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1.
Invest New Drugs ; 41(5): 629-637, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37452982

RESUMO

The discovery and development of effective novel compounds is paramount in oncology for improving cancer therapy. In this study, we developed a new derivative of spiroindolone (7',8'-Dimethoxy-1',3'-dimethyl-1,2,3',4'-tetrahydrospiro[indole-3,5'- pyrazolo[3,4-c]isoquinolin]-2-one) and evaluated its anticancer- and immunomodulatory potential in a vitro model of chronic leukemia. We utilized the chronic leukemia cell line K562, as well as non-cancerous peripheral blood mononuclear cells (PBMC) and Vero cells (kidney epithelium of Cercopithecus aethiops). We assessed the cytotoxicity of the compound using the MTT assay, and performed cell cycle assays to determine its impact on different stages of the cell cycle. To evaluate its antineoplastic activity, we conducted a colony formation test to measure the effect of the compound on the clonal growth of cancer cells. Furthermore, we evaluated the immunomodulatory activity of the compound by measuring the levels of pro and anti-inflammatory cytokines. The study findings demonstrate that the spiroindolone-derived compound exerted noteworthy cytotoxic effects against K562 cells, with an IC50 value of 25.27 µg/mL. Additionally, it was observed that the compound inhibited the clonal proliferation of K562 cells while displaying minimal toxicity to normal cells. The compound exhibited its antiproliferative activity by inducing G2/M cell cycle arrest, preventing the entry of K562 cells into mitosis. Notably, the compound demonstrated an immunomodulatory effect by upregulating the production of cytokines IL-6 and IL-12/23p40. In conclusion, the spiroindolone-derived compound evaluated in this study has demonstrated significant potential as a therapeutic agent for the treatment of chronic myeloid leukemia. Further investigations are warranted to explore its clinical applications.


Assuntos
Antineoplásicos , Leucemia Mielogênica Crônica BCR-ABL Positiva , Humanos , Animais , Chlorocebus aethiops , Leucócitos Mononucleares , Células Vero , Proliferação de Células , Apoptose , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Células K562 , Citocinas/farmacologia , Indóis/farmacologia
2.
POCUS J ; 7(2): 253-261, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36896375

RESUMO

Acute pain is one of the most frequent, and yet one of the most challenging, complaints physicians encounter in the emergency department (ED). Currently, opioids are one of several pain medications given for acute pain, but given the long-term side effects and potential for abuse, alternative pain regimens are sought. Ultrasound-guided nerve blocks (UGNB) can provide quick and sufficient pain control and therefore can be considered a component of a physician's multimodal pain plan in the ED. As UGNB are more widely implemented at the point of care, guidelines are needed to assist emergency providers to acquire the skill necessary to incorporate them into their acute pain management.

3.
J Clin Virol ; 146: 105056, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34923322

RESUMO

BACKGROUND: Neurological viral infection is frequently associated to enterovirus, herpesvirus and arboviruses. These infections may cause severe clinical outcomes, long lasting sequelae or death. Few studies have addressed viral neurological infections etiology in Brazil. OBJECTIVES: Identification of viruses in the cerebral spinal fluid (CSF) of human neurological infections suspected of viral etiology during January and May 2019 in Midwestern Brazil. MATERIALS AND METHODS: Clinical, laboratory and epidemiological information was gathered from medical records. In addition, an aliquot of the sampled CSF was subjected to viral RNA/DNA extraction, randomic dscDNA amplification by PCR, DNA purification and Ilumina HiSeq 2500 sequencing. RESULTS: Six viral genomes belonging to Chikungunya virus (CHIKV) East-Central-South African (ECSA) genotype (10.834-11.804 nt in length) confirmed lately by RT-PCR for CHIKV envelope were present in all six liquor samples. These genomes present two mutations, nsP2:T31I and nsP3:A388V, shared with other Mato Grosso State strains from 2019, not present in sequences of the virus from previous years obtained in the State. One case was a triple co-infection also confirmed through RT-PCR, with Dengue virus serotype 4 genotype II (NS5; 874 nt) and Oropouche virus genotype IA (segment S; 302 nt). CSF was clear and colorless (5/6 patients), with >10% of lymphomononuclear cells (6/6), 1-99 erythrocytes/mm3 (5/6), glucose levels >50 mg/dl (4/5) e > 10 mg/dl of proteins (4/4). One patient evolved to death, and another, a newborn, presented sequelae after recovery. CONCLUSIONS: Despite herpesviruses and enteroviruses are frequent etiologies of neurological infections, the casuistic here reported was associated to arboviruses already known to be responsible for acute febrile illness outbreaks in the state of Mato Grosso, Midwestern Brazil.


