Saccharin Research Articles

Histopathological Effects of Sodium Saccharin Toxicity on Liver and Kidney of Rats in Duhok City-Iraq

Histopathological Effects of Sodium Saccharin Toxicity on Liver and Kidney of Rats in Duhok City-Iraq

Re-evaluation of saccharin and its sodium, potassium and calcium salts (E 954) as food additives.

This opinion deals with the re-evaluation of saccharin and its sodium, potassium and calcium salts (E 954) as food additives. Saccharin is the chemically manufactured compound 1,2-benzisothiazol-3(2H)-one-1,1-dioxide. Along with its sodium (Na), potassium (K) and calcium (Ca) salts, they are authorised as sweeteners (E 954). E 954 can be produced by two manufacturing methods i.e. Remsen-Fahlberg and Maumee. No analytical data on potential impurities were provided for products manufactured with the Maumee process; therefore, the Panel could only evaluate saccharins (E 954) manufactured with the Remsen-Fahlberg process. The Panel concluded that the newly available studies do not raise a concern for genotoxicity of E 954 and the saccharins impurities associated with the Remsen-Fahlberg manufacturing process. For the potential impurities associated with the Maumee process, a concern for genotoxicity was identified. The data set evaluated consisted of animals and human studies. The Panel considered appropriate to set a numerical acceptable daily intake (ADI) and considered the decrease in body weight in animal studies as the relevant endpoint for the derivation of a reference point. An ADI of 9 mg/kg body weight (bw) per day, expressed as free imide, was derived for saccharins (E 954). This ADI replaces the ADI of 5 mg /kg bw per day (expressed as sodium saccharin, corresponding to 3.8 mg /kg bw per day saccharin as free imide) established by the Scientific Committee on Food. The Panel considered the refined brand-loyal exposure assessment scenario the most appropriate exposure scenario for the risk assessment. The Panel noted that the P95 exposure estimates for chronic exposure to saccharins (E 954) were below the ADI. The Panel recommended the European Commission to consider the revision of the EU specifications of saccharin and its sodium, potassium and calcium salts (E 954).

Taste receptor T1R3 regulates testosterone synthesis via the cAMP-PKA-SP1 pathway in testicular Leydig cells

Taste receptor type 1 subunit 3 (T1R3) is a G protein-coupled receptor encoded by the TAS1R3 gene that can be specifically activated by certain sweeteners or umami agents for sweet/umami recognition. T1R3 is a potential target for regulating male reproduction. However, studies on the impact of non-nutritive sweeteners on reproduction are limited. In the present study, we evaluated the impact of the non-nutritive sweeteners (saccharin sodium, sucralose and acesulfame-K) on testosterone synthesis in testicular Leydig cells of Xiang pigs by comparing the relative abundance of mRNA transcripts and protein expression of T1R3, steroidogenic related factors, and intracellular cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), as well as testosterone levels using Western blotting, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA). To clarify the specific mechanism, a dual luciferase assay was used to uncover the relationship between the transcription factors and steroidogenic enzyme. The acute intratesticular injection of a typical non-nutritive sweeteners was conducted to verify this impact in mouse. The results showed that saccharin sodium not only enhanced T1R3 expression in Leydig cells of Xiang pigs, but also caused significant increases in testosterone, cAMP, PKA, phosphorylation of specificity protein 1 (p-SP1), total protein of specificity protein 1 (SP1), steroidogenic acute regulatory protein (StAR), and 3β-hydroxysteroid dehydrogenase type 1 (3β-HSD1) (P < 0.05). Similarly, treatment of Leydig cells with sucralose and acesulfame-K also increased testosterone level, protein expression of T1R3, 17-α-hydroxylase/17, 20-lyase (CYP17A1), and 3β-HSD1 (P < 0.05). Treatment with SQ22536 (an adenylate cyclas inhibitor) or H89 (a PKA inhibitor) significantly reduced saccharin sodium-induced protein levels of p-SP1, StAR, CYP17A1, and 3β-HSD1 (P < 0.05). In addition, a dual luciferase assay further demonstrated that SP1 significantly increased the promoter activity of CYP17A1 (P < 0.05). When mouse testes were injected with saccharin sodium, T1R3, p-SP1, CYP17A1, and 3β-HSD1 were upregulated, leading to a significant testicular increase in testosterone and cAMP levels (P < 0.05). These results suggest a mechanism by which the taste receptor T1R3 regulates testosterone production, and this mechanism may be linked to the cAMP-PKA pathway. Understanding the interrelationship between T1R3 and the cAMP-PKA-SP1 pathway contributes to clarify the regulatory mechanisms of male reproduction.

The potential of supramolecular synthon to develop coamorphous systems with tailored physical stability: Mechanistic insights integrating kinetics and thermodynamics

Coamorphous drug delivery systems have received increasing interest owing to their potential to improve the solubility, dissolution and bioavailability of poorly water-soluble drugs. However, the crystallization risk is one of major limitations in their application. It has been widely recognized that the coformer plays a vital role in physical stability of coamorphous formulation. Unfortunately, the screen of optimal coformer still adopts a trial-and-error method, which is time-consuming and expensive. Herein, a supramolecular synthon approach based on the interaction between functional groups, was exploited to design coamorphous systems (CMs) consisting of lurasidone hydrochloride (LH) and three coformers, saccharin (SAC), L-tryptophan (TRP), and L-cysteine hydrochloride (CYS). X-ray powder diffraction suggested the order of physical stability of the coamorphous systems was ranked as LH-CYS CM > LH-TRP CM > LH-SAC CM. The charge-assisted hydrogen bond between LH and coformer was confirmed by infrared spectroscopy and solid-state 13C NMR. Moreover, structural, electronic, and molecular interaction information, especially hydrogen bonding interactions, were quantified by theoretical calculations, including miscibility calculations, molecular dynamics simulations and quantum chemical calculations. It was revealed that LH-CYS CM exhibited the best miscibility, strongest binding energy and strongest H-bond with partially covalent character, demonstrating the significant role of supramolecular synthon in stabilizing coamorphous formulations. Interestingly, LH-TRP CM, not LH-CYS CM, exhibited the lowest molecular mobility among three coamorphous systems, which was inconsistent with their physical stability. But from thermodynamic perspective, the order of configurational entropy and physical stability of coamorphous systems was completely consistent. We shed light on the comprehensive effects of molecular mobility and configurational entropy on physical stability of coamorphous systems. Importantly, the relationship between supramolecular synthon and kinetic/thermodynamic mechanisms was also discussed, and the positive correlation between configurational entropy and intermolecular interactions was proposed in this paper. Our findings demonstrated the great potential of supramolecular synthon in designing coamorphous systems with tailored physical stability, and further provided a deeper insight into the mechanisms of physical stability of coamorphous systems.

Physicochemical and microbiological stability of 40mg/mL amiodarone hydrochloride oral suspension.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Amiodarone hydrochloride is an antiarrhythmic drug used to treat supraventricular tachycardia. However, there are currently no commercial pediatric forms available to treat young patients. Various oral formulations were previously reported in the literature, but the concentration was lower than the doses prescribed in clinical practice (a loading dose of 500mg/m2/day for 7-10 days followed by a maintenance dose of 250mg/m2/day). The objective of this study was to develop an oral liquid formulation of amiodarone hydrochloride at an optimal concentration for use in children and to evaluate its physicochemical and microbiological stability. No commercial suspension vehicle was used, allowing the choice of excipients. Compounding was performed using hydroxypropylmethylcellulose as thickener, potassium sorbate preservative, citric acid/sodium citrate buffer, sodium saccharin as a , and a strawberry flavoring agent. A concentration of 40mg/mL was selected based on a 5-year compilation of prescribed doses. Analyses performed were the following: visual and microscopic inspection, testing for antimicrobial preservation, osmolality and pH measurements, quantification of amiodarone hydrochloride by a stability-indicating liquid chromatography method, and a microbiological count. At least 95% of the initial amiodarone hydrochloride remained stable during the 60-day study period under refrigeration. All other tested parameters remained stable at 5 °C. A targeted log reduction of the microorganism inoculum by day 14 and no microbial growth by day 28 were demonstrated in the test for antimicrobial preservation. The stability of 40mg/mL amiodarone hydrochloride oral suspension was maintained under refrigeration for 60 days before opening bottles and for 1 month after opening bottles.

