RESUMO
BACKGROUND: Graft-versus-host disease (GVHD) is an immune system reaction that occurs in patients with a history of hematopoietic stem cell transplantation (HSCT), in which the grafted donor's cells attack those of the host. The objective of this systematic review was to present a study on oral squamous cell carcinoma (OSSC) that developed from GVHD areas in patients undergoing HSCT. MATERIAL AND METHODS: An electronic search was conducted in the databases PUBMED, WEB OF SCIENCE, SCOPUS, MEDLINE and SCIENCE DIRECT, according to PRISMA guidelines. RESULTS: Of the 1582 results, 23 articles were included, resulting in 81 cases. The most common underlying disease for performing the transplant was Myeloid Leukemia (55.6%). The mean age was 39 years, with a predilection for males (64.2%). The tongue was the site of GVHD that most frequently underwent transformation to SCC (59.3%). The average time between transplantation and the development of GVHD was of approximately of 8 months, while the average period of development between transplantation and the development of OSCC was of approximately of 111 months. The most common treatment to GVHD was cyclosporine associated with corticosteroids. CONCLUSIONS: OSCCs arising from areas of GVHD present a different evolution from conventional oral carcinomas, since they affect younger patients, smoking and alcohol are not important etiological factors and finally because they present good prognosis, but further studies with larger number cases followed are needed to confirm our findings.
Assuntos
Carcinoma de Células Escamosas , Doença Enxerto-Hospedeiro , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Masculino , Humanos , Adulto , Carcinoma de Células Escamosas/complicações , Carcinoma de Células Escamosas de Cabeça e Pescoço/complicações , Neoplasias Bucais/etiologia , Doença Enxerto-Hospedeiro/complicações , Neoplasias de Cabeça e Pescoço/complicaçõesRESUMO
We describe one case of polypoidal choroidal vasculopathy with persistent subretinal fluid despite multiple treatment with intravitreal Bevacizumab, Ranibizumab and Aflibercept, as well as Aflibercept associated with photodynamic therapy. The patient reached complete resolution after intravitreal Brolucizumab injection, but experienced recurrence of subretinal fluid 12 weeks after discontinuation. Brolucizumab might be an option in treating subretinal fluid after failure of other anti-VEGF agents associated with photodynamic therapy.
Assuntos
Doenças da Coroide , Fotoquimioterapia , Humanos , Doenças da Coroide/tratamento farmacológico , Doenças da Coroide/complicações , Vasculopatia Polipoidal da CoroideRESUMO
BACKGROUND: Skeletal muscle wasting is a common phenotypic feature of several types of cancer, and it is associated with functional impairment, respiratory complications, and fatigue. However, equivocal evidence remains regarding the impact of cancer-induced muscle wasting on the different fiber types. AIM: The aim of this study was to investigate the impact of urothelial carcinoma induced in mice on the histomorphometric features and collagen deposition in different skeletal muscles. MATERIALS AND METHODS: Thirteen ICR (CD1) male mice were randomly assigned into two groups: exposed to 0.05% N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) in drinking water for 12 weeks, plus 8 weeks of tap water (BBN, n = 8) or with access to tap water for 20 weeks (CONT, n = 5). Tibialis anterior, soleus, and diaphragm muscles were collected from all animals. For cross-sectional area and myonuclear domain analysis, muscle sections were stained with hematoxylin and eosin, and for collagen deposition assessment, muscle sections were stained with picrosirius red. RESULTS: All animals from the BBN group developed urothelial preneoplastic and neoplastic lesions, and the tibialis anterior from these animals presented a reduced cross-sectional area (p < 0.001), with a decreased proportion of fibers with a higher cross-sectional area, increased collagen deposition (p = 0.017), and higher myonuclear domain (p = 0.031). BBN mice also showed a higher myonuclear domain in the diaphragm (p = 0.015). CONCLUSION: Urothelial carcinoma induced muscle wasting of the tibialis anterior, expressed by a decreased cross-sectional area, higher infiltration of fibrotic tissue, and increased myonuclear domain, which also increased in the diaphragm, suggesting that fast glycolytic muscle fibers are more susceptible to be affected by cancer development.
Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Camundongos , Masculino , Animais , Carcinoma de Células de Transição/patologia , Neoplasias da Bexiga Urinária/complicações , Neoplasias da Bexiga Urinária/patologia , Camundongos Endogâmicos ICR , Músculo Esquelético/patologia , Músculo Esquelético/fisiologia , Fibras Musculares de Contração Rápida/patologia , Atrofia Muscular/etiologia , Atrofia Muscular/patologiaRESUMO
Ultraviolet radiation (UV) and triclosan (TCS) affect the early development of marine fish; however, the corresponding molecular mechanisms are still not fully understood. Therefore, this work aims to study the effects of the single and combined exposure to these stressors during the thyroid-regulated metamorphosis of the flatfish Solea senegalensis. Sub-lethal exposure (5.89 kJ m-2 UV and/or 0.546 and 1.090 mg L-1 TCS for 48 h) was performed at the beginning of metamorphosis (13 days after hatching, dah), followed by a period in clean media until complete metamorphosis (24 dah). Malformations, metamorphosis progression, length, behavior and the expression of thyroid axis-related genes were studied. TCS induced malformations, decreased swimming performance, and induced metamorphosis acceleration at 15 dah, followed by a significant metamorphosis delay. Such effects were more noticeable in the presence of UV. The down-regulation of five thyroid axis-related genes occurred after exposure to TCS (15 dah), and after 9 days in clean media two genes were still down-regulated. UV exposure increased the effect of TCS by further down-regulating gene expression immediately after the exposure. Since several effects persisted after the period in clean media, implications of these stressors (mainly TCS) on the ecological performance of the species are suggested.
Assuntos
Linguados , Triclosan , Animais , Linguados/genética , Linguados/metabolismo , Larva , Metamorfose Biológica , Triclosan/metabolismo , Raios UltravioletaRESUMO
AIMS: In recent years, major improvements in breast cancer treatments have led to a significant increase in survival. Despite that, this population's quality of life (QoL) information is lacking, especially real-world data. MATERIALS AND METHODS: This was a prospective, multicentre, observational study of female breast cancer patients, without prior systemic treatment, treated between 2012 and 2019 in private health care in Brazil. QoL was assessed by two questionnaires, the EQ-5D-5L and the EORTC-QLQ-BR23. Additional data were retrospectively collected. RESULTS: The study comprised 1372 patients, most with early-stage disease (80.2% stages 0-II). At a median follow-up of 25.6 months, the estimated 3-year overall survival was 93.6%. Patients with locally advanced and metastatic breast cancer had the lowest visual analogue scale scores and the highest symptom burden in all dimensions of EQ-5D-5L, but with the most significant improvement after treatment. With the EORTC-QLQ-BR23 questionnaire, patients undergoing lumpectomy had a better perception of body image. Axillary dissection led to greater arm symptoms after 12 months, radiotherapy enhanced breast symptoms and patients treated with chemotherapy had significant worsening in the effects of systemic therapy compared with endocrine or HER2 therapy. Staging and immunohistochemical subtype correlated with survival and with several QoL parameters, but overall survival was not independently affected by patient-reported outcomes in this cohort. CONCLUSION: Our results show that early diagnosis and access to treatments with fewer side-effects, such as endocrine or targeted therapy, and less aggressive surgeries are the best strategies to achieve a better QoL for breast cancer patients.
Assuntos
Neoplasias da Mama , Qualidade de Vida , Neoplasias da Mama/terapia , Feminino , Humanos , Assistência Centrada no Paciente , Estudos Prospectivos , Estudos Retrospectivos , Inquéritos e QuestionáriosRESUMO
Premedication in the pediatric population is of vital importance to reduce anxiety and facilitate anesthetic induction. Midazolam and ketamine have been used for this purpose, drugs that have shown long-term changes in neurodevelopment. Dexmedetomidine promotes a sedative, analgesic effect and lacks neurotoxic effects, its intranasal application is easy and minimally invasive. We studied the sedative and behavioral effect of intranasal dexmedetomidine 2 mcg/kg in ASA 1 and 2 children for elective surgery. They were evaluated at 10, 20 and 30 minutes of administered, in the separation of the parents and placement of the mask for inhalation induction with behavioral and sedation scores (classified from 1 to 4), we considered acceptable for admission to operating room categories 3 and 4. RESULTS: Thirty patients between 1 and 10 years old were included in the period from September 2017 to April 2018. The sedation score obtained at 30minutes was acceptable in 46.6% of the patients and the behavior score was in 96% of the cases. In 63% of cases the acceptance of the facial mask placement for inhalation induction was achieved. The procedure was well tolerated in all cases and parents were satisfied in 100% of the cases.
