Cross-sectional evaluation of the saccharin transit time test for primary ciliary dyskinesia: did we discard this tool too soon?

ABSTRACT BACKGROUND: Primary ciliary dyskinesia (PCD) is a rare and heterogeneous disease that is difficult to diagnose and requires complex and expensive diagnostic tools. The saccharin transit time test is a simple and inexpensive tool that may assist in screening patients with PCD. OBJECTIVES: This study aimed to compare changes in the electron microscopy findings with clinical variables and saccharin tests in individuals diagnosed with clinical PCD (cPCD) and a control group. DESIGN AND SETTING: An observational cross-sectional study was conducted in an otorhinolaryngology outpatient clinic from August 2012 to April 2021. METHOD: Patients with cPCD underwent clinical screening questionnaires, nasal endoscopy, the saccharin transit time test, and nasal biopsy for transmission electron microscopy. RESULTS: Thirty-four patients with cPCD were evaluated. The most prevalent clinical comorbidities in the cPCD group were recurrent pneumonia, bronchiectasis, and chronic rhinosinusitis. Electron microscopy confirmed the clinical diagnosis of PCD in 16 of the 34 (47.1%) patients. CONCLUSION: The saccharin test could assist in screening patients with PCD due to its association with clinical alterations related to PCD.

Consumo de edulcorantes no calóricos en la población adulta de Argentina / Non-caloric sweeteners consumption in the adult population of Argentina

Resumen Introducción: Los edulcorantes no calóricos (ENC) se utilizan para sustituir azúcares en alimentos y bebidas. Para que este reemplazo sea beneficioso para la salud, la ingesta de cada ENC no de bería superar su ingesta diaria admisible (IDA). El objetivo principal de este estudio es determinar el consumo de aspartamo, acesulfame-K, sucralosa y sacarina en la población argentina de 15 a 65 años y evaluar este consumo en relación con la IDA. Otros objetivos son estratificar el consumo en función de distintas variables sociodemográficas y determinar las principales fuentes de ENC consumidas por la población argentina. Métodos: La muestra fue de 1266 individuos (población urbana 15-65 años), estratificada por región, edad, sexo y nivel socioeconómico. Los datos de ingesta fueron recolectados con dos recordatorios de 24 horas. Resultados: En Argentina, el consumo promedio de sacarina, aspartamo, acesulfame-K y sucralosa está muy por debajo de su respectiva IDA: 8.4%, 3.2%, 2% y 0.3% de la IDA respectivamente. Los consumos máximos reportados tampoco superan la IDA. Hay una mayor proporción de mujeres consumidoras de ENC. La proporción de consumidores de ENC aumenta con la edad. Las regiones noreste y sur presentan el menor porcentaje de consumidores de ENC. Las bebidas constituyen la principal fuente de ENC, seguidas por los edulcorantes de mesa. La contri bución de los alimentos al consumo de ENC es despreciable. Discusión: En Argentina existe un buen margen de seguridad para la reformulación de productos azucarados tendiente a disminuir el exceso de calorías y el consumo de azúcares añadidos.

Abstract Introduction: Non-caloric sweeteners (NCS) are used to replace added sugars in foods and bev erages. For this replacement to be a health benefit, the intake of each NCS should not exceed its Acceptable Daily Intake (ADI). The main objective of this study is to determine the consumption of aspartame, acesulfame-K, sucralose, and saccharin in the argentine population aged 15 to 65 years and to evaluate this consumption in relation to the ADI. Other objectives are to stratify the consumption based on different sociodemographic vari ables and to determine the main sources of NCS consumed by the argentine population. Methods: The sample consisted of 1266 individuals (urban population aged 15-65), stratified by region, age, sex, and socioeconomic level. Intake data was collected with two 24-hour recalls. Results: In Argentina, the average consumption of saccharin, aspartame, acesulfame-K and sucralose is well below their respective ADI: 8.4%, 3.2%, 2% and 0.3% of the ADI, respectively. The maximum reported consumptions do not exceed the ADI either. There is a higher proportion of women who consume NCS. The proportion of NCS consumers increases with age. The Northeast and South regions have the lowest percentage of NCS consumers. Beverages constitute the main source of NCS, followed by tabletop sweeteners. The contribution of food to NCS consumption is negligible. Discussion: In Argentina there is a good safety margin for the reformulation of sugary products aimed at reduc ing the excess calories and added sugars consumed by the population.

