The complete nucleotide sequence of a virus isolated from Olea europaea L. (GP isolate), previously identified as an isolate of Tobacco necrosis virus D (TNV-D) based on its coat protein sequence, ...was determined. The viral RNA genome consists of 3683 nucleotides and contains five open reading frames. The putative RNA-dependent RNA polymerase shows 91.2% amino acid identity with that of an isolate of Olive latent virus 1 (OLV-1) and the coat protein reveals highest sequence identity with that of TNV-D. Based on the deduced genome organization and phylogenetic analysis of predicted functional translation products with that of other necroviruses, the GP isolate genome appears to represent an example of a new virus arisen by gene exchange and is proposed to be a new necrovirus, provisionally named Olive mild mosaic virus.
Relatar um caso de Guillain – Barré em paciente de 12 anos de idade que utilizou plasmaférese terapêutica como primeira linha, focando nos aspectos técnicos do procedimento; Discutir as possíveis ...causas para o desabastecimento de imunoglobulina intravenosa (IGIV) atual.
Coleta de dados clínicos no prontuário. Revisão de literatura, com ênfase em plasmaférese na população pediátrica, suas indicações, paticularidades técnicas e eventos adversos.
Paciente de 12 anos de idade, sexo feminino, 35 quilos, previamente hígida, deu entrada no pronto – socorro com quadro de tetraparesia desproporcional – força grau III em MMII e grau IV em MMSS – associada à mialgia difusa. Sem quadro infeccioso ou vacinação recente antecedendo. Equipe da neurologia levantou hipótese de síndrome de Guillain- Barré e solicitou plasmaférese terapêutica, pois não havia disponibilidade de IGIV. Foram realizadas 04 sessões utilizando o sistema COM.TEC (Fresenius Kabi) com troca de uma volemia cada. O fluxo médio de extração foi de 37,5ml/min (30-45ml/min). A taxa média de ACD infundido na paciente foi de 234ml e a proporção ACD:sangue foi de 1:16. A duração média foi de 73 minutos por procedimento. Em todas as sessões foi utilizado reposição profilática com solução de 10ml de gluconato de cálcio 10%. A paciente apresentou tontura e parestesia perioral nas duas primeiras sessões. Sem outros eventos adversos. Recebeu alta após quarta sessão, já sendo capaz de deambular sem auxílio.
A Síndrome de Guillain Barré corresponde a um grupo de polirradiculopatias autoimunes, inflamatórias e desmielinizantes. Os tratamentos de primeira linha constituem IGIV e plasmaférese. A IGIV costuma ser preferida principalmente em crianças por maior facilidade posológica e não envolver uso de dispositivos invasivos. O desabastecimento de IGIV desde 2019 em diversos países do mundo, inclusive no Brasil, tem dificultado o acesso a este tratamento. Entre as possíveis causas para este desabastecimento, podemos citar: aumento da demanda não acompanhada por aumento na produção, impactos da pandemia de COVID- 19 sobre matéria-prima (doadores de sangue) e logística (transporte, etc), descontinuação do produto por alguns laboratórios, entre outros. Segundo o último guideline da Sociedade Americana de Aférese não há diferença no desfecho entre IGIV e plasmaférese. Entre os principais eventos adversos da plasmaférese em pacientes pediátricos, destacam- se os relacionados ao acesso central (infecções, complicações mecânicas, entre outros), hipocalcemia, o volume extracorpóreo utilizado no procedimento e riscos de intoxicação por citrato. A paciente do caso apresentou apenas sintomas leves de hipocalcemia, que melhoraram após redução do fluxo de extração.
A plasmaférese terapêutica em pacientes pediátricos tem se mostrado eficaz, seja em primeira linha ou como tratamento complementar. Ajustes na taxa de extração, reposição profilática de cálcio e cuidados com o acesso central aumentam a segurança do procedimento.
Smoke particulate matter was sampled by high volume filtration from a controlled burn of forest litter in the northern forest reserve of INPA about 70 km north of Manaus, Amazonas. The extract of the ...filter was separated after methylation into hydrocarbon, ketone, carboxylic acid ester and polar fractions and then analyzed by gas chromatography and gas chromatography-mass spectrometry. The total lipid extract yield was ∼13 mg/m
3 of smoke. The major organic components of the smoke particles were straight-chain aliphatic and triterpenoid compounds from vegetation wax, biopolymers, and gum/resin. Polynuclear aromatic hydrocarbons (PAH) from the combustion process were found at high levels and aromatized derivatives from natural product precursors were also important components. Petroleum hydrocarbons representing urban and vehicular emissions were not detectable. The
n-alkanes ranged from C
19 to C
35, with a carbon number maximum (C
max) at C
29/C
31 and an odd-to-even carbon predominance > C
25 (CPI
20–35 = 3.6). Terminal olefins (
n-alk-1-enes) were also present and ranged from C
17 to C
35, with a C
max at C
22 and an even-to-odd carboon predominance (CPI
17–35 = 0.8). The
n-alkanes are derived mainly from vegetation wax and the alk-1-enes with other oxygenated compounds (e.g., ketones, acids, triterpenoids) are thermal alteration products from gum/resin and biopolymers. These alteration products coupled with the PAH are the tracers for biomass combustion.
Alpinia zerumbet, known popularly as “colônia” in Northeastern Brazil, is a medicinal plant that has been used widely in folk medicine as teas and infusions for the treatment of intestinal and ...cardiovascular diseases, including arterial hypertension. Our previous studies have demonstrated that the essential oil of
A. zerumbet (OEAZ) is very active on excitable tissues, such as smooth muscle, and in this study we verified its effects on the compound action potential (CAP) of rat sciatic nerve. EOAZ induced a dose-dependent blockade of the CAP. Control peak-to-peak amplitude and conduction velocity of CAPs were 7.6±0.43
mV and 80.6±3.19
m/s, respectively. At 60
μg/ml, EOAZ induced no demonstrable effect. Conduction velocity was significantly reduced at 180
min of preparation exposure to 100
μg/ml of EOAZ. At 300, 600 and 2000
μg/ml doses of EOAZ, the peak-to-peak amplitudes of CAPs following 180
min exposure of the nerve to the drug were reduced significantly, to 75.3±7.36%, 50.45±2.17% and 0% respectively, of control value. Conduction velocity was reduced significantly by 300, 600 and 2000
μg/ml of EOAZ, at 180
min, to 83.61±3.28%, 64.06±8.21% and 22.7±5.79%, respectively, of control value. All these effects developed slowly and were reversible upon a 180-min wash.
Serum homocysteine concentrations have been shown to be a sensitive functional indicator of intracellular folate, vitamin B-12, and vitamin B-6 status. Chronic alcoholism is known to interfere with ...one-carbon metabolism, for which the above vitamins serve as coenzymes. In the present study, these vitamins were assessed in 32 chronic alcoholics and 31 healthy volunteers by measuring blood vitamin concentrations as well as serum homocysteine concentrations. In chronic alcoholics, serum pyridoxal 5'-phosphate and red blood cell folate concentrations were significantly lower than in the control subjects (P < 0.001 and P = 0.008, respectively). Mean serum homocysteine was twice as high in chronic alcoholics than in nondrinkers (P < 0.001). Beer consumers had significantly lower concentrations of homocysteine compared with drinkers of wine or spirits (P = 0.05). These results suggest that by interfering with folate or vitamin B-6 metabolism, chronic alcohol intake may impair the disposal of homocysteine through the transmethylation or transsulfuration pathways.
Antibody-drug conjugates (ADCs) have surfaced as a promising group of anticancer agents employing the precise targeting capacity of monoclonal antibodies to transport highly effective cytotoxic ...payloads. Compared to conventional chemotherapy, they aim to selectively eradicate cancer cells while minimizing off-target toxicity on healthy tissues. An increasing body of evidence has provided support for the efficacy of ADCs in treating breast cancer across various contexts and tumor subtypes, resulting in significant changes in clinical practice. Nevertheless, unlocking the full potential of these therapeutic agents demands innovative molecular designs to address complex clinical challenges, including drug resistance, tumor heterogeneity, and treatment-related adverse events. This thorough review provides an in-depth analysis of the clinical data on ADCs, offering crucial insights from pivotal clinical trials that assess the efficacy of ADCs in diverse breast cancer settings. This aids in providing a comprehensive understanding of the current state of ADCs in breast cancer therapy, while also providing valuable perspectives for the future.
In familial amyloidotic polyneuropathy, TTR (transthyretin) variants are deposited as amyloid fibrils. It is thought that this process involves TTR tetramer dissociation, which leads to partially ...unfolded monomers that aggregate and polymerize into amyloid fibrils. This process can be counteracted by stabilization of the tetramer. Several small compounds, such as diclofenac, diflunisal and flufenamic acid, have been reported to bind to TTR in vitro, in the T4 (thyroxine) binding channel that runs through the TTR tetramer, and consequently are considered to stabilize TTR. However, if these agents bind plasma proteins other than TTR, decreased drug availability will occur, compromising their use as therapeutic agents for TTR amyloidosis. In the present work, we compared the action of these compounds and of new derivatives designed to increase both selectivity of binding to TTR and inhibitory potency in relation to TTR amyloid fibril formation. We found two diflunisal derivatives that, in contrast with diclofenac, flufenamic acid and diflunisal, displaced T4 from TTR in plasma preferentially over binding to albumin and thyroxine binding globulin. The same diflunisal derivatives also had a stabilizing effect on TTR tetramers in plasma, as studied by isoelectric focusing of whole plasma under semi-denaturing conditions. In addition, by transmission electron microscopy, we demonstrated that, in contrast with other proposed TTR stabilizers (namely diclofenac, flufenamic acid and diflunisal), one of the diflunisal derivatives tested efficiently inhibited TTR aggregation. Taken together, our ex vivo and in vitro studies present evidence for the selectivity and efficiency of novel diflunisal derivates as TTR stabilizers and as inhibitors of fibril formation.
► A new example of a small rigid molecule with a complex polymorphic behavior. ► Two crystalline structures, forms I and III, solved at room temperature. ► In forms I and III the hydrogen formyl does ...not participate in the hydrogen bonds. ► XRPD diffractograms point to preferential orientation effects. ► XRPD point to the existence of structures with only slight differences amongst them.
This work reports an investigation on the polymorphism of 2-quinolinecarboxaldehyde, a quinoline derivative, frequently used as a ligand in the synthesis of metal complexes.
2-Quinolinecarboxaldehyde lacks both molecular flexibility and the ability to form strong hydrogen bonds, two characteristics often seen as driving forces for the occurrence of polymorphism. Nevertheless, a rich polymorphic behavior was found for this substance. Polymorphic forms were generated by crystallization from solutions, and by melt cooling. Four polymorphic forms could be clearly identified by thermal analysis investigation and the crystalline structures of forms I and III were solved by single-crystal X-ray diffraction, at room temperature. In polymorph I, molecules are joined by π–π and weak C−H⋯O interactions while in polymorph III helicoidal chiral chains are formed and very weak C−H⋯O intermolecular interactions can be identified. Neither of these intermolecular interactions involves the formyl hydrogen atom. Concomitant polymorph crystallization from the melt was often observed.
XRPD diffractograms which showed similarities to that of polymorph I but presented striking differences were obtained in some experiments. In certain cases the discrepancies may be ascribed to effects of preferential orientation. However, the existence of multiple but slightly different structures with small differences seems to be a better explanation for these experimental observations.
Summary Prosthodontics should be one of the means of establishing conditions for the maintenance of periodontal health. The forces applied to the abutment teeth and their effects are very important ...considerations in the design and construction of the removable partial dentures. This 6‐month follow‐up clinical study evaluated the degree of mobility of abutment teeth of distal extension and tooth supported removable partial dentures by using Periotest. Two types of clasp design were selected for evaluation. In cases with unilateral and bilateral distal‐extension, a clasp design including a T clasp of Roach retentive arm, a rigid reciprocal arm and a mesial rest were used. For the abutments of tooth‐supported removable partial dentures, a second clasp design with a cast circumferential buccal retentive arm, a rigid reciprocal clasp arm and a rest adjacent to the edentulous ridges was selected. A total of 68 abutment teeth was analysed. Periotest values were made at the time of denture placement (control) and at 1, 3 and 6 months after the denture placement. The statistical analysis was performed using Friedman test. All analysis was performed at a 0·05 level of significance. The results revelled that no significant changes in tooth mobility were observed during the 6‐months follow‐up (P > 0·05). In conclusion, our findings suggest that adequate oral hygiene instructions, careful prosthetic treatment planning and regular recall appointments play an important role in preventing changes in abutment tooth mobility caused by removable partial denture placement.
The understanding of the role of the immune response in the development of gastrointestinal and cardio-digestive (CD) forms of Chagas disease has received little attention. In this paper, the ...commitment of each leukocyte population of peripheral blood to the production of IFN-gamma, TNF-alpha, IL-12, IL-4, IL-5 and IL-10 was studied in patients with the CD form of Chagas disease. The data show that cells from patients with the CD form of the disease have distinct cytokine profiles when compared with the other clinical forms of Chagas disease and suggest that eosinophils are the major source of cytokine production in this clinical entity. The data presented in this paper demonstrate that patients with CD form can be distinguished from patients with gastrointestinal or cardiac forms of the disease by the distinct cytokine profile of peripheral blood cells.
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