Efficacy and sustainability of natural products in COVID-19 treatment development: opportunities and challenges in using agro-industrial waste from Citrus and apple.

Natural products have been used in the treatment of illnesses throughout the history of humankind. Exploitation of bioactive compounds from natural sources can aid in the discovery of new drugs, provide the scaffold of new medicines. In the face of challenging diseases, such as the COVID-19 pandemic, for which there was no effective treatment, nature could offer insights as to novel therapeutic options for control measures. However, the environmental impact and supply chain of bioactive production must be carefully evaluated to ensure the detrimental effects will not outweigh the potential benefits gained. History has already proven that highly bioactive compounds can be rare and not suitable for medicinal exploitation; therefore, the sustainability must be accessed before expensive, time-demanding, and large trials can be initialized. A sustainable option to readily produce a phytotherapy with minimal environmental stress is the use of agro-industry wastes, a by-product produced in high quantities. In this review we evaluate the sustainability issues associated with the production of phytotherapy as a readily available tool for pandemic control.

Short-Time Recurrences of Plasmodium vivax Malaria as a Public Health Proxy for Chloroquine-Resistance Surveillance: A Spatio-Temporal Study in the Brazilian Amazon.

In Brazil, malaria caused by Plasmodium vivax presents control challenges due to several reasons, among them the increasing possibility of failure of P. vivax treatment due to chloroquine-resistance (CQR). Despite limited reports of CQR, more extensive studies on the actual magnitude of resistance are still needed. Short-time recurrences of malaria cases were analyzed in different transmission scenarios over three years (2005, 2010, and 2015), selected according to malaria incidence. Multilevel models (binomial) were used to evaluate association of short-time recurrences with variables such as age. The zero-inflated Poisson scan model (scanZIP) was used to detect spatial clusters of recurrences up to 28 days. Recurrences compose less than 5% of overall infection, being more frequent in the age group under four years. Recurrences slightly increased incidence. No fixed clusters were detected throughout the period, although there are clustering sites, spatially varying over the years. This is the most extensive analysis of short-time recurrences worldwide which addresses the occurrence of P. vivax CQR. As an important step forward in malaria elimination, policymakers should focus their efforts on young children, with an eventual shift in the first line of malaria treatment to P. vivax.

The genus Capsicum: a phytochemical review of bioactive secondary metabolites.

The Capsicum genus is one of the most popular plants consumed and cultivated worldwide, containing approximately 50 000 varieties of pepper. Due to its wide biodiversity, the chemical composition within the genus also presents a great variability. Its major applications are in food and pharmacological industry, as pepper presents a chemical composition rich in capsaicinoids, carotenoids, flavonoids and volatile compounds which is attributed to the ability of the fruit to remove insipidity, produce aromas and act against oxidative diseases. Due the existence of several cultivars there is a huge intraspecific chemical variability within each species, which can be considered as an obstacle when selecting and cultivating a species to be applied as a natural product source for a specific objective. The usage of pepper-based products in different industrial areas requires pre-established ranges of chemical compounds, such as capsaicinoids, which in high concentration are toxic when consumed by humans. Applying a pepper with a chemical profile closely related to the concentration that is required after industrial processing can improve efficacy and effectiveness of the process. An insight into the chemical characteristics of major secondary bioactive compounds within Capsicum, the factors that affect their concentration and their chemosystematic implication are reported and discussed.

Seasonal variation of gastroprotective terpenoids in Maytenus robusta (Celastraceae) quantified by gas chromatography-flame ionization detection (GC-FID).

The triterpenes friedelin (1), ß-friedelinol (2) and 3,15-dioxo-21α-hydroxyfriedelane (3) in the aerial parts of Maytenus robusta, a Brazilian medicinal plant with antiulcer potential, were seasonally quantified by gas chromatography flame-ionization detection (GC-FID) using an external standard. The method was found to be linear, precise and sensitive. Compounds 1 and 2 were found in M. robusta leaves and branches, with highest concentrations in the leaves collected in autumn, i.e. 3.21 ± 0.16 and 12.60 ± 1.49 mg g-1 dry weight of 1 and 2, respectively. On the other hand, compound 3 was found only in the branches, with the highest concentrations in winter and autumn (0.21 ± 0.01 and 0.20 ± 0.02 mg g-1). The results allow to define the optimal season and plant parts for the collection of M. robusta as a phytotherapeutic drug.

Effects of Benzodiazepines on Acinar and Myoepithelial Cells.

BACKGROUND: Benzodiazepines (BZDs), the most commonly prescribed psychotropic drugs with anxiolytic action, may cause hyposalivation. It has been previously shown that BZDs can cause hypertrophy and decrease the acini cell number. In this study, we investigated the effects of BZDs and pilocarpine on rat parotid glands, specifically on acinar, ductal, and myoepithelial cells. METHODS: Ninety male Wistar rats were divided into nine groups. Control groups received a saline solution for 30 days (C30) and 60 days (C60), and pilocarpine (PILO) for 60 days. Experimental groups received lorazepam (L30) and midazolam (M30) for 30 days. Another group (LS60 or MS60) received lorazepam or midazolam for 30 days, respectively, and saline for additional 30 days. Finally, other groups (LP60 or MP60) received either lorazepam or midazolam for 30 days, respectively, and pilocarpine for additional 30 days. The expression of calponin in myoepithelial cells and the proliferating cell nuclear antigen (PCNA) in acinar and ductal cells were evaluated. RESULTS: Animals treated with lorazepam showed an increase in the number of positive staining cells for calponin as compared to control animals (p < 0.05). Midazolam administered with pilocarpine (MP60) induced an increase in the proliferation of acinar and ductal cells and a decrease in the positive staining cells for calponin as compared to midazolam administered with saline (MS60). CONCLUSION: We found that myoepithelial cells might be more sensitive to the effects of BZD than acinar and ductal cells in rat parotid glands.

Stereoselective synthesis and antitumoral activity of Z-enyne pseudoglycosides.

An efficient approach for the synthesis of Z-1,3-enynes based on the coupling reaction of Z-vinyl tellurides and alkynes containing a pseudoglycoside moiety is described. The products were obtained in good yields via a stereoselective way. Preliminary screening against three tumor cell lines indicated that the synthesized compounds are promising intermediates for the synthesis of an array of more potent target structures.

Histomorphometric analysis of salivary gland in wistar rats treated chronically with two benzodiazepines.

Benzodiazepines (BZDs), the most commonly prescribed psychotropic drugs with anxiolytic action, may cause hyposalivation. Therefore, this study sought to quantify the acini (N) in parotid glands of Wistar rats treated chronically with two BZDs (Lorazepam and Midazolan) and to verify the action of the pilocarpine when administered with these drugs. Ninety male Wistar rats were distributed in 9 groups according to the administration of: a) S30 - saline solution for 30 days; b) S60 - saline solution for 60 days; c) P60 - pilocarpine for 60 days; d) L30 - Lorazepam for 30 days; e) M30 - Midozolam for 30 days; f) LS60 - Lorazepam for 60 days and, after this period, 30 more days of saline solution; g) MS60 - Midazolam for 30 days and, after this period, 30 more days of saline solution; h) LP60 - Lorazepam and Pilocarpine for 60 days; i) MP60 - Midazolam and Pilocarpine for 60 days. A surgery was performed on the animals to remove the glands. After this, histological cuts were stained by hematoxylin and eosin, from which the N was quantified. The ANOVA and Games-Howell tests were used for statistical analysis. The L30 and M30 groups presented less N than did the S30 group (p<0.05). The LS60, MS60, and LP60 groups presented less N than did the S60 and P60 groups (p<0.05). No differences could be observed between the MP60 and S60 groups. The chronic administration of Midazolam and Lorazepam reduced acini, which may well have collaborated in the reduction of salivary flow previously verified. The association of Midazolam with Pilocarpine led to the reestablishment of acinar cells, which may have favored the restoration of the salivary flow formerly shown.

Physical vapor deposited thin films of lignins extracted from sugar cane bagasse: morphology, electrical properties, and sensing applications.

The concern related to the environmental degradation and to the exhaustion of natural resources has induced the research on biodegradable materials obtained from renewable sources, which involves fundamental properties and general application. In this context, we have fabricated thin films of lignins, which were extracted from sugar cane bagasse via modified organosolv process using ethanol as organic solvent. The films were made using the vacuum thermal evaporation technique (PVD, physical vapor deposition) grown up to 120 nm. The main objective was to explore basic properties such as electrical and surface morphology and the sensing performance of these lignins as transducers. The PVD film growth was monitored via ultraviolet-visible (UV-vis) absorption spectroscopy and quartz crystal microbalance, revealing a linear relationship between absorbance and film thickness. The 120 nm lignin PVD film morphology presented small aggregates spread all over the film surface on the nanometer scale (atomic force microscopy, AFM) and homogeneous on the micrometer scale (optical microscopy). The PVD films were deposited onto Au interdigitated electrode (IDE) for both electrical characterization and sensing experiments. In the case of electrical characterization, current versus voltage (I vs V) dc measurements were carried out for the Au IDE coated with 120 nm lignin PVD film, leading to a conductivity of 3.6 × 10(-10) S/m. Using impedance spectroscopy, also for the Au IDE coated with the 120 nm lignin PVD film, dielectric constant of 8.0, tan δ of 3.9 × 10(-3), and conductivity of 1.75 × 10(-9) S/m were calculated at 1 kHz. As a proof-of-principle, the application of these lignins as transducers in sensing devices was monitored by both impedance spectroscopy (capacitance vs frequency) and I versus time dc measurements toward aniline vapor (saturated atmosphere). The electrical responses showed that the sensing units are sensible to aniline vapor with the process being reversible. AFM images conducted directly onto the sensing units (Au IDE coated with 120 nm lignin PVD film) before and after the sensing experiments showed a decrease in the PVD film roughness from 5.8 to 3.2 nm after exposing to aniline.

Metal and ceramic bracket effects on human buccal mucosa epithelial cells.

OBJECTIVE: To test the null hypothesis that metal and ceramic brackets have no effect on the epithelial cells of the buccal mucosa. MATERIALS AND METHODS: Two metal and two ceramic brackets were bonded in 21 individuals of both sexes. With the use of liquid-based exfoliative cytology, morphometric and morphologic changes in buccal mucosa cells adjacent to these brackets were determined and were compared at three time points: baseline (T0), 60 days after placement (T1), and 30 days after removal of the brackets (T2). RESULTS: A decrease in nuclear area and an increase in cytoplasmic area occurred in the buccal mucosa cells adjacent to the brackets at T1 (P < .01). At T2, this altered morphometry persisted only in cells adjacent to the metal brackets, although to a lesser degree than at T1 (P < .01). A greater decrease in nuclear area was noted in cells adjacent to the metal brackets than in those next to the ceramic brackets (P < .01). At T0, the proportions of surface and subsurface cells were similar, but at T1, a predominance of surface cells was observed (P < .05). At all time points, smears of cells appeared normal or normal with some inflammatory changes. CONCLUSION: The hypothesis is rejected. Placement of metal and ceramic brackets in the buccal cavity induces cellular alterations. These alterations do not suggest malignancy.

[Detection of antibodies against Anaplasma sp. in small ruminants from the semi-arid region against Pernambuco State, Brazil]. / Detecção de anticorpos para Anaplasma sp. em pequenos ruminantes no semi-árido do Estado de Pernambuco, Brasil.

This paper reports the detection of antibodies against Anaplasma sp. in goats and sheep from the semi-arid region from Pernambuco State, Brazil, using an enzyme-linked immunosorbent assay with recombinant MSP5 of Anaplasma marginale. Sera from 243 goats and 68 sheep from Ibimirim municipality were analyzed and frequencies of antibodies of 11.93% (29/243) and 16.17% (11/68) were found for goats and sheep, respectively. The epidemiological relevance of the findings was discussed.

Detecção de anticorpos para Anaplasma sp. em pequenos ruminantes no semi-árido do estado de Pernambuco, Brasil / Detection of antibodies against Anaplasma sp. in small ruminants from the semi-arid region against Pernambuco State, Brazil

Neste trabalho é descrita a detecção de anticorpos para Anaplasma sp. em caprinos e ovinos da região do semi-árido do Estado de Pernambuco, Brasil, utilizando-se um ensaio de imunoadsorção enzimática baseado em MSP5 recombinante de Anaplasma marginale. Foram analisados soros de 243 caprinos e 68 ovinos provenientes do município de Ibimirim, e observadas freqüências de anticorpos de 11,93 por cento (29/243) e 16,17 por cento (11/68) para caprinos e ovinos, respectivamente. A importância epidemiológica dos achados foi discutida.

This paper reports the detection of antibodies against Anaplasma sp. in goats and sheep from the semi-arid region from Pernambuco State, Brazil, using an enzyme-linked immunosorbent assay with recombinant MSP5 of Anaplasma marginale. Sera from 243 goats and 68 sheep from Ibimirim municipality were analyzed and frequencies of antibodies of 11.93 percent (29/243) and 16.17 percent (11/68) were found for goats and sheep, respectively. The epidemiological relevance of the findings was discussed.

Copper (II) adsorbed on SiO(2)/SnO(2) obtained by the sol-gel processing method: application as electrochemical sensor for ascorbic acid.

With the objective of producing a material showing better conductive properties to be used as a support for electroactive species, a SiO(2)/SnO(2) mixed oxide was prepared. The procedure for SiO(2)/SnO(2) mixed oxide preparation using the sol-gel processing method, starting from tetraethylorthosilicate and SnI(4) as precursor reagents, is described. SiO(2)/SnO(2) with composition Sn=15.6 wt% and S(BET) = 525 m(2)g(-1), V(p)=0.28 mlg(-1), and D(p)= 1.5 nm, where S(BET), V(p) and D(p) are the specific surface area, the average pore volume, and the average pore diameter, respectively, was obtained. The X-ray photoelectron spectroscopy showed that the mixed oxide was thermally very stable for samples heat-treated at up to 1073 K. The Brønsted acid sites, probed with pyridine molecules for samples heat-treated at various temperatures, were chemically stable up to 473 K. Segregation of SnO(2) crystalline phase was observed at 1473 K but no crystalline phase was verified for SiO(2) at this temperature. The porous SiO(2)/SnO(2) matrix was used as base for Cu(II) immobilization and an electrode was developed for application in electrochemical detection of vitamin C in tablets.

Systemic and regional hemodynamic effects of angiotensin-(1-7) in rats.

The systemic and regional hemodynamics effects of ANG-(1-7) were examined in urethane-anesthetized rats. The blood flow distribution (kidneys, skin, mesentery, lungs, spleen, brain, muscle, and adrenals), cardiac output, and total peripheral resistance were investigated by using fluorescent microspheres. Blood pressure and heart rate were recorded from the brachial artery. ANG-(1-7) infusion (110 fmol x min(-1) x 10 min(-1) iv) significantly increased blood flow to the kidney (5.10 +/- 1.07 to 8.30 +/- 0.97 ml x min(-1) x g(-1)), mesentery (0.73 +/- 0.16 to 1.17 +/- 0.49 ml x min(-1) x g(-1)), brain (1.32 +/- 0.44 to 2.18 +/- 0.85 ml x min(-1) x g(-1)), and skin (0.07 +/- 0.02 to 0.18 +/- 0.07 ml x min(-1) x g(-1)) and the vascular conductance in these organs. ANG-(1-7) also produced a significant increase in cardiac index (30%) and a decrease in total peripheral resistance (2.90 +/- 0.55 to 2.15 +/- 0.28 mmHg x ml(-1) x min x 100 g). Blood flow to the spleen, muscle, lungs, and adrenals, as well as the blood pressure and heart rate, were not altered by the ANG-(1-7) infusion. The selective ANG-(1-7) antagonist A-779 reduced the blood flow in renal, cerebral, mesenteric, and cutaneous beds and blocked the ANG-(1-7)-induced vasodilatation in the kidney, mesentery, and skin, suggesting a significant role of endogenous ANG-(1-7) in these territories. The effects of ANG-(1-7) on the cerebral blood flow, cardiac index, systolic volume, and total peripheral resistance were partially attenuated by A-779. A high dose of ANG-(1-7) (11 pmol x min(-1) x 10 min(-1)) caused an opposite effect of that produced by the low dose. Our results show for the first time that ANG-(1-7) has a previously unsuspected potent effect in the blood flow distribution and systemic hemodynamics.

Banco de dados e folha de estilo ABNT para gerenciador de referências bibliográficas

Descreve o desenvolvimento de um banco de dados e duas folhas de estilos de modo a automatizar as referências, obtidas nos principais bancos de dados de bibliotecas eletrônicas, de acordo com as recomendações definidas pela ABNT. Este banco foi construído usando ferramenta de software do gerenciador bibliográfico Reference Manager 10(AU)

Banco de dados e folha de estilo ABNT para gerenciador de referências bibliográficas / Data bank and styles for organization of citations and references according to ABNT (Brazilian Association for Technical Norms)

Descreve o desenvolvimento de um banco de dados e duas folhas de estilos de modo a automatizar as referências, obtidas nos principais bancos de dados de bibliotecas eletrônicas, de acordo com as recomendações definidas pela ABNT. Este banco foi construído usando ferramenta de software do gerenciador bibliográfico Reference Manager 10.

Hiponatremia e hipernatremia: análise de 70 lactentes internados nos últimos dois anos no Instituto da Criança do Hospital das Clínicas da FMUSP / Hyponatremia and hypernatremia: analysis of 70 infants hospitalized in the last 2 years in the Instituto da Criança do Hospital das Clínicas da FMUSP

Com finalidade de se avaliar dados clinicolaboratoriais e mortalidade na desidrataçäo que ocorre com distúrbios da natremia, foram estudados, retrospectivamente, 70 lactentes internados no Instituto da Criança, nos anos de 1983 e 1984. Foram constatadas 72 alteraçöes da natremia, definidas como concentraçöes séricas de sódio fora do intervalo 130-159mEq/L, das quais 64 episódios foram hiponatrêmicos (Na+ < 130mEq/L) e oito, hipernatrêmicos (Na+ > 150mEq/L). Sessenta e oito lactentes tinham menos de 12 meses de idade. Houve predominância do sexo masculino: 41, contra 29 do sexo feminino. Os principais dados clínicos associados à hiponatremia foram: diarréia 90%, acidose 47%, prostraçäo 44%, sepse 25% e convulsöes 20%. Em relaçäo a hipernatremia, os dados clínicos mais freqüentes foram: diarréia 88%, acidose 88%, agitaçäo 50%, convulsöes 37% e sepse 25%. Quando se analisou o tratamento da hiponatremia e seus resultados pôde-se constatar que em 46% dos pacientes com concentraçöes séricas de sódio abaixo de 124mEq/L (29 pacientes) a correçäo rápida da natremia foi indicada em apenas sete pacientes (11%). Destes, em apenas dois obtiveram-se concentraçöes de sódio normais (e abaixo de 134mEq/L) após quatro a seis horas da administraçäo de cloreto de sódio a 3%. O tratamento da hipernatremia foi o mais heterogêneo possível. Em nenhum dos pacientes procurou-se melhorar as condiçöes circulatórias, inicialmente, com soluçäo de cloreto de sódio a 0,45% como preconizado por vários autores. A mortalidade desta série foi elevada: 16% no grupo hiponatrêmico e 38% no hipernatrêmico. Pela elevada mortalidade conclui-se que o tratamento deve ser individualizado e perfeitamente controlado nestes pacientes de alto risco com alteraçöes da natremia