Effects of polyvinylpyrrolidone and poly (ethylene glycol) on preparation of ibuprofen pharmaceutical cocrystal

Abstract In this study, we investigated the effects of polymers on the pharmaceutical cocrystal formation process. Ibuprofen (IBU) was selected as the active pharmaceutical ingredient (API), nicotinamide (NIC) and saccharin (SAC) as the cocrystal coformer (CCF), ethanol/water as the solvent, polyvinylpyrrolidone (PVP) and poly (ethylene glycol) (PEG) as the representative polymers. We prepared IBU-NIC and IBU-SAC cocrystals in ethanol-water cosolvent in the absence or presence of polymers. Cocrystal screening products were characterized by FTIR, DSC, PXRD, and HPLC. The results showed that the mixture of IBU and IBU-NIC cocrystal can be prepared in ethanol-water cosolvent without polymers. The addition of PVP facilitates the formation of pure IBU-NIC cocrystal; however, no cocrystal was formed in PEG solutions. SAC could not cocrystallize with IBU in the ethanol-water solvent in the absence of polymers. Neither PVP nor PEG could facilitate the formation of the IBU-SAC cocrystal.

Mucociliary Clearance of Different Respiratory Conditions: A Clinical Study

Abstract Introduction Mucociliary clearance (MCC) is the first line of defense of the pulmonary system. Mucociliary clearance impairment may lead to increased risk of respiratory infections, lung injury, pulmonary repair problems, chronic dysfunctions and progression of respiratory diseases. Objective To characterize the MCC of active and passive smokers and individuals with chronic obstructive pulmonary disease (COPD) and compare the MCC behaviors between men and women of different age groups. Methods Patients with COPD (current smokers and ex-smokers) and apparently healthy individuals (current smokers, passive smokers and nonsmokers) were evaluated. All of the subjects underwent lung function and MCC evaluation (saccharin transport test [STT]). Smokers (with or without COPD) were questioned about the smoking history. Results A total of 418 individuals aged 16 to 82 years old, of both genders, were evaluated. The STT values of active and passive smokers were statistically higher than those of the control group (p < 0.01). Men of the control group had lower values of STT than active smokers (9.7 ± 7.1 and 15.4 ± 10.1 minute, respectively, p < 0.01). In addition, higher MCC velocity was observed in women that are current smokers (11.7 ± 6.8 minute) compared with men (15.4 ± 10.1 minute) in this group (p = 0.01). Among the younger age groups (< 50 years old), only passive smokers presented higher STT in relation to the control group. Conclusion Passive and active smoking are factors that influence negatively the MCC, and passive smokers may present losses of this mechanism at a younger age. Additionally, male smokers present worse MCC than male nonsmokers.

Effect of saccharin on inflammation in 3T3-L1 adipocytes and the related mechanism

BACKGROUND/OBJECTIVES: Excessive intake of simple sugars induces obesity and increases the risk of inflammation. Thus, interest in alternative sweeteners as a sugar substitute is increasing. The purpose of this study was to determine the effect of saccharin on inflammation in 3T3-L1 adipocytes.MATERIALS/METHODS: 3T3-L1 preadipocytes were differentiated into adipocytes. The adipocytes were treated with saccharin (0, 50, 100, and 200 µg/mL) for 24 h. Inflammation was induced by exposure of treated adipocytes to lipopolysaccharide (LPS) for 18 h and cell proliferation was measured. The concentration of nitric oxide (NO) was measured by using Griess reagent. Protein expressions of nuclear factor kappa B (NF-κB) and inhibitor κB (IκB) were determined by western blot analysis. The mRNA expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin 1β (IL-1β), interleukin 6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor-α (TNF-α) were determined by real-time PCR.RESULTS: Compared with the control group, the amount of NO and the mRNA expression of iNOS in the LPS-treated group were increased by about 17.6% and 46.9%, respectively, (P < 0.05), and those parameter levels were significantly decreased by saccharin treatment (P < 0.05). Protein expression of NF-κB was decreased and that of IκB was increased by saccharin treatment (P < 0.05). Saccharin decreased the mRNA expression of COX-2 and the inflammation cytokines (IL-1β, IL-6, MCP-1, and TNF-α) (P < 0.05).CONCLUSIONS: The results of this study suggest that saccharin can inhibit LPS-induced inflammatory responses in 3T3-L1 adipocytes via the NF-κB pathway.

Air pollution and nasal mucociliary clearance time among urban and rural residents in two Philippine communities

Objective@#To measure the nasal mucociliary clearance (NMC) time among adults residing in two Philippine communities with different air quality indices using the saccharin and methylene blue test. @*Methods@#Design: Cross-Sectional Study. Setting: Diliman, Quezon City and Puerto Princesa, Palawan. Participantss: Fifty (50) participants, 25 residing in an urban city with fair air quality index and 25 residing in a rural province with good air quality index. @*Results@#The mean NMC time of the urban group was 22.15±12.68 mins and was significantly longer than the NMC time of the rural group which was 5.29±2.87mins; t(48) = 6.643, p<0.0001). @*Conclusion@#Increased air pollution may be associated with significant prolongation of nasal mucociliary clearance time among urban residents with fair quality air index compared to rural residents with good quality air index.

Análisis teórico de la posibilidad de la detección electroquímica de la sacarina, asistida por oxihidróxido de vanadio / The theoretical analysis of the possibility of the electrochemical determination of saccharin, assisted by vanadium (III) oxyhydroxide

RESUMEN Mediante el análisis mecanístico teórico, ha sido evaluada la posibilidad del empleo del oxihidróxido de vanadio como modificador de electrodo para la detección electroquímica de sacarina. El proceso electroanalítico se realiza a través de un proceso catódico. El modelo matemático correspondiente ha sido analizado mediante la teoría de estabilidad lineal y análisis de bifurcaciones. El análisis del modelo ha mostrado que el oxihidróxido de vanadio puede ser un modificador eficiente para la detección electroquímica de la sacarina en las condiciones del pH suficientemente ácido para mover el proceso, pero insuficiente para disolver el oxihidróxido. Las causas de los comportamientos oscilatorio y monotónico también fueron estipuladas.

SUMMARY By means of the theoretical mechanistic analysis, the possibility of the use of vanadium oxyhydroxide as electrode modifier for saccharin electrochemical determination has been evaluated. The electroanalytical process is realizing by a cathodic route. The correspondent mathematical model has been analyzed by means of the linear stability theory and bifurcation analysis. The analysis of the model has shown that the vanadium oxyhydroxide is an efficient electrode modifier for saccharin electrochemical detection in pH sufficiently low to maintain the process, but insufficiently acidic to dissolve the oxyhydroxide. The causes for the oscillatory and monotonic instabilities have also been derived.

Nasal mucociliary transportability of male and female smokers / Transportabilidade mucociliar nasal de homens e mulheres tabagistas

Abstract Introduction: Female smoker's present increased susceptibility to several diseases when compared to the opposite gender. However, there are no studies showing differences in nasal mucociliary transport behavior between male and female smokers. Objective: To compare the nasal mucociliary transportability in male and female smokers and non-smokers, taking into consideration age, anthropometric data, smoking load and pulmonary function. Methods: The analysis included 139 individuals (33 men and 37 women smokers and 32 men and 37 women non-smokers). All participants answered an initial interview to obtain personal data and smoking load. Anthropometric data and carbon monoxide in the exhaled air were assessed. Individuals also performed pulmonary function test and Saccharin Transit Time test. To compare saccharin transit time values between men and women, smokers and non-smokers, stratification of all independent variables was performed (sociodemographic, smoking and respiratory variables) into two categories: below and above the median values. Results: There was no difference between men and women, smokers and non-smokers, regarding nasal mucociliary transportability. Significant differences were only observed between non-smokers. Among those with less forced vital capacity values (<97.37% of predicted), women presented mucociliary transport faster than men. Moreover, it was observed influence of BMI and COex (women smokers), FCV and FEV1 (men non-smokers) and FEF25-75% (women non-smokers) on saccharin transit time values. Conclusion: Based on the findings of this study, nasal mucociliary transport in male and female adult smokers, apparently healthy, are similar.