Assuntos
Arbovírus , Febre de Chikungunya , Coinfecção , Brasil/epidemiologia , Febre de Chikungunya/complicações , Febre de Chikungunya/epidemiologia , Coinfecção/epidemiologia , Genótipo , Humanos , Filogenia
4.
J Pharm Biomed Anal ; 191: 113635, 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-32998105

RESUMO

Solanum paniculatum L. is species whose fruits are widely consumed in Brazil as a tonic beverage with higher content of steroidal saponins. In this work, we developed an analytical method for the quantification of the eight saponins present in the 70 % ethanol extract from the leaves using ultra-high-performance liquid chromatography coupled to mass spectrometry (UHPLC-MS). Besides, the eight spirostanic saponins were screened for in vitro antileishmanial activity against promastigote and amastigote forms of Leishmania (L.) amazonensis. Substances 1, 2 and 3 were found to be the most active compounds, with inhibitory concentration (IC50) values of 8.51 ± 4.38, 10.75 ± 6.85 and 10.45 ± 4.21 µM, respectively, against promastigote forms and effective concentration (EC50) values of >25, 17.73 ± 0.99 and 19.57 ± 0.84 µM, respectively, against amastigote forms. The cytotoxic test with compounds 1-3 evidenced low toxicity in murine macrophage cells, with values above 50 µM at concentration lower than 25 µM. These findings show that saponins 1-3 should be evaluated in further studies for the treatment of cutaneous leishmaniasis.


Assuntos
Antiprotozoários , Saponinas , Solanum , Animais , Antiprotozoários/toxicidade , Brasil , Concentração Inibidora 50 , Camundongos , Folhas de Planta , Saponinas/farmacologia
5.
Rev. MVZ Córdoba ; 24(3): 7314-7321, sep.-dic. 2019. tab, graf
Artigo em Espanhol | LILACS | ID: biblio-1115256

RESUMO

RESUMEN Objetivo. Presentar una revisión moderna de la fauna de nematodos de la rana esculenta Pelophylax lessonae (Camerano, 1882) de las poblaciones de la cuenca del Río Volga. Materiales y métodos. Este trabajo consolida los datos de diferentes trabajos helmintológicos de los últimos 80 años, respaldados por los resultados de nuestras propias investigaciones. Durante el período de 1936 a 2016 diferentes autores examinaron 1460 especímenes de rana esculenta, utilizando el método de autopsia helmintológica completa de 13 regiones de la cuenca del Río Volga. Resultados. En total se registraron 9 especies de nematodos. Nematodo Icosiella neglecta encontrado por primera vez en el huésped estudiado en el territorio de Rusia y la cuenca del Río Volga. Tres especies parecían estar más extendidas: Oswaldocruzia filiformis, Cosmocerca ornata e Icosiella neglecta. Para cada especie de helmintos se incluyó la siguiente información: posición sistemática, áreas de detección, localización, biología, lista de hospederos definitivos, nivel de especificidad del hospedero. Conclusiones. Los nematodos de la rana esculenta, excepto I. neglecta, pertenecen al grupo de helmintos transmitidos por el suelo (geohelmintos) y parasitan en estadios adultos. Algunas especies (O. filiformis, C. ornata, I. neglecta) están muy extendidas en el área de distribución del hospedador. Estos dos últimos son capaces de alcanzar altos índices de invasión y también de ser los parásitos subyacentes de la rana esculenta. Esto sucede debido a la especificidad del ciclo de vida de estas especies de nematodos y a la conexión a largo plazo del anfibio con el agua.


ABSTRACT Objetive. Present a modern review of the nematodes fauna of the pool frog Pelophylax lessonae (Camerano, 1882) from Volga basin populations on the basis of our own research and literature sources analysis. Materials and methods. Present work consolidates data from different helminthological works over the past 80 years, supported by our own research results. During the period from 1936 to 2016 different authors examined 1460 specimens of pool frog, using the method of full helminthological autopsy, from 13 regions of the Volga basin. Results. In total 9 nematodes species were recorded. Nematode Icosiella neglecta found for the first time in the studied host from the territory of Russia and Volga basin. Three species appeared to be more widespread: Oswaldocruzia filiformis, Cosmocerca ornata and Icosiella neglecta. For each helminth species the following information included: systematic position, areas of detection, localization, biology, list of definitive hosts, the level of host-specificity. Conclusions. Nematodes of pool frog, excluding I. neglecta, belong to the group of soil-transmitted helminthes (geohelminth) and parasitize in adult stages. Some species (O. filiformis, C. ornata, I. neglecta) are widespread in the host range. The latter two are able to reach high invasion indices and also to be the background parasites of the pool frog. It happens due to these nematode species life cycle specificity and the long-term connection of the amphibian with water.