Composite electroforming of precision Ni-P-PTFE mold inserts with low internal stress and self-lubricating properties

An electrolyte solution incorporating sodium saccharin and an alkynyl compound was provided to electroform Ni-P-PTFE mold inserts with both low internal stress and good self-lubricating properties. The results showed that with 5 g·L−1 sodium saccharin and 1 mL·L−1 alkynyl compound, the internal stress reached a minimum of −114 MPa, an 82 % reduction from the −646 MPa observed without additives. The presence of sodium saccharin and alkynyl compound in the electrolyte solution reduced the hydrogen evolution reaction current from 15.2 to 12.9 mA at the operating cathode potential of −1 V and decreased the RTC(111) from 100 % to 90 %. The reduction of internal stress in the electrodeposited Ni-P-PTFE composites was attributed to the decreased hydrogenation strain, diminished Ni (111) texture intensity, and the partial incorporation of alkynyl compound reaction products into the cathode surface, which weakened the connections between crystallites. Finally, 5 g·L−1 sodium saccharin and 1 mL·L−1 alkynyl compound was applied to electroform Ni-P-PTFE mold insert with micro features. Only slightly pile-up defects at the corner of grooves were observed on the polymer chips demolded from Ni-P-PTFE mold insert, demonstrating its good self-lubricating property.

Detection of Non-caloric artificial sweetener saccharine in soft drinks and ice-creams through intermolecular H-bonding by using AuNPs-based fluorescent probe

Artificial sweeteners (ASs) are widely utilized as sugar substitutes in food products. However, excessive consumption of ASs poses potential health risks, necessitating their early detection. In this study, pamoic acid (PA)-functionalized gold nanoparticles (PA@AuNPs) were employed for the detection of ASs using fluorescence spectroscopy. The PA@AuNPs exhibited high selectivity and excellent sensitivity towards saccharine (SAC) (LoD (limit of detection) = 0.14 × 10−6 M and LoQ (limit of quantification) = 0.47 × 10−6 M), compared to other commercially available ASs. The fluorescence emission intensity of PA@AuNPs was significantly quenched (∼3-fold) upon the addition of SAC (0 → 50 × 10−6 M) through the formation of a ground state complex, PA@AuNPs•SAC. This complex formation was corroborated by FTIR analysis. The non-radiative process validated by time-resolved fluorescence analysis. Morphological analysis revealed that the spherical morphology of PA@AuNPs remained unchanged upon SAC interaction. PA@AuNPs effectively detected SAC in soft drinks and ice creams, with recovery ranges from 121 % to 105 %.

Study on the characteristics of sweetener reference material (aspartame, acesulfame potassium, sodium saccharin) in orange juice

