Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 83
Filtrar
1.
Clin Transl Oncol ; 24(3): 407-431, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34595736

RESUMO

An antibody-drug conjugate (ADC) is an advanced chemotherapeutic option with immense promises in treating many tumor. They are designed to selectively attack and kill neoplastic cells with minimal toxicity to normal tissues. ADCs are complex engineered immunoconjugates that comprise a monoclonal antibody for site-directed delivery and cytotoxic payload for targeted destruction of malignant cells. Therefore, it enables the reduction of off-target toxicities and enhances the therapeutic index of the drug. Hepatocellular carcinoma (HCC) is a solid tumor that shows high heterogeneity of molecular phenotypes and is considered the second most common cause of cancer-related death. Studies show enormous potential for ADCs targeting GPC3 and CD24 and other tumor-associated antigens in HCC with their high, selective expression and show potential outputs in preclinical evaluations. The review mainly highlights the preclinical evaluation of different antigen-targeted ADCs such as MetFab-DOX, Anti-c-Met IgG-OXA, Anti CD 24, ANC-HN-01, G7mab-DOX, hYP7-DCand hYP7-PC, Anti-CD147 ILs-DOX and AC133-vcMMAF against hepatocellular carcinoma and its future relevance.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Imunoconjugados/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Avaliação Pré-Clínica de Medicamentos , Humanos
2.
Clin Transl Oncol ; 23(11): 2206-2219, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33991328

RESUMO

Cancer genomics has evolved over the years from understanding the pathogenesis of cancer to screening the future possibilities of cancer occurrence. Understanding the genetic profile of tumors holds a prognostic as well as a predictive value in this era of therapeutic surveillance, molecular remission, and precision medicine. Identifying molecular markers in tumors is the current standard of approach, and requires an efficient combination of an accessible sample type and a profoundly sensitive technique. Liquid biopsy or cell-free DNA has evolved as a novel sample type with promising results in recent years. Although cell-free DNA has significant role in various cancer types, this review focuses on its application in Non-Hodgkin's Lymphoma. Beginning with the current concept and clinical relevance of minimal residual disease in Non-Hodgkin's lymphoma, we discuss the literature on circulating DNA and its evolving application in the realm of cutting-edge technology.


Assuntos
DNA Tumoral Circulante/sangue , Linfoma não Hodgkin/genética , Linfoma não Hodgkin/patologia , Biomarcadores Tumorais/sangue , Ácidos Nucleicos Livres/sangue , Citometria de Fluxo , Marcadores Genéticos , Técnicas de Genotipagem , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Biópsia Líquida , Linfoma/sangue , Linfoma/genética , Linfoma não Hodgkin/sangue , Linfoma não Hodgkin/diagnóstico por imagem , Mutação , Neoplasia Residual/sangue , Neoplasia Residual/genética , Neoplasia Residual/patologia , Reação em Cadeia da Polimerase/métodos , Tomografia por Emissão de Pósitrons , Medicina de Precisão , Prognóstico , Transcriptoma , Translocação Genética
3.
Sci Total Environ ; 751: 141728, 2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-32890797

RESUMO

Trees significantly impact land-atmosphere feedbacks through evapotranspiration, photosynthesis and isoprene emissions. These processes influence the local microclimate, air quality and can mitigate temperature extremes and sequester carbon dioxide. Despite such importance, currently only 5 out of 15 atmospheric chemistry climate models even partially account for the presence of cropland trees. We first show that the tree cover over intensely farmed regions in Asia, Australia and South America is significantly underestimated (e.g. only 1-3% tree cover over north-India) in the Model of Emissions of Gases and Aerosol from Nature (MEGAN) and absent in Noah land-surface module of the Weather Research and Forecasting (WRF-Chem) Model. By including the actual tree cover (~10%) over the north-west Indo Gangetic Plain in the Noah land-surface module of the WRF-Chem and the MEGAN module, during the rice growing monsoon season in August, we find that the latent heat flux alone increases by 100%-300% while sensible heat flux reduces by 50%-100%, leading to a reduction in daytime boundary layer height by 200-400 m. This greatly improves agreement between the modelled and measured temperature, boundary layer height and surface ozone, which were earlier overestimated and isoprene and its oxidation products which were earlier underestimated. Mitigating peak daytime temperatures and ozone improves rice production by 10 to 20%. Our findings from north west Indo-Gangetic Plain establish that such plantations mitigate heat stress, and have beneficial effects on crop yields while also sequestering carbon. Expanding agroforestry practices to 50% of the cropland area could result in up to 40% yield gain regionally. Implementing such strategies globally could increase crop production and sequester 0.3-30 GtC per year, and therefore future climate mitigation and food security efforts should consider stakeholder participation for increased cropland agroforestry in view of its beneficial effects.


Assuntos
Poluentes Atmosféricos , Ozônio , Poluentes Atmosféricos/análise , Ásia , Atmosfera , Austrália , Produtos Agrícolas , Monitoramento Ambiental , Índia , Ozônio/análise , América do Sul , Temperatura , Árvores
4.
J Mater Sci Mater Med ; 29(8): 123, 2018 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-30032462

RESUMO

Dicalcium phosphate dihydrate (DCPD) brushite coating with flake like crystal structure for the protection of AZX310 and AM50 magnesium (Mg) alloys was prepared through chemical deposition treatment. Chemical deposition treatment was employed using Ca(NO3)2·4H2O and KH2PO4 along with subsequent heat treatment. The morphological results revealed that the brushite coating with dense and uniform structures was successfully deposited on the surface of AZX310 and AM50 alloys. The X-ray diffraction (XRD) patterns and Attenuated total reflectance infrared (ATR-IR) spectrum also revealed the confirmation of DCPD layer formation. Hydrophilic nature of the DCPD coatings was confirmed by Contact angle (CA) measurements. Moreover, electrochemical immersion and in vitro studies were evaluated to measure the corrosion performance and biocompatibility performance. The deposition of DCPD coating for HTI AM50 enables a tenfold increase in the corrosion resistance compared with AZX310. Hence the ability to offer such significant improvement in corrosion resistance for HTI AM50 was coupled with more bioactive nature of the DCPD coating is a viable approach for the development of Mg-based degradable implant materials.


Assuntos
Materiais Biocompatíveis/química , Fosfatos de Cálcio/química , Materiais Revestidos Biocompatíveis/química , Ligas/química , Osso e Ossos/patologia , Corrosão , Cristalografia por Raios X , Espectroscopia Dielétrica , Eletroquímica , Humanos , Magnésio/química , Teste de Materiais , Microscopia Eletrônica de Varredura , Propriedades de Superfície , Difração de Raios X
5.
Epidemiol Infect ; 146(8): 1048-1055, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29655390

RESUMO

Using the dengue surveillance program, we prospectively collected data on all the suspected and confirmed cases of dengue in Barbados from 2006 to 2015. Data were analysed for demographic, seasonal and temporal dynamics of this disease in this country. The overall mean annual incidence rate of suspected and confirmed dengue over the study period was 0.49% (range 0.15%-0.99%) and 0.16% (range 0.05%-0.48%), respectively. There was a significant correlation between the mean monthly number of confirmed cases, the mean monthly rainfall and the mean monthly relative humidity percentage. Dengue in this population is predominantly an infection affecting children and young adults. The median age of the patients with both, suspected and confirmed dengue was 25 years and the highest proportion of cases was seen in the age group 0-15 years. The annual incidence rates of both the suspected and the confirmed cases showed an upward trend during the study period and this upward trend was more pronounced among children.


Assuntos
Dengue/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Barbados/epidemiologia , Criança , Pré-Escolar , Dengue/virologia , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estações do Ano , Adulto Jovem
6.
Mycologia ; 109(5): 804-814, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29345534

RESUMO

A new Asian species of Crepidotus (Basidiomycota, Agaricales), C. asiaticus, is presented based on morphological and nuc rDNA internal transcribed spacer (ITS1-5.8S-ITS2 = ITS) and large subunit (28S) sequence data. This new species, found in India and Thailand, is characterized by the centrally stipitate medium-sized basidiomata, orange to reddish brown pileus, white to brownish orange lamellae, and white stipe. Based on morphology, C. asiaticus is similar to the neotropical C. thermophilus. However, the microscopic characters, especially the size and shape of the basidiospores, can be used to distinguish these two taxa, as well as their geographic distributions. Further, the phylogenetic position of C. asiaticus is unique based on ITS and 28S nuc rDNA sequences. Melanomphalia argipoda, described by Singer from Ecuador, is also a stipitate Crepidotus based on an ITS sequence of the type specimen, so the new combination is proposed here. Phylogenetically, the three species form a monophyletic group with the Asiatic C. asiaticus forming the sister lineage to the neotropical C. argipodus and C. thermophilus.


