Transcriptome and Metabolome Analyses Reveal Sugar and Acid Accumulation during Apricot Fruit Development.

The apricot (Prunus armeniaca L.) is a fruit that belongs to the Rosaceae family; it has a unique flavor and is of important economic and nutritional value. The composition and content of soluble sugars and organic acids in fruit are key factors in determining the flavor quality. However, the molecular mechanism of sugar and acid accumulation in apricots remains unclear. We measured sucrose, fructose, glucose, sorbitol, starch, malate, citric acid, titratable acid, and pH, and investigated the transcriptome profiles of three apricots (the high-sugar cultivar 'Shushanggan', common-sugar cultivar 'Sungold', and low-sugar cultivar 'F43') at three distinct developmental phases. The findings indicated that 'Shushanggan' accumulates a greater amount of sucrose, glucose, fructose, and sorbitol, and less citric acid and titratable acid, resulting in a better flavor; 'Sungold' mainly accumulates more sucrose and less citric acid and starch for the second flavor; and 'F43' mainly accumulates more titratable acid, citric acid, and starch for a lesser degree of sweetness. We investigated the DEGs associated with the starch and sucrose metabolism pathways, citrate cycle pathway, glycolysis pathway, and a handful of sugar transporter proteins, which were considered to be important regulators of sugar and acid accumulation. Additionally, an analysis of the co-expression network of weighted genes unveiled a robust correlation between the brown module and sucrose, glucose, and fructose, with VIP being identified as a hub gene that interacted with four sugar transporter proteins (SLC35B3, SLC32A, SLC2A8, and SLC2A13), as well as three structural genes for sugar and acid metabolism (MUR3, E3.2.1.67, and CSLD). Furthermore, we found some lncRNAs and miRNAs that regulate these genes. Our findings provide clues to the functional genes related to sugar metabolism, and lay the foundation for the selection and cultivation of high-sugar apricots in the future.

l-Glutamate maintains the quality of apple fruit by mediating carotenoid, sorbitol and sucrose metabolisms.

BACKGROUND: l-Glutamate is involved in many important chemical reactions in horticultural products and improves postharvest disease resistance. Quality decline of apple fruit caused by senescence and fungus invasion often leads to tremendous losses during logistics. This study was performed to evaluate the variations of quality attributes, carotenoid, sorbitol and sucrose metabolisms in apples (cv. Qiujin) after l-glutamate dipping treatment. RESUITS: l-Glutamate immersion maintained high values of L*, a* and b*, flesh firmness, titratable acidity, as well as the total soluble solids, soluble sugar, reducing sugar and ascorbic acid contents in apples. l-Glutamate also decreased mass loss, respiratory rate and ethylene release, enhanced sucrose synthase-cleavage, acid invertase and neutral invertase activities, whereas reduced sorbitol dehydrogenase, sucrose phosphate synthase, sucrose synthase synthesis and sorbitol oxidase activities in apples. Moreover, l-glutamate inhibited lutein, ß-carotene and lycopene accumulation, and down-regulated phytoene synthase, lycopene ß-cyclase, ζ-carotene desaturase, phytoene desaturase, carotenoid isomerase, ζ-carotene isomerase and carotenoids cleavage dioxygenase gene expressions, but up-regulated 9-cis-epoxycarotenoid dioxygenase gene expression in apples. CONCLUSION: Postharvest l-glutamate dipping treatment can keep apple quality by modulating key enzyme activity and gene expression in sorbitol, sucrose and carotenoid metabolisms. © 2023 Society of Chemical Industry.

Untargeted metabolomic analysis of aqueous humor in diabetic macular edema.