Assuntos
Parasitos , Ranidae , Nematoides
6.
In. The University of the West Indies, Faculty of Medical Sciences. Faculty of Medical Sciences, Research Day. St. Augustine, Caribbean Medical Journal, March 21, 2019. .
Não convencional em Inglês | MedCarib | ID: biblio-1023495

RESUMO

Objectives: Stargardt's disease is an autosomal recessive macular dystrophy caused by mutations in the photoreceptor cell-specific ATP-binding cassette sub-family A member 4, transporter (ABCA4) gene. We studied (i) the predicted effects of mutations on the function of the ABCA4 transporter and (ii) the existence of four common mutations in local Stargardt patients. Design and Methodology: (i) The freeware PROVEAN (Protein VariationEffect Analyzer; J. Craig Venter Institute, CA,USA) was used to predict the deleterious effect257 mutations in the ABCA4 gene. PROVEANscores below -2.5 were considered deleterious.One-way ANOVAs were used to detect anysignificant differences in mean (±SE) PROVEANscores among mutation types or protein domains I,II, III or IV. (ii) Using saliva, DNA was isolated from three Stargardt patients. Chromosomal regions were amplified by PCR, sequenced (Macrogen Inc., Seoul, Korea) and sequence alignment (NCBI, MD, USA) used to detect the presence of four mutations; c.768G>T (p.Val256=), c.4469G>A (p.Cys1490Tyr), c.6079C>T (p.Leu2027Phe) and c.1804C>T (p.Arg602Trp). Results: (i) Sixty-three percent of mutations predicted deleterious effects. There were no significant (p<0.05) differences between mean PROVEAN scores among mutation types (substitutions, - 4.49±0.20; deletions/insertions, -6.35±0.67) or protein domains (domain I, -4.79 ± 0.39; domain II, -4.65 ± 0.36; domain III, -5.48 ± 0.51; domain IV, -4.39 ± 0.34). (ii) These mutations were not detected in Stargardt's patients. Conclusion: (i) Functionality of the ABCA4 protein is affected by multiple mutations. (ii) Novel mutations are present in local patients. Currently, we seek to profile novel mutations in six families using molecular inversion probes.


Assuntos
Humanos , Masculino , Feminino , Membro 4 da Subfamília A de Transportadores de Cassetes de Ligação de ATP , Trinidad e Tobago
7.
Proc Natl Acad Sci U S A ; 115(43): E10275-E10282, 2018 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-30297399

RESUMO

Bottom trawlers land around 19 million tons of fish and invertebrates annually, almost one-quarter of wild marine landings. The extent of bottom trawling footprint (seabed area trawled at least once in a specified region and time period) is often contested but poorly described. We quantify footprints using high-resolution satellite vessel monitoring system (VMS) and logbook data on 24 continental shelves and slopes to 1,000-m depth over at least 2 years. Trawling footprint varied markedly among regions: from <10% of seabed area in Australian and New Zealand waters, the Aleutian Islands, East Bering Sea, South Chile, and Gulf of Alaska to >50% in some European seas. Overall, 14% of the 7.8 million-km2 study area was trawled, and 86% was not trawled. Trawling activity was aggregated; the most intensively trawled areas accounting for 90% of activity comprised 77% of footprint on average. Regional swept area ratio (SAR; ratio of total swept area trawled annually to total area of region, a metric of trawling intensity) and footprint area were related, providing an approach to estimate regional trawling footprints when high-resolution spatial data are unavailable. If SAR was ≤0.1, as in 8 of 24 regions, there was >95% probability that >90% of seabed was not trawled. If SAR was 7.9, equal to the highest SAR recorded, there was >95% probability that >70% of seabed was trawled. Footprints were smaller and SAR was ≤0.25 in regions where fishing rates consistently met international sustainability benchmarks for fish stocks, implying collateral environmental benefits from sustainable fishing.


