Hashimoto thyroiditis (HT) is the most common autoimmune disease worldwide, characterized by chronic inflammation and circulating autoantibodies against thyroid peroxidase and thyroglobulin. Patients ...require hormone replacement with oral levothyroxine, and if untreated, they can develop serious adverse health effects and ultimately death. There is a lot of evidence that the intestinal dysbiosis, bacterial overgrowth, and increased intestinal permeability favor the HT development, and a thyroid-gut axis has been proposed, which seems to impact our entire metabolism. Here, we evaluated alterations in the gut microbiota in Brazilian patients with HT and correlated this data with dietary habits, clinical data, and systemic cytokines and zonulin concentrations. Stool samples from 40 patients with HT and 53 controls were analyzed using real-time PCR, the serum cytokine levels were evaluated by flow cytometry, zonulin concentrations by ELISA, and the dietary habits were recorded by a food frequency questionnaire. We observed a significant increase (
< 0.05) in the
species and a decrease in
in samples of patients with HT. In addition,
species were higher in patients without thyroid hormone replacement, compared with those who use oral levothyroxine. Regarding dietary habits, we demonstrated that there are significant differences in the consumption of vegetables, fruits, animal-derived proteins, dairy products, saturated fats, and carbohydrates between patients and control group, and an inverse correlation between animal-derived protein and
genus was detected. The microbiota modulation by diet directly influences the inflammatory profile due to the generated microbiota metabolites and their direct or indirect action on immune cells in the gut mucosa. Although there are no differences in systemic cytokines in our patients with HT, we detected increased zonulin concentrations, suggesting a leaky gut in patients with HT. These findings could help understand the development and progression of HT, while further investigations to clarify the underlying mechanisms of the diet-microbiota-immune system axis are still needed.
Ferulic acid (4-hydroxy-3-methoxycinnamic acid) is a phytochemical constituent from the polyphenols group commonly found in whole grains, spinach, parsley, grapes and rhubarb. It has been widely ...applied in skin care formulations as photoprotective agent and delayer of cutaneous photoaging processes. This work aims to establish a protocol to the development of cosmetic formulations using thermoanalytical techniques (TG/DTG and DSC) and Pearson’s correlation by FTIR data, in order to evaluate the compatibility between ferulic acid and excipients used in skin care formulations. The results obtained from the thermoanalytical techniques indicated compatibility between ferulic acid and the following excipients: passion fruit seed oil, Carbopol
®
Ultrez 30, EDTA, Crodabase CR2
®
, Crodamol™ GTCC and Dow Corning
®
RM 2051. Nevertheless, the analysis also demonstrated the possibility of some interaction between ferulic acid and the following excipients: glyceryl stearate, Rapithix
®
A-60 and Optiphen
®
. To validate these results, it was demonstrated by Pearson’s correlation that passion fruit seed oil, Carbopol
®
Ultrez 30, EDTA, Crodabase CR2
®
, Crodamol™ GTCC, Dow Corning
®
RM 2051, glyceryl stearate and Rapithix
®
A-60 do not have any incompatibility that may compromise ferulic acid properties. Finally, it was also proved a meaningful incompatibility between ferulic acid and Optiphen
®
using Pearson’s correlation. Thus, it is not recommended to use Optiphen
®
in the development of cosmetic formulations to carry ferulic acid.
Abstract
Objective
The purpose of this study was to compare high-intensity interval training (HIIT) with moderate-intensity continuous training (MICT) for feasibility, safety, adherence, and short- ...and long-term efficacy in improving functioning and health-related quality of life in survivors of coronavirus disease 2019 (COVID-19).
Methods
COVIDEX is a two-pronged, parallel-group, randomized controlled trial with an 8-week training intervention. The study participants will be 94 patients aged >18 years, admitted to a specialized post-COVID center. Participants will be randomized to HIIT (4 × 4 minutes of high-intensity work periods at 85% to 90% of peak heart rate) and MICT (47 minutes at 70% to 75% peak heart rate) groups for biweekly sessions for 8 weeks. The participants will undergo 2 phases of supervised training (phases 1 and 2) of 4 weeks each, in a public, specialized, post-COVID center. In phase 1, we will assess and compare the feasibility, acceptability, and short-term efficacy of HIIT and MICT intervention. In phase 2, the long-term efficacy of HIIT and MICT will be assessed and compared regarding function and health-related quality of life. To prevent any expectation bias, all study participants and assessors will be blinded to the study hypotheses. Group allocation will be masked during the analysis. All statistical analyses will be conducted following intention-to-treat principles.
Impact
This study is the first randomized controlled trial that will compare the feasibility, safety, adherence, and efficacy of the HIIT and MICT intervention programs in this population. The findings will potentially provide important information and assist in clinical decision making on exercise to optimize the benefits of clinical health care in survivors of COVID-19.
