Exploring Natural Alkaloids from Brazilian Biodiversity as Potential Inhibitors of the Aedes aegypti Juvenile Hormone Enzyme: A Computational Approach for Vector Mosquito Control.

This study explores the potential inhibitory activity of alkaloids, a class of natural compounds isolated from Brazilian biodiversity, against the mJHBP enzyme of the Aedes aegypti mosquito. This mosquito is a significant vector of diseases such as dengue, zika, and chikungunya. The interactions between the ligands and the enzyme at the molecular level were evaluated using computational techniques such as molecular docking, molecular dynamics (MD), and molecular mechanics with generalized Born surface area (MMGBSA) free energy calculation. The findings suggest that these compounds exhibit a high binding affinity with the enzyme, as confirmed by the binding free energies obtained in the simulation. Furthermore, the specific enzyme residues that contribute the most to the stability of the complex with the compounds were identified: specifically, Tyr33, Trp53, Tyr64, and Tyr129. Notably, Tyr129 residues were previously identified as crucial in the enzyme inhibition process. This observation underscores the significance of the research findings and the potential of the evaluated compounds as natural insecticides against Aedes aegypti mosquitoes. These results could stimulate the development of new vector control agents that are more efficient and environmentally friendly.

Extraction, Characterization, and Evaluation of the Cytotoxic Activity of Piperine in Its Isolated form and in Combination with Chemotherapeutics against Gastric Cancer.

Gastric cancer is one of the most frequent types of neoplasms worldwide, usually presenting as aggressive and difficult-to-manage tumors. The search for new structures with anticancer potential encompasses a vast research field in which natural products arise as promising alternatives. In this scenario, piperine, an alkaloid of the Piper species, has received attention due to its biological activity, including anticancer attributes. The present work proposes three heating-independent, reliable, low-cost, and selective methods for obtaining piperine from Piper nigrum L. (Black pepper). Electronic (SEM) and optical microscopies, X-ray diffraction, nuclear magnetic resonance spectroscopies (13C and 1H NMR), and optical spectroscopies (UV-Vis, photoluminescence, and FTIR) confirm the obtention of piperine crystals. The MTT assay reveals that the piperine samples exhibit good cytotoxic activity against primary and metastasis models of gastric cancer cell lines from the Brazilian Amazon. The samples showed selective cytotoxicity on the evaluated models, revealing higher effectiveness in cells bearing a higher degree of aggressiveness. Moreover, the investigated piperine crystals demonstrated the ability to act as a good cytotoxicity enhancer when combined with traditional chemotherapeutics (5-FU and GEM), allowing the drugs to achieve the same cytotoxic effect in cells employing lower concentrations. These results establish piperine as a promising molecule for therapy investigations in aggressive gastric cancer, both in its isolated form or as a bioenhancer.

[Indicators of rational prescription of medicines: feasibility of application in institutions in the AmericasIndicadores de prescrição racional de medicamentos: viabilidade de aplicação em instituições das Américas]. / Indicadores de prescripción racional de medicamentos: factibilidad de aplicación en instituciones de las Américas.

OBJECTIVE: Evaluate the feasibility of monitoring the quality of use of medicines in health institutions in countries of the Region of the Americas by means of rational prescription indicators. METHODOLOGY: A quantitative study of the use of medicines was conducted during the period 2016-2018. Rational prescription indicators were developed and selected in accordance with international reference values and the best available evidence for: 1) anti-inflammatory drugs: prescription of ibuprofen and/or naproxen as a percentage of all prescribed non-steroidal anti-inflammatory drugs; 2) oral antidiabetics: metformin as a percentage of all prescribed antidiabetics, and metformin and/or sulfonylureas as a percentage of all prescribed antidiabetics; 3) insulins: crystalline insulin and NPH as a percentage of total prescribed insulins; and 4) antihypertensive drugs: angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs-II), and thiazide diuretics as a percentage of all prescribed antihypertensives. The defined daily dose (DDD) per 1 000 inhabitants was used as a measure of consumption per institution. RESULTS: Prescription of metformin as a percentage of all antidiabetics was lower than the value of the reference indicator (27.9%-67.6% vs. 88%), while the prescription of metformin and/or a sulfonylurea was comparable with that value (80.9%-97.5% vs. 88%). The values of NPH, crystalline, and NPH/crystalline insulin in relation to all prescribed insulins were variable with respect to the reference indicator (37.1%-100% vs. 75%). Prescription of ibuprofen and naproxen was below the value of the indicator (20%-50% vs. 80%). The percentage of ACE inhibitors, ARBs, and thiazides with respect to all antihypertensives ranged from 65.2%-77.2% to 65%, consistent with the value of the proposed indicator. CONCLUSIONS: The feasibility of applying the selected and constructed indicators of rational prescription was demonstrated. These indicators provide useful information for analyzing the quality of prescription in health institutions in countries in the Region and are a useful tool for periodically monitoring it.