Assuntos
Pesqueiros/estatística & dados numéricos , Alaska , Animais , Austrália , Biodiversidade , Chile , Ecossistema , Invertebrados/fisiologia , Nova Zelândia , Oceanos e Mares , Alimentos Marinhos/estatística & dados numéricos
8.
J Agric Food Chem ; 66(33): 8703-8713, 2018 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-30048138

RESUMO

Solanum paniculatum L. is widely used in Brazilian folk medicine for the treatment of liver and gastrointestinal disorders as well as for culinary purposes and beverage production. Fractionation of hydroalcoholic [ethanol (EtOH) 70%] tincture from S. paniculatum leaves led to the isolation of six new spirostanic saponins which included 6- O-α-l-rhamnopyranosyl-(1''→3')-ß-d-quinovopyranosyl-(22 S,23 R,25 S)-3ß,6α,23-trihydroxy-5α-spirostane (1), 6- O-ß-d-xylopyranosyl-(1''→3')-ß-d-quinovopyranosyl-(22 S,23 R,25 R)-3ß,6α,23-trihydroxy-5α-spirostane (4), 3- O-α-l-rhamnopyranosyl-(1''→3')-ß-d-quinovopyranosyl-(22 S,23 S,25 R)-3ß,6α,23-trihydroxy-5α-spirostane (5), 3- O-ß-d-xylopyranosyl-(1''→3')-ß-d-quinovopyranosyl-(22 S,23 S,25 R)-3ß,6α,23-trihydroxy-5α-spirostane (6), 6- O-α-l-rhamnopyranosyl-(1''→3')-ß-d-quinovopyranosyl-(22 S,25 S)-1ß,3ß,6α-trihydroxy-5α-spirostane (7), and 6- O-ß-d-xylopyranosyl-(1''→3')-ß-d-quinovopyranosyl-(22 S,25 S)-3ß,4ß,6α-trihydroxy-5α-spirostane (8) together with two known spirostanic saponins (2, 3). The structures of these compounds were determined by one-dimensional (1D) and two-dimensional (2D) NMR experiments in addition to high-resolution electrospray ionization mass spectrometry (HRESIMS) analyses. The 70% alcohol tincture, used as phytomedicine, exhibited promising activities against oral pathogens, including, Steptococcus sanguinis, St. oralis, St. mutans, St. mitis, and Lactobacillus casei with minimal inhibitory concentration (MIC) values ranging from 6.25 to 50 µg/mL. The saponin fraction, nonetheless, showed lower activity against all the strains tested (from 100 to >400 µg/mL).


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Doenças da Boca/microbiologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Solanum/química , Antibacterianos/isolamento & purificação , Brasil , Humanos , Espectrometria de Massas , Testes de Sensibilidade Microbiana , Estrutura Molecular , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , Saponinas , Streptococcus/efeitos dos fármacos , Streptococcus/crescimento & desenvolvimento
9.
Zootaxa ; 4378(4): 451-479, 2018 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-29689992

RESUMO

We describe Melanosternarchus amaru as a new genus and species of Apteronotidae from the deep channels of blackwater and clearwater tributaries of the Amazon River in Brazil and Peru. The new species superficially resembles members of the widespread "Apteronotus" bonapartii species group, from which it can be readily distinguished by expanded bones of the infraorbital laterosensory canal. It can further be distinguished from all other apteronotids by a unique combination of characters: reduced premaxillary dentition, a large gape, and an absence of scales from the entire dorsum. A molecular phylogenetic analysis using three mitochondrial loci and one nuclear locus (~3000 bp) places this genus as sister to Compsaraia, and these two genera together as a clade sister to Pariosternarchus; all nodes with strong statistical support. The clade formed by these three genera includes five species, four of which are restricted to the Amazon basin. The apparent habitat preference of the new species for low-conductivity blackwater and clearwater rivers has not been reported in other apteronotid species.


Assuntos
Gimnotiformes , Animais , Brasil , Peru , Filogenia , Rios
10.
Brachytherapy ; 17(3): 564-570, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29426745

RESUMO

PURPOSE: Vaginal brachytherapy (VBT) alone has been shown to be a viable adjuvant treatment strategy for most patients with Stage I endometrioid endometrial cancer. We sought to examine our institutional data following practice pattern changes resulting from the publications of GOG-99 and PORTEC-2. METHODS AND MATERIALS: We retrospectively analyzed women who underwent adjuvant VBT after surgical staging for Stage 1 endometrioid endometrial cancer at our institution from 2007 to 2014. RESULTS: We identified 297 women. Median time to last followup or death was 52.3 months (interquartile range: 32.3-72.3 months). By International Federation of Gynecology and Obstetrics 2009 staging, 162 patients (54.5%) had Stage IA and 128 (43.1%) had Stage IB disease. Ninety-nine (33.3%) patients had Grade 1, 153 (51.5%) had Grade 2, and 45 (15.2%) had Grade 3 disease. According to GOG-249 and PORTEC-2 criteria, 167 (56.2%) and 127 (42.7%) patients were with high-intermediate-risk disease. Two women had Stage IB Grade 3 disease. The most common high-dose-rate-VBT regimen was 2100 cGy/three fractions to a depth of 5 mm. Four (two acute and two late) (1.3%) Grade 3 genitourinary toxicities were reported: three episodes of vaginal dehiscence (after second course of VBT, 2 months after completion of VBT, and 1 year after completion of VBT) and one episode of radiation necrosis. Twenty-one (7%) women recurred: three recurred in the vagina, two recurred in the pelvic lymph nodes, and 16 recurred distantly. CONCLUSIONS: Outcomes appear consistent with published randomized data in women with high-intermediate-risk endometrial cancer who are treated with brachytherapy alone. Recurrence and complication rates were minimal.