Background: The mechanism of diabetic macular edema (DME) was explored by comparing the intraocular metabolite profiles of the aqueous humor of patients with DME to those of diabetic patients without DME using untargeted metabolomic analysis. Methods: Aqueous samples from 18 type 2 diabetic patients with DME and 18 type 2 diabetic patients without DME used as controls were analyzed using liquid chromatography-mass spectrometry (LCMS). The two groups of patients were age and gender matched and had no systemic diseases other than diabetes mellitus (DM). The metabolites were analyzed using orthogonal partial least square discriminant analysis. Results: The metabolite profiles in DME patients differed from those in DM controls. This indicates the following metabolic derangements in DME: (a) a higher amount of oxidized fatty acids but a lower amount of endogenous antioxidants (oxidative stress); (b) higher levels of ß-glucose and homocysteine but a lower level of sorbitol (hyperglycemia); (c) a higher amount of prostaglandin metabolites (inflammation); (d) higher amounts of acylcarnitines, odd-numbered fatty acids, and 7,8-diaminononanoate (respiration deterioration); (e) a higher amount of neurotransmitter metabolites and homovanillic acid (neuronal damage); (f) a lower amount of extracellular matrix (ECM) constituents (ECM deterioration); and (g) a higher amount of di-amino peptides (microvascular damage). Conclusions: The change in the metabolic profiles in the aqueous humor of DME patients compared to DM controls without DME indicates that DME patients may have less capability to resist various stresses or damaging pathological conditions, such as oxidative stress, mitochondrial insufficiency, inflammation, and ECM deterioration.

Measuring perceived sweetness by monitoring sorbitol concentration in apples using a non-destructive polarization-based readout.

The determination and qualification of sugars in fruits are important for quality control and assurance of horticultural produce. The sugars determine the sweetness levels in fruits. The requirement for a universal technique that is also robust to predict the sweetness of the fruit in a non-destructive fashion is immense. The handheld refractometer, hydrometer, electronic tongues, and high-pressure liquid chromatography (HPLC) in combination with other detectors have long been used to determine the sweetness of horticultural produce. Though these techniques are very accurate and useful, they require extensive sample preparation and are generally time-consuming and expensive. Optical techniques like visible to near-infrared spectroscopy (vis/NIRS) are simple in use and can rapidly predict the sweetness of the fruit in a non-destructive fashion. The instrumentation used in these techniques is simple and cost-effective for routine analysis of the fruits. However, their systems need calibration for each sample, and the measurement variation depends on the type of horticultural produce on which measurements are done. An optical-based technique is proposed that uses reflected phase information of the incident light and correlates the same to the presence of sorbitol concentration in apples. The refractive index of sorbitol varies as the fruit ripens due to its change in concentration, and the reflected phase information accordingly changes. Monitoring the reflected phase information allows a prediction mechanism of the sweetness content in the fruit.

Elevated myocardial fructose and sorbitol levels are associated with diastolic dysfunction in diabetic patients, and cardiomyocyte lipid inclusions in vitro.

Diabetes is associated with cardiac metabolic disturbances and increased heart failure risk. Plasma fructose levels are elevated in diabetic patients. A direct role for fructose involvement in diabetic heart pathology has not been investigated. The goals of this study were to clinically evaluate links between myocardial fructose and sorbitol (a polyol pathway fructose precursor) levels with evidence of cardiac dysfunction, and to experimentally assess the cardiomyocyte mechanisms involved in mediating the metabolic effects of elevated fructose. Fructose and sorbitol levels were increased in right atrial appendage tissues of type 2 diabetic patients (2.8- and 1.5-fold increase respectively). Elevated cardiac fructose levels were confirmed in type 2 diabetic rats. Diastolic dysfunction (increased E/e', echocardiography) was significantly correlated with cardiac sorbitol levels. Elevated myocardial mRNA expression of the fructose-specific transporter, Glut5 (43% increase), and the key fructose-metabolizing enzyme, Fructokinase-A (50% increase) was observed in type 2 diabetic rats (Zucker diabetic fatty rat). In neonatal rat ventricular myocytes, fructose increased glycolytic capacity and cytosolic lipid inclusions (28% increase in lipid droplets/cell). This study provides the first evidence that elevated myocardial fructose and sorbitol are associated with diastolic dysfunction in diabetic patients. Experimental evidence suggests that fructose promotes the formation of cardiomyocyte cytosolic lipid inclusions, and may contribute to lipotoxicity in the diabetic heart.

NMR spectral fingerprint patterns as diagnostics for the unambiguous configurational analysis of the classic organo-gelator 1,3:2,4-dibenzylidene-d-sorbitol (DBS) and its derivatives.

On the basis of experimental data and density functional theory (DFT) chemical shift and scalar coupling predictions, simple spectral nuclear magnetic resonance (NMR) fingerprint patterns have been established for the determination of the configuration in 1,3:2,4-dibenzylidene-d-sorbitol (DBS), a classic low molecular weight gelator, and its derivatives. The results rigorously prove the orientation of the phenyl rings in DBS that had been previously assumed in the literature on the basis of thermodynamic arguments.