Resumo Introdução: Mulheres tabagistas apresentam maior susceptibilidade à diversas doenças quando comparadas ao sexo masculino. No entanto, não há estudos mostrando diferenças no comportamento do transporte mucociliar nasal entre tabagistas do sexo masculino e feminino. Objetivo: Comparar a transportabilidade mucociliar nasal em homens e mulheres fumantes e não fumantes, levando em consideração idade, dados antropométricos, carga tabágica e função pulmonar. Método: A análise incluiu 139 indivíduos (33 homens e 37 mulheres fumantes e 32 homens e 37 mulheres não fumantes). Todos os participantes responderam a uma entrevista inicial para a obtenção de dados pessoais e a carga tabágica. Dados antropométricos e monóxido de carbono no ar expirado foram avaliados. Os indivíduos também fizeram teste de função pulmonar e o teste de trânsito de sacarina. Para comparar os valores do teste de trânsito de sacarina entre homens e mulheres, fumantes e não fumantes, foi feita a estratificação de todas as variáveis independentes (variáveis sociodemográficas, tabágicas e respiratórias) em duas categorias: abaixo e acima dos valores médios. Resultados: Não houve diferenças entre homens e mulheres, fumantes e não fumantes, em relação à transportabilidade mucociliar nasal. Diferenças significativas foram observadas apenas entre não fumantes. Entre os que apresentaram valores menores de capacidade vital forçada (< 97,37% do previsto), as mulheres apresentaram transporte mucociliar mais rápido do que os homens. Além disso, observou-se influência do IMC e COex (mulheres fumantes), CVF e VEF1 (homens não fumantes) e FEF25%-75% (mulheres não fumantes) sobre os valores do teste de trânsito de sacarina. Conclusão: Com base nos achados deste estudo, o transporte mucociliar nasal em tabagistas masculinos e femininos adultos, aparentemente saudáveis, são semelhantes.

Comparison of nonnutritive artificial sweetener consumption among university students in latin american: multicentric study

The Objective this study is to compare the consumption of artificial sweeteners by sex and BMI status among university students in Peru, Chile, Guatemala and Panama. Survey of consumption of artificial sweeteners containing foods was designed and applied, adapted for each country with pictures of surveyed foods. After the survey application, a total of 1,229 participants male and female both university students from 4 different Latin American countries: Chile (n=473); Panama (n=300); Guatemala (n=253); Peru (n=204) were submitted to a anthropometry measeurement. Over 80% of students ate at least 1 food that contained artificial sweeteners, acesulphame-k, sucralose, and aspartame had the highest levels of consumption. Females in Chile and Guatemala ate the most sucralose (25.7 (6.6-50.9), p<0.05; 38.3 (15.1-82.5). Males in Panama ate the most acesulphame-k, (35.3 (11.5-91.5), p<0,05). Females had a positive correlation between artificial sweetener consumption and BMI for: acesulphame-k, aspartame and cyclamate. Males had a negative relationship between acesulphame-k, aspartame and BMI (p<0.05). We found a high consumption of artificial sweeteners among both male and female Latin Americ an university students, with differences by country, sex and BMI status(AU)

El objetivo del estudio es comparar el consumo de edulcorantes artificiales no nutritivos por sexo y estado nutricional (IMC) entre los estudiantes universitarios en Perú, Chile, Guatemala y Panamá. Se diseñó y aplicó una encuesta de consumo de alimentos que contienen edulcorantes artificiales no nutritivos, adaptado para cada país con fotos de alimentos encuestas. Posteriormente se aplicó la encuesta y una evaluación antropometrica entre 1.229 estudiantes universitarios en 4 diferentes países de América Latina: Chile (n = 473); Panamá (n = 300); Guatemala (n = 253); Perú (n = 204). Más del 80% de los estudiantes comía al menos 1 alimento que contiene edulcorantes artificiales, acesulfamo-K, sucralosa, aspartame y tenían los niveles más altos de consumo. Las mujeres en Chile y Guatemala comsumieron más sucralosa (25,7 (6,6-50,9), p <0,05; 38,3 (15,1-82,5). Los hombres de Panama comsumían más acesulfamo-K, (35,3 (11,5-91,5), p <0,05) Las mujeres tenían una correlación positiva entre el consume de edulcorante artificial y el IMC para: acesulfamo-K, aspartamo y ciclamato hombres tenían una relación negativa entre el acesulfamo K, aspartamo y el IMC (p <0,05). Encontramos un alto consumo de edulcorantes artificiales entre los estudiantes de ambos sexos en las universidades de América Latina, con diferencias por país, sexo e IMC(AU)

¿Se pueden recomendar en el embarazo los edulcorantes no nutritivos? / Can we recommend nonnutritive sweeteners during pregnancy?

Pregnancy is a condition of special concern due to the need to care for both mother and fetus. One of the main recommendations during this time is weight control. Exceeding weight gain recommendations increases the risk of gestational diabetes, hypertension, obesity, pre-eclampsia, cesarean delivery, premature birth, neural tube defects, and macrosomia, among others. Thus, weight gain within guidelines decreases the chances of these complications. One recommended way to avoid excess weight gain is to replace sugar for nonnutritive sweeteners (NNS), bearing in mind that the sale of these substances, especially sodas and sweets, have increased worldwide. The aim of this study was to review the literature regarding the possible risks and benefits of perigestational consumption of NNS. NNS are widely consumed to substitute sugar and provide a sweet taste without contributing to energy intake; however there are no long-term studies in humans that confirm their safety. A study of the legal regulations of the use of NNS requires ongoing review, especially when it comes to pregnancy, since the statements of different health departments around the world are conflicting.

El embarazo es un momento de especial preocupación debido a que la atención se centra en la salud de la madre y el feto. Una de las recomendaciones para embarazadas es el control de peso. Exceder las recomendaciones sobre el incremento de peso gestacional aumenta el riesgo de padecer diabetes gestacional, hipertensión arterial, sobrepeso, obesidad, pre-eclampsia, parto por cesárea, partos prematuros, defectos del tubo neural, macrosomía, entre otros. Por lo tanto, un incremento de peso adecuado en el embarazo permite evitar estas complicaciones. Algunas de las recomendaciones para evitar el aumento de peso excesivo, es reemplazar la sacarosa por Edulcorantes no nutritivos (ENN), considerando que su consumo, y en especial de bebidas y productos azucarados, se ha incrementado a nivel mundial en los últimos años. El objetivo de este trabajo fue revisar la bibliografía disponible en relación a los posibles riesgos y beneficios de consumir ENN en el embarazo. Los ENN son ampliamente consumidos en la población, en reemplazo del azúcar, como una estrategia para el ahorro de calorías extras, sin embargo, su utilización en mujeres embarazadas no cuenta con estudios en humanos a largo plazo que avalen su seguridad. En relación al marco legal que regula el uso de ENN, se requiere de la revisión permanente para actualizar la información en relación a la seguridad de su consumo, especialmente en mujeres embarazadas, ya que al revisar las directrices de ministerios de salud de diversos países en relación a recomendar o no la utilización de ENN son discordantes.

Proficiency Testing for Melting Point Determination of Chemical Drugs in Laboratory / 中国药师

Objective:To evaluate the capacity and level of melting point determination of chemical drugs in the laboratories par-ticipating in the proficiency testing. Methods:Two test samples were prepared, and the labs volunteered to participate in the proficien-cy testing program ( PTP) . The melting point determination was performed according to the general principle 0612 in part four of Chi-nese Pharmacopoeia (2015 edition), and the results were analyzed by robust statistics and the determination proficiency of the laborato-ries were evaluated by Z-score. Results:The analysis showed that two test samples were homogeneous and stable, which met the re-quirements of the PTP. Totally 31 laboratories had satisfactory results, which accounted for 83. 8%. Conclusion:The majority of the participant laboratories can accurately determine the melting points of test samples, and the information is very helpful to the next profi-ciency testing program.

Blind Sample Assessment of Sodium Saccharin in Drinks / 中国药师

Objective: To evaluate the testing level of the relevant items in food inspection agency laboratory objectively, analyze the existing problems and help them enhance the ability of detection.Methods: The blind sample assessment of sodium saccharin in drinks was organized and performed.The test samples at high and low concentrations were prepared and studied by the tests of homogeneity and stability.Those met the requirements of blind sample assessment were randomly distributed to 193 laboratories and the returned data were analyzed statistically.Results: Totally 182 valid data were collected.Among the reported results, those from 85 laboratories were satisfied in the low concentration group with the satisfaction rate of 87.6% , those from 12 laboratories were not satisfied, and no results were suspicious;as for the high concentration group, the above data was 67(78.8%), 12 and 6, respectively.The overall satisfaction rate was 83.5%.The results, especially the dissatisfied and suspicious data, were analyzed by the original records of each participating laboratory, the analysis focused on 8 aspects including detection method, instrument brand, control product variety, pretreatment method, recovery rate, column selection and the other influencing factors, and suggestions were given to every laboratory to improve its own situation.Conclusion: The statistical data reflect that our food testing laboratory has strong detection ability in the determination of saccharin sodium in beverages, and can provide powerful technical support for the regulatory authorities.

Effects of smoking on lung mucociliary movement and pulmonary function in patients with chronic obstructive pulmonary disease and healthy people / 中国医师进修杂志

Objective To observe the effects of smoking on lung mucociliary movement and pulmonary function in patients with chronic obstructive pulmonary disease (COPD) and healthy people. Methods Ninety-two patients with COPD (COPD group) were selected, including 48 smoking patients (COPD smoking group) and 44 non-smoking patients (COPD non-smoking group). Another 76 healthy people (control group) were selected, including 37 smokers (control smoking group) and 39 non-smokers (control non-smoking group). The saccharin test and pulmonary function were carried out respectively, including mucociliary clearance time (MCT), forced vital capacity (FVC) and forced expired volume in 1 s (FEV1), and the ratio of FEV1 and FVC (FEV1/FVC) and FEV1 percentage of predicted (FEV1%pre) were calculated. Results The MCT in COPD group was significantly higher than that in control group:(26.17 ± 19.23) min vs. (15.28 ± 11.34) min, the FEV1/FVC and FEV1%pre were significantly lower than those in control group:(54.25 ± 12.76)%vs. (83.04 ± 5.98)%and (53.26±9.84)%vs. (85.38 ± 5.72)%, and there were statistical differences (P0.05). The Pearson correlation analysis result showed that there was positive correlation between MCT and smoking intensity, age (r = 0.346 and 0.256, P<0.05), and there was negative correlation between MCT and FEV1/FVC, FEV1%pre (r = -0.327 and -0.414, P<0.05). Conclusions Smoking can destroy the mucociliary function and aggravate the deterioration of lung function in patients with COPD.

The unbiased truth about artificial sweeteners

Sugar contribute to tooth decay and obesity but still we spoon it. Artificial sweeteners are used in one of two ways. They may be used directly in commercially processed foods or they are mixed with one or more starch based sweeteners before sale to consumers. Artificial sweeteners are so intensely sweet so small Amounts are required to imitate sugars sweet taste. In this review paper, it is going to discuss about the basic five Artificial sweeteners like Aspartame, Acesulfame, Saccharin, Sucralose and Neotame.

Effect of sweetener and flavoring agent on oxidative indices, liver and kidney function levels in rats.

Food additives while attract consumers, improve quality, control weight and replace sugar, may affect seriously children and adults health. Here, we investigated the adverse effects of saccharin and methylsalicyltaes as sweetener and flavoring agent on lipid profile, blood glucose, renal, hepatic function and oxidative stress/antioxidants (lipid peroxidation, catalase and reduced glutathione in liver tissues). Saccharin and methylsalicylate were administered orally in young male albino rats at low and high dose for 30 days. Rats were divided into 5 groups, 1st control group, 2nd and 3rd (low and high saccharin-treated groups) and 4th and 5th (low and high methylsalicylate-treated group). Serum total cholesterol, triglyceride, glucose levels and body weight gain were found decreased in saccharin high dose group compared to control. Rats consumed high dose of saccharin showed a significant decrease in serum triglycerides, cholesterol and LDL levels. Low and high doses of saccharin exhibited a significant increase in liver function marker of ALT, AST, ALP activity, total proteins and albumin levels and renal function test (urea and creatinine levels) in comparison with control group. Further, saccharin at high dose induced significant decrease in liver GSH levels, catalase and SOD activity and increase in hepatic MDA level. Overall saccharin harmfully altered biochemical markers in liver and kidney at higher as well as lower doses. Whereas, methyl salicylates did not pose a risk for renal function and hepatic oxidative markers.

Effect of Saccharin Intake in Restraint-induced Stress Response Reduction in Rats

PURPOSE: Stress activates the sympathetic nervous system and hypothalamic-pituitary-adrenal (HPA) axis and induces the release of glucocorticoids. Saccharin is 300 times sweeter than sucrose, but does not increase blood insulin levels. Thus, this study was designed to evaluate the effect of saccharin intake in restraint-induced stress response reduction in rats. METHODS: Adult male Sprague-Dawley (SD) rats had stress induced by restraint for 2 hours/day for 1 week. Saccharin was provided in sufficient amounts to allow them to intake it voluntarily at 0.1% diluted in water. The Y-maze test and forced swim test (FST) were performed to evaluate cognitive function and the depressive behavior of the rats. The protein expression of the glucocorticoid receptor (GR) in hippocampal cornu ammonis (CA) 1 was investigated by using immunohistochemistry. RESULTS: It was found that, the percentage of alternation in the Y-maze test was significantly (p<.01) higher in the Stress + saccharin group than in the Stress group. Immobility time in the FST was significantly (p<.01) lower in the Stress + saccharin group than in the Stress group. Also, the positive cells of GR in hippocampus CA1 were significantly (p<.05) lower in the Stress + saccharin group than in the Stress group. CONCLUSION: This study showed that there was an effect of saccharin intake in restraint-induced stress response reduction in rats.

Virtual screening of co-formers for ketoprofen co-crystallization and the molecular properties of the co-crystal.

Ketoprofen or [2-(3-benzoylphenyl)propionic acid] is a nonsteroidal antiinflammatory and analgesic agent. The positive qualities of ketoprofen are based on optimal physicochemical and structural characteristics, its ability to penetrate into and accumulate in the inflammation centers and compatibility with other classes of drugs. This compound is practically insoluble in water, therefore as most of NSAID drugs, it is categorized as Biopharmaceutics Classification System (BCS) class II. A widely used to enhance the solubility of poorly water soluble drugs is co-crystallization. A co-crystal is a multi-component crystal which involves non-covalent interactions between API and its co-formers. In this work, we developed virtual screening of co-formers for ketoprofen by employing molecular docking method. AutoDock was used for docking. Parameters observed were type and energy (Ei) of interaction. The work was continued by co-crystallization process and solubility assay of the mixtures according to Higuchi and Connor method using UV spectrophotometer. Based on molecular docking, the best co-former is saccharin (Ei = -3.14 kcal/mol). The docking result fits the solubility assay of the ketoprofen-saccharin co-crystal (300.62 μg/mL in water or 256.54% increasing of solubility compared to ketoprofen). Ketoprofen co-crystal shows better curve (90.15 % in 60 minutes) than ketoprofen (78.87 % in 60 minutes). Co-crystallization of ketoprofen with saccharin increases the dissolution profile of ketoprofen.

Risk Assessments of Cyclamate, Saccharin, Neohesperidine DC, Steviol Glycosides and Neotamefrom Soft Drinks, “Saft” and Nectar.

The Norwegian Scientific Committee for Food Safety (Vitenskapskomiteen for mattrygghet, VKM), Panel on Food Additives, Flavourings, Processing Aids, Materials in Contact with Food and Cosmetics, has at the request of the Norwegian Food Safety Authority (Mattilsynet) conducted a risk assessment of the intense sweeteners cyclamate, saccharin, neohesperidine DC, steviol glycosides and neotame in soft drinks, “saft” and nectar. The risk assessment includes exposure assessments and the calculated exposures are compared to the acceptable daily intake (ADI) for the respective sweeteners. VKM was also requested to compare the current calculated intake of saccharin and cyclamate to the calculated intake reported by VKM in 2007 (the VKM report «Impact on health when sugar is replaced with intense sweeteners in soft drinks, “saft” and nectar») when possible (VKM, 2007). Six different intake scenarios with varying concentrations of added sweeteners (either the average concentration or the highest reported concentration for the respective sweetener) and varying consumption of beverages with sweeteners (either the actual reported consumption of beverages added sweetener or the assumption that all reported beverages were added sweeteners) were used for the exposure calculations. • Scenario 1 gives the best estimate of the current situation in the population (average content of sweeteners, actual reported consumption). • Scenario 2 is based on the average content of sweeteners and that all consumed beverages contain sweeteners. • Scenario 3 is based on the highest reported content of sweeteners and the actual reported consumption. • Scenario 4 is based on the highest reported content of sweeteners and that all consumed beverages contain sweeteners. Scenarios 5 and 6 are based on the maximum allowed amounts of sweeteners within a category in accordance with the Regulation on food additives, within the categories soft drinks, “saft” and nectar in Norway (Regulation No 668 of 6 June 2011 on food additives, 2011). • In scenario 5 the consumption of beverages with added sweeteners or sugar reported in dietary surveys were used for the calculations. • In scenario 6 it was assumed that all consumed soft drinks, “saft” and nectar contained sweeteners (no sugar). In the current risk assessment, the intake of the sweeteners was calculated for 2-year-old children and 18-70 year old men and women. Due to lack of new dietary surveys, the other age groups of children and adolescents were not included. For all age groups in all scenarios, the intake of the sweeteners cyclamate, saccharin, neohesperidine DC, steviol glycosides and neotame was below their respective established ADI values. Due to possible differences in the calculation, it was not possible to compare the current calculated intake of saccharin and cyclamate to the calculated intake reported by VKM in 2007. VKM concludes that there is no major health concern related to the intake of the sweeteners cyclamate, saccharin, neohesperidine DC, steviol glycosides and neotame from the beverage categories included in this risk assessment per today. VKM further concludes that among young women who are high consumers of beverages with cyclamate, and 2-year-old children who are high consumers of beverages with steviol glycosides, the estimated intake approaches the ADI values. The high intakes approaching ADI are considered conservative estimates, as the highest reported content of sweetener or the maximum allowed amounts is used. Thus, these estimates are only relevant for the part of the population that are both loyal to beverages with sweeteners and a particular brand of sweetened beverage. It should be noted that intake of sweeteners from other foods or from tabletop sweeteners is not included in the intake estimates, and that a considerable contribution from these sources cannot be excluded.

Evaluación de la Nicotina como Estímulo Aversivo / Nicotine Assessment as an Aversive Stimulus

La nicotina es el ingrediente psicoactivo del tabaco y se ha descrito como aversiva, reforzante o procognitiva. Sin embargo no existe mucha investigación sobre el sobrelapamiento de los efectos dosis-dependientes como estímulo aversivo y procognitiva. Por lo que evaluaremos los efectos de la nicotina en el paradigma de condicionamiento aversivo al sabor (CAS), con el objetivo de obtener una curva dosis-respuesta del efecto aversivo y compararlo con los efectos procognitivos reportados. Se utilizaron 20 ratas macho Wistar asignadas aleatoriamente a cinco grupos (0.0, 0.2, 0.4, 0.8 y 1.6 mg/kg i.p.). Los resultados muestran tendencia al decremento dosis-dependiente con efecto máximo en la dosis de 1.6 mg/kg, sin embargo se hallaron efectos a partir de la dosis de 0.8 mg/kg lo cual sobrelapa con las dosis propuestas con efectos procognitivos. Esto nos permite proponer que algunos efectos puedan deberse a efectos aversivos periféricos más que a centrales.

Nicotine is the main ingredient of tobacco and it has been described as aversive, reinforce and procognitive. However there is not enough research about the overlapping of the dose-dependent effects as aversive stimulus and precognitive effects. For those reasons we evaluated the nicotine effects on the Conditioned Taste Aversion paradigm (CTA) to evaluated the dose-response curve of the aversive effects of nicotine and to compare such effects with the procognitive effects reported. 20 male Wistar rats in standard laboratory conditions were randomly assigned to 5 groups (0.0, 0.2, 0.4, 0.8 y 1.6 mg/kg i.p.). The obtained results showed a dose-dependent decrease with a maximum effect at 1.6 mg/kg dose, however we founded effects from the 0.8 mg/kg dose, such dose overlapped with procognitive doses reported. These results allow us to propose that some effects could be due the periferical aversive effects instead of the central procognitive effects.

Evaluación de la nicotina como estímulo aversivo / Nicotine Assessment as an Aversive Stimulus

La nicotina es el ingrediente psicoactivo del tabaco y se ha descrito como aversiva, reforzante o procognitiva. Sin embargo no existe mucha investigación sobre el sobrelapamiento de los efectos dosis-dependientes como estímulo aversivo y procognitiva. Por lo que evaluaremos los efectos de la nicotina en el paradigma de condicionamiento aversivo al sabor (CAS), con el objetivo de obtener una curva dosis-respuesta del efecto aversivo y compararlo con los efectos procognitivos reportados. Se utilizaron 20 ratas macho Wistar asignadas aleatoriamente a cinco grupos (0.0, 0.2, 0.4, 0.8 y 1.6 mg/kg i.p.). Los resultados muestran tendencia al decremento dosis-dependiente con efecto máximo en la dosis de 1.6 mg/kg, sin embargo se hallaron efectos a partir de la dosis de 0.8 mg/kg lo cual sobrelapa con las dosis propuestas con efectos procognitivos. Esto nos permite proponer que algunos efectos puedan deberse a efectos aversivos periféricos más que a centrales.

Nicotine is the main ingredient of tobacco and it has been described as aversive, reinforce and procognitive. However there is not enough research about the overlapping of the dose-dependent effects as aversive stimulus and precognitive effects. For those reasons we evaluated the nicotine effects on the Conditioned Taste Aversion paradigm (CTA) to measure the dose-response curve of the aversive effects of nicotine and to compare such effects with the procognitive effects reported. 20 male Wistar rats in standard laboratory conditions were randomly assigned to 5 groups (0.0, 0.2, 0.4, 0.8 y 1.6 mg/kg i.p.). The obtained results showed a dose-dependent decrease with a maximum effect at 1.6 mg/kg dose; however we founded effects from the 0.8 mg/kg dose, such dose overlapped with procognitive doses reported. These results allow us to propose that some effects could be due the periferical aversive effects instead of the central procognitive effects.