To conduct the validity of test results, various measures such as proficiency testing, inter-laboratory comparisons, or the use of standard samples and quality control samples, etc. may be chosen. Participation in proficiency testing or inter-laboratory comparisons is sometimes not feasible for laboratories due to objective conditions such as funding sources, lack of suppliers, or absence of a suitable program for the sample matrix and criteria needed. Therefore, the use of standard samples or quality control samples is a good option. However, most standard samples are not readily available in Vietnam and often have to be imported, which is costly, and many specific types of samples are not yet produced. In this study, sweetener standards (aspartame, acesulfame potassium, sodium saccharin) in natural orange juice and flavored orange juice were created to investigate the characteristics of these two types of reference material. The samples achieved homogeneity and stability over 360 days for natural orange juice and 530 days for flavored orange juice from the production date. The certified values of aspartame, acesulfame potassium, sodium saccharin, and the measurement uncertainty in natural orange juice were 430 &amp;plusmn; 24.2 mg/L, 270 &amp;plusmn; 12.0 mg/L, 258 &amp;plusmn; 16.2 mg/L, respectively, and in flavored orange juice were 588 &amp;plusmn; 28.4 mg/L, 711 &amp;plusmn; 31.2 mg/L, 355 &amp;plusmn; 20.8 mg/L, respectively, which are consistent with the concentrations of sweeteners (aspartame, acesulfame potassium, sodium saccharin) in beverages according to Circular No. 24/2019/TT-BYT of the Ministry of Health.

Development and validation of RP-HPLC method with UV-DAD detection for simultaneous determination of acesulfame K, sodium saccharin and aspartame in beverages

AbstractArtificial sweeteners are low-calorie substances used as food additives with aim to impart a sweet taste to beverages without adding significant calories. Due to the regulatory compliance regarding the type and the amount of artificial sweetener, and due to the large consumption of beverages and the effects of artificial sweeteners on human health, their identification and quantification is of a great importance. In this research simultaneous determination of acesulfame K (ACE-K), sodium saccharin (Na-SAC) and aspartame (ASP) as the most commonly used sweeteners in beverages was performed with a reversed – phase high performance liquid chromatography (RP – HPLC) with diode array detection (DAD). The best separation of the analytes was achieved on a Poroshell 120 EC-C18 (3.0 × 50 mm, 2.7 µm) column and isocratic elution with a mobile phase consisted of acetonitrile and diluted phosphoric acid (pH = 3.8) with 7/93 volume ratio (V/V), and flow rate of 1 mL min−1. The chromatographic process was followed at 195, 220 and 230 nm, under constant column temperature (25 °C). Under these chromatographic conditions, the total time of analysis was less than 5 min. The developed method was validated for linearity, precision, accuracy, limit of detection (LOD) and limit of quantification (LOQ). The LOD under established chromatographic conditions was 0.03, 0.07 and 0.17 mg L−1 for Na-SAC, ACE-K and ASP, respectively. The amount of artificial sweeteners in analyzed samples ranged from 30.32 to 148.37 mg L−1 for ACE-K, from 16.10 to 93.05 for Na-SAC, and from 6.06 to 512.72 for ASP. The validated method was successfully applied for determination of analytes in different commercially available beverages.

Formulation and evaluation of bioadhesive buccal Films of Domperidone co-crystals by using Tamarind kernel powder as mucoadhesive polymer

As solubility plays key role in drug dissolution and bioavailability lots of techniques to enhance solubility are evolved. One of the techniques is co crystallization. The main aim of the work is to enhance the solubility of domperidone by co crystallization using coformers like Para amino benzoic acid and succinic acid. The cocrystals were evaluated for melting point and solubility enhancement. these cocrystals were used to prepare buccal films by solvent casting method. In the preparation of buccal films Tamarind kernel powder obtained from the seeds of Tamarind is used as mucoadhesive polymer and Hydroxy propyl methyl cellulose as film former, Polyethylene glycol 6000 as plasticizer, dehydrated banana powder as super disintegrant, sodium saccharin as sweetener and mixture of ethanol and water as solvents. The mucoadhesive strength of Tamarind kernel powder was determined using modified physical balance method. Four buccal films were prepared in which PDBF1 and PDBF2 are the two buccal films prepared using cocrystals of domperidone and Para amino benzoic acid and other two buccal films SDBF1 and SDBF2 with cocrystals of domperidone and Succinic acid. The buccal films were evaluated for different tests like folding endurance, swelling index and Surface pH. In vitro diffusion studies were conducted by Franz diffusion cell using egg membrane as semipermeable membrane and phosphate buffer of pH 7.4. The buccal films prepared with cocrystals of domperidone and succinic acid at weight ratio 1:2 has shown 86%drug release. The work has concluded that there is fold increase in aqueous solubility of Domperidone and the optimized formula is SDBF2 and Tamarind kernel powder can be used as mucoadhesive polymer in novel drug delivery systems. Keywords: co crystals, solvent evaporation, muco adhesive, buccal films, solvent evaporation