Assuntos
Anestésicos , Dexmedetomidina , Anestesia Geral , Criança , Pré-Escolar , Dexmedetomidina/efeitos adversos , Método Duplo-Cego , Humanos , Lactente , Pré-MedicaçãoRESUMO
During the necropsies of Iberian hares obtained in 2018/2019, along with signs of the nodular form of myxomatosis, other unexpected external lesions were also observed. Histopathology revealed nuclear inclusion bodies in stromal cells suggesting the additional presence of a nuclear replicating virus. Transmission electron microscopy further demonstrated the presence of herpesvirus particles in the tissues of affected hares. We confirmed the presence of herpesvirus in 13 MYXV-positive hares by PCR and sequencing analysis. Herpesvirus-DNA was also detected in seven healthy hares, suggesting its asymptomatic circulation. Phylogenetic analysis based on concatenated partial sequences of DNA polymerase gene and glycoprotein B gene enabled greater resolution than analysing the sequences individually. The hare' virus was classified close to herpesviruses from rodents within the Rhadinovirus genus of the gammaherpesvirus subfamily. We propose to name this new virus Leporid gammaherpesvirus 5 (LeHV-5), according to the International Committee on Taxonomy of Viruses standards. The impact of herpesvirus infection on the reproduction and mortality of the Iberian hare is yet unknown but may aggravate the decline of wild populations caused by the recently emerged natural recombinant myxoma virus.
Assuntos
Lebres/virologia , Infecções por Herpesviridae/veterinária , Animais , Células Cultivadas , Feminino , Geografia , Herpesviridae/isolamento & purificação , Infecções por Herpesviridae/patologia , Infecções por Herpesviridae/virologia , Masculino , Pênis/patologia , Pênis/virologia , Filogenia , PortugalRESUMO
Progesterone (P4) plays a key role in pregnancy establishment and maintenance; during early pregnancy, P4 stimulates the production and release of uterine secretions necessary for conceptus growth prior to implantation; therefore, exogenous P4 supplementation may improve embryo development. This study evaluated the effects of supplementation during early pregnancy with long-acting injectable progesterone or altrenogest on embryonic characteristics of sows and gilts. Thus, a total of 32 sows and 16 gilts were used. On day 6 of pregnancy sows and gilts were allocated to one of the following groups: non-supplemented; supplemented with 20 mg of altrenogest, orally, from days 6 to 12 of pregnancy; supplemented with 2.15 mg/kg of long-acting injectable progesterone on day 6 of pregnancy. Animals were killed on day 28 of pregnancy, and ovulation rate, embryo survival, embryo weight, crown-to-rump length, uterine glandular epithelium and endometrial vascularization were assessed. Treatments had no effect on pregnancy rate, embryo survival or endometrial vascular density (P > 0.05). Non-supplemented gilts presented larger and heavier embryos compared to gilts from supplemented groups (P < 0.05). Sows in the altrenogest group presented larger and heavier embryos compared to non-supplemented sows and sows supplemented with long-acting injectable progesterone. In conclusion, supplementation of sows and gilts with progestagen from day 6 of pregnancy can be used as a means to improve embryo survival without deleterious effects.
Assuntos
Implantação do Embrião/efeitos dos fármacos , Desenvolvimento Embrionário/efeitos dos fármacos , Prenhez , Suínos/fisiologia , Acetato de Trembolona/análogos & derivados , Animais , Suplementos Nutricionais , Embrião de Mamíferos , Endométrio , Feminino , Ovulação/fisiologia , Gravidez , Taxa de Gravidez , Prenhez/efeitos dos fármacos , Progestinas/administração & dosagem , Progestinas/farmacologia , Acetato de Trembolona/administração & dosagem , Acetato de Trembolona/farmacologiaRESUMO
AIM: The aim of this study was to test the hypothesis that Manuka honey (MH) chelates iron and promotes an iron-limiting environment, which contributes to its antimicrobial activity. METHODS AND RESULTS: Employing a ferrozine-based assay, we observed that MH is an iron chelator that depletes iron from solution. Siderophores are small molecules that bind ferric iron (III) with high affinity and their levels are upregulated by bacteria under iron-limiting conditions. We demonstrated by quantitating siderophore production that Escherichia coli and Pseudomonas aeruginosa treated with MH sub-minimum inhibitory concentrations (sub-MIC) experience an iron-limiting environment and increase siderophore production. In addition, supplementation with ferrous iron (II) significantly increased growth of E. coli, Staphylococcus aureus and P. aeruginosa cultured at their MH MIC above that observed in nonsupplemented controls. By contrast, supplementation with ferric iron (III) significantly increased growth for only E. coli and P. aeruginosa, above their nonsupplemented controls. CONCLUSIONS: Manuka honey chelates iron, thereby generating an iron-limiting environment for E. coli and P. aeruginosa, and to a lesser extent S. aureus, which contributes to its antimicrobial properties. SIGNIFICANCE AND IMPACT OF THE STUDY: Our work demonstrates that MH-induced iron chelation is an antimicrobial mechanism that differentially impacts the bacterial species tested here. Iron chelation affects multiple diverse physiological processes in bacteria and would contribute to the lack of bacterial resistance to MH. Iron metabolism is tightly regulated; bacteria require this essential nutrient for survival, but in excess it is toxic. Additional exploration of MH's iron chelation mechanism will facilitate its future use in mainstream medicine.
Assuntos
Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Mel , Quelantes de Ferro/farmacologia , Ferro/metabolismo , Antibacterianos/metabolismo , Bactérias/classificação , Bactérias/crescimento & desenvolvimento , Bactérias/metabolismo , Quelantes de Ferro/metabolismo , Testes de Sensibilidade Microbiana , Sideróforos/metabolismo , Especificidade da EspécieRESUMO
Drug therapy for Chagas disease remains a major challenge as potential candidate drugs have failed clinical trials. Currently available drugs have limited efficacy and induce serious side effects. Thus, the discovery of new drugs is urgently needed in the fight against Chagas' disease. Here, we synthesized and evaluated the biological effect of pyrazole-imidazoline (1a-i) and pyrazole-tetrahydropyrimidine (2a-i) derivatives against relevant clinical forms of Trypanosoma cruzi. The structure-activity relationship (SAR), drug-target search, physicochemical and ADMET properties of the major active compounds in vitro were also assessed in silico. Pyrazole derivatives showed no toxicity in Vero cells and also no cardiotoxicity. Phenotypic screening revealed two dichlorinated pyrazole-imidazoline derivatives (1c and 1d) with trypanocidal activity higher than that of benznidazole (Bz) against trypomastigotes; these were also the most potent compounds against intracellular amastigotes. Replacement of imidazoline with tetrahydropyrimidine in the pyrazole compounds completely abolished the trypanocidal activity of series 2(a-i) derivatives. The physicochemical and ADMET properties of the compounds predicted good permeability, good oral bioavailability, no toxicity and mutagenicity of 1c and 1d. Pyrazole nucleus had high frequency hits for cruzipain in drug-target search and structure activity relationship (SAR) analysis of pyrazole-imidazoline derivatives revealed enhanced activity when chlorine atom was inserted in meta-positions of the benzene ring. Additionally, we found evidence that both compounds (1c and 1d) have the potential to interact non-covalently with the active site of cruzipain and also inhibit the cysteine proteinase activity of T. cruzi. Collectively, the data presented here reveal pyrazole derivatives with promise for further optimization in the therapy of Chagas disease.
Assuntos
Doença de Chagas/tratamento farmacológico , Imidazolinas/farmacologia , Pirazóis/farmacologia , Pirimidinas/farmacologia , Tripanossomicidas/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Animais , Células Cultivadas , Chlorocebus aethiops , Relação Dose-Resposta a Droga , Humanos , Imidazolinas/química , Estrutura Molecular , Testes de Sensibilidade Parasitária , Pirazóis/química , Pirimidinas/química , Relação Estrutura-Atividade , Tripanossomicidas/síntese química , Tripanossomicidas/química , Células VeroRESUMO
Abstract Triatoma lecticularia (Hemiptera: Reduviidae) (Stal, 1859) is a potential vector of Chagas's disease and the comprehension of its reproductive biology is an important tool to control this insect. In the reproductive tract of female insects, the spermatheca plays a crucial role storing male spermatozoa after mating. Whithin insects the spermatheca shows a wide morphological diversity and the analysis of this characteristic can contribute to understand the reproductive biology of the species. This study describes the histology and histochemistry of the spermatheca of T. lecticularia. Females have a pair of elongated spermathecal reservoirs without associated accessory gland. The reservoir opens into the common oviduct via a narrow muscular duct. The reservoir epithelium has single layer of columnar secretory cells. The control of the release of spermatozoa from the spermatheca occurs via the muscular duct. The anatomical features of the spermatheca of T. lecticularia resemble those described of other Reduviidae. However, the histological and histochemical features of spermatheca observed in T. lecticularia were important to explain the maintenance of the viability of the spermatozoa stored.
Resumo Triatoma lecticularia (Hemiptera: Reduviidae) (Stal, 1859) é um potencial vetor da doença de Chagas e a compreensão de sua biologia reprodutiva é um importante fator para seu controle populacional. No aparelho reprodutor feminino dos insetos, a espermateca desempenha a importante funcão de armazenar os espermatozoides após cópula. Nos insetos, a espermateca apresenta uma ampla diversidade morfológica e a análise destas características pode contribuir com o entendimento da biologia reprodutiva das espécies. Este estudo descreve histológica e histoquimicamente a espermateca de T. lecticularia. As fêmeas tem um par de espermatecas alongadas sem glândulas acessórias associadas. O reservatório conecta-se ao oviduto comum através de um ducto muscular curto que controla a liberação dos espermatozoides. O epitélio do reservatório possui uma camada de células secretoras colunares. As características anatômicas da espermateca de T. lecticularia são semelhantes às encontradas em outros Reduviidae. Entretanto, as características histológicas e histoquímicas observadas na espermateca são importantes para explicar a manutenção da viabilidade dos espermatozoides armazenados.
Assuntos
Animais , Masculino , Feminino , Triatoma/fisiologia , Reprodução , Espermatozoides/citologia , Espermatozoides/fisiologia , Triatoma/citologiaRESUMO
O objetivo deste estudo foi avaliar o efeito da suplementação do diluidor de congelação de sêmen ovino com o flavonoide miricetina contra os danos ocasionados aos espermatozoides. Oito pools de sêmen, obtidos de quatro reprodutores ovinos, foram congelados com diferentes concentrações de miricetina (0, 1, 10, 100 e 1000nM). Após o descongelamento, o sêmen foi avaliado quanto à cinética espermática, à integridade das membranas plasmática e acrossomal, ao potencial de membrana mitocondrial, aos níveis de ROS intracelular, à peroxidação lipídica e à estabilidade de membrana. Amostras tratadas com miricetina 10nM apresentaram menor percentual de células rápidas (P≤0,05), quando comparadas ao grupo miricetina 1000nM. Amostras do grupo controle apresentaram maior (P≤0,05) VAP que o grupo 10nM de miricetina, enquanto amostras criopreservadas com miricetina (10, 100 e 1000nM) evidenciaram maior (P<0,05) BCF, quando comparadas ao grupo controle. O grupo tratado com miricetina 1000nM apresentou maior percentual (P<0,05) de células com peroxidação lipídica, quando comparado ao grupo controle. Em conclusão, a suplementação do diluidor de criopreservação de sêmen ovino com 10 e 100nM de miricetina afeta a cinética espermática sem provocar alterações na estrutura geral do gameta, enquanto 1000nM de miricetina provoca mudanças na cinética associadas à danos peroxidativos.(AU)
The aim of this study was to evaluate the effect of the supplementation of ram semen frozen with extender with the flavonoid myricetin against damage to sperm. Eight pools of semen obtained from four ram breeders, were frozen with different concentrations of myicetin (0, 1, 10, 100 and 1000nM). After thawing, the semen was evaluated for spermatic kinetics, plasma and acrosome membrane integrity, mitochondrial membrane potential, intracellular ROS levels, lipid peroxidation, and membrane stability. Samples treated with 10nM myricetin preserved a lower percentage of rapid cells (P≤0.05) when compared to the 1000nM myricetin group. Samples from the control group presented higher (P≤0.05) VAP than 10nM group of myricetin, while cryopreserved samples with myicetin (10, 100 and 1000nM) showed greater (P<0.05) BCF, when compared to control group. The group treated with 1000nM myricetin had a higher percentage (P<0.05) of cells with lipid peroxidation, when compared to the control group. In conclusion, supplementation of ram semen cryopreservation extender with 10 and 100nM myricetin affects sperm kinetics, without causing changes in the overall structure of the gamete, while 1000nM myricetin causes changes in the kinetics associated with peroxidative damage.(AU)
Assuntos
Preservação do Sêmen/métodos , Preservação do Sêmen/veterinária , Ovinos/embriologia , Flavanonas , Análise do SêmenRESUMO
AIMS: The comparative efficacy of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy on Type 2 diabetes remission and the role of weight loss are unclear. The DiaRem diabetes remission prediction score uses HbA1c , age and diabetes medications but not diabetes duration. The aim of this study was to compare the DiaRem with the DiaBetter score that includes diabetes duration, upon combined (complete plus partial) 2-year post-surgery diabetes remission in people following RYGB and sleeve gastrectomy, and to investigate the relationship between weight loss and diabetes remission. METHODS: A retrospective single-centre cohort study of obese people with diabetes who underwent RYGB (107) or sleeve gastrectomy (103) and a validation cohort study (173) were undertaken. Diabetes remission, % weight loss, DiaRem, DiaBetter scores and areas under receiving operator characteristic (ROC) curves were calculated. The relationship between % weight loss and diabetes remission was investigated using logistic regression. RESULTS: The proportion of people achieving diabetes remission was highest for those with the lowest DiaBetter and DiaRem scores. Areas under the ROC curves were comparable [DiaBetter: 0.867 (95%CI: 0.817-0.916); DiaRem: 0.865 (95%CI: 0.814-0.915), P=0.856]. Two-year % weight loss was higher post RYGB [26.6 (95%CI: 24.8-28.4)] vs post-sleeve gastrectomy [20.6 (95%CI: 18.3-22.8), P<0.001]. RYGB had 151% higher odds of diabetes remission [OR 2.51 (95%CI: 1.12-5.60), P=0.025]. This association became non-significant when adjusted for % weight loss. CONCLUSION: DiaBetter and DiaRem scores predict diabetes remission following both procedures. Two-year % weight loss plays a key role in determining diabetes remission.
Assuntos
Cirurgia Bariátrica/métodos , Diabetes Mellitus Tipo 2/cirurgia , Gastrectomia/métodos , Redução de Peso/fisiologia , Diabetes Mellitus Tipo 2/sangue , Feminino , Derivação Gástrica/métodos , Hemoglobinas Glicadas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Probabilidade , Indução de Remissão , Resultado do TratamentoRESUMO
Brain glucose metabolism is altered in sporadic Alzheimer's disease (sAD), whose pathologies are reproduced in rodents by intracerebroventricular (icv) infusion of streptozotocin (STZ) in subdiabetogenic doses. The icv-STZ model also culminates in central cholinergic dysfunctions, which in turn are known to underlie both the sAD cognitive decline, and synaptic plasticity impairments. Considering the cognitive-enhancing potential of chronic nicotine (Nic), we investigated whether it attenuates icv-STZ-induced impairments in recognition memory and synaptic plasticity in a cognition-relevant substrate: the hippocampal CA1-medial prefrontal cortex (mPFC) pathway. Rats treated with icv-STZ were submitted to a chronic Nic regime, and were evaluated for recognition memory. We then examined long-term potentiation (LTP), paired-pulse facilitation (PPF) under urethane anesthesia, and brains were also evaluated for hippocampus-mPFC cell density. We found that Nic treatment prevents icv-STZ-induced disruptions in recognition memory and LTP. STZ did not precipitate neuronal death, while Nic alone was associated with higher neuronal density in CA1 when compared to vehicle-injected animals. Through combining behavioral, neurophysiological, and neuropathological observations into the Nic-STZ interplay, our study reinforces that cholinergic treatments are of clinical importance against early-stage Alzheimer's disease and mild cognitive impairments.
Assuntos
Doença de Alzheimer/fisiopatologia , Doença de Alzheimer/psicologia , Região CA1 Hipocampal/efeitos dos fármacos , Potenciação de Longa Duração/efeitos dos fármacos , Nicotina/administração & dosagem , Córtex Pré-Frontal/efeitos dos fármacos , Reconhecimento Psicológico/efeitos dos fármacos , Doença de Alzheimer/induzido quimicamente , Animais , Região CA1 Hipocampal/fisiologia , Contagem de Células , Modelos Animais de Doenças , Locomoção/efeitos dos fármacos , Masculino , Neurônios/efeitos dos fármacos , Córtex Pré-Frontal/fisiologia , Ratos Wistar , Reconhecimento Psicológico/fisiologia , Estreptozocina , Potenciais Sinápticos/efeitos dos fármacosRESUMO
BACKGROUND: Our aim was to characterize the influence of time-of-flight (TOF) and point spread function (PSF) recovery corrections, as well as ordered subset expectation maximization (OSEM) reconstruction parameters, in 82Rb PET/CT quantification of myocardial blood flow (MBF) and myocardial flow reserve (MFR). Rest and stress list-mode dynamic 82Rb PET acquisition data from 10 patients without myocardial flow defects and 10 patients with myocardial blood flow defects were reconstructed retrospectively. OSEM reconstructions were performed with Gaussian filters of 4, 6, and 8 mm, different iterations, and subset numbers (2 × 24; 2 × 16; 3 × 16; 4 × 16). Rest and stress global, regional, and segmental MBF and MFR were computed from time activity curves with FlowQuant© software. Left ventricular segmentation using the 17-segment American Heart Association model was obtained. RESULTS: Whole left ventricle (LV) MBF at rest and stress were 0.97 ± 0.30 and 2.30 ± 1.00 mL/min/g, respectively, and MFR was 2.40 ± 1.13. Concordance was excellent and all reconstruction parameters had no significant impact on MBF, except for the exclusion of TOF which led to significantly decreased concordance in rest and stress MBF in patients with or without perfusion defects on a coronary artery basis and in MFR in patients with perfusion defects. CONCLUSIONS: Changes in reconstruction parameters in perfusion 82Rb PET/CT studies influence quantitative MBF analysis. The inclusion of TOF information in the tomographic reconstructions had significant impact in MBF quantification.
RESUMO
Abstract Triatoma lecticularia (Hemiptera: Reduviidae) (Stal, 1859) is a potential vector of Chagass disease and the comprehension of its reproductive biology is an important tool to control this insect. In the reproductive tract of female insects, the spermatheca plays a crucial role storing male spermatozoa after mating. Whithin insects the spermatheca shows a wide morphological diversity and the analysis of this characteristic can contribute to understand the reproductive biology of the species. This study describes the histology and histochemistry of the spermatheca of T. lecticularia. Females have a pair of elongated spermathecal reservoirs without associated accessory gland. The reservoir opens into the common oviduct via a narrow muscular duct. The reservoir epithelium has single layer of columnar secretory cells. The control of the release of spermatozoa from the spermatheca occurs via the muscular duct. The anatomical features of the spermatheca of T. lecticularia resemble those described of other Reduviidae. However, the histological and histochemical features of spermatheca observed in T. lecticularia were important to explain the maintenance of the viability of the spermatozoa stored.
Resumo Triatoma lecticularia (Hemiptera: Reduviidae) (Stal, 1859) é um potencial vetor da doença de Chagas e a compreensão de sua biologia reprodutiva é um importante fator para seu controle populacional. No aparelho reprodutor feminino dos insetos, a espermateca desempenha a importante funcão de armazenar os espermatozoides após cópula. Nos insetos, a espermateca apresenta uma ampla diversidade morfológica e a análise destas características pode contribuir com o entendimento da biologia reprodutiva das espécies. Este estudo descreve histológica e histoquimicamente a espermateca de T. lecticularia. As fêmeas tem um par de espermatecas alongadas sem glândulas acessórias associadas. O reservatório conecta-se ao oviduto comum através de um ducto muscular curto que controla a liberação dos espermatozoides. O epitélio do reservatório possui uma camada de células secretoras colunares. As características anatômicas da espermateca de T. lecticularia são semelhantes às encontradas em outros Reduviidae. Entretanto, as características histológicas e histoquímicas observadas na espermateca são importantes para explicar a manutenção da viabilidade dos espermatozoides armazenados.
RESUMO
BACKGROUND/OBJECTIVES: Obese adipose tissue, especially the visceral depot, exhibits altered production of several molecules that could have a role on the initiation/promotion of breast cancer development. The aim of this work was to evaluate the effect of excess adipose tissue and its secreted factors on the expression of genes involved in the early steps of tumor promotion on the mammary gland. SUBJECTS AND METHODS: Carcinogenesis-related gene expression was evaluated in mammary gland tissue from female diet-induced obese (DIO) Sprague-Dawley rats and circulating leukocytes isolated from a group of breast cancer diagnosed and non-diagnosed obese women and compared with their normal weight counterparts. In addition, the human non-tumoral mammary epithelial cell line MCF10A was treated in vitro with the visceral (retroperitoneal adipose tissue (RPAT)) or subcutaneous adipose tissue (SAT) secretome and with rising concentrations of the lipid peroxidation by-product 4-hydroxynonenal (4-HNE). RESULTS: DIO rats were classified as susceptible to DIO (DIO-S) or partially resistant to DIO (DIO-R) according to the maximum fat mass gain of the lean group as a cut-off. As compared with lean and DIO-R, the DIO-S group showed a higher fat mass and lower lean mass. The anatomical characteristic of DIO-S was correlated with differential expression of cellular proliferation (ALDH3A1 and MYC) and antioxidant and DNA protection (GSTM2, SIRT1), and tumor suppression (TP53, PTEN, TGFB1) genes. Remarkably, this carcinogenesis-related gene expression pattern was reproduced in MCF10A treated with the RPAT secretome from DIO-S rats and with the lipid peroxidation by-product 4-HNE. Moreover, this pattern was also detected in leukocytes from obese women compared with normal weight women without evidence of breast cancer. CONCLUSIONS: Lipid peroxides secreted by the obese visceral adipose tissue could be among the relevant factors that promote changes involved in the early steps of tumor development in mammary gland. These changes can be detected even before histological alterations and in circulating leukocytes.
Assuntos
Neoplasias da Mama/patologia , Transformação Celular Neoplásica/patologia , Proteínas de Neoplasias/metabolismo , Obesidade/patologia , Gordura Subcutânea/patologia , Animais , Apoptose , Western Blotting , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Predisposição Genética para Doença , Estresse Oxidativo , Ratos , Ratos Sprague-DawleyRESUMO
In invasive candidiasis, there has been an epidemiological shift from Candida albicans to non-albicans species infections, including infections with C. glabrata, C. parapsilosis, C. tropicalis, and C. krusei. Although the prevalence of C. krusei remains low among yeast infections, its intrinsic resistance to fluconazole raises epidemiological and therapeutic concerns. Echinocandins have in vitro activity against most Candida spp. and are the first-line agents in the treatment of candidemia. Although resistance to echinocandin drugs is still rare, individual cases of C. krusei resistance have been reported in recent years, especially with strains that have been under selective pressure. A total of 15 C. krusei strains, isolated from the blood, urine, and soft tissue of an acute lymphocytic leukemia patient, were analyzed. Strains developed echinocandin resistance during 10 days of caspofungin therapy. The molecular epidemiology of the isolates was investigated using two different typing methods: PCR-based amplification of the species-specific repetitive polymorphic CKRS-1 sequence and multilocus sequence typing. All isolates were genetically related, and the mechanism involved in decreased echinocandin susceptibility was characterized. Clinical resistance was associated with an increase in echinocandin MICs in vitro and was related to three different mutations in hot spot 1 of the target enzyme Fks1p. Molecular evidence of the rapid acquisition of resistance by different mutations in FKS1 highlights the need to monitor the development of resistance in C. krusei infections treated with echinocandin drugs.
Assuntos
Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Equinocandinas/farmacologia , Antifúngicos/uso terapêutico , Candida/genética , Candida/patogenicidade , Candidíase/tratamento farmacológico , Candidíase/microbiologia , Caspofungina , Equinocandinas/uso terapêutico , Feminino , Humanos , Lipopeptídeos , Pessoa de Meia-Idade , Reação em Cadeia da PolimeraseRESUMO
We report a case of a 76-year-old woman with metastases to both parotid glands almost 25 years after mastectomy and chemotherapy for primary carcinoma of the breast. Immunohistochemical staining is invaluable in establishing the origin of metastatic deposits, in this case, expression of oestrogen receptors in a previously resected adenocarcinoma of the breast. The information can be used to target treatment accurately in selected cases of advanced malignancy.