Quantification of γ-sorbitol crystal growth rate and solubility in the presence of mannitol and maltitol.

In many confectionery systems, an understanding of crystallization behavior is essential for proper control of product texture. While this knowledge is well developed in sucrose-based systems, there is little information on controlling crystallization in sugar-free systems, such as those formulated with sorbitol. By leveraging such advances in time domain-nuclear magnetic resonance (TD-NMR) methodology, the impact of mannitol and maltitol on modulating sorbitol crystal growth in sugar-free systems. Binary and ternary systems of sorbitol mixed with mannitol, maltitol, or a mixture thereof were evaluated at total impurity addition levels of 10% and 20%. Polyol mixtures were dissolved in water, evaporated to 10% moisture, and mixed with γ sorbitol seed crystals to create a sugar-free fondant. Fondants were crystallized at 25 °C, and crystal content was measured using TD-NMR over time. Crystal content increased rapidly at the start but quickly tapered off to a final asymptote indicating phase equilibrium. In all systems, the addition of impurities decreased the extent and rate of sorbitol crystallization, with mannitol having the greatest impact on rate. When both mannitol and maltitol were present as impurities, the rate of crystallization was reduced to a greater extent. At the highest level of mannitol, the final crystal content increased, presumably because mannitol also crystallized. PRACTICAL APPLICATION: Controlling sorbitol crystallization in the presence of impurities is a key to controlling quality in certain confections.

How Do Trichoderma Genus Fungi Win a Nutritional Competition Battle against Soft Fruit Pathogens? A Report on Niche Overlap Nutritional Potentiates.

We present a case study report into nutritional competition between Trichoderma spp. isolated from wild raspberries and fungal phytopathogenic isolates (Colletotrichum sp., Botrytis sp., Verticillium sp. and Phytophthora sp.), which infect soft fruit ecological plantations. The competition was evaluated on the basis of nutritional potentiates. Namely, these were consumption and growth, calculated on the basis of substrate utilization located on Biolog® Filamentous Fungi (FF) plates. The niche size, total niche overlap and Trichoderma spp. competitiveness indices along with the occurrence of a stressful metabolic situation towards substrates highlighted the unfolding step-by-step approach. Therefore, the Trichoderma spp. and pathogen niche characteristics were provided. As a result, the substrates in the presence of which Trichoderma spp. nutritionally outcompete pathogens were denoted. These were adonitol, D-arabitol, i-erythritol, glycerol, D-mannitol and D-sorbitol. These substrates may serve as additives in biopreparations of Trichoderma spp. dedicated to plantations contaminated by phytopathogens of the genera Colletotrichum sp., Botrytis sp., Verticillium sp. and Phytophthora sp.

Bioengineered Polymer/Composites as Advanced Biological Detection of Sorbitol: An Application in Healthcare Sector.

Bioengineered polymers and nanomaterials have emerged as promising and advanced materials for the fabrication and development of novel biosensors. Nanotechnology-enabled biosensor methods have high sensitivity, selectivity and more rapid detection of an analyte. Biosensor based methods are more rapid and simple with higher sensitivity and selectivity and can be developed for point-of-care diagnostic testing. Development of a simple, sensitive and rapid method for sorbitol detection is of considerable significance to efficient monitoring of diabetes-associated disorders like cataract, neuropathy, and nephropathy at initial stages. This issue encourages us to write a review that highlights recent advancements in the field of sorbitol detection as no such reports have been published till the date. The first section of this review will be dedicated to the conventional approaches or methods that had been playing a role in detection. The second part focused on the emerging field i.e. biosensors with optical, electrochemical, piezoelectric, etc. approaches for sorbitol detection and the importance of its detection in healthcare application. It is expected that this review will be very helpful for readers to know the different conventional and recent detection techniques for sorbitol at a glance.

Analysis of sorbitol content variation in wild and cultivated apples.

BACKGROUND: Sorbitol is the major sugar alcohol in apple and its accumulation in fruit is associated with fruit sweetness. However, little is known about variation in sorbitol content in fruits of apple germplasm. In this study, we investigated sorbitol content in mature fruits of 243 apple cultivars and 20 wild relatives using high-performance liquid chromatography (HPLC). RESULTS: Sorbitol accumulation showed a significant variation in apple germplasm. Overall, cultivated fruits had significantly lower content of sorbitol than wild fruits. Fruit sorbitol concentration was significantly correlated with fruit size and acidity that are extensively domesticated traits. Hence, the variation in sorbitol accumulation between cultivated and wild fruits may be the indirect result of fruit size and acidity selection during domestication. Moreover, sorbitol content was maintained at low levels throughout fruit development, with a dramatic decrease at the middle stage. The SDH1 gene was highly expressed throughout fruit development, and its expression showed a significant correlation with fruit sorbitol concentration, suggesting its potential role in apple fruit sorbitol accumulation. CONCLUSIONS: The finding that there is a great variation in fruit sorbitol content among apple germplasm will be helpful for genetic improvement of fruit sorbitol content in apple breeding programs. © 2019 Society of Chemical Industry.

Prevalence of ethanol and other potentially harmful excipients in pediatric oral medicines: survey of community pharmacies in a Nigerian City.

OBJECTIVE: Excipients are needed in the formulation of oral liquid medicines intended for children; they have however been reported to trigger safety issues. This study evaluated the concentrations and prevalence of ethanol and other potentially harmful excipients in pediatric formulations marketed in South Eastern Nigeria in line with international labeling guidelines and allowable daily limits (ADL). The study sampled oral pediatric formulations offered for sale in registered pharmacies. Those with accessible information leaflets were assessed for the presence and quantity of previously flagged excipients with potential to harm the pediatric population. RESULT: Of the 380 oral pediatric medicines, 140 provided access to list/quantity of ingredients. 47.9% (67) of the formulations contain at least one of the flagged excipients while the remaining only listed the active ingredients. Ethanol had the highest occurrence (62.7%) and was more in cough/cold medicines. A homeopathic cough and cold remedy had concentration of 90% v/v. Ethanol and sucrose in some formulations exhibited concentrations with a potential of crossing their approved daily intake (ADI) (1-90% v/v and 1.7 g-3.7 g/5 ml respectively). Ethanol use in studied pediatric formulations was quite high, with ethanol-containing formulations being prescribed for children 0-6 years and older. Only 26 (38.8%) completely satisfied the labelling requirements for ethanol containing formulations.

Nutrient, fibre, sorbitol and chlorogenic acid content of prunes (Prunus domestica): an updated analysis and comparison of different countries of origin and database values.

Current prune composition data are outdated and require a comprehensive and comparative re-analysis. This novel study aimed to: (i) analyse and compare prune composition from major countries of origin; and (ii) provide a comprehensive compositional analysis of prunes of USA origin and compare this with UK and USA database data. Prune samples were analysed for major nutrients and bioactive compounds and compared between countries of origin. Total fibre was higher in prunes from the USA (12.0 g/100 g) and Chile (11.5 g/100 g) compared with France (8.4 g/100 g) and Argentina (8.9 g/100 g), while prunes from all countries contained high levels of sorbitol (11.2-15.5 g/100 g). Differences in energy and starch values compared with national databases reflected different approaches to sampling and analysis. In conclusion, prunes contain high levels of fibre and other bioactive compounds. Variations between country of origin and database values highlight the importance of transparency in documenting sampling and analysis methods.

Visualization of soluble carbohydrate distribution in apple fruit flesh utilizing MALDI-TOF MS imaging.

To confirm availability of Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry imaging (MSI) for visualizing distribution of soluble carbohydrates in apple (Malus domestica) fruits a horizontal fruit flesh specimen was cut from a matured 'Fuji' fruit, mounted on a glass slide, lyophilized and then ion intensities of individual soluble carbohydrates were probed around the specimen using a MALDI-TOF MSI apparatus automatically. Contents of soluble carbohydrates in adjacent tissue of the same fruit were also determined using HPLC to compare the distribution of individual carbohydrate based on the ion intensities from MALDI-TOF MSI with those from HPLC. Positive correlation (P < 0.001, R2 > 0.95) was confirmed between the concentration of each standard carbohydrate and the relative ion intensity of MALDI-TOF mass spectrometry (MS), and thus it seems possible to use the ion intensity of MALDI-TOF MS for determining the relative concentration of carbohydrates in a sample. Singly charged ions attached with a potassium ion only were detected from the apple fruit specimen when DHB was used as a matrix for MALDI-TOF MSI. Graded increase of sucrose content from center to cortex side of the fruit flesh was confirmed by both MALDI-TOF MSI and HPLC. When pseudo color images on the distribution of individual carbohydrates based on the results from MALDI-TOF MSI were compared with the content of carbohydrates in the adjacent 16 tissue blocks quantified using HPLC, strong (P < 0.001, R2 = 0.6222) and weak (P < 0.10, R2 = 0.2123) correlation was confirmed between the brightness and the content of sucrose and sorbitol, respectively. These facts indicate that distribution of sucrose and sorbitol in apple fruit tissue can be visualized using MALDI-TOF MSI. Thus, MALDI-TOF MSI will be useful for examining carbohydrate metabolism during the maturing of apple fruit.

Effect of sorbitol content on microstructure and thermal properties of chitosan films.

In this work, the influence of sorbitol content on the microstructure and thermal properties of chitosan films was investigated by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), Thermogravimetric analysis (TGA) and Differential scanning calorimetry (DSC). It showed that the addition of sorbitol weakened the hydrogen bonding between chitosan molecules as well as the electrostatic interactions existed in chitosan films. Structural analysis revealed that a small amount of sorbitol (~10 wt%) could facilitate the crystallization of chitosan, whereas it was seriously hindered at high content of sorbitol (~50 wt%). The thermal behavior of composite films indicated that the sorbitol addition did not reduce the thermal stability of polymer films. When the sorbitol content rose to above 30 wt%, phase separation may occur and two glass transitions presented in composite films. The lower temperature transition was associated with the glass-rubber transition of sorbitol-rich phase, and the higher one was related to chitosan-rich phase. These results implied that the microstructure as well as properties of the plasticized chitosan films can be controlled by adding sorbitol, which is important for their usage as packaging materials.

Protective effect of sugars on storage stability of microwave freeze-dried and freeze-dried Lactobacillus paracasei F19.

AIMS: Microwave freeze drying (MWFD) in comparison with conventional freeze drying allows for intensification of the preservation process of lactic acid bacteria without imposing additional processing stress. Viability as a function of storage time of microwave freeze-dried Lactobacillus paracasei ssp. paracasei F19 was investigated in comparison to conventionally lyophilized bacteria of the same strain. Furthermore, the impact of the protectants, sorbitol, trehalose and maltodextrin, on shelf life was analysed. METHODS AND RESULTS: The highest inactivation rates of 0·035 and 0·045 day-1 , respectively, were found for cultures without protectants. Thus, all additives were found to exhibit a protective effect during storage with inactivation rates between 0·015 and 0·040 day-1 . Although trehalose and maltodextrin samples were in the glassy state during storage, in contrast to samples containing sorbitol as protectant, the best protective effect could be found for sorbitol with the lowest inactivation rate of 0·015 day-1 . CONCLUSIONS: Due to its low molecular weight, it might protect cells owing to better adsorption to the cytoplasma membrane. Sorbitol additionally shows antioxidative properties. Storage behaviour of microwave freeze-dried cultures follows the typical behaviour of a product dried by conventional lyophilization. No significant influence of the drying technique on storage behaviour was detected. SIGNIFICANCE AND IMPACT OF THE STUDY: General findings concerning storage behaviour in freeze drying are likely to be applicable in MWFD with only slight adjustments.

Sorbitol production and optimization of photosynthetic supply in the cyanobacterium Synechocystis PCC 6803.

Biochemicals production is a major theme in the application of photosynthesis to address global warming and organic-resource problems. Among biochemicals, sugar alcohols have attracted research attention because they are directly derived from two photosynthetic products, sugars and reductants. Here, we produced sorbitol photosynthetically by using cyanobacteria and modified the supply of its substrates through genetic engineering. Expression of an NADPH-dependent enzyme that generates sorbitol-6-phosphate, S6PDH, was highly toxic to cyanobacteria likely due to the sorbitol production, whereas expression of an NADH-dependent enzyme, SrlD2, yielded no sorbitol. The toxicity was partly overcome by introducing a theophylline-inducible riboswitch for S6PDH expression and optimizing induction, but sorbitol production was still low and severely inