Quercetin-1,2,3-Triazole Hybrids as Multifunctional Anti-Alzheimer's Agents.

The number of patients with Alzheimer's disease (AD) continues to rise and, despite the efforts of researchers, there are still no effective treatments for this multifaceted disease. The main objective of this work was the search for multifunctional and more effective anti-Alzheimer agents. Herein, we report the evaluation of a library of quercetin-1,2,3-triazole hybrids (I-IV) in antioxidant, hydrogen peroxide-induced oxidative stress protection, and cholinesterases (AChE and BuChE) inhibitory activities. Hybrids IIf and IVa-d showed potent in vitro inhibitory activity on eqBuChE (IC50 values between 11.2 and 65.7 µM). Hybrid IIf, the best inhibitor, was stronger than galantamine, displaying an IC50 value of 11.2 µM for eqBuChE, and is also a competitive inhibitor. Moreover, toxicity evaluation for the most promising hybrids was performed using the Artemia salina toxicity assay, showing low toxicity. Hybrids IIf, IVb, and IVd did not affect viability at 12.5 µM and also displayed a protective effect against oxidative stress induced by hydrogen peroxide in cell damage in MCF-7 cells. Hybrids IIf, IVb, and IVd act as multifunctional ligands in AD pathologies.

Outdoor airborne allergens: Characterization, behavior and monitoring in Europe.

Aeroallergens or inhalant allergens, are proteins dispersed through the air and have the potential to induce allergic conditions such as rhinitis, conjunctivitis, and asthma. Outdoor aeroallergens are found predominantly in pollen grains and fungal spores, which are allergen carriers. Aeroallergens from pollen and fungi have seasonal emission patterns that correlate with plant pollination and fungal sporulation and are strongly associated with atmospheric weather conditions. They are released when allergen carriers come in contact with the respiratory system, e.g. the nasal mucosa. In addition, due to the rupture of allergen carriers, airborne allergen molecules may be released directly into the air in the form of micronic and submicronic particles (cytoplasmic debris, cell wall fragments, droplets etc.) or adhered onto other airborne particulate matter. Therefore, aeroallergen detection strategies must consider, in addition to the allergen carriers, the allergen molecules themselves. This review article aims to present the current knowledge on inhalant allergens in the outdoor environment, their structure, localization, and factors affecting their production, transformation, release or degradation. In addition, methods for collecting and quantifying aeroallergens are listed and thoroughly discussed. Finally, the knowledge gaps, challenges and implications associated with aeroallergen analysis are described.

Spectral CT: Current Liver Applications.

Using two different energy levels, dual-energy computed tomography (DECT) allows for material differentiation, improves image quality and iodine conspicuity, and allows researchers the opportunity to determine iodine contrast and radiation dose reduction. Several commercialized platforms with different acquisition techniques are constantly being improved. Furthermore, DECT clinical applications and advantages are continually being reported in a wide range of diseases. We aimed to review the current applications of and challenges in using DECT in the treatment of liver diseases. The greater contrast provided by low-energy reconstructed images and the capability of iodine quantification have been mostly valuable for lesion detection and characterization, accurate staging, treatment response assessment, and thrombi characterization. Material decomposition techniques allow for the non-invasive quantification of fat/iron deposition and fibrosis. Reduced image quality with larger body sizes, cross-vendor and scanner variability, and long reconstruction time are among the limitations of DECT. Promising techniques for improving image quality with lower radiation dose include the deep learning imaging reconstruction method and novel spectral photon-counting computed tomography.

Analysis of 665 thyroid nodules using both EU-TIRADS and ACR TI-RADS classification systems.

BACKGROUND: Ultrasound-based classification systems allow stratification of thyroid nodules to recommend fine-needle aspiration (FNA) based on their malignancy risk. However, these have discrepancies that may have an impact in thyroid cancer detection. We aimed to compare European Thyroid Association (EU-TIRADS) and American College of Radiology (ACR TI-RADS), in terms of FNA indication and diagnostic performance. METHODS: Retrospective study of 665 thyroid nodules from 598 patients who underwent ultrasound and fine-needle aspiration at a tertiary-care institution between January 1st of 2016 and July 31st of 2019. Based on their sonographic features they were classified according to the EU-TIRADS and ACR TI-RADS classification and then their cytological results were obtained. Differences in FNA indications according to these two classifications were analysed. In patients who underwent surgical removal of the nodules, the final pathological diagnosis was obtained. RESULTS: A statistically significant association was found between EU-TIRADS and ACR TI-RADS classification systems (p < 0.001). ACR TI-RADS allowed greatest reduction in FNA performed (32% vs 24.5%). A different risk category was obtained in 174 (26.1%) nodules, mostly higher with EU-TIRADS. The indication to FNA changed in 54 (8.1%) nodules (49 only indicated following EU-TIRADS recommendations), of which 4 had Bethesda IV and 5 had Bethesda III cytology. The FNA indication in a higher number of nodules using EU-TIRADS was due to difference in the dimensional threshold for FNA on low-risk nodules; to the fact that hypoechogenicity in a mixed nodule ascribes it moderate risk, while using ACR TI-RADS it would only be considered of low risk, and to the use of isolated sonographic features, namely marked hypoechogenicity, microcalcifications and irregular margins, to automatically categorize a nodules as high risk in EU-TIRADS, while ACR TI-RADS requires a group of potentially suspicious features to consider a nodule of high risk. The analysis of pathology proven nodules revealed equally good sensitivity of both systems in the detection of malignancy, but weak specificity, slightly greater with ACR TI-RADS (27.1% vs 18.6%). CONCLUSIONS: The EU-TIRADS and ACR TI-RADS are both suitable to assess thyroid nodules and through risk stratification avoid unnecessary FNA. FNA was less performed using ACR TI-RADS, which was slightly more efficiency in excluding malignancy.

Antimicrobial, Antibiofilm and Toxicological Assessment of Propolis.

Antimicrobial resistance is a serious problem for the control of infections and infectious diseases. Propolis is a substance produced by honeybees with antimicrobial and antibiofilm properties. To consider propolis as an alternative to the use of antimicrobials for infection control, we assessed its antimicrobial and antibiofilm activities. To assess propolis for topical medical use, toxicological studies were also performed. A Portuguese 70% propolis ethanolic extract was chemically evaluated and studied for antimicrobial activity on staphylococcal field isolates (n = 137) and antibiofilm action (n = 45). Cell toxicological assessment was performed using keratinocytes and fibroblasts. Pinobanksin, chrysin, acacetin, apigenin, pinocembrin, and kaempferol-dimethyl-ether were detected. All 137 isolates were susceptible to 6.68 mg/mL or lower propolis concentration (80% isolates were susceptible to <1 mg/mL). The mean percentage of biofilm inhibition was 71%, and biofilm disruption was 88.5%. Propolis (<1 mg/mL) was well-tolerated by fibroblasts and moderately tolerated by keratinocytes. The combined antimicrobial and antibiofilm effect of propolis, together with its low toxicity to connective tissue and epithelial cells, suggests a good applicability for topical antibacterial treatment. Therefore, propolis seems to be a good alternative to antimicrobials for the treatment of infections with Staphylococcus spp. that deserves to be evaluated in vivo.

Pros and Cons of Dual-Energy CT Systems: "One Does Not Fit All".

Dual-energy computed tomography (DECT) uses different energy spectrum x-ray beams for differentiating materials with similar attenuation at a certain energy. Compared with single-energy CT, it provides images with better diagnostic performance and a potential reduction of contrast agent and radiation doses. There are different commercially available DECT technologies, with machines that may display two x-ray sources and two detectors, a single source capable of fast switching between two energy levels, a specialized detector capable of acquiring high- and low-energy data sets, and a filter splitting the beam into high- and low-energy beams at the output. Sequential acquisition at different tube voltages is an alternative approach. This narrative review describes the DECT technique using a Q&A format and visual representations. Physical concepts, parameters influencing image quality, postprocessing methods, applicability in daily routine workflow, and radiation considerations are discussed. Differences between scanners are described, regarding design, image quality variabilities, and their advantages and limitations. Additionally, current clinical applications are listed, and future perspectives for spectral CT imaging are addressed. Acknowledging the strengths and weaknesses of different DECT scanners is important, as these could be adapted to each patient, clinical scenario, and financial capability. This technology is undoubtedly valuable and will certainly keep improving.

Prevalence of celiac artery compression by median arcuate ligament in patients with splanchnic artery aneurysms/pseudoaneurysms submitted to endovascular embolization.

PURPOSE: To study the association between median arcuate ligament compression (MALC) of celiac artery (CA) and splanchnic artery aneurysms/pseudoaneurysms (SAAPs) submitted to endovascular embolization. METHODS: Single center retrospective study of embolized SAAPs between 2010 and 2021, to evaluate the prevalence of MALC, and compare demographic data and clinical outcomes between patients with and without MALC. As a secondary objective, patient characteristics and outcomes were compared between patients with different causes of CA stenosis. RESULTS: MALC was found in 12.3% of 57 patients. SAAPs were more prevalent in the pancreaticoduodenal arcades (PDAs) in patients with MALC, compared to those without MALC (57.1% vs. 10%, P = .009). Patients with MALC had a greater proportion of aneurysms (71.4% vs. 24%, P = .020), as opposed to pseudoaneurysms. Rupture was the main indication for embolization in both groups (71.4% and 54% of patients with and without MALC, respectively). Embolization was successful in most cases (85.7% and 90%), with 5 immediate (28.6% and 6%) and 14 non-immediate (28.6% and 24%) post-procedure complications. Thirty and 90-day mortality rate were 0% in patients with MALC, and 14% and 24% in patients without MALC. Atherosclerosis was the only other cause of CA stenosis, in 3 cases. CONCLUSIONS: In patients with SAAPs submitted to endovascular embolization, the prevalence of CA compression by MAL is not uncommon. The most frequent location for aneurysms in patients with MALC is in the PDAs. Endovascular management of SAAPs is very effective in patients with MALC, with low complications, even in ruptured aneurysms.

Atmospheric pollen allergen load and environmental patterns in central and southwestern Iberian Peninsula.

Over one quarter of the population in industrialised countries suffers from some type of allergy and inhaled aeroallergens from pollen are the primary cause of allergic ailments. The networks for monitoring biological air quality measure the airborne pollen concentrations that characterize periods of exposure to major airborne aeroallergens but there are certain discrepancies in relation to the allergen-pollen dynamic. In this paper we analyse the airborne allergens Ole e 1, Phl p 1, Phl p 5 and Pla a 1, and interpreted the adjustments and mismatches in their concentrations in relation to airborne pollen. The influence of main environmental patterns was considered. The study was conducted in two urban areas of the centre and southwest of the Iberian Peninsula (Toledo in Spain and Évora in Portugal). Monitoring for pollen followed the standard protocol using Hirst volumetric spore traps and allergenic particles were quantified by ELISA assay. The results indicate that the discrepancies in this relationship were affected by the weather conditions up to 6 days prior. Precipitation and humidity above normal values caused a higher concentration of the allergen Pla a 1. This effect occurred in reverse in the case of humidity for the allergens Ole e 1 and Phl p 1. Humidity and precipitation generated the same pattern in the allergen-pollen relationship in both Phl p 1 and Phl p 5. Our findings show consistent results that allow to interpret the rate of discrepancy between allergen and pollen, and it can be used to improve allergy risk prediction models generated from atmospheric pollen.

Differential Quercus spp. pollen-particulate matter interaction is dependent on geographical areas.

Particulate matter (PM) and pollen interaction, either airborne or at the respiratory mucosa needs further clarification, as allergic reaction intensification can be related to the PM physical characteristics and toxicity. This study aimed to investigate the physical-chemical properties of PM that can adhere to the pollen wall during its transport or inhalation, using Quercus spp. as a model, in three Portuguese cities with different geographical locations, meteorological influence and urbanization levels. Possible sources were evaluated through air masses trajectory analysis using the HYSPLIT model and correlation with meteorological factors. The sampling was performed using a 7-days Hirst-type volumetric sampler, and the pollen grains were observed using a Field Emission Electron Probe Microanalyser for PM analysis. A secondary electron image of each pollen grain was taken, to determine the adhered particles characteristics and energy dispersive x-ray spectroscopy (EDS) spectra were obtained for individual particles. A total of 484 pollen grains was observed, with 7683 particles counted and 1914 EDS spectra analyzed. The particle's equivalent diameter ranged from 0.3-16 µm, with most having a diameter < 3 µm. For the three cities, there were significant differences in the number of particles per pollen and the % area occupied by the particles. Particles adhered were mainly Si-rich, but variations in other dominant groups were observed. For Évora and Guarda, Ca-rich, SO-rich were second and third more representative, while Porto were Organic and Cl-rich. Metals&Oxides were found in all cities with the highest number in Porto. P-rich particles were only found in Évora. Sea salt particles were observed in Évora, coincide with air mass trajectories possible carrying them from the Mediterranean Sea. In conclusion, the PM physical characteristics are similar between the studied cities, however, the dominant chemical composition is different, certainly impacting the exposome influence and pollen-allergy intensification towards the same pollen type and concentration.

Serous Borderline Tumor in Transgender Female-to-Male Individuals: A Case Report of Androgen Receptor-Positive Ovarian Cancer.

Ovarian cancer is the most fatal gynecologic malignancy. The incidence of ovarian cancer among female-to-male transsexuals receiving treatment with testosterone is unknown, and few cases have been reported in the literature. We report a recent case in our institution, a 23-year-old female-to-male transsexual patient who received testosterone supplementation. The patient underwent a pelvic magnetic resonance imaging to study an ovarian complex cyst that revealed the presence of a bilateral ovarian tumor with imaging features of borderline serous tumor. These masses were surgically removed and the pathology report confirmed the diagnosis associated with noninvasive peritoneal implants and the presence of numerous androgen receptors in the tumor cells. Although there is still insufficient data to validate a direct correlation between hormonotherapy and ovarian cancer in these patients, this case may reinforce previous reports on this association and highlights the relevance of radiological follow-up and bilateral salpingo-oophorectomy as part of gender reassignment surgery.

Recognizing dysphagia: implementation of an in-hospital screening protocol.

BACKGROUND: Dysphagia affects up to 30% of hospitalized patients, and it is associated with numerous complications. AIMS: Assess the impact of a 24/7 dysphagia screening protocol in an Internal Medicine Unit regarding respiratory complications (such as aspiration pneumonia) as the primary outcome. Length of stay and discharge destination were secondary outcomes. METHODS: Case-control hospital-based analysis comparing the outcomes before and after the implementation of the screening protocol. We analysed demographic data (such as age and gender) and clinical data (presence of dysphagia, vascular risk factors and other comorbidities, respiratory complications, in hospital length of stay and discharge destination). Patients with at least one of the following risk factors were included: COPD (chronic obstructive pulmonary disease), neurodegenerative disorders including dementia, acute stroke or chronic cerebrovascular disease, head and neck neoplasms/surgery or radiotherapy. Statistical analysis was performed with SPSS®. RESULTS: One hundred twenty-eight consecutive patient files were reviewed as the historical control, while 125 consecutive patients were evaluated after the screening protocol was implemented. Even though the second group had less evidence of dysphagia (33 vs 36), since it was detected earlier, respiratory complications were significantly lower (11.7% before vs 2.4%, p < 0.001), allowing more patients to be discharged home (65.6% vs 84%, p = 0.005) and less mortality (15.6% vs 4%, p = 0.005). CONCLUSIONS: Despite its limitations, this study demonstrates that dysphagia screening produces a significant impact on patients' lives, as well as healthcare professionals and resources. We hope that our results will encourage others to adopt a patient-centred multidisciplinary approach that includes a dysphagia screening protocol.

Taste sensitivity and lifestyle are associated with food preferences and BMI in children.

Oral food perception together with lifestyle may affect food preferences and choices, influencing weight gain and obesity development. The present study was designed to evaluate the association of biological (taste sensitivity) and lifestyle variables with children food preferences, assessing whether all these variables contribute to explain BMI percentile. After anthropometric evaluation, 387 children were classified for bitter and sweet taste sensitivities. Socioeconomic/lifestyle aspects and hedonics for 36 foods were collected. Watching TV during meals associate with lower preference for several vegetables, as well as being sweet taste low sensitive, in the case of girls. Moreover, regression analysis showed that bitter taste sensitivity is one of the variables contributing to explain high BMI percentiles. These results present evidences that both biological and socioeconomic and the attention that is given to food (eating in the presence or absence of distractors) are aspects that should be considered in children nutrition to prevent obesity.

Comparison of salivary proteome of children with different sensitivities for bitter and sweet tastes: association with body mass index.

BACKGROUND/OBJECTIVES: Oral sensorial perception is a key aspect in food choices and knowing the mechanisms modulating such perception is of major importance in the context of child obesity, which is reaching high rates in Mediterranean countries. Salivary proteome has been linked to taste sensitivity in adults. The aim of this study was to search for differences in salivary proteomes of children with different bitter or sweet taste sensitivities and to assess if these potential differences are associated with their body mass index percentile (BMI percentile). SUBJECTS/METHODS: 387 children aged 8-9 years old were assessed for BMI percentile and classified according to their sensitivity to bitter and sweet tastes, according to their caffeine and sucrose detection thresholds, respectively. Saliva protein composition was compared among taste sensitivity groups, taking into account BMI percentile and gender, using gel-based proteomics approaches, coupled to mass spectrometry for protein identification. RESULTS: Among the salivary proteins related to bitter taste sensitivity, higher levels of cystatins were observed in bitter-sensitive children, in the case of those of normal weight, and in bitter low-sensitive, in the case of overweight children. For sweetness, the relationship between saliva and taste perception was also dependent on BMI percentile, with several proteins (including salivary cystatins) differing between taste sensitivity groups, with disparities arising between normal-weight and overweight children. Cystatin isoforms A, B and SA were observed to be considerably increased in saliva from obese children. CONCLUSIONS: Salivary proteome is related with sensitivities to bitter and sweet tastes in children, but the association is dependent on BMI percentile and gender.

Effects of hyperleptinemia in rat saliva composition, histology and ultrastructure of the major salivary glands.

OBJECTIVE: To study the effect of the satiety hormone, leptin, in saliva proteome and salivary gland histology and ultrastructure. DESIGN: Increases in blood leptin levels were induced through mini-pump infusion in male Wistar rats, during a period of 7 days. Saliva was collected before and at the end of the experimental period, for proteomic analysis, and major salivary glands were collected, at the end, for biochemical, histological and ultrastructural analysis. RESULTS: Immunohistochemistry revealed the presence of leptin receptors in major salivary glands. Salivary amylase levels and enzymatic activity were decreased in saliva, whereas the enzymatic activity of this protein was increased in the cytosol of parotid gland cells. Transmission electron microscopy allowed the observation of high number of electron-dense granules in cytosol of parotid acinar cells, from leptin treated animals. CONCLUSIONS: Increased levels of plasmatic leptin result in changes in saliva composition and salivary glands function. To our knowledge, this is the first study providing evidences for a potential role of leptin in salivary gland secretion and saliva composition. An understanding of how appetite/satiety factors influence saliva composition and how this composition influences food processing in mouth may be relevant in understanding ingestivebehaviour.

Association between Salivary Leptin Levels and Taste Perception in Children.

The satiety inducing hormone leptin acts not only at central nervous system but also at peripheral level. Leptin receptors are found in several sense related organs, including the mouth. A role of leptin in sweet taste response has been suggested but, until now, studies have been based on in vitro experiments, or in assessing the levels of the hormone in circulation. The present study investigated whether the levels of leptin in saliva are related to taste perception in children and whether Body Mass Index (BMI) affects such relationship. Sweet and bitter taste sensitivity was assessed for 121 children aged 9-10 years and unstimulated whole saliva was collected for leptin quantification, using ELISA technique. Children females with lower sweet taste sensitivity presented higher salivary leptin levels, but this is only in the normal weight ones. For bitter taste, association between salivary leptin and caffeine threshold detection was observed only in preobese boys, with higher levels of salivary hormone in low sensitive individuals. This study is the first presenting evidences of a relationship between salivary leptin levels and taste perception, which is sex and BMI dependent. The mode of action of salivary leptin at taste receptor level should be elucidated in future studies.

Application of the adverse outcome pathway (AOP) concept to structure the available in vivo and in vitro mechanistic data for allergic sensitization to food proteins.

BACKGROUND: The introduction of whole new foods in a population may lead to sensitization and food allergy. This constitutes a potential public health problem and a challenge to risk assessors and managers as the existing understanding of the pathophysiological processes and the currently available biological tools for prediction of the risk for food allergy development and the severity of the reaction are not sufficient. There is a substantial body of in vivo and in vitro data describing molecular and cellular events potentially involved in food sensitization. However, these events have not been organized in a sequence of related events that is plausible to result in sensitization, and useful to challenge current hypotheses. The aim of this manuscript was to collect and structure the current mechanistic understanding of sensitization induction to food proteins by applying the concept of adverse outcome pathway (AOP). MAIN BODY: The proposed AOP for food sensitization is based on information on molecular and cellular mechanisms and pathways evidenced to be involved in sensitization by food and food proteins and uses the AOPs for chemical skin sensitization and respiratory sensitization induction as templates. Available mechanistic data on protein respiratory sensitization were included to fill out gaps in the understanding of how proteins may affect cells, cell-cell interactions and tissue homeostasis. Analysis revealed several key events (KE) and biomarkers that may have potential use in testing and assessment of proteins for their sensitizing potential. CONCLUSION: The application of the AOP concept to structure mechanistic in vivo and in vitro knowledge has made it possible to identify a number of methods, each addressing a specific KE, that provide information about the food allergenic potential of new proteins. When applied in the context of an integrated strategy these methods may reduce, if not replace, current animal testing approaches. The proposed AOP will be shared at the www.aopwiki.org platform to expand the mechanistic data, improve the confidence in each of the proposed KE and key event relations (KERs), and allow for the identification of new, or refinement of established KE and KERs.

CT evaluation after neoadjuvant FOLFIRINOX chemotherapy for borderline and locally advanced pancreatic adenocarcinoma.

AIM: To assess anatomic changes on computed tomography (CT) after neoadjuvant FOLFIRINOX (5-fluorouracil/leucovorin/irinotecan/oxaliplatin) chemotherapy for secondary resected borderline resectable (BR) and locally advanced (LA) pancreatic adenocarcinoma and their accuracy to predict resectability and pathological response. METHODS: Thirty-six patients with secondary resected BR/LA pancreatic adenocarcinoma after neoadjuvant FOLFIRINOX chemotherapy (± chemoradiotherapy) were retrospectively included. Two radiologists reviewed baseline and pre-surgical CTs in consensus. NCCN (National Comprehensive Cancer Network) classification, largest axis, product of the three axes (P3A), and arterial/venous involvement were studied and compared to pathological response and resection status and to disease-free survival (DFS). RESULTS: Thirty-one patients had R0 resection, including only six exhibiting a downstaging according to the NCCN classification. After treatment, the largest axis and P3A decreased (P < 0.0001). The pre-surgical largest axis and P3A were smaller in case of R0 resection (P = 0.019/P = 0.021). The largest axis/P3A variations were higher in case of complete pathological response (P = 0.011/P = 0.016). A decrease of the arterial/venous involvement was not able to predict R0 or ypT0N0 (P > 0.05). Progression of the vascular involvement was seen in two (5 %) patients and led to a shorter DFS. CONCLUSION: In BR/LA pancreatic adenocarcinoma after the neoadjuvant FOLFIRINOX regimen (± chemoradiotherapy), significant tumour size decreases were observed on CT. However, CT staging was not predictive of resectability and pathological response. KEY POINTS: • Significant tumour size decreases were observed on CT after FOLFIRINOX (± chemoradiotherapy). • CT is not able to predict R0 resection accurately after FOLFIRINOX (± chemoradiotherapy). • CT is not able to predict complete response accurately after FOLFIRINOX (± chemoradiotherapy). • Even with a stable NCCN classification, BR/LA pancreatic adenocarcinoma could have R0 resection.

Novel hydroxyamides and amides containing D-glucopyranose or D-fructose units: Biological assays in MCF-7 and MDST8 cell lines.

A novel library of 15 compounds, hydroxyamides and amides containing a ß-D-glucopyranose (D-Gluc) or a ß-D-fructose (D-Fruc) units was designed and synthesized for antiproliferative assays in breast (MCF-7) and colon (MDST8) cancer cell lines. Twelve of them were hydroxyamides and were successfully synthesized from ß-D-glucuronic acid (D-GluA). Six of these hydroxyamides which were acetylated hydroxy-ß-D-glucopyranuronamide 2a-2f (1st Family) and the other six were their respective isomers, that is, hydroxy-ß-D-fructuronamide 3a-3f (2nd Family), obtained by acid-base catalyzed isomerization. These compounds have the general structure, D-Gluc-C=ONH-CHR-(CH2)n-OH and D-Fruc-C=ONH-CHR-(CH2)n-OH, where R=an aromatic, alkyl or a hydrogen substituent, with n=0 or 1. Eight of these contained a chiral aminoalcohol group. Three compounds were amides containing a D-glucopyranose unit (3rd Family). SAR studies were conducted with these compounds. Antiproliferative studies showed that compound 4a, the bromo-amide containing the ß-D-glucopyranose ring, potently inhibits the proliferation of the MDST8 cells. Five compounds (2e, 2f, 3d, 3e, and 3f) were shown to potently selectively inhibit the proliferation of the MCF-7 cells. Compound 4b was the only one showing inhibition in both cell lines. In general, the more active compounds were the amides and hydroxyamides containing the ß-D-fructose moiety, and containing an alkyl group or hydrogen. Half-inhibitory concentrations (IC50) of between 0.01 and 10 µM, were observed.

Changes in the salivary protein profile of morbidly obese women either previously subjected to bariatric surgery or not

Saliva is a non-invasive source of biomarkers useful in the study of physiological mechanisms. Moreover, this fluid has diverse functions, among which food perception and ingestion, making it particularly suitable for the study of obesity. The aims of this study were to assess changes in salivary proteome among morbidly obese women, with a view to provide information about mechanisms potentially related to the development of obesity, and to evaluate whether these changes persist after weight loss. Mixed saliva samples from morbidly obese women (N = 18) who had been either subjected (group O-BS) or not (group O) to bariatric surgery and women with normal weight (N = 14; group C) were compared for protein profiles, alpha-amylase abundance and enzymatic activity, and carbonic anhydrase (CA) VI abundance. Differences in salivary obese profiles were observed for 23 different spots. Zinc-alpha-2 glycoprotein-containing spots showed higher abundance in group O only, whereas cystatin S-containing spots presented higher abundance in the two groups of obese subjects. Most of the spots identified as salivary amylase were present at lower levels in group O-BS. With regard to the amylase enzymatic activity, increases were observed for group O and decreases for group O-BS. One interesting finding was the high correlation between levels of CA VI and body mass index in group O, which was not observed for groups O-BS or C. The differences between groups, mainly regarding salivary proteins involved in taste sensitivity and metabolism, point to the potential of using saliva in the study of obesity development