Assuntos
Braquiterapia/métodos , Carcinoma Endometrioide/radioterapia , Neoplasias do Endométrio/radioterapia , Vagina/efeitos da radiação , Adulto , Idoso , Idoso de 80 Anos ou mais , Braquiterapia/efeitos adversos , Carcinoma Endometrioide/patologia , Carcinoma Endometrioide/cirurgia , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Lesões por Radiação/epidemiologia , Radioterapia Adjuvante/efeitos adversos , Radioterapia Adjuvante/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Sistema de Registros , Estudos Retrospectivos , Terapia de Salvação/estatística & dados numéricos , Taxa de Sobrevida , Resultado do Tratamento
11.
J Agric Food Chem ; 66(6): 1419-1427, 2018 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-29345910

RESUMO

Although Jatropha aethiopica, popularly known in Cuba as "mata diabetes", is used in salads and as a dietary supplement, its chemical composition and antidiabetic properties yet remains unclear. In this work, we evaluate the qualitative and quantitative composition of ethanolic extract (EE) and phenolic fraction (PF) of Jatropha aethiopica leaves and their hypoglycemic and hypolipidemic activity. Chemical fractionation of the ethanolic extract yielded nine compounds, which included protocatechuic acid (1), chlorogenic acid (2), caffeic acid (3), quercetin 3-O-α-l-rhamnopyranosyl-(1 → 2)-[α-l-rhamnopyranolsyl-(1 → 6)]-ß-d-galactopyranoside (4), a new kaempferol 3-O-α-l-rhamnopyranosyl-(1 → 4)-[α-l-rhamnopyranolsyl-(1 → 6)]-ß-d-galactopyranoside (5), kaempferol 3-O-α-l-rhamnopyranosyl-(1 → 2)-[α-l-rhamnopyranolsyl-(1 → 6)]-ß-d-glucopyranoside (6), rutin (7), kaempferol 3-O-α-l-rhamnopyranosyl-(1 → 6)-ß-d-glucopyranoside (8), and quercetin (9). The compounds (1, 4-7) were quantified by high-performance liquid chromatography photodiode array detection (HPLC-PDA) in both the ethanolic extract (62.65 ± 0.15 mg/g) and phenolic fraction (61.72 ± 0.23 mg/g). The results obtained show that both ethanolic extract and phenolic fraction contributed toward the improvement of glucose tolerance, which in turn led to a decline in the glucose levels. Remarkably, the ethanolic extract presented a relatively higher promising effect compared to metformin.


Assuntos
Diabetes Mellitus/tratamento farmacológico , Hipoglicemiantes/química , Hipoglicemiantes/isolamento & purificação , Jatropha/química , Fenóis/química , Fenóis/isolamento & purificação , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Animais , Glicemia/metabolismo , Diabetes Mellitus/metabolismo , Humanos , Hipoglicemiantes/administração & dosagem , Masculino , Camundongos , Fenóis/administração & dosagem , Extratos Vegetais/administração & dosagem , Folhas de Planta/química
12.
Int J Gynecol Cancer ; 27(6): 1149-1154, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-26825835

RESUMO

OBJECTIVES: Recent data have shown high rates of clinical and pathologic responses to neoadjuvant radiation therapy for locally advanced endometrial cancer. There are limited data on the surgical outcomes of these patients in the era of modern radiation and surgical techniques. We sought to characterize surgical outcomes after extrafascial hysterectomy in this population. METHODS: Patients with endometrial cancer of all histologies clinically involving the cervix or parametria treated with neoadjuvant brachytherapy followed by extrafascial hysterectomy from 1999 to 2014 were identified. Patient charts were reviewed for data regarding treatment characteristics and postoperative outcomes. Pearson χ and logistic regression analyses were used to assess correlations between surgical complications and treatment-related variables. RESULTS: Twenty-nine patients met inclusion criteria. Mean operating time for the cohort was 115 minutes. Mean estimated blood loss was 100 mL. No visceral injuries occurred. Mean length of hospital stay was 1 and 4 days for the minimally invasive and laparotomy groups, respectively. Rates of postoperative ileus, blood transfusion, wound infection, and readmission were 3%, 3%, 6%, and 3%, respectively. No case of prolonged urodynamic dysfunction was noted. The rate of vaginal complications was significantly higher in the group of patients who underwent minimally invasive surgery as compared with laparotomy (33% vs 5%, P < 0.041). CONCLUSIONS: These data support adjuvant extrafascial hysterectomy after neoadjuvant radiotherapy for endometrial cancer with cervical or parametrial involvement as a safe and viable procedure, with low rates of postoperative complications. Extra care should be taken when closing the vaginal cuff to reduce the risk of vaginal cuff complications.


Assuntos
Braquiterapia/métodos , Neoplasias do Endométrio/cirurgia , Adulto , Idoso , Colo do Útero/patologia , Quimiorradioterapia Adjuvante , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/radioterapia , Feminino , Humanos , Histerectomia/efeitos adversos , Histerectomia/métodos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Invasividade Neoplásica , Radioterapia Adjuvante , Estudos Retrospectivos , Resultado do Tratamento
14.
Brachytherapy ; 14(1): 9-15, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25456026

RESUMO

PURPOSE: To investigate the clinical feasibility and treatment outcomes of image-based high-dose-rate (HDR) brachytherapy using an intracavitary multichannel vaginal cylinder for the definitive treatment of vaginal cancers. METHODS AND MATERIALS: A total of 41 patients with vaginal cancer (24% primary vaginal and 76% recurrence from other gynecologic primaries) treated with definitive radiotherapy ± chemotherapy including image-based HDR brachytherapy with a multichannel vaginal cylinder were included in the study. Image-based brachytherapy was completed using either CT- (41%) or MR-based planning (59%) with each fraction. The high-risk clinical target volume was defined based on the pre- and postexternal beam radiotherapy gross tumor volume. Doses were converted to equivalent dose of 2Gy per fraction. Endpoints examined were dose-volume parameters and early clinical outcomes. RESULTS: The median high-risk clinical target volume was 24.2 cc (interquartile range [IQR], 12.6), with a median dose to 90% (D90) of 77.1 Gy (IQR, 3.4). The median dose to 2 cc (D(2 cc)) for the bladder, rectum, and sigmoid were 59.4 Gy (IQR, 5.6), 58.2 Gy (IQR, 4.1), and 52.3 Gy (IQR, 5.5), respectively. After a median followup of 16 months (range, 3-35), complete clinical response was documented in 98% of the patients. The 2-year local, regional, and distant control; and disease-free and overall survival were 93%, 100%, 81%, 78%, and 88%, respectively. The 2-year actuarial rate of late Grade 3 or higher toxicity was 4% overall with 0%, 0%, 0%, and 4% for vaginal, bladder, urethral, and gastrointestinal, respectively. CONCLUSIONS: Image-based HDR brachytherapy using an intracavitary multichannel cylinder seems feasible in definitive vaginal cancer treatment. The described clinical implementation shows promising early clinical outcomes with high rates of local control and little toxicity, which should be validated with extended followup.


Assuntos
Braquiterapia/instrumentação , Neoplasias Vaginais/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Braquiterapia/efeitos adversos , Braquiterapia/métodos , Colo Sigmoide/efeitos da radiação , Estudos de Viabilidade , Feminino , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/radioterapia , Órgãos em Risco/efeitos da radiação , Doses de Radiação , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Reto/efeitos da radiação , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Bexiga Urinária/efeitos da radiação , Neoplasias Vaginais/patologia
15.
Brachytherapy ; 13(6): 542-7, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25127122

RESUMO

PURPOSE: Definitive radiotherapy is a viable option for medically inoperable patients with early stage endometrial cancer. We present our experience using image-based brachytherapy (BT). METHODS AND MATERIALS: Patients with medically inoperable clinical Stage I endometrial adenocarcinoma received definitive BT with or without external beam radiotherapy. High-dose-rate BT was delivered using MRI- or CT-based planning for each fraction. For patients with an MRI, gross tumor volume (GTV) was contoured although dose was still prescribed to the clinical treatment volume (CTV), including the entire uterus, cervix, and upper 1-2 cm of vagina. Equivalent 2 Gy doses (EQD2) were calculated. RESULTS: Thirty-eight patients were treated from 2007 to 2013, 20 receiving BT alone with a median dose of 37.5 Gy in five to six fractions. For combined therapy, median external beam and BT doses were 45 and 25 Gy in four to five fractions. With 15-month median followup, the 2-year actuarial local control and overall survival were 90.6% and 94.4%. No Grade 2-5 late toxicities were observed. Mean CTV D90 EQD2 for BT alone and combined therapy was 48.6 ± 5.6 and 72.4 ± 6.0 Gy, whereas mean GTV D90 EQD2 was 172.3 ± 59.6 and 138.0 ± 64.6 Gy. CONCLUSIONS: Image-based BT is feasible for medically inoperable early stage endometrial cancer with excellent early results. Despite low CTV doses, high doses delivered to GTV with BT likely accounts for high local control. Endometrial cancer guidelines for image-based planning are needed to define target volumes based on risk with differential dose delivery.


Assuntos
Adenocarcinoma/radioterapia , Braquiterapia/métodos , Neoplasias do Endométrio/radioterapia , Radioterapia Conformacional , Idoso , Idoso de 80 Anos ou mais , Fracionamento da Dose de Radiação , Feminino , Humanos , Imageamento Tridimensional , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Planejamento da Radioterapia Assistida por Computador/métodos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
16.
Glob Health Action ; 6: 20444, 2013 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-23680267

RESUMO

OBJECTIVES: To elicit the views of primary healthcare providers from Bolivia, Ecuador, and Nicaragua on how adolescent sexual and reproductive health (ASRH) care in their communities can be improved. METHODS: Overall, 126 healthcare providers (46 from Bolivia, 39 from Ecuador, and 41 from Nicaragua) took part in this qualitative study. During a series of moderated discussions, they provided written opinions about the accessibility and appropriateness of ASRH services and suggestions for its improvement. The data were analyzed by employing a content analysis methodology. RESULTS: Study participants emphasized managerial issues such as the prioritization of adolescents as a patient group and increased healthcare providers' awareness about adolescent-friendly approaches. They noted that such an approach needs to be extended beyond primary healthcare centers. Schools, parents, and the community in general should be encouraged to integrate issues related to ASRH in the everyday life of adolescents and become 'gate-openers' to ASRH services. To ensure the success of such measures, action at the policy level would be required. For example, decision-makers could call for developing clinical guidelines for this population group and coordinate multisectoral efforts. CONCLUSIONS: To improve ASRH services within primary healthcare institutions in three Latin American countries, primary healthcare providers call for focusing on improving the youth-friendliness of health settings. To facilitate this, they suggested engaging with key stakeholders, such as parents, schools, and decision-makers at the policy level.


Assuntos
Atitude do Pessoal de Saúde , Melhoria de Qualidade , Serviços de Saúde Reprodutiva/normas , Saúde Reprodutiva , Adolescente , Adulto , Bolívia , Equador , Feminino , Pessoal de Saúde/psicologia , Prioridades em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Nicarágua
17.
PLoS One ; 7(10): e46461, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23077508

RESUMO

Cochleates are phospholipid-calcium precipitates derived from the interaction of anionic lipid vesicles with divalent cations. Proteoliposomes from bacteria may also be used as a source of negatively charged components, to induce calcium-cochleate formation. In this study, proteoliposomes from V. cholerae O1 (PLc) (sized 160.7±1.6 nm) were transformed into larger (16.3±4.6 µm) cochleate-like structures (named Adjuvant Finlay Cochleate 2, AFCo2) and evaluated by electron microscopy (EM). Measurements from transmission EM (TEM) showed the structures had a similar size to that previously reported using light microscopy, while observations from scanning electron microscopy (SEM) indicated that the structures were multilayered and of cochleate-like formation. The edges of the AFCo2 structures appeared to have spaces that allowed penetration of negative stain or Ovalbumin labeled with Texas Red (OVA-TR) observed by epi-fluorescence microscopy. In addition, freeze fracture electron microscopy confirmed that the AFCo2 structures consisted of multiple overlapping layers, which corresponds to previous descriptions of cochleates. TEM also showed that small vesicles co-existed with the larger cochleate structures, and in vitro treatment with a calcium chelator caused the AFCo2 to unfold and reassemble into small proteoliposome-like structures. Using OVA as a model antigen, we demonstrated the potential loading capacity of a heterologous antigen and in vivo studies showed that with simple admixing and administration via intragastric and intranasal routes AFCo2 provided enhanced adjuvant properties compared with PLc.