Assuntos
Agaricales/classificação , Agaricales/isolamento & purificação , Agaricales/genética , Agaricales/fisiologia , Análise por Conglomerados , DNA Fúngico/química , DNA Fúngico/genética , DNA Ribossômico/química , DNA Ribossômico/genética , DNA Espaçador Ribossômico/química , DNA Espaçador Ribossômico/genética , Índia , Microscopia , Filogenia , Pigmentos Biológicos/metabolismo , RNA Ribossômico 28S/genética , RNA Ribossômico 5,8S/genética , Análise de Sequência de DNA , Esporos Fúngicos/citologia , Tailândia
7.
Antimicrob Agents Chemother ; 60(8): 4701-7, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27216059

RESUMO

The current treatment of Chagas disease (CD), based on nifurtimox and benznidazole (Bz), is unsatisfactory. In this context, we performed the phenotypic in vitro screening of novel mono- and diamidines and drug interaction assays with selected compounds. Ten novel amidines were tested for their activities against bloodstream trypomastigote (BT) and amastigote forms of Trypanosoma cruzi (Y and Tulahuen strains) and their toxicities for mammalian host cells (L929 cells and cardiac cells). Seven of 10 molecules were more active than Bz against BT, with the most active compound being the diamidine DB2267 (50% effective concentration [EC50] = 0.23 µM; selectivity index = 417), which was 28-fold more active and about 3 times more selective than the standard drug. Five of the six monoamidines were also more active than Bz. The combination of DB2267 and DB2236 in fixed-ratio proportions showed an additive effect (sum of fractional inhibitory concentrations < 4) on BT. Interestingly, when intracellular forms were exposed to DB2267, its activity was dependent on the parasite strain, being effective (EC50 = 0.87 ± 0.05 µM) against a discrete typing unit (DTU) II strain (strain Y) but not against a representative DTU VI strain (strain Tulahuen) even when different vehicles (ß-cyclodextrin and dimethyl sulfoxide) were used. The intrinsic fluorescence of several diamidines allowed their uptake to be studied. Testing of the uptake of DB2236 (inactive) and DB2267 (active) by amastigotes of the Y strain showed that the two compounds were localized intracellularly in different compartments: DB2236 in the cytoplasm and DB2267 in the nucleus. Our present data encourage further studies regarding the activities of amidines and provide information which will help with the identification of novel agents for the treatment of CD.


Assuntos
Amidinas/farmacologia , Tripanossomicidas/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Animais , Linhagem Celular , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/parasitologia , Doença de Chagas/tratamento farmacológico , Doença de Chagas/parasitologia , Citoplasma/efeitos dos fármacos , Citoplasma/parasitologia , Mamíferos/parasitologia , Testes de Sensibilidade Parasitária/métodos , Fenótipo
8.
West Indian Med J ; 64(3): 226-9, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26426174

RESUMO

OBJECTIVE: Death due to burn occurs frequently. This study investigated time-dependent alterations in cardiac troponin T (cTnT) associated with fatal burns. METHODS: Cardiac tissue samples were collected from 10 medico-legal autopsies after informed consent from the relatives and post-mortem degradation by incubation of the cardiac tissue was studied at room temperature for different time periods. The cases included in this study were the subjects of burns without any prior history of disease who died in the hospital and their exact time of death was known. An efficient extraction protocol to analyse the banding pattern of cTnT in post-mortem tissue was developed. RESULTS: The data show a distinct time-dependent profile corresponding to the degradation of cTnT by proteases found in cardiac muscle. Both post-mortem interval and cardiac tissue of burned corpses had a statistically significant effect where the greatest amount of protein breakdown was observed within the first 41.20 hours, after which intact protein slowly disappears. The average molecular weight of all fragments showed intact cTnT to be rapidly degraded into smaller fragments. CONCLUSION: In cases of burns, such knowledge will assist in knowing if there were previous scars that might have mimicked a burn and also help to properly evaluate the real cause of death.

9.
West Indian Med J ; 64(1): 37-42, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26035814

RESUMO

OBJECTIVE: To describe the epidemiological characteristics and the clinical manifestations of the confirmed dengue cases over a ten-year period in Barbados, one of the English-speaking Caribbean countries. METHODS: All the cases of confirmed dengue from 2000 to 2009 were retrospectively studied. Long-term trends in incidence rate, demographic characteristics such as age, gender and seasonal distribution; clinical manifestations, immunological characteristics, need for hospitalization and mortality were studied. RESULTS: There were 3413 confirmed cases of dengue including 778 (22.8%) children and 2635 (77.2%) adults. The mean annual incidence rate of dengue was 1.36/1000 population. The median age of the persons with confirmed dengue was 27 years. The largest number of cases was seen in the 11 to 16-year age group. Hospitalization was required in 13.1% of dengue cases; 72.5% and 84% of all dengue were secondary infections among the children and adults, respectively. Dengue haemorrhagic fever accounted for 2.2% and 6% of all confirmed dengue among children and adults, respectively. The overall case fatality rate in this study was 0.35%. CONCLUSIONS: Dengue is a significant health problem primarily in adolescents and young adults. It is characterized by less severe cases and lower mortality rate.

10.
In. Caribbean Public Health Agency. Caribbean Public Health Agency: 60th Annual Scientific Meeting. Kingston, The University of the West Indies. Faculty of Medical Sciences, 2015. p.[1-75]. (West Indian Medical Journal Supplement).
Monografia em Inglês | MedCarib | ID: med-18042

RESUMO

OBJECTIVES: To study the prevalence and pattern of major congenital malformations of the gastrointestinal tract among the newborns in Barbados. DESIGN AND METHODS: This study includes all newborns with major congenital malformations of the gastrointestinal tract in Barbados from 1993 to 2012. The birth register and the neonatal admission register at the Queen Elizabeth Hospital, where over 90% of all deliveries in this country take place, were the main source of data. RESULTS: The overall prevalence of major congenital malformations of the digestive system in newborns was 7.28 per 10,000 live births. There were 15 (32.6%) cases of congenital absence, atresia, and stenosis of the small intestine giving a prevalence rate of 2.37 / 10,000 live births and 13 cases (28.3%) of esophageal atresia giving a prevalence rate of 2.06 / 10,000 live births. The overall prevalence of major congenital malformations of the gastrointestinal tract increased from 4.46 / 10,000 live births during 1993 – 1997 to 10.50 / 10,000 live births during 2008 – 2012. The prevalence of the absence, atresia or stenosis of the small intestine increased from 0.64 / 10,000 live births during 1993 – 1997 to 5.25 / 10,000 live births during 2008 – 2012. Overall, 1.1% of all neonatal deaths were attributed to major malformations of the digestive system. CONCLUSIONS: Congenital absence, atresia and stenosis of the small intestine were the most common malformations, with increasing prevalence over the study period. Tracheoesophageal fistula was the second most prevalent malformation and it had a high case fatality rate.


Assuntos
Anormalidades Congênitas , Recém-Nascido , Trato Gastrointestinal , Prevalência , Barbados
11.
In. Caribbean Public Health Agency. Caribbean Public Health Agency: 60th Annual Scientific Meeting. Kingston, The University of the West Indies. Faculty of Medical Sciences, 2015. p.[1-75]. (West Indian Medical Journal Supplement).
Monografia em Inglês | MedCarib | ID: med-18060

RESUMO

OBJECTIVES: To describe the seroprevalence of dengue antibodies in febrile suspected persons and investigated for dengue in this country. DESIGN AND METHODS: This was a retrospective population based study of all febrile children and adults with probable dengue from 2006 to 2013. Persons with probable dengue were investigated for dengue IgM and IgG antibodies in the blood sample drawn between days 3 to 5 of their illness. RESULTS: Among the 8296 cases that were tested for IgM antibodies, 2605 (36.6%) cases tested positive. Of the 7227 suspected cases who were tested for IgG, 5473 (75.7%) were positive. During the study years, between 80% and 90% of persons older than 20 years had a positive IgG antibody. Among the persons younger than five years (excluding the first year), between 10% and 20% had a positive IgM titre and a negative IgG titre, between 5 and10% had a positive IgM and IgG titre, 5% had a positive IgG titre and a negative IgM titre and between 45% and 65% had a negative IgM and a negative IgG titre. Between 37% and 59% had a serological evidence of past dengue in absence of any current dengue. CONCLUSIONS: The pattern of IgG antibodies seen in this study was comparable to those seen in the countries known to be hyperendemic for dengue. Based on the pattern of antibodies, the age of infection was likely to shift down to younger age groups with the likelihood of more severe forms of dengue in the future.


Assuntos
Imunoglobulina M , Imunoglobulina G , Dengue , Dengue/imunologia , Anticorpos , Estudos Soroepidemiológicos , Barbados
12.
Parasitology ; 141(10): 1272-6, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24735493

RESUMO

Chagas' disease is a neglected tropical disease caused by Trypanosoma cruzi and constitutes a serious public health problem for Latin America. Its unsatisfactory chemotherapy stimulates the search for novel antiparasitic compounds. Amidines and related compounds exhibit well-known activity towards different microbes including T. cruzi. In this vein, our present aim was to evaluate the biological effect of 10 novel structurally related amidines in vitro against bloodstream and intracellular forms of the parasite as well as their potential toxicity on cardiac cell cultures. Our results show that although active against the extracellular forms, with some of them like DB2247 being 6-fold more effective than benznidazole and displaying very low toxicity (>96 µm), none presented superior trypanocidal effect against intracellular forms as compared with the reference drug. These results may be due to differences in susceptibility profiles related to distinct uptake/extrusion mechanisms and cellular targets between bloodstream and amastigote forms. The present study adds to the knowledge base for the future design of novel amidines that may provide promising activity against T. cruzi.


Assuntos
Amidinas/farmacologia , Doença de Chagas/tratamento farmacológico , Pentamidina/farmacologia , Tripanossomicidas/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Animais , Técnicas de Cultura de Células , Doença de Chagas/parasitologia , Relação Dose-Resposta a Droga , Coração , Humanos , Nitroimidazóis/farmacologia , Testes de Sensibilidade Parasitária
13.
Anim. Reprod. (Online) ; 11(2): 63-73, April/June 2014.
Artigo em Inglês | VETINDEX | ID: biblio-1461104

RESUMO

Ovarian Cyst (OC) is an important ovarian dysfunction and a major cause of reproductive failure in dairy cattle. Previously defined as enlarged an ovulatory follicle like structures (< 2.5 cm) and persisting for 10 or more days OC in dairy cows are currently defined as cystic ovarian follicular structures of at least 17 mm that persist for more than 6 days in the absence of corpus luteum. However, clear cut definitions of this disorder are yet to be made. Past evaluations of OC using transrectal palpations have increased, and accurate diagnosis currently employs a combination of transrectal palpation, transrectal ultrasonography and plasma progesterone assay. However, the accurate diagnosis of the type of OC seems less important as therapies are similar for both the types of OC and clinicians often evaluate the OC again under conditions of pregnancy failures. During earlier time s, the manual rupture of OC was advocated, yet during the past several years single or combination hCG, GnRH, progesterone and prostaglandins have been frequent in clinical practice. Other therapies include estrogen receptor blocker clomiphene citrate and transvaginal ultrasound guided cystic follicle aspiration. Among the various therapies suggested the OvSynch treatment appears to be the most logical approach, yet the pregnancy rates with timed inseminations following therapy with the OvSynch treatment are low , as with other hormonal treatments. The success of therapy is governed by many confounding variables such as persistence of the cystic follicles and initiation of therapy as pathological alterations that occur following OC persistence require some time for spontaneous recovery. It can be concluded that OC can be diagnosed easily yet in spite of many therapeutic options the establishment of pregnancy in cows with OC requires a longer time.


Assuntos
Feminino , Animais , Bovinos , Cistos Ovarianos/diagnóstico , Cistos Ovarianos/terapia , Cistos Ovarianos/veterinária , Doenças dos Bovinos/patologia , Reprodução , Ultrassonografia/veterinária
14.
Anim. Reprod. ; 11(2): 63-73, April/June 2014.
Artigo em Inglês | VETINDEX | ID: vti-11169

RESUMO

Ovarian Cyst (OC) is an important ovarian dysfunction and a major cause of reproductive failure in dairy cattle. Previously defined as enlarged an ovulatory follicle like structures (< 2.5 cm) and persisting for 10 or more days OC in dairy cows are currently defined as cystic ovarian follicular structures of at least 17 mm that persist for more than 6 days in the absence of corpus luteum. However, clear cut definitions of this disorder are yet to be made. Past evaluations of OC using transrectal palpations have increased, and accurate diagnosis currently employs a combination of transrectal palpation, transrectal ultrasonography and plasma progesterone assay. However, the accurate diagnosis of the type of OC seems less important as therapies are similar for both the types of OC and clinicians often evaluate the OC again under conditions of pregnancy failures. During earlier time s, the manual rupture of OC was advocated, yet during the past several years single or combination hCG, GnRH, progesterone and prostaglandins have been frequent in clinical practice. Other therapies include estrogen receptor blocker clomiphene citrate and transvaginal ultrasound guided cystic follicle aspiration. Among the various therapies suggested the OvSynch treatment appears to be the most logical approach, yet the pregnancy rates with timed inseminations following therapy with the OvSynch treatment are low , as with other hormonal treatments. The success of therapy is governed by many confounding variables such as persistence of the cystic follicles and initiation of therapy as pathological alterations that occur following OC persistence require some time for spontaneous recovery. It can be concluded that OC can be diagnosed easily yet in spite of many therapeutic options the establishment of pregnancy in cows with OC requires a longer time. (AU)


Assuntos
Animais , Feminino , Bovinos , Doenças dos Bovinos/patologia , Cistos Ovarianos/veterinária , Cistos Ovarianos/diagnóstico , Cistos Ovarianos/terapia , Reprodução , Ultrassonografia/veterinária
15.
Antimicrob Agents Chemother ; 58(7): 4191-5, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24590476

RESUMO

Fifteen novel arylimidamides (AIAs) (6 bis-amidino and 9 mono-amidino analogues) were assayed against Trypanosoma cruzi in vitro and in vivo. All the bis-AIAs were more effective than the mono-AIAs, and two analogues, DB1967 and DB1989, were further evaluated in vivo. Although both of them reduced parasitemia, protection against mortality was not achieved. Our results show that the number of amidino-terminal units affects the efficacy of arylimidamides against T. cruzi.


Assuntos
Amidinas/uso terapêutico , Doença de Chagas/tratamento farmacológico , Parasitemia/tratamento farmacológico , Tripanossomicidas/uso terapêutico , Trypanosoma cruzi/efeitos dos fármacos , Amidinas/química , Animais , Doença de Chagas/mortalidade , Doença de Chagas/parasitologia , Masculino , Camundongos , Parasitemia/mortalidade , Parasitemia/parasitologia , Testes de Sensibilidade Parasitária , Tripanossomicidas/química
16.
West Indian Med J ; 63(7): 687-92, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25867554

RESUMO

Asthma is a chronic disease caused by the inflammation of the main air passages of the lungs. This paper outlines a review of the published literature on asthma. While a few studies show a trend of rising asthma cases in the Caribbean region, even fewer have explored the genetic epidemiological factors of asthma. This is a literature review that seeks to sum the body of knowledge on the epidemiology of asthma. Specifically, the major objective of the literature review is to provide a unified information base on the current state of factors involved in the genetic epidemiology of asthma. The review is a simple, yet detailed summary of the literature sources and their methodology and findings on the genetic epidemiology of asthma. Further, it seeks to direct this effort to the Caribbean region. The paper then reviews a summarized and synthesized collection of the body of previous research. Of specific interest are peer-reviewed sources that have been published in recent times. The paper provides more recent insight and recapitulates on the previous research, while tracing the intellectual progress on the debate. Where possible, reviewing and discussing the results of the previous literature, this review singles out the gaps and potential future research directions for studying the genetic epidemiology of asthma. Overall, we hope to contribute to a more synthesized knowledge and improved understanding of the previous literature and future potential direction of genetic and epidemiological asthma research.

17.
Mol Biol (Mosk) ; 46(4): 598-604, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23113348

RESUMO

Abelmoschus esculentus (okra) is one of the polysaccharide rich crop plants. The polysaccharides interfere with nucleic acids and protein isolation thereby affecting the downstream molecular analysis. So, to understand the molecular systematics of okra, high quality DNA, RNA and proteins are essential. In this study we present a method for extracting genomic DNA, RNA and proteins from polysaccharide rich okra tissues. The conventional extraction procedures were integrated with purification treatments with pectinase, RNase and proteinase K, which improved the quality and quantity of DNA as well. Using SDS, additional washes with CIA and NaCl precipitation improved the RNA isolation both quantitatively and qualitatively. Finally, ammonium acetate mediated protein precipitation and re-solubilization increased the quality of total protein extracts from the okra leaves. All of the methods above not only eliminated the impurities but also improved the quality and quantity of nucleic acids and proteins. Further, we subjected these samples to versatile downstream molecular analyses such as restriction endonuclease digestion, RAPD, Southern, reverse transcription-PCR and Western analysis and were proved to be successful.


Assuntos
Abelmoschus/metabolismo , DNA de Plantas/isolamento & purificação , Biologia Molecular/métodos , Proteínas de Plantas/isolamento & purificação , Polissacarídeos/isolamento & purificação , Abelmoschus/química , Acetatos/química , Precipitação Química , DNA de Plantas/química , Endopeptidase K/metabolismo , Ácidos Nucleicos/química , Proteínas de Plantas/química , Poligalacturonase/metabolismo , Polissacarídeos/química , RNA de Plantas/isolamento & purificação , Ribonucleases/metabolismo
18.
Curr Med Chem ; 18(25): 3853-70, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21824101

RESUMO

Podophyllotoxin (1) has been known to possess anti-tumor activity and is still considered an important lead for research and development of antineoplastic agents. Derivatives of podophyllotoxin, namely etoposide (2), etopophos (3) and teniposide (4) have been developed and are currently used in clinic for the treatment of a variety of malignancies. These agents are also used in combination therapies with other drugs. Due to the drug resistance developed by cancer cells as well as side effects associated with the use of these agents in clinic, the search for new effective anticancer analogues of podophyllotoxin remains an intense area of research. The structural complexity of podophyllotoxin, arising from the presence of four stereogenic carbons in ring C has restricted most of the structural activity relationship (SAR) studied by derivatization of the parent natural product rather than by de novo multi-step chemical synthesis. These issues provide strong impetus to a search for analogues of 1 with simplified structures, which can be accessible via short synthetic sequences from simple starting materials. Even if such initial compounds might have diminished cytotoxic potencies compared with the parent cyclolignan, the ease of preparation of carefully designed libraries of analogues would lead to more informative SAR studies and expeditious structure optimization. In this regard, during the last two decades considerable efforts have been made to synthesize aza- analogs of podophyllotoxin, i. e. aza-podophyllotoxins, with hetero atoms at different positions of the podophyllotoxin skeleton, while keeping the basic podophyllotoxin structure. Recently, there have been significant efforts towards the convenient synthesis of aza-analogs of 1. The use of multicomponent reactions (MCRs) and the synergies of ultrasound and microwave irradiations have increased the synthetic speed and variety of azapodophyllotoxins which are and will be available to be tested against a diverse population of carcinomas and other diseases. It has been reported that several aza-podophyllotoxins retain a great fraction of the cytotoxicity associated with the parent lignan. This review focuses on the strategies towards synthesis of various aza-podophyllotoxin analogues and their biological activities.


Assuntos
Antineoplásicos Fitogênicos/síntese química , Antineoplásicos Fitogênicos/farmacologia , Técnicas de Química Sintética/métodos , Podofilotoxina/síntese química , Podofilotoxina/farmacologia , Podophyllum/química , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/uso terapêutico , Humanos , Neoplasias/tratamento farmacológico , Podofilotoxina/química , Podofilotoxina/uso terapêutico
19.
Antimicrob Agents Chemother ; 55(10): 4765-73, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21807972

RESUMO

Due to limited efficacy and considerable toxicity, the therapy for Chagas' disease is far from being ideal, and thus new compounds are desirable. Diamidines and related compounds such as arylimidamides have promising trypanocidal activity against Trypanosoma cruzi. To better understand the mechanism of action of these heterocyclic cations, we investigated the kinetoplast DNA (kDNA) binding properties and trypanocidal efficacy against T. cruzi of 13 compounds. Four diamidines (DB75, DB569, DB1345, and DB829), eight arylimidamides (DB766, DB749, DB889, DB709, DB613, DB1831, DB1852, and DB2002), and one guanylhydrazone (DB1080) were assayed in thermal denaturation (T(m)) and circular dichroism (CD) studies using whole purified T. cruzi kDNA and a conserved synthetic parasite sequence. The overall CD spectra using the whole kDNA were similar to those found for the conserved sequence and were indicative of minor groove binding. Our findings showed that some of the compounds that exhibited the highest trypanocidal activities (e.g., DB766) caused low or no change in the T(m) measurements. However, while some active compounds, such as DB766, induced profound alterations of kDNA topology, others, like DB1831, although effective, did not result in altered T(m) and CD measurements. Our data suggest that the strong affinity of amidines with kDNA per se is not sufficient to generate and trigger their trypanocidal activity. Cell uptake differences and possibly distinct cellular targets need to be considered in the final evaluation of the mechanisms of action of these compounds.


Assuntos
Amidinas/metabolismo , Amidinas/farmacologia , DNA de Cinetoplasto/metabolismo , Tripanossomicidas/metabolismo , Tripanossomicidas/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Amidinas/química , Sequência Conservada , DNA de Cinetoplasto/química , Relação Dose-Resposta a Droga , Testes de Sensibilidade Parasitária , Relação Estrutura-Atividade , Termodinâmica , Tripanossomicidas/química
20.
Parasitology ; 137(2): 251-9, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19765349

RESUMO

No vaccines or safe chemotherapy are available for Chagas disease. Pentamidine and related di-cations are DNA minor groove-binders with broad-spectrum anti-protozoal activity. Therefore our aim was to evaluate the in vitro efficacy of di-cationic compounds - DB1645, DB1582, DB1651, DB1646, DB1670 and DB1627 - against bloodstream trypomastigotes (BT) and intracellular forms of Trypanosoma cruzi. Cellular targets of these compounds in treated parasites were also analysed by fluorescence and transmission electron microscopy (TEM). DB1645, DB1582 and DB1651 were the most active against BT showing IC50 values ranging between 0.15 and 6.9 microm. All compounds displayed low toxicity towards mammalian cells and DB1645, DB1582 and DB1651 were also the most effective against intracellular parasites, with IC50 values ranging between 7.3 and 13.3 microm. All compounds localized in parasite nuclei and kDNA (with greater intensity in the latter structure), and DB1582 and DB1651 also concentrated in non-DNA-containing cytoplasmic organelles possibly acidocalcisomes. TEM revealed alterations in mitochondria and kinetoplasts, as well as important disorganization of microtubules. Our data provide further information regarding the activity of this class of compounds upon T. cruzi which should aid future design and synthesis of agents that could be used for Chagas disease therapy.


Assuntos
Amidinas/farmacologia , Antiprotozoários/farmacologia , Núcleo Celular/metabolismo , DNA de Cinetoplasto/metabolismo , Frações Subcelulares/metabolismo , Trypanosoma cruzi/efeitos dos fármacos , Amidinas/química , Animais , Antiprotozoários/química , Doença de Chagas/tratamento farmacológico , Citoplasma/metabolismo , Citoplasma/ultraestrutura , DNA de Cinetoplasto/genética , Concentração Inibidora 50 , Microscopia Eletrônica de Transmissão , Microscopia de Fluorescência , Microtúbulos/metabolismo , Mitocôndrias/metabolismo , Organelas/metabolismo , Testes de Sensibilidade Parasitária/métodos , Trypanosoma cruzi/fisiologia , Trypanosoma cruzi/ultraestrutura
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA