RESUMO
OBJECTIVES: Automated systems to analyse nailfold videocapillaroscopy (NVC) images are needed to promptly and comprehensively characterise patients with systemic sclerosis (SSc) or Raynaud's phenomenon (RP). We previously developed, and validated in-house, a deep convolutional neural network-based algorithm to classify NVC-captured images according to the presence/absence of structural abnormalities and/or microhaemorrhages. We present its external clinical validation. METHODS: A total of 1,164 NVC images of RP patients were annotated by 5 trained capillaroscopists according to the following categories: normal capillary; dilation; giant capillary; abnormal shape; tortuosity; microhaemorrhage. The images were also presented to the algorithm. Matches and discrepancies between algorithm predictions and those annotations obtained by consensus of ≥3 or ≥4 interobservers were analysed. RESULTS: Consensus among ≥3 capillaroscopists was achieved in 86.9% of images, 75.8% of which were correctly predicted by the algorithm. Consensus among ≥4 experts occurred in 52.0% of cases, in which 87.1% of the algorithm's results matched with those of the expert panel. The algorithm's positive predictive value was >80% for microhaemorrhages and unaltered, giant or abnormal capillaries. Sensitivity was >75% for dilations and tortuosities. Negative predictive value and specificity were >89% for all categories. CONCLUSIONS: This external clinical validation suggests that this algorithm is useful to assist in the diagnosis and follow-up of SSc or RP patients in a timely manner. It may also be helpful in the management of patients with any pathology presenting with microvascular changes, as the algorithm has been designed to also be useful for research aiming at extending the usage of nailfold capillaroscopy to more conditions.
Assuntos
Doença de Raynaud , Escleroderma Sistêmico , Humanos , Angioscopia Microscópica/métodos , Unhas/irrigação sanguínea , Escleroderma Sistêmico/diagnóstico por imagem , Escleroderma Sistêmico/patologia , Doença de Raynaud/diagnóstico por imagem , Software , Capilares/diagnóstico por imagem , Capilares/patologiaRESUMO
BACKGROUND: Pancreatic panniculitis is a rare form of panniculitis generally associated with acute or chronic pancreatitis, and less frequently with pancreatic carcinoma. Clinically, it presents with subcutaneous nodules usually located in the lower extremities, however, it presents an almost pathognomonic histopathological finding with enzymatic fat necrosis in the adipose tissue. METHODS: In this retrospective case series of five hospitals, biopsy specimens of cutaneous lesions of pancreatic panniculitis were reviewed. Clinical information was obtained through medical records. RESULTS: A total of 34 cases were included, 23 women and 11 men, aged between 31 and 92 years. The most common associated pancreatic disease was acute pancreatitis (23 cases) and its main triggering cause was gallstones (17 cases). In two patients it was related to chronic pancreatitis and six cases were associated with malignancy. Histopathological findings were always the key to diagnosis. In the biopsies reviewed, mostly lobular panniculitis with the characteristic necrosis of the adipocytes was observed. In addition, nine of the cases presented with Splendore-Hoeppli phenomenon. CONCLUSIONS: We present the largest series of pancreatic panniculitis. Clinically, the female predominance and biliary lithiasis as the main cause of acute pancreatitis are to be emphasized. Histopathologically, a peripheral eosinophilic striated rim surrounding aggregates of ghost adipocytes consistent with Splendore-Hoeppli is an additional clue to its diagnosis.
RESUMO
Hybrid oncocytic/chromophobe tumor (HOCT) of the kidney arising from a precursor oncocytosis not associated with the Birt-Hogg-Dubé (BHD) syndrome is an unusual and highly interesting neoplasm. Immunohistochemical and molecular findings suggest that HOCT is an entity distinct from both oncocytoma and chromophobe carcinoma. Although uncertainty persists regarding the factors predisposing to the development of HOCT, experimental findings suggest that it may arise due to the effect of toxins or in association with chronic kidney failure. The potential role of prior renal lymphoma in the development of oncocytosis has not hitherto been examined. We present a morphological, immunohistochemical, and molecular analysis of an HOCT arising from renal oncocytosis in conjunction with CLL affecting the kidney. The findings suggest that this tumor belongs to a family of similar neoplasms including oncocytoma, the eosinophilic variant of chromophobe renal-cell carcinoma (CRCC), and low-grade oncocytic tumor, even though these neoplasms may arise from different precursor lesions. HOCT and oncocytosis revealed the same immunohistochemical profile consistent on positivity for epithelial membrane antigen (EMA), cytokeratin 7 (Ck7), E-cadherin, CAM 5.2 and negativity for Pax-8, vimentin, renal-cell carcinoma (RCC) antigen, CD117, racemase, progesterone receptor, and CD10. The Ki-67 proliferation index was <1%. Molecular analysis of the tumor revealed the AKT3 gene mutation variant, classified as probably pathogenic, together with FOS1 gene amplification and no copy number variations (CNVs). Finally, we present a case of HOCT arising from a nonhereditary renal oncocytosis in conjunction with B lymphoma that raises interesting questions regarding pathogenesis.
Assuntos
Adenoma Oxífilo/patologia , Carcinoma de Células Renais/genética , Neoplasias Renais/genética , Rim/patologia , Leucemia Linfocítica Crônica de Células B/genética , Linfoma/patologia , Adenoma Oxífilo/etiologia , Idoso , Biomarcadores Tumorais/análise , Humanos , Rim/diagnóstico por imagem , Neoplasias Renais/diagnóstico , Leucemia Linfocítica Crônica de Células B/diagnóstico , Linfoma/complicações , Masculino , Tomografia Computadorizada por Raios XRESUMO
An optimal uptake of mineral elements is crucial to ensure both crop yield and quality. The use of biostimulants is taking relevance to improve the nutrition of crops. Sulphur (S) is one of the elements with great potential within biostimulants. Furthermore, soil contamination by heavy metals such as cadmium (Cd) has become a serious environmental problem. Different studies have suggested the use of thiosulphate (TS) as a biostimulant and to increase the phytoremediation capacity of plants. Therefore, in the present study, we use a crop plant with high S requirements such as Brassica oleracea, to test whether TS serves as a biostimulant and whether affects Cd accumulation and tolerance. B. oleracea plants were grown with two different TS doses (2 mM and 4 mM), under Cd toxicity, and with the combination of Cd toxicity and both TS doses. Parameters of biomass, mineral elements accumulation, and stress tolerance were analyzed. The results showed that TS reduced biomass of B. oleracea plants. The application of 2 mM TS increased Cd accumulation whereas the 4 mM dose reduced it. On the other hand, TS incremented micronutrient accumulation on plants subjected to Cd toxicity and increased Zn contents. Besides, the application of 2 mM to Cd-stressed plants enhanced photosynthesis performance and reduced oxidative stress. Finally, TS increased the antioxidant capacity of B. oleracea plants. Briefly, although TS can not be used as a biostimulant it could be used for Cd phytoremediation purposes and to enhance Zn accumulation in B. oleracea plants.
Assuntos
Adaptação Fisiológica/efeitos dos fármacos , Bioacumulação , Brassica/efeitos dos fármacos , Cádmio/toxicidade , Poluentes do Solo/toxicidade , Tiossulfatos/farmacologia , Antioxidantes/metabolismo , Biodegradação Ambiental , Biomassa , Brassica/metabolismo , Cádmio/metabolismo , Produtos Agrícolas , Estresse Oxidativo/efeitos dos fármacos , Fotossíntese/efeitos dos fármacos , Poluentes do Solo/metabolismoRESUMO
The objective of this study was to evaluate the impact of digital ulcers (DUs) in daily life of systemic sclerosis (SSc) Spanish patients. We developed a multicenter observational study to compare functional disability in SSc patients with active DUs vs. those without DUs. An additional correlation between perception of patients and physicians on disability due to DUs was performed. A total of 199 patients were enrolled, 70 (35%) with DUs. Patients with DUs were younger (48 vs. 58 years; p < 0.001) and had more frequently the diffuse subtype of SSc (45 vs. 24%; p = 0.004) than patients without DUs. Patients with DUs showed significantly higher scores in the Cochin Hand Function Scale overall (p < 0.002) and for each of its five dimensions. They also showed higher scores in the Systemic Sclerosis Health Assessment Questionnaire items related to hand function such as, dress and self-care (p < 0.013), eat (p < 0.013) and grip (p < 0.03), and higher Visual Analogic Scale scores for pain (p < 0.013), trouble related with Raynaud's Phenomenon (p < 0.001) and sense of severity (p < 0.004). Impact on daily activities was significantly higher in patients with DUs (p = 0.002), with a non-significant trend to experience higher impact on work productivity (p = 0.07). A high correlation was found between DUs patients and physicians opinion on the impact of DUs (daily life: Pearson R = 0.86; work productivity: Pearson R = 0.87). Study findings show an impaired hand function and increased disability for daily life activities and work productivity in SSc patients with DUs compared with patients without DUs in Spanish population.
Assuntos
Atividades Cotidianas , Eficiência , Doença de Raynaud/etiologia , Escleroderma Sistêmico/complicações , Úlcera Cutânea/etiologia , Local de Trabalho , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Avaliação da Deficiência , Feminino , Dedos/irrigação sanguínea , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Adulto JovemRESUMO
BACKGROUND: Stimulation of the vagus nerve in the so-called cholinergic antiinflammatory pathway (CAP) attenuates systemic inflammation, improving survival in animal sepsis models via α7 nicotinic acetylcholine receptors on immunocompetent cells. Because the relevance of this regulatory pathway is unknown in human sepsis, this pilot study assessed whether the α7 gene expression level in septic patients' peripheral blood mononuclear cells (PBMC) might be used to assess CAP activity and clinical outcome. METHODS: The PBMCs α7 messenger RNA levels were determined by real-time quantitative reverse-transcription polymerase chain reaction in 33 controls and 33 patients at enrollment and after their hospital discharge. Data were analyzed to find significant associations between α7 level, vagally mediated heart rate variability as an indirect reflection of CAP activity, serum concentrations of different inflammation markers, and clinical course. RESULTS: Septic patients' α7 levels were significantly increased and returned to control values after recovery. These α7 levels correlated directly with the vagal heart input and inversely with the magnitude of the patient's inflammatory state, disease severity, and clinical outcome. CONCLUSIONS: This study reveals that the PBMC α7 gene expression level is a clinically relevant marker for CAP activity in sepsis: the higher the α7 expression, the better the inflammation control and the prognosis.
Assuntos
Leucócitos Mononucleares/metabolismo , RNA Mensageiro/sangue , Sepse/genética , Receptor Nicotínico de Acetilcolina alfa7/genética , Adulto , Idoso , Anti-Inflamatórios/uso terapêutico , Biomarcadores/metabolismo , Estudos de Casos e Controles , Linhagem Celular , Colinérgicos/uso terapêutico , Feminino , Expressão Gênica/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Humanos , Inflamação/tratamento farmacológico , Inflamação/genética , Inflamação/microbiologia , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Sepse/sangue , Sepse/tratamento farmacológico , Sepse/metabolismo , Nervo Vago/fisiologia , Receptor Nicotínico de Acetilcolina alfa7/metabolismoRESUMO
The aim of this work was to study the effect of Fe deficiency on the protein profile of phloem sap exudates from Brassica napus using 2DE (IEF-SDS-PAGE). The experiment was repeated thrice and two technical replicates per treatment were done. Phloem sap purity was assessed by measuring sugar concentrations. Two hundred sixty-three spots were consistently detected and 15.6% (41) of them showed significant changes in relative abundance (22 decreasing and 19 increasing) as a result of Fe deficiency. Among them, 85% (35 spots), were unambiguously identified. Functional categories containing the largest number of protein species showing changes as a consequence of Fe deficiency were signaling and regulation (32%), and stress and redox homeostasis (17%). The Phloem sap showed a higher oxidative stress and significant changes in the hormonal profile as a result of Fe deficiency. Results indicate that Fe deficiency elicits major changes in signaling pathways involving Ca and hormones, which are generally associated with flowering and developmental processes, causes an alteration in ROS homeostasis processes, and induces decreases in the abundances of proteins involved in sieve element repair, suggesting that Fe-deficient plants may have an impaired capacity to heal sieve elements upon injury.
Assuntos
Brassica napus/metabolismo , Ferro/metabolismo , Floema/metabolismo , Proteínas de Plantas/metabolismo , Eletroforese em Gel de Poliacrilamida , Estresse Oxidativo , Reguladores de Crescimento de Plantas/metabolismo , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Espectrometria de Massas em TandemRESUMO
AIMS: To report on 15 cases of Merkel cell carcinoma (MCC) with divergent differentiation, to characterize its clinicopathological spectrum and its relationship with Merkel cell polyomavirus (MCV). METHODS AND RESULTS: Fifteen patients with a mean age of 81 years were included. Follow-up was available for 13 cases (range 12 days to 6 years; median 6 months). Recurrence, metastasis and mortality rates were 15.4%, 53.8% and 61.5%, respectively. All tumours showed the typical histological and immunohistochemical features of MCC, with at least one additional divergent component. Eight cases had a single aberrant component (squamous in six cases, follicular in one case, and porocarcinoma in one case), six cases had two aberrant components (squamous and sarcomatous in three cases, glandular and squamous in two cases, and sarcomatous and neuroblastic in one case), and one case had three aberrant components (glandular, squamous, and sarcomatous). All cases had dysplastic changes in the overlying epithelium, and four of 15 showed epidermotropism. PCR analysis for Merkel cell polyomavirus (MCV) gave negative results in all 12 cases tested. CONCLUSIONS: Merkel cell carcinoma with divergent differentiation is a highly aggressive tumour that might be difficult to recognize, owing to its wide histological variability. Negativity for MCV suggests that the virus is not implicated in the development of this subtype of MCC.
Assuntos
Carcinoma de Célula de Merkel/secundário , Transformação Celular Neoplásica , Poliomavírus das Células de Merkel/isolamento & purificação , Infecções por Papillomavirus/patologia , Neoplasias Cutâneas/patologia , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Célula de Merkel/metabolismo , Carcinoma de Célula de Merkel/virologia , DNA Viral/genética , Feminino , Humanos , Imuno-Histoquímica/métodos , Linfonodos/patologia , Metástase Linfática , Masculino , Poliomavírus das Células de Merkel/genética , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/metabolismo , Reação em Cadeia da Polimerase , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/virologiaRESUMO
Alkalinity is an important environmental factor that affects crop production and will be exacerbated in the current climate change scenario. Thus, the presence of carbonates and high pH in soils negatively impacts nutrient assimilation and photosynthesis and causes oxidative stress. A potential strategy to improve tolerance to alkalinity could be the modification of cation exchanger (CAX) activity, given that these transporters are involved in calcium (Ca2+) signaling under stresses. In this study, we used three Brassica rapa mutants (BraA.cax1a-4, BraA.cax1a-7, and BraA.cax1a-12) from the parental line 'R-o-18' that were generated by Targeting Induced Local Lesions in Genomes (TILLING) and grown under control and alkaline conditions. The objective was to assess the tolerance of these mutants to alkalinity stress. Biomass, nutrient accumulation, oxidative stress, and photosynthesis parameters were analyzed. The results showed that BraA.cax1a-7 mutation was negative for alkalinity tolerance because it reduced plant biomass, increased oxidative stress, partially inhibited antioxidant response, and lowered photosynthesis performance. Conversely, the BraA.cax1a-12 mutation increased plant biomass and Ca2+ accumulation, reduced oxidative stress, and improved antioxidant response and photosynthesis performance. Hence, this study identifies BraA.cax1a-12 as a useful CAX1 mutation to enhance the tolerance of plants grown under alkaline conditions.
Assuntos
Brassica rapa , Brassica rapa/genética , Antioxidantes , Mutação , Estresse OxidativoRESUMO
BACKGROUND AND AIMS: Leafy vegetable Brassica crops are an important source of dietary calcium (Ca) and magnesium (Mg) and represent potential targets for increasing leaf Ca and Mg concentrations through agronomy or breeding. Although the internal distribution of Ca and Mg within leaves affects the accumulation of these elements, such data are not available for Brassica. The aim of this study was to characterize the internal distribution of Ca and Mg in the leaves of a vegetable Brassica and to determine the effects of altered exogenous Ca and Mg supply on this distribution. METHODS: Brassica rapa ssp. trilocularis 'R-o-18' was grown at four different Ca:Mg treatments for 21 d in a controlled environment. Concentrations of Ca and Mg were determined in fully expanded leaves using inductively coupled plasma-mass spectrometry (ICP-MS). Internal distributions of Ca and Mg were determined in transverse leaf sections at the base and apex of leaves using energy-dispersive X-ray spectroscopy (EDS) with cryo-scanning electron microscopy (cryo-SEM). KEY RESULTS: Leaf Ca and Mg concentrations were greatest in palisade and spongy mesophyll cells, respectively, although this was dependent on exogenous supply. Calcium accumulation in palisade mesophyll cells was enhanced slightly under high Mg supply; in contrast, Mg accumulation in spongy mesophyll cells was not affected by Ca supply. CONCLUSIONS: The results are consistent with Arabidopsis thaliana and other Brassicaceae, providing phenotypic evidence that conserved mechanisms regulate leaf Ca and Mg distribution at a cellular scale. The future study of Arabidopsis gene orthologues in mutants of this reference B. rapa genotype will improve our understanding of Ca and Mg homeostasis in plants and may provide a model-to-crop translation pathway for targeted breeding.
Assuntos
Transporte Biológico Ativo/efeitos dos fármacos , Brassica rapa/efeitos dos fármacos , Brassica rapa/metabolismo , Cálcio/farmacocinética , Magnésio/farmacocinética , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/metabolismo , Cálcio/administração & dosagem , Magnésio/administração & dosagem , Distribuição Tecidual , Verduras/efeitos dos fármacos , Verduras/metabolismoRESUMO
Currently, brachytherapy is the most commonly used therapeutic approach for uveal melanomas. Surgical resection by means of endoresection or exoresection is an alternative approach. The present report recounts our experience over 15 years in the treatment of uveal melanoma using a combined approach of resection surgery with brachytherapy. This is a single-center observational retrospective cohort study in which we describe clinical outcomes, complications and survival in 35 cases of melanoma of the iris or the ciliary body after a combination of surgery and brachytherapy or brachytherapy alone. Local treatment of the tumor was successful in all cases with surgery and brachytherapy. The most frequent complications were scleromalacia, bullous keratopathy, retinal toxicity, cataracts, hypotonia, and photophobia. There were three cases of recurrence, all of which were found in the group of patients who had received brachytherapy alone, and in one case we had to perform a secondary enucleation due to tumor growth after brachytherapy. At present, only one patient has died during follow-up due to liver metastases six years after the start of treatment. In carefully selected patients, this approach can be effective and safe, as long as a close follow-up is carried out after surgery.
RESUMO
Salinity is an important environmental factor that reduces plant productivity in many world regions. It affects negatively photosynthesis causing a growth reduction. Likewise, calcium (Ca2+) is crucial in plant stress response. Therefore, the modification of Ca2+ cation exchangers (CAX) transporters could be a potential strategy to increase plant tolerance to salinity. Using Targeting Induced Local Lesions in Genomes (TILLING), researchers generated three mutants of Brassica rapa CAX1a transporter: BraA.cax1a-7, BraA.cax1a-4, and BraA.cax1a-12. The aim of this study was to test the effect of those mutations on salt tolerance focusing on the response to the photosynthesis process. Thus, the three BraA.cax1a mutants and the parental line (R-o-18) were grown under salinity conditions, and parameters related to biomass, photosynthesis performance, glucose-6-phosphate dehydrogenase (G6PDH, EC 1.1.1.49), and soluble carbohydrates were measured. BraA.cax1a-4 provided higher biomass and a better photosynthetic performance manifested by higher water use efficiency (WUE), Fv/Fm, electron fluxes, and Rubisco (EC 4.1.1.39) values. In addition, BraA.cax1a-4 presented increased osmotic protection through myo-inositol accumulation. On the other hand, BraA.cax1a-7 produced some negative effects on photosynthesis performance and lower G6PDH and Rubisco accumulations. Therefore, this study points out BraA.cax1a-4 as a useful mutation to improve photosynthetic performance in plants grown under saline conditions.
Assuntos
Brassica rapa/genética , Brassica rapa/fisiologia , Fotossíntese/genética , Fotossíntese/fisiologia , Tolerância ao Sal/efeitos dos fármacos , Tolerância ao Sal/genética , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Variação Genética , Genótipo , Mutação , Folhas de Planta/genética , Folhas de Planta/fisiologiaRESUMO
A 60-year-old man was diagnosed with retroperitoneal fibrosis. Curiously, his back pain became intense immediately after the performance of a colonoscopy. The fibrotic mass was seen on computed tomography (CT) of the abdomen. The patient developed obstructive nephropathy secondary to bilateral encasing of the ureters. Early diagnosis and combined therapy with corticosteroids and ureteral stents led to clinical and radiological remission of the disease.
Assuntos
Dor nas Costas/etiologia , Fibrose Retroperitoneal/diagnóstico , Anti-Inflamatórios/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Fibrose Retroperitoneal/complicações , Fibrose Retroperitoneal/tratamento farmacológico , Obstrução Ureteral/etiologiaRESUMO
Foliar fertilization is becoming very popular since it is highly efficient, minimizes contamination, and is target oriented. However, the low mobility of several nutrients and low penetration through the leaf cuticle should be addressed, to establish an efficient leaf applied fertilizer. During the last few years, nanotechnologies - such as nanocarriers - have been studied with regard to improving the penetration and delivery of compounds. This work describes the use of membrane vesicles obtained from Brassica oleracea L. as nanobiocarriers of Zn and the evaluation of their potential as a foliar fertilizer, also in Brassica. The results show a high Zn encapsulation efficiency and high delivery into protoplasts. Also, the foliar fertilization experiments demonstrated a very effective system of Zn nanofertilization.
Assuntos
Materiais Biocompatíveis/química , Fertilizantes , Nanocápsulas/química , Nanopartículas/química , Folhas de Planta/metabolismo , Protoplastos/metabolismo , Zinco/química , Brassica , Membrana Celular/metabolismo , Quelantes/química , Luz , Lipídeos/química , Oryza , Tamanho da Partícula , Fotossíntese , Ligação Proteica , Espalhamento de Radiação , Sementes/metabolismo , Solo , Poluentes do SoloRESUMO
In animals and plants, membrane vesicles containing proteins have been defined as key for biological systems involving different processes such as trafficking or intercellular communication. Docking and fusion of vesicles to the plasma membrane occur in living cells in response to different stimuli, such as environmental changes or hormones, and therefore play an important role in cell homeostasis as vehicles for certain proteins or other substances. Because aquaporins enhance the water permeability of membranes, their role as proteins immersed in vesicles formed of natural membranes is a recent topic of study. They regulate numerous physiological processes and could hence serve new biotechnological purposes. Thus, in this review, we have explored the physiological implications of the trafficking of aquaporins, the mechanisms that control their transit, and the proteins that coregulate the migration. In addition, the importance of exosomes containing aquaporins in the cell-to-cell communication processes in animals and plants have been analyzed, together with their potential uses in biomedicine or biotechnology. The properties of aquaporins make them suitable for use as biomarkers of different aquaporin-related diseases when they are included in exosomes. Finally, the fact that these proteins could be immersed in biomimetic membranes opens future perspectives for new biotechnological applications.
RESUMO
Cigarette smoking is associated with increased risk for all histologic types of lung cancer, but why the strength of this association is stronger for squamous cell carcinoma than adenocarcinoma of the lung (SQC-L, ADC-L) is not fully understood. Because nicotine and tobacco-specific nitrosamines contribute to carcinogenesis by activating nicotinic acetylcholine receptors (nAChRs) on lung tumors and epithelial cells, we investigated whether differential expression of nAChR subtypes in these tumors could explain their different association with smoking. Expression of nAChR subunit genes in paired tumor and non-tumor lung specimens from 40 SQC-L and 38 ADC-L patients was analyzed by quantitative PCR. Compared to normal lung, both tumors share: i) transcriptional dysregulation of CHRNA3/CHRNA5/CHRNB4 (α3, α5, ß4 subunits) at the chromosomal locus that predisposes to lung cancer; and ii) decreased expression of CHRFAM7A (dupα7 subunit); this last subunit negatively modulates α7-nAChR activity in oocytes. In contrast, CHRNA7 (α7 subunit) expression was increased in SQC-L, particularly in smokers and non-survivors, while CHRNA4 (α4 subunit) expression was decreased in ADC-L. Thus, over-representation of cancer-stimulating α7-nAChR in SQC-L, also potentiated by smoking, and under-representation of cancer-inhibiting α4ß2-nAChR in ADC-L could explain the different tobacco influences on the tumorigenic process in each cancer type.
RESUMO
Peak age at onset of systemic sclerosis (SSc) is between 20 and 50 years, although SSc is also described in both young and elderly patients. We conducted the present study to determine if age at disease onset modulates the clinical characteristics and outcome of SSc patients. The Spanish Scleroderma Study Group recruited 1037 patients with a mean follow-up of 5.2 ± 6.8 years. Based on the mean ± 1 standard deviation (SD) of age at disease onset (45 ± 15 yr) of the whole series, patients were classified into 3 groups: age ≤ 30 years (early onset), age between 31 and 59 years (standard onset), and age ≥ 60 years (late onset). We compared initial and cumulative manifestations, immunologic features, and death rates. The early-onset group included 195 patients; standard-onset group, 651; and late-onset, 191 patients. The early-onset group had a higher prevalence of esophageal involvement (72% in early-onset compared with 67% in standard-onset and 56% in late-onset; p = 0.004), and myositis (11%, 7.2%, and 2.9%, respectively; p = 0.009), but a lower prevalence of centromere antibodies (33%, 46%, and 47%, respectively; p = 0.007). In contrast, late-onset SSc was characterized by a lower prevalence of digital ulcers (54%, 41%, and 34%, respectively; p < 0.001) but higher rates of heart conduction system abnormalities (9%, 13%, and 21%, respectively; p = 0.004). Pulmonary hypertension was found in 25% of elderly patients and in 12% of the youngest patients (p = 0.010). After correction for the population effects of age and sex, standardized mortality ratio was shown to be higher in younger patients. The results of the present study confirm that age at disease onset is associated with differences in clinical presentation and outcome in SSc patients.
Assuntos
Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/fisiopatologia , Adulto , Idade de Início , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Resultado do TratamentoRESUMO
Wild Type (WT) and transgenic tobacco plants expressing isopentenyltransferase (IPT), a gene encoding the enzyme regulating the rate-limiting step in cytokinins (CKs) synthesis, were grown under limited nitrogen (N) conditions. We analyzed nitrogen forms, nitrogen metabolism related-enzymes, amino acids and photorespiration related-enzymes in WT and P(SARK)â·IPT tobacco plants. Our results indicate that the WT plants subjected to N deficiency displayed reduced nitrate (NO3â») assimilation. However, an increase in the production of ammonium (NH4âº), by the degradation of proteins and photorespiration led to an increase in the glutamine synthetase/glutamate synthase (GS/GOGAT) cycle in WT plants. In these plants, the amounts of amino acids decreased with N deficiency, although the relative amounts of glutamate and glutamine increased with N deficiency. Although the transgenic plants expressing P(SARK)â·IPT and growing under suboptimal N conditions displayed a significant decline in the N forms in the leaf, they maintained the GS/GOGAT cycle at control levels. Our results suggest that, under N deficiency, CKs prevented the generation and assimilation of NH4⺠by increasing such processes as photorespiration, protein degradation, the GS/GOGAT cycle, and the formation of glutamine.
Assuntos
Nicotiana/metabolismo , Nitrogênio/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Compostos de Amônio Quaternário/metabolismo , Alquil e Aril Transferases/genética , Alquil e Aril Transferases/metabolismo , Aminoácido Oxirredutases/metabolismo , Aminoácidos/biossíntese , Regulação da Expressão Gênica de Plantas , Variação Genética , Genótipo , Glutamato Sintase/metabolismo , Glutamato-Amônia Ligase/metabolismo , Nitrato Redutase/metabolismo , Nitratos/metabolismo , Fotossíntese/genética , Reguladores de Crescimento de Plantas/metabolismo , Plantas Geneticamente Modificadas/genética , Proteólise , Nicotiana/genéticaRESUMO
Nitrate assimilation diminishes under water stress. This can augment the photorespiratory rate as a protection mechanism, increasing the ammonium concentration, which must be rapidly assimilated. We therefore examined the effect of moderate water stress in photorespiration and N assimilation, as possible tolerance mechanisms in cherry tomato. Five cherry tomato cultivars with different degrees of water stress tolerance were submitted to two water treatments: well-watered (100% FC) and water stress (50% FC). In the susceptible cultivars, nitrate assimilation declined but without stimulating photorespiration. Zarina, a stress-tolerant cultivar, showed increased activity of the main enzymes involved in photorespiration, together with greater assimilation of nitrates and of the resulting ammonium. This translates as higher concentrations of N as well as amino acids and proteins. We characterize these mechanisms in the cv. Zarina (tolerant) as essential to water stress tolerance, acting on N metabolism as well as helping to maintain or augment biomass.
Assuntos
Amônia/metabolismo , Secas , Nitratos/metabolismo , Solanum lycopersicum/fisiologia , Adaptação Fisiológica , Aminoácidos/metabolismo , Amônia/análise , Biomassa , Respiração Celular/fisiologia , Desidratação/metabolismo , Solanum lycopersicum/metabolismo , Nitrato Redutase/genética , Nitrato Redutase/metabolismo , Nitrogênio/metabolismo , Folhas de Planta/metabolismo , Folhas de Planta/fisiologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estresse FisiológicoRESUMO
Plants produce low levels of reactive oxygen species (ROS), which form part of basic cell chemical communication; however, different types of stress can lead to an overexpression of ROS that can damage macromolecules essential for plant growth and development. Iodine is vital to human health, and iodine biofortification programs help improve the human intake through plant consumption. This biofortification process has been shown to influence the antioxidant capacity of lettuce plants, suggesting that the oxidative metabolism of the plant may be affected. The results of this study demonstrate that the response to oxidative stress is variable and depends on the form of iodine applied. Application of iodide (I(-)) to lettuce plants produces a reduction in superoxide dismutase (SOD) activity and an increase in catalase (CAT) and L-galactono dehydrogenase enzyme activities and in the activity of antioxidant compounds such as ascorbate (AA) and glutathione. This did not prove a very effective approach since a dose of 80 µM produced a reduction in the biomass of the plants. For its part, application of iodate (IO (3) (-) ) produced an increase in the activities of SOD, ascorbate peroxidase, and CAT, the main enzymes involved in ROS detoxification; it also increased the concentration of AA and the regenerative activities of the Halliwell-Asada cycle. These data confirm the non-phytotoxicity of IO (3) (-) since there is no lipid peroxidation or biomass reduction. According to our results, the ability of IO (3) (-) to induce the antioxidant system indicates that application of this form of iodine may be an effective strategy to improve the response of plants to different types of stress.