Assuntos
Cálcio/química , Imunidade nas Mucosas , Fosfolipídeos/química , Proteolipídeos/química , Vibrio cholerae/química , Animais , Ensaio de Imunoadsorção Enzimática , Feminino , Técnica de Fratura por Congelamento , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Vibrio cholerae/ultraestrutura
18.
Phytopathology ; 102(11): 1034-44, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22877312

RESUMO

ABSTRACT Pseudomonas syringae pv. actinidiae, the causal agent of canker in kiwifruit (Actinidia spp.) vines, was first detected in Japan in 1984, followed by detections in Korea and Italy in the early 1990s. Isolates causing more severe disease symptoms have recently been detected in several countries with a wide global distribution, including Italy, New Zealand, and China. In order to characterize P. syringae pv. actinidiae populations globally, a representative set of 40 isolates from New Zealand, Italy, Japan, South Korea, Australia, and Chile were selected for extensive genetic analysis. Multilocus sequence analysis (MLSA) of housekeeping, type III effector and phytotoxin genes was used to elucidate the phylogenetic relationships between P. syringae pv. actinidiae isolates worldwide. Four additional isolates, including one from China, for which shotgun sequence of the whole genome was available, were included in phylogenetic analyses. It is shown that at least four P. syringae pv. actinidiae MLSA groups are present globally, and that marker sets with differing evolutionary trajectories (conserved housekeeping and rapidly evolving effector genes) readily differentiate all four groups. The MLSA group designated here as Psa3 is the strain causing secondary symptoms such as formation of cankers, production of exudates, and cane and shoot dieback on some kiwifruit orchards in Italy and New Zealand. It is shown that isolates from Chile also belong to this MLSA group. MLSA group Psa4, detected in isolates collected in New Zealand and Australia, has not been previously described. P. syringae pv. actinidiae has an extensive global distribution yet the isolates causing widespread losses to the kiwifruit industry can all be traced to a single MLSA group, Psa3.


Assuntos
Actinidia/microbiologia , Doenças das Plantas/microbiologia , Pseudomonas syringae/genética , Ásia , Australásia , DNA Bacteriano/química , DNA Bacteriano/genética , Europa (Continente) , Evolução Molecular , Frutas/microbiologia , Genes Bacterianos/genética , Família Multigênica , Tipagem de Sequências Multilocus , Filogenia , Pseudomonas syringae/classificação , Pseudomonas syringae/isolamento & purificação , América do Sul
19.
PLoS One ; 7(6): e37354, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22701566

RESUMO

The task of an organism to extract information about the external environment from sensory signals is based entirely on the analysis of ongoing afferent spike activity provided by the sense organs. We investigate the processing of auditory stimuli by an acoustic interneuron of insects. In contrast to most previous work we do this by using stimuli and neurophysiological recordings directly in the nocturnal tropical rainforest, where the insect communicates. Different from typical recordings in sound proof laboratories, strong environmental noise from multiple sound sources interferes with the perception of acoustic signals in these realistic scenarios. We apply a recently developed unsupervised machine learning algorithm based on probabilistic inference to find frequently occurring firing patterns in the response of the acoustic interneuron. We can thus ask how much information the central nervous system of the receiver can extract from bursts without ever being told which type and which variants of bursts are characteristic for particular stimuli. Our results show that the reliability of burst coding in the time domain is so high that identical stimuli lead to extremely similar spike pattern responses, even for different preparations on different dates, and even if one of the preparations is recorded outdoors and the other one in the sound proof lab. Simultaneous recordings in two preparations exposed to the same acoustic environment reveal that characteristics of burst patterns are largely preserved among individuals of the same species. Our study shows that burst coding can provide a reliable mechanism for acoustic insects to classify and discriminate signals under very noisy real-world conditions. This gives new insights into the neural mechanisms potentially used by bushcrickets to discriminate conspecific songs from sounds of predators in similar carrier frequency bands.


Assuntos
Algoritmos , Percepção Auditiva/fisiologia , Ecossistema , Gryllidae/fisiologia , Interneurônios/fisiologia , Estimulação Acústica , Potenciais de Ação/fisiologia , Animais , Inteligência Artificial , Feminino , Masculino , Panamá , Especificidade da Espécie , Árvores , Clima Tropical
20.
Rev Obstet Gynecol ; 5(1): 28-34, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22582124

RESUMO

Despite a shift from clinical to surgical staging of endometrial cancer in 1988, performance of comprehensive surgical staging for clinically early-stage endometrial cancer remains controversial. Low-, intermediate-, and high-risk groups have been defined pathologically. Herein, we describe the risks and benefits of comprehensive surgical staging. Comprehensive surgical staging is encouraged in high-risk histologies, whereas a method of triage should be used to determine who among the low-grade endometrioid histology may benefit from comprehensive staging.

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