21230316

RESUMO

Weak bonds are ubiquitous in biological structures. They often act as adhesive contacts within an extended structure, for example, the internal bonds in a folded protein or a DNA/RNA loop. They also act as linkers between two structures, for example, a protein grafted in a cell membrane or a protein linking the cell membranes of two neighboring cells. Typically, the breakage of a bond depends on the strength of the binding potential and viscosity of the medium. But when extended structures couple to the bond, as in the above examples, the dynamics of the structure also has to be considered in order to understand the bond breakage phenomenon. Here we consider a generic model, a stretched polymer (an extended structure) tethered to a soft bond and study how the dynamics of the polymer, in addition to thermal noise, influences bond breakage. We also explore how the hydrodynamic interaction due to the fluid medium, which couples the distant parts of the polymer, change the bond breakage rate. We find that hydrodynamic interaction enhances the breakage rate and also makes the motion of the unstable collective mode of the polymer more coherent.

17.
Indian J Surg Oncol ; 1(4): 303-4, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22693382

RESUMO

Hyperthermia, total anoxia and low pH have shown selective lethal effect on malignant cells. A perfusion system was devised to combine these modalities and was tried in 4 cases of advanced malignancy. A perfusion lasting for 45 minutes was found safe for normal tissue and yet selectively injurious to malignant cells. Technically this is a very simple procedure and its principles can be utilized in regional infusion also. Though the clinical material is scanty,the method deserves further trial.

18.
Cancer Biomark ; 5(6): 261-72, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-20037202

RESUMO

All the anti-cancer drugs proved to be highly cytotoxic agents to normal cells like lymphocyte cells used in our study which do not come under rapidly dividing cells like bone marrow cells, fetal cells, germ cells, hair follicle cells, intestinal cells, etc. but will proliferate when maintained in growth media with proliferation agents. In this investigation, we determined the effect of anti-cancer drugs on lymphocyte cultures from peripheral blood of healthy non-smoking donors under in vitro conditions by employing MTT assay. All the experiments were carried out with seven anti-cancer drugs; Carboplatin, Avastin, Vinorelbine, Tamoxifen Citrate, Methotrexate, Gemcitabine and Paclitaxel which are broad-spectrum cancer drugs and being used in six different types of chemotherapy in cancers. We have documented the results that were evaluated by statistical analysis. The MTT assay is now widely adopted by researchers and industry, as it is a rapid spectrophotometric method for determining cell viability in cell lines and in vitro. The initial or dose-finding studies determine the drug toxicity relative to dose and subsequent studies define the spectrum of activity of the drug. And moreover, no anti-neoplastic drug is devoid of side effects. Hence, this investigation determines the lethal concentrations and thereby the dosages at which individual anti-neoplastic drugs and also combinations can bring about certain degree of cytotoxicity in human lymphocytes which with comparative study on cancer cell lines would be useful in defining drug dosages.


Assuntos
Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Linfócitos/efeitos dos fármacos , Células Cultivadas , Humanos , Espectrofotometria/métodos
19.
Cancer Biomark ; 5(1): 33-40, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19242060

RESUMO

Human Cytochrome P450 3A4 is a major P450 enzyme in the liver and gastrointestinal tract. It plays an important role in the metabolism of a wide variety of drugs, some endogenous steroids, and harmful environmental contaminants. To investigate the interindividual variation in CYP3A4 levels we have carried out a study on the genetic polymorphism of 100 breast cancer subjects using fine needle aspiration cytology (FNAC) sampling procedure. DNA was extracted from all the samples and PCR was carried out for detecting the CYP3A4 gene polymorphisms. We selected exon-7 and 10 which are present on the 5'-flanking coding region of the gene using the respective primers for PCR followed by direct automated sequencing method for detecting the mutations. These mutations were compared to the wild type sequence structures obtained from GenBank database (accession no. AF209389). We found two novel point mutations which are heterozygous mutant alleles. The two variant alleles were Ile222Arg and Phe175Val occurring in coding region of exon-7. Ile222Arg mutation was found in 3 malignant cases whereas Phe175Val mutation was found in 4 malignant cases. This is the first report of these two novel point mutations in CYP3A4 gene. These mutations in the gene in respective patients were found to relate to drug response in invasive ductal carcinomas of breast cancer.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Carcinoma Ductal de Mama/genética , Citocromo P-450 CYP3A/genética , Mutação/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha Fina , Neoplasias da Mama/diagnóstico , Carcinoma Ductal de Mama/diagnóstico , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase , Polimorfismo de Nucleotídeo Único/genética , Prognóstico , Taxa de Sobrevida
20.
Asian Pac J Cancer Prev ; 10(6): 1025-30, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-20192577

RESUMO

Ovarian cancer has emerged as one of the most common malignancies affecting women in India. The present communication reports the trends in the incidence rate of ovarian cancer for Indian women. The data published in Cancer Incidence in Five Continents for various Indian registries for different periods and / or publication by the individual registries served as the source material. Mean annual percentage change (MAPC) in rates was computed using relative differences between two time periods. During the period 2001-06, the age-standardized incidence rates (ASR) for ovarian cancer varied from 0.9 to 8.4 per 100,000 person years amongst various registries. The highest incidence was noted in Pune and Delhi registries. The Age Specific Incidence Rate (ASIR) for ovarian cancer revealed that the disease increases from 35 years of age and reaches a peak between the ages 55-64. The trend analysis by period showed an increasing trend in the incidence rate of ovarian cancer in most of the registries, with a mean annual percentage increase in ASR ranged from 0.7% to 2.4 %. Analysis of data by ASIR revealed that the mean annual percentage increase was higher for women in the middle and older age groups in most of the registries. Estimation of annual percent change (EAPC) in ovarian cancer by Poisson regression model through Maximum Likelihood Estimation (MLE) for the data of 3 population-based cancer registries vs. Mumbai, Chennai and Bangalore for the period 1983-2002 revealed that linear regression was found to be satisfactory fit between period and incidence rate. Statistically significant increase in EAPC was noted with the crude rate (CR,) ASR, and ASIR for several age-groups. Efforts should be made to detect ovarian cancer at an early stage by educating population about the risk factors. Most of the ovarian cancers are environmental in origin and consequently, at least in principle avoidable.


Assuntos
Neoplasias Ovarianas/epidemiologia , Adolescente , Adulto , Fatores Etários , Idoso , Feminino , Humanos , Incidência , Índia/epidemiologia , Modelos Lineares , Pessoa de Meia-Idade , Distribuição de Poisson , Sistema de Registros
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