Guanylhydrazones are molecules with great pharmacological potential in various therapeutic areas, including antitumoral activity. Factorial design is an excellent tool in the optimization of a ...chromatographic method, because it is possible quickly change factors such as temperature, mobile phase composition, mobile phase pH, column length, among others to establish the optimal conditions of analysis. The aim of the present work was to develop and validate a HPLC and UHPLC methods for the simultaneous determination of guanylhydrazones with anticancer activity employing experimental design. Precise, exact, linear and robust HPLC and UHPLC methods were developed and validated for the simultaneous quantification of the guanylhydrazones LQM10, LQM14, and LQM17. The UHPLC method was more economic, with a four times less solvent consumption, and 20 times less injection volume, what allowed better column performance. Comparing the empirical approach employed in the HPLC method development to the DoE approach employed in the UHPLC method development, we can conclude that the factorial design made the method development faster, more practical and rational. This resulted in methods that can be employed in the analysis, evaluation and quality control of these new synthetic guanylhydrazones.
Ferulic acid (FA) is a phenolic acid of plant kingdom presenting antioxidant activity, a fundamental pharmaceutical property. This property suggests FA can be used in cosmetic skin formulations as a ...photoprotective and anti-aging agent. The purpose of this work is to investigate the kinetics of FA thermal decomposition process in non-isothermic conditions applying Friedman, Flynn–Wall–Ozawa and Kissinger–Akahira–Sunose methodologies and in isothermal conditions using a neural network. All these isoconversional results showed coherent values of apparent activation energy under nitrogen atmosphere. For the isothermal analysis, R2 model presented best performance to individually describe the data. However, the neural network assumed the decomposition as a combined event, in which ten models have contributions to describe experimental data. The DRX results showed the sample is not at steadier configuration and require a pre-treatment before the analysis by the non-isothermal experiments. From this, the sample was prepared with heat treatment up to 130 °C, and the determined activation energy showed reduction of 5 kJ mol
−1
. The isothermal analysis endorses activation energy about 40 kJ mol
−1
. These results proved the FA thermal decomposition is strongly influenced by experimental conditions.
Objectives
To determine the physicochemical and microbiological stability of sulfadiazine suspensions (100 mg/mL) in simple syrup (A) and sorbitol (B) formulations prepared from commercially ...available tablets.
Methods
An ultra‐performance liquid chromatographic assay was developed and validated to determine the chemical stability of sulfadiazine. Three samples were prepared and stored at 5 and 25 °C and assayed at 0, 7, 14 and 30 days. Physical parameters (appearance, pH, particle size and viscosity) were also monitored. Microbiological examination was performed through the suitable counting method.
Results
The formulations presented a sulfadiazine concentration of around 95% at the beginning at both temperatures. There was some variation in pH, viscosity and particle size distribution over time. The samples met the pharmacopoeia criteria of microbiological quality over 30 days, but only sulfadiazine formulated in syrup stored at 25 °C was suitable for use after one week.
Conclusion
The sulfadiazine suspension in simple syrup was chosen as the most suitable formulation because it demonstrated stability for 14 days at room temperature, providing an alternative liquid dosage form of sulfadiazine for congenital toxoplasmosis treatment.
Objectifs
Déterminer la stabilité physicochimique et microbiologique de suspensions de sulfadiazine (100 mg/mL) dans des formulations de sirop simple (A) et de sorbitol (B) préparées à partir de comprimés disponibles dans le commerce.
Méthodes
Un test de chromatographie liquide ultra‐performante a été développé et validé pour déterminer la stabilité chimique de la sulfadiazine. Trois échantillons ont été préparés et stockés à 5 ºC et à 25 ºC et analysés à 0, 7, 14 et 30 jours. Les paramètres physiques (apparence, pH, granulométrie et viscosité) ont également été contrôlés. Un examen microbiologique a été effectué par la méthode de comptage appropriée.
Résultats
Les formulations présentaient une concentration en sulfadiazine d'environ 95% au début aux deux températures. Il y avait une certaine variation du pH, de la viscosité et de la distribution de la taille des particules au fil du temps. Les échantillons répondaient aux critères de pharmacopée pour la qualité microbiologique aprè 30 jours, mais seule la sulfadiazine formulée dans du sirop conservé à 25 ºC pouvait être utilisée après une semaine.
Conclusion
La suspension de sulfadiazine dans un sirop simple a été choisie comme la formulation la plus appropriée car elle a démontré une stabilité à 14 jours à température ambiante, fournissant une forme galénique liquide alternative de sulfadiazine pour le traitement de la toxoplasmose congénitale.
Stigmurin is a peptide with amidated C-terminus (FFSLIPSLVGGLISAFK-NH
2
) identified in the transcriptome of the scorpion
Tityus stigmurus
that has shown antimicrobial action against ...methicillin-resistant pathogens and low antihemolytic activity, and recently proved to be efficient in controlling sepsis. Despite its pharmacological potential, there is no report about thermal studies for the characterization of the amorphous solid. The objective of this work is to characterize stigmurin using thermoanalytical techniques in the solid state in an inert and oxidative atmosphere. Stigmurin presents glass transition temperature at 149 °C. The results of TG–FTIR and pyrolysis suggest that the pathways for decomposition include homolytic breakdown of the side chains of amino acid residues. Decomposition possibly begins at the N-terminus, with formation of the aromatic compounds, amines, nitriles, alcohols, and ethers among others followed by defragmentation reactions (mainly decarboxylation and deamination) and intramolecular condensation reactions. It generates compounds similar to 2,5-diketopiperazine or DKP, and releases water and low molecular mass products (CO
2
, NH
3
, CO, HCNO). The decomposition of stigmurin is an endothermic process where the product of decomposition is originated in the liquid state according to DSC-photovisual images. Stigmurin is more stable in nitrogen atmosphere than synthetic air. This approach provides important information about the thermal decomposition of stigmurin, a molecule endowed with potent antimicrobial activity, supplying relevant parameters (temperature, degradation products, etc.) for technological strategies focusing on quality control and development studies of preformulation involving stigmurin and synthetic peptides in general.
Although low-middle income countries have been disproportionately affected by the COVID-19 pandemic, there is scarce information about the impact of long COVID on their population. This study aimed ...to evaluate long COVID symptomatology, complications (hospital readmission and metabolic disorders), and main clinical features that impact Quality of Life (QoL). This cross-sectional study provides a detailed clinical and laboratory picture of individuals who presented residual symptoms after mild to severe acute COVID-19. Between Aug-2020 to Sep-2021, long COVID patients were evaluated in a reference center for long COVID in Bahia State, Brazil. The EQ-5D-5L questionnaire accessed QoL. A total of 1164 (52 ±13.4 years, 57% female, 88% black/mixed-race) were evaluated 2.3 IQR = 1.6-3.7 months after mild (n = 351, 30.2%), moderate (338, 29.0%) or severe (475, 40.8%) acute illness. Dyspnea (790, 67.9%), fatigue (738, 63.5%), and chest pain (525, 42.9%) were the most frequent residual symptoms regardless of acute severity, affecting the QoL of 88.9% of patients (n/N-826/925), mainly the domains of anxiety/depression and pain/discomfort. High levels of HbA1c were detected for 175 out of 664 patients (26.6%), 40% of them without a previous diagnosis of diabetes mellitus. Of note, hospital admission one-to-three months after the acute phase of disease was required for 51 (4.4%) patients. In this majority-black/mixed-race population, long COVID was associated with post-acute hospitalization, newly diagnosed diabetes mellitus, and decreased QoL, particularly in women and regardless of disease severity of acute infection, suggesting important implications for health care system.
Dissatisfaction with body image may extend to the genital region, and the most dissatisfied with their bodies are women. To analyze the relation between body image and genital image in female, and to ...verify demographic and/or clinical factors related to body image and genital image.
This is a cross-sectional study in 421 women. The Body Shape Questionnaire-34 (BSQ-34) was used to evaluate body image perception; scores ≤110 indicate no dissatisfaction. Also, the female genital self-image scale-7 (FGSIS-7) was used to evaluate genital self-image; scores range between 7 and 28, with higher values considered to indicate a more positive genital self-image. The relation between body image and genital image was determined using the Pearson Correlation test, as well as the relation of these with body mass index (BMI) and age. The relation between these data and genital image was determined by using the ANOVA test or the independent t-test (statistical difference was accepted as p<0.05). In order to verify predictors of dissatisfaction with body image, variables with p<0.10 were inserted into the logistic regression model and checked if they remained significant (p<0.05).
Three hundred eighty-nine women were analyzed. The mean age was 34.7±10.2 years. The mean BMI was 24.1±3.6 kg/m², 49% were single, and the mean BSQ-34 and FGSIS scores were 83.2±30.8 and 23.8±3.4, respectively. The correlation (r=-0.24) was found between body image and genital image (p<0.001). A total of 315 women indicated to be satisfied with their body and presented an FGSIS-7 score of 24±3.3. Participants who were dissatisfied with their body had an average FGSIS-7 score of 22.6±3.3.
Genital image, age, and BMI influence body image. Change in the perception of body image seems to have low correlation with genital self-image in women.
Successful SARS-CoV-2 inactivation allows its safe use in Biosafety Level 2 facilities, and the use of the whole viral particle helps in the development of analytical methods and a more reliable ...immune response, contributing to the development and improvement of in vitro and in vivo assays. In order to obtain a functional product, we evaluated several inactivation protocols and observed that 0.03% beta-propiolactone for 24 h was the best condition tested, as it promoted SARS-CoV-2 inactivation above 99.99% and no cytopathic effect was visualized after five serial passages. Moreover, RT-qPCR and transmission electron microscopy revealed that RNA quantification and viral structure integrity were preserved. The antigenicity of inactivated SARS-CoV-2 was confirmed by ELISA using different Spike-neutralizing monoclonal antibodies. K18-hACE2 mice immunized with inactivated SARS-CoV-2, formulated in AddaS0
, presented high neutralizing antibody titers, no significant weight loss, and longer survival than controls from a lethal challenge, despite RNA detection in the oropharyngeal swab, lung, and brain. This work emphasizes the importance of using different techniques to confirm viral inactivation and avoid potentially disastrous contamination. We believe that an efficiently inactivated product can be used in several applications, including the development and improvement of molecular diagnostic kits, as an antigen for antibody production as well as a control for non-clinical trials.
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