Effect of various flavors in starter diets on growth, behavior, and blood parameters of Holstein calves

This study investigated the effect of adding various flavors to calf starter concentrates on the performance, behavior, and blood parameters of Holstein dairy calves. The hypothesis was that an optimal flavor enhancer would increase starter intake, improve growth performance, and possibly enable earlier weaning without adverse physiological effects. In Experiment 1, a cafeteria test was conducted with 80 pre-weaned calves to evaluate four synthetic flavor enhancers (salty, sweet, sour, bitter) at levels of 3.3, 6.6, and 9.9 g/kg dry matter (DM)11DM; Dry matter, and a control without a flavor enhancer. Experiment 2 tested higher levels (9.9, 19.8, 29.7 g/kg DM) of the sweet flavor enhancer sodium saccharin in a single cafeteria test with 20 calves. Experiment 3 compared three sweet flavor enhancers (sodium saccharin, stevia, sucralose) at 9.9 g/kg DM in another cafeteria test with 20 calves. After selecting sodium saccharin at 9.9 g/kg DM as the optimal flavor enhancer, Experiment 4 was conducted with 40 calves divided into a treatment group receiving the flavored starter and a control group without flavor. In Experiment 1, sodium saccharin at 9.9 g/kg DM resulted in the highest dry matter intake (DMI)22DMI; Dry matter intake of 347 g/d, significantly higher than the control (173 g/d). Experiment 2 revealed a quadratic effect with DMI peaking at 9.9 g/kg DM sodium saccharin (201.0 g/d) and declining at higher levels. Experiment 3 confirmed that sodium saccharin outperformed other sweet flavor enhancers, increasing DMI to 350 g/d compared to 251 g/d for the control. In Experiment 4, calves fed the starter concentrate with 9.9 g/kg DM sodium saccharin showed significantly higher DMI (1749 g/d), average daily gain (ADG33ADG; Average daily gain; 730 g/d), and feed conversion ratio (FCR;44FCR; feed conversion ratio 2.05) compared to the control group (DMI 1470 g/d, ADG 650 g/d, FCR 2.36). Furthermore, calves in the flavored treatment were weaned earlier (59 days) than the control group (64 days). Behavioral observations showed that the sweet flavor treatment increased the time spent on solid feed intake, rumination, and standing behavior. Calves fed the flavored starter had lower levels of cholesterol, triglycerides, and blood urea nitrogen, suggesting improved nutrient utilization. Overall, the results demonstrated the potential benefits of incorporating sodium saccharin as a sweet flavor enhancer in calf starter concentrates, leading to improved feed intake, growth performance, feed efficiency, final body weight (FBW)55FBW; final body weight, and behavioral patterns during the critical pre-weaning and post-weaning periods.

The effects of moderate prenatal alcohol exposure on performance in hippocampal-sensitive spatial memory and anxiety tasks by adult male and female rat offspring

Moderate prenatal alcohol exposure (mPAE) results in structural alterations to the hippocampus. Previous studies have reported impairments in hippocampal-sensitive tasks, but have not compared performance between male and female animals. In the present study, performance in hippocampal-sensitive spatial memory and anxiety behavior tests were compared across adult male and female saccharin (SACC) control mPAE Long-Evans rat offspring. Two tests of spatial memory were conducted that were aimed at assessing memory for recently acquired spatial information: A delayed spatial alternation task using an M-shaped maze and a delayed match-to-place task in the Morris water task. In both tasks, rats in SACC and mPAE groups showed similar learning and retention of a spatial location even after a 2-h interval between encoding and retention. A separate group of adult male and female SACC and mPAE rat offspring were tested for anxiety-like behaviors in the elevated plus-maze paradigm. In this test, both male and female mPAE rats exhibited a significantly greater amount of time and a greater number of head dips in the open arms, while locomotion and open arm entries did not differ between groups. The results suggest that mPAE produces a reduction in anxiety-like behaviors in both male and female rats in the elevated plus-maze.

Loading co-amorphous on Metal-Organic Frameworks for gelation elimination and anti-cancer drug delivery enhancement

Troublesome gelation occurring during the dissolution of special co-amorphous (COAM) systems poses a limitation on their further applications. Metal-Organic Frameworks (MOFs) are promising porous materials for nano-scale drug delivery due to their high loading capacity and ability to control drug release. Examples of MOFs as drug carriers with the confinement effect for COAM drugs have never been reported. In this study, to eliminate the gelation of the COAM of an anti-cancer drug gefitinib (GTB) and co-former saccharin (SAC) for enhancing their anti-cancer drug delivery, a Zr-based MOF, nanoUiO-67, was selected as drug carrier. The loading process of GTB-SAC COAM on nanoUiO-67 was revealed via a real-time spinning disk confocal fluorescence microscope. The maintenance of molecular interactions between GTB and SAC in GTB-SAC COAM after loaded on nanoUiO-67 was proven experimentally and computationally, along with the host (nanoUiO-67)-guest (drug) interactions. The combined advantages of porous materials nanoMOFs and GTB-SAC COAM were fully demonstrated in terms of excellent physical stability, desirable drug release, good bio-compatibility and higher cytotoxicity towards HeLa cells. It is expected that this novel strategy could have potential application in gelation elimination and developing multi-component drug-loaded MOFs.

Fast Determination of Eleven Food Additives in River Water Using C18 Functionalized Magnetic Organic Polymer Nanocomposite Followed by High-Performance Liquid Chromatography.

A novel magnetic nanomaterial with Fe3O4 as the core, PS-DVB as the shell layer, and the surface modified with C18 (C18-PS-DVB-Fe3O4) had been synthesized by seeded emulsion polymerization. C18-PS-DVB-Fe3O4 retains the advantages of the chemical stability, large porosity, and uniform morphology of organic polymers and has the magnetic properties of Fe3O4. A simple, flexible, and efficient magnetic dispersive solid phase extraction (Mag-dSPE) method for the extraction of preservatives, sweeteners, and colorants in river water was established. C18-PS-DVB-Fe3O4 was used as an adsorbent for Mag-dSPE and was coupled with high-performance liquid chromatography (HPLC) to detect 11 food additives: acesulfame, amaranth, benzoic acid, tartrazine, saccharin sodium, sorbic acid, dehydroacetic acid, sunset yellow, allura red, brilliant blue, and erythrosine. Under the optimum extraction conditions, combined with ChromCoreTMAQC18 (5 μm, 4.6 × 250 mm), 20 mmol/L ammonium acetate aqueous solution and methanol were used as mobile phases, and the detection wavelengths were 240 nm and 410 nm. The limits of detection (LODs) of 11 food additives were 0.6-3.1 μg/L with satisfactory recoveries ranging from 86.53% to 106.32%. And the material could be reused for five cycles without much sacrifice of extraction efficiency. The proposed method has been used to determine food additives in river water samples, and results demonstrate the applicability of the proposed C18-PS-DVB-Fe3O4 Mag-dSPE coupled with the HPLC method to environment monitoring analysis.

A study on the Process of Containing Tablets from the Rind of Small-Grain Coffee in Yunnan, China

An innovative Yunnan small-grain coffee pericarp tablet was developed by using high-speed grinding technology to convert Yunnan small-grain coffee pericarp into dry powder, and then combining other main and auxiliary ingredients. The quality of the product was evaluated by sensory scores, and a one-way test was applied to select the appropriate ratio of ingredients and formulation, and an orthogonal test was used to optimize the formulation of the tablets. The results showed that the optimal formulation for the production of Yunnan small-grain coffee pericarp tablets included 45.69% of Yunnan small-grain coffee pericarp powder, 19.58% of dextrin, 15.66% of mannitol, 15.66% of microcrystalline cellulose, 2.61% of magnesium stearate, 0.52% of calcium sulphate and 0.26% of sodium saccharin. Under this formula, the tablets had a unique taste, consistent color, smooth appearance, delicate texture and sensory score of 95. Its physical and chemical indexes and microbiological indexes meet the corresponding food safety standards, and it is a new product, which is of great significance to promote the food development of Yunnan small-grain coffee peel resources.

Testing of Sodium Saccharin Levels in Hard Candy with High Performance Liquid Chromatography (HPLC) Method

Testing of Sodium Saccharin Levels in Hard Candy with High Performance Liquid Chromatography (HPLC) Method

Potential exacerbation of polycystic ovary syndrome by saccharin sodium Via taste receptors in a letrozole rat model

The most common cause of anovulatory infertility is polycystic ovarian syndrome (PCOS), which is closely associated with obesity and metabolic syndrome. Artificial sweetener, notably saccharin sodium (SS), has been utilized in management of obesity in PCOS. However, accumulating evidence points towards SS deleterious effects on ovarian physiology, potentially through activation of ovarian sweet and bitter taste receptors, culminating in a phenotype reminiscent of PCOS. This research embarked on exploration of SS influence on ovarian functions within a PCOS paradigm. Rats were categorized into six groups: Control, Letrozole-model, two SS groups at 2 dose levels, and two groups receiving 2 doses of SS with Letrozole. The study underscored SS capability to potentiate PCOS-related anomalies. Elevated cystic profile with outer thin granulosa cells, were discernible. This owed to increased apoptotic markers as cleaved CASP-3, mirrored by high BAX and low BCL-2, with enhanced p38-MAPK/ERK1/2 pathway. This manifestation was accompanied by activation of taste receptors and disruption of steroidogenic factors; StAR, CYP11A1, and 17β-HSD. Thus, SS showed an escalation in testosterone, progesterone, estrogen, and LH/FSH ratio, insinuating a perturbation in endocrine regulation. It is found that there is an impact of taste receptor downstream signaling on ovarian steroidogenesis and apoptosis instigating pathophysiological milieu of PCOS.

Dietary saccharin sodium supplementation improves the production performance of dairy goats without residue in milk in summer

The purpose of this study was to investigate the effects of dietary saccharin sodium supplementation on production performance, serum biochemical indicators, and rumen fermentation of dairy goats in summer. Twelve Guanzhong dairy goats with similar body weight, days in milk, and milk yield were randomly divided into two dietary treatments: (1) CON: basal diet; (2) SS: basal diet + 150 mg/kg saccharin sodium on the basis of dry matter. The experiment lasted 35 d, including 7 d for adaptation and 28 d for dietary treatments, sampling and data collection. Each dairy goat was housed individually in a clean separate pen with ad libitum access to diet and water. The goats fed SS diet had increased dry matter intake (DMI; P = 0.037), 4% fat corrected milk yield (P = 0.049), energy corrected milk yield (P = 0.037), milk protein yield (P = 0.031), and total solids yield (P = 0.036). Serum activity of aspartate aminotransferase (P = 0.047) and concentrations of 70-kDa heat shock protein (P = 0.090), malondialdehyde (P = 0.092), and total protein (P = 0.057) were lower in goats fed SS diet than those fed CON diet. Supplementation of saccharin sodium tended to increase activity of glutathione peroxidase in serum (P = 0.079). The concentrations of rumen total volatile fatty acid (P = 0.042) and butyrate (P = 0.038) were increased by saccharin sodium supplementation. Dietary supplementation of saccharin sodium increased the relative abundance of Lachnobacterium (P = 0.022), Pseudoramibacter (P = 0.022), Shuttleworthia (P = 0.025), and Syntrophococcus (P = 0.037), but reduced the relative abundance of Prevotella_1 (P = 0.037) and Lachnospiraceae_UCG_008 (P = 0.037) in rumen. Saccharin sodium was observed in feces and urine of goats fed diet supplemented with saccharin sodium, but saccharin sodium was undetectable in the milk of goats receiving SS diet. In conclusion, administration of saccharin sodium was effective in increasing fat and energy corrected milk yield by increasing DMI and improving rumen fermentation and antioxidant capacity of dairy goats in summer. In addition, saccharin sodium residue was undetectable in the milk.

Atrial Natriuretic Peptide Alleviates Motion Sickness Potentially through Regulating Endolymph Volume in the Inner Ear Increased by Arginine Vasopressin

Introduction: Dimenhydrinate and scopolamine are frequently used drugs, but they cause drowsiness and performance decrement. Therefore, it is crucial to find peripheral targets and develop new drugs without central side effects. This study aimed to investigate the anti-motion sickness action and inner ear-related mechanisms of atrial natriuretic peptide (ANP). Methods: Endolymph volume in the inner ear was measured with magnetic resonance imaging and expression of AQP2 and p-AQP2 was detected with Western blot analysis and immunofluorescence method. Results: Both rotational stimulus and intraperitoneal arginine vasopressin (AVP) injection induced conditioned taste aversion (CTA) to 0.15% sodium saccharin solution and an increase in the endolymph volume of the inner ear. However, intraperitoneal injection of ANP effectively alleviated the CTA behaviour and reduced the increase in the endolymph volume after rotational stimulus. Intratympanic injection of ANP also inhibited rotational stimulus-induced CTA behaviour, but anantin peptide, an inhibitor of ANP receptor A (NPR-A), blocked this inhibitory effect of ANP. Both rotational stimulus and intraperitoneal AVP injection increased the expression of AQP2 and p-AQP2 in the inner ear of rats, but these increases were blunted by ANP injection. In in vitro experiments, ANP addition decreased AVP-induced increases in the expression and phosphorylation of AQP2 in cultured endolymphatic sac epithelial cells. Conclusion: Therefore, the present study suggests that ANP could alleviate motion sickness through regulating endolymph volume of the inner ear increased by AVP, and this action of ANP is potentially mediated by activating NPR-A and antagonising the increasing effect of AVP on AQP2 expression and phosphorylation.

Synthesis of Nano-electrolytic Manganese Dioxide for Alkaline Batteries Mediated by Organic Additives

This article discusses the impact of adding organic additives like glycine (GLY), sucrose (SUC), and saccharine (SACCH) on the electrical characteristics and microstructure of electrolytic manganese dioxide (EMD), which is made from an acidic aqueous sulphate solution. The structure and chemistry of EMD were ascertained by means of Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and X-ray diffraction (XRD). To assess the material's potential for use in alkaline batteries, its charge-discharge properties were ascertained. It was found that the majority of MnO2 in all the EMD samples was in the γ-phase, which is electrochemically active and useful for energy storage applications. When glycine, sucrose, and saccharine were added to the solution as organic additives, the electrochemical deposition of manganese dioxide (MnO2) resulted in an increase in current efficiency and a decrease in energy consumption. The SEM images demonstrated that when EMD was deposited with an additive, small grain sizes and discrete particles free of agglomeration were formed, but large grain sizes were obtained in the absence of additives. Charge-discharge characteristics suggested that the additions improve the ability of MnO2 structure to store energy. This suggested that the additions may have an impact on the morphology and size of the particles, and consequently, the electrochemical activities of the material that was electrodeposited. In the case of the additives examined in this paper, the outcome was the creation of a material with possible use in battery technology.