OBJETIVO: Avaliar a viabilidade de monitorar a qualidade do uso de medicamentos em instituições de saúde em países da Região das Américas por meio de indicadores de prescrição racional. MÉTODOS: Foi realizado um estudo quantitativo do uso de medicamentos durante o período 2016-2018. Indicadores de prescrição racional foram desenvolvidos e selecionados de acordo com referências internacionais e as melhores evidências disponíveis para: 1) anti-inflamatórios: prescrições de ibuprofeno e/ou naproxeno como porcentagem da prescrição total de anti-inflamatórios não esteroidais; 2) antidiabéticos orais: prescrições de metformina como porcentagem de todos os antidiabéticos prescritos, metformina e/ou sulfonilureias como porcentagem de todos os antidiabéticos prescritos; 3) insulinas: insulina cristalina e NPH como porcentagem do total de insulinas prescritas; e 4) anti-hipertensivos: porcentagem de inibidores da enzima de conversão da angiotensina (IECA), antagonistas do receptor da angiotensina II (BRA) e diuréticos tiazídicos sobre o total de anti-hipertensivos prescritos. A dose diária definida (DDD) por 1 000 habitantes por dia (DHD) foi usada como medida de consumo por instituição. RESULTADOS: A prescrição de metformina em relação a todos os antidiabéticos foi inferior ao valor do indicador de referência (27,9%-67,6% x 88%), enquanto a prescrição de metformina e/ou uma sulfonilureia foi comparável ao valor de referência (80,9%-97,5% x 88%). As porcentagens de prescrição de insulina NPH, cristalina e NPH/cristalina em relação a todas as insulinas prescritas foram variáveis em relação ao valor de referência (37,1%-100% x 75%). A prescrição de ibuprofeno e naproxeno foi inferior ao valor de referência (20%-50% x 80%). A porcentagem de IECA, BRA e tiazídicos em relação a todos os anti-hipertensivos variou entre 65,2% e 77,2%, compatível com o valor do indicador proposto (65%). CONCLUSÕES: Demonstrou-se a viabilidade de aplicação dos indicadores de prescrição racional aqui selecionados e construídos, os quais fornecem informações úteis para analisar a qualidade da prescrição nas instituições de saúde dos países da Região e representam uma ferramenta útil para seu monitoramento periódico.

Evaluation of Bioactive Compounds and Antioxidant and Cytotoxic Effects of Oil and Pulp without Açaí Fat (Euterpe oleracea) Obtained by Supercritical Extraction.

For bioactivity studies, it is necessary to use products with a high degree of purity, which may influence the cytotoxic effects. Supercritical technology presents itself as an alternative to obtain these products. Therefore, the objective of this work was to obtain the bioactive compounds of oil and pulp of açaí fat-free supercritical technology and evaluate the cytotoxicity of products in MRC-5 and VERO cells in vitro. The açaí pulp was subjected to extraction with supercritical CO2 to obtain the oil and pulp without fat, under conditions of 323.15 K at 35 MPa, 333.15 K at 42 MPa, and 343.15 K at 49 MPa. The largest yields (51.74%), carotenoids (277.09 µg/g), DPPH (2.55 µmol TE/g), ABTS (2.60 µmol TE/g), and FRAP (15.25 µm of SF/g) of oil and ABTS (644.23 µmol TE/g) of pulp without fat were found in the condition 343.15 K at 49 MPa. The highest levels of compounds phenolics (150.20 mg GAE/g), DPPH (414.99 µmol TE/g), and FRAP (746.2 µm SF/g) of the pulp without fat were found in the condition of 323.15 K to 35 MPa. The fat-free pulp presented high levels of anthocyanins without significant variation in cytotoxicity. The developed process was efficient in obtaining oil rich in carotenoids, and the supercritical technology elucidated an efficient way to obtain açaí fat-free pulp.

Structural and Thermal Characteristics of Buriti Tree Gum (Mauritia flexuosa).

A polysaccharide was isolated from the exudate of a buriti tree trunk (Mauritia flexuosa). The molecular structure, thermal stability, morphology, crystallinity, and elemental composition of the product were investigated through spectroscopic techniques, such as Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR 1H and 13C), and energy-dispersive X-ray spectroscopy (EDS); thermogravimetric analysis (TG), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and X-ray diffraction (XRD). In addition to NMR molecular modeling studies, were performed to confirm the 1H and 13C chemical shifts to Gal and Xyl conformers. Buriti tree gum (BG) is an arabinogalactan, containing Rha, Ara, Xyl, and Gal, and degrades almost completely (98.5%) at 550 °C and has a maximum degradation peak at 291.97 °C, with a mass loss of 56.33%. In the temperature range of 255-290 °C, the energy involved in the BG degradation process was approximately 17 J/g. DSC indicated a glass transition temperature of 27.2 °C for BG, which had an irregular and heterogeneous morphology, with smooth or crumbling scaly regions, demonstrating the amorphous nature of BG that was confirmed by the XRD standard. EDS revealed the presence of carbon and oxygen, as well as calcium, magnesium, aluminum, silicon, chlorine, and potassium, in the BG composition.

Optimization of fish gelatin drying processes and characterization of its properties.

Fish skin is a raw material used for gelatin production. It can satisfy consumers with specific socio-cultural and religious needs. Different technologies have been studied for drying gelatin. Therefore, it is relevant to understand the influence of drying conditions on the final product. This study aims to optimize drying methods such as convection hot air alone and combined with infrared radiation to obtain gelatin from acoupa weakfish skin by using composite central rotational designs 22 and 23 and response surface methodology. The gelatin obtained from the optimized conditions were characterized based on their physical, chemical, technological, and functional properties. The desirability function results show the convection hot air as the most effective method when conducted at 59.14 °C for 12.35 h. Infrared radiation at 70 °C for 2.0 h and convective drying at 70 °C for 3.5 h were the best condition of the combined process. The gelatins obtained had gel strength of 298.00 and 507.33 g and emulsion activity index of 82.46 and 62.77 m2/g in the combined and convective methods, respectively, and protein content above 90%. These results indicate that the processes studied can be used to produce gelatin with suitable technological and functional properties for several applications.

Differing patterns of peripheral blood leukocyte telomere length in rheumatologic diseases.

Telomeres progressively shorten with repeated somatic tissue cell division, their length being an indicator of cellular ageing. Telomeric dysfunction may be implicated in a variety of diseases. We measured mean telomere length in peripheral blood leukocytes (PBL) from patients with various rheumatologic diseases. Mean PBL telomere length was measured using real-time quantitative polymerase chain reaction (Q-PCR) assay in a control population (n=130; age range: 3-94 years) and in subjects diagnosed with rheumatoid arthritis (RA; n=86; age range: 31-82 years), psoriatic arthritis (PA; n=56; age range: 26-79 years) and ankylosing spondylitis (AS; n=59; age range: 21-75 years). These diseases are associated with chronic systemic inflammatory activity. Telomere length was also quantified in subjects with osteoarthritis (OA; n=34; age range: 43-82 years) and osteoporosis (OP; n=35; age range: 59-95 years), diseases without a chronic systemic inflammatory component. Telomere length in OA showed no differences from age-matched controls (p=0.234), but was significantly shorter in OP (p=0.001). Telomere length was significantly longer than controls in RA (p=0.015), PA (p<0.001) and AS (p<0.001). Different patterns in telomere length from PBL are evidenced in rheumatologic pathologies, possibly dependent on the presence or absence of chronic systemic inflammation.

Spectroscopic methods and in silico analyses using density functional theory to characterize and identify piperine alkaloid crystals isolated from pepper (Piper Nigrum L.).

Communicated by Ramaswamy H. Sarma.

[Craniotomy without trichotomy: analysis of 640 cases]. / Craniotomia sem tricotomia: avaliação de 640 casos.

The hair shaving in preparation for neurosurgery is frequently used in most of neurosurgical centers to perform craniotomy. We question about its necessity after our retrospective analysis of 640 patients undergoing cranial procedures without previous hair shaving. We had the overall surgical wound infection rate of 1.09%, not higher than tricotomy in the review of the literature. In 7 cases with infection, 3 patients were undergoing to CSF shunts, 3 patients had head injury, and one had brain tumor. The technique for preparing skin and hair for cranial procedures, its advantages and disadvantages are described and discussed.

"Ears of the lynx" sign in a marchiafava-bignami patient: structural basis and fiber-tracking DTI contribution to the understanding of this imaging abnormality.

The "ears of the lynx" sign was previously reported as a neuroimaging finding observed in patients with autosomal recessive hereditary spastic paraplegia in association with a thin corpus callosum (ARHSP-TCC). We report a patient with a chronic form of Marchiafava-Bignami disease (MBD) that presented with this imaging feature. Diffusion tensor imaging (DTI) and fiber-tracking data support that this finding is a consequence of the structural derangement, which enlarges a preexisting border zone of the bundles of fibers from the corpus callosum (CC) genu to the forceps minor and anterior corona radiata. Therefore, we assume that despite their pathological differences, damage to the anterior portion of the CC is responsible for the imaging similarities between MBD and ARHSP-TCC.

Comparative analysis of MR sequences to detect structural brain lesions in tuberous sclerosis.

BACKGROUND: Tuberous sclerosis (TS) is a neurocutaneous genetically inherited disease with variable penetrance characterized by dysplasias and hamartomas affecting multiple organs. MR is the imaging method of choice to demonstrate structural brain lesions in TS. OBJECTIVE: To compare MR sequences and determine which is most useful for the demonstration of each type of brain lesion in TS patients. MATERIALS AND METHODS: We reviewed MR scans of 18 TS patients for the presence of cortical tubers, white matter lesions (radial bands), subependymal nodules, and subependymal giant cell astrocytoma (SGCA) on the following sequences: (1) T1-weighted spin-echo (T1 SE) images before and after gadolinium (Gd) injection; (2) nonenhanced T1 SE sequence with an additional magnetization transfer contrast medium pulse on resonance (T1 SE/MTC); and (3) fluid-attenuated inversion recovery (FLAIR) sequence. RESULTS: Cortical tubers were found in significantly (P<0.05) larger numbers and more conspicuously in FLAIR and T1 SE/MTC sequences. The T1 SE/MTC sequence was far superior to other methods in detecting white matter lesions (P<0.01). There was no significant difference between the T1 SE/MTC and T1 SE (before and after Gd injection) sequences in the detection of subependymal nodules; FLAIR sequence showed less sensitivity than the others in identifying the nodules. T1 SE sequences after Gd injection demonstrated better the limits of the SGCA. CONCLUSION: We demonstrated the importance of appropriate MRI sequences for diagnosis of the most frequent brain lesions in TS. Our study reinforces the fact that each sequence has a particular application according to the type of TS lesion. Gd injection might be useful in detecting SGCA; however, the parameters of size and location are also important for a presumptive diagnosis of these tumors.

[Computerized physician order entry of pharmacotherapeutic protocols in a colorectal surgery unit]. / Prescripción electrónica asistida de protocolos farmacoterapéuticos en una unidad de cirugía coloproctológica.

INTRODUCTION: Computerized physician order entry was introduced in our hospital. We present the pharmacotherapeutic protocols that we use in patient care. MATERIAL AND METHODS: Six pharmaceutical protocols were designed by consensus in a colorectal surgery unit and were applied over a 2-year period. Patients undergoing ambulatory or urgent surgery were excluded. RESULTS: We treated 772 patients. Two hundred twenty patients (28.5%) were assigned to the preoperative protocol for minor proctologic surgery. After surgery, all 220 patients were included in the postoperative protocol for minor proctologic surgery. The remaining 552 patients (71.5%) were assigned to the protocol for major colorectal surgery. The preoperative protocol for major colorectal surgery was indicated in 542 patients (98.2%) and its variant for patients allergic to beta-lactam antibiotics was used in 10 patients (1.8%). The postoperative pharmacotherapeutic protocol assigned depended on whether a central venous line (317 patients; 57.4%) or only peripheral venous access (235 patients; 42.6%) was used. CONCLUSIONS: Each clinical unit has a duty to carry out and update consensus protocols (always based on the best scientific evidence available) that can be used in the processes managed in that unit. The use of these protocols shows a high degree of acceptance among physicians and nurses, allowing clinical practice to be standardized and healthcare processes to be homogenized.

Craniotomia sem tricotomia: avaliação de 640 casos / Craniotomy without tricotomy: analysis of 640 cases

A remoção do cabelo para realização de craniotomia utilizada rotineiramente na maioria dos serviços de neurocirurgia para procedimentos cranianos diversos questionada em sua necessidade a partir da avaliação retrospectiva de 640 pacientes submetidos a cirurgias cranianas, em que foi observada uma porcentagem de infecção de ferida cirúrgica de 1,09 por cento, não superior àquelas com tricotomia revisadas na literatura. Nos 7 casos com infecção, 3 pacientes foram submetidos a derivações liquóricas, 3 pacientes eram vítimas de traumatismo crânio-encefálico e uma paciente substituida a craniotomia para tratamento de tumor cerebral. A técnica para preservação e manuseio do cabelo, suas vantagens e desvantagens são descritas e discutidas.

Herida por arma blanca penetrante en craneo. Reporte de un caso / Cranial stabbing. Case report

Objective: to describe the case of a penetrating cranial knife wound. Description: a 18 years old male patient arrived to the hospital with a knife stabbed into the left temporal cranial region. He presented a Glasgow coma scale of 9/15 and a right hemiplegia. He was studied with x-rays and a CT scan. Intervention: he was taken to surgery and the knife was removed. Postoperative outcome was uneventful. He made rehabilitation for a right hemiparesis. Conclusion: good results can be obtained with removal at surgery of a stabbed knife into the cranium

Aplopejia pituitaria: comunicacion de un caso / Pituitary apoplexy: case report

OBJETIVO: Describir un nuevo caso de aplopejia pituitaria. DESCRIPCION: paciente de sexo masculino y 65 años de edad que en forma repjetina comienza con cefaleas, diplopia y rigidez de nuca. La resonancia magnetica mostro una lesion expansiva selar de 30 x 30 mm. INTERVENCION: Se opero por via subfrontal, evacuando un hematoma y resecando el tumor. La evolucion postoperatoria a los 3 meses mostro ausencia del tumor y desaparicion de los sintomas. CONCLUSION: la apoplejia pituitaria es poco frecuente. El diagnostico con resonancia magnetica es sencillo. La cirugia precoz es el tratamiento de eleccion

Meningioma craneofacial. Reporte de un caso / Craniofacial meningioma. Case report

Objective: to describe a craniofacial meningioma. Description: a 50 years old female patient presented progressive headaches and left exoftalmus during the last year. MRI showed a tumoral lesion that involved the etmoidorbitalmaxilary region. Intervention: the lesion was resected through the subfrontal approach after performing a bifrontal craniotomy with a supraorbital osteotomy. Pathology informed meningioma. Postoperatively the patient showed transient left ptosis, diplopia and CSF fistula. After 19 months the patient was asymptomatic and control MRI showed no tumor. Conclusion: the craniofacial meningioma was totally resected using a combined approach with low morbidity at 18 months

Prevalência de aleitamento materno de crianças com patologia no período neonatal / Prevalence of breast feeding of children with pathology in neonatal period

O presente estudo tem como objetivo avaliar o aleitamento materno exclusivo até seis meses de idade de recém-nascidos a termo que tiveram que ser separados de suas mäes por patologia no período neonatal. O tempo médio de internaçäo no Berçário de Cuidados Intensivos foi de 4,15 dias. O grupo-controle foi constituído por recém-nascidos a termo, sem patologia, em regime de alojamento conjunto desde o nascimento. Näo encontramos diferenças estatisticamente significativas no tempo de aleitamento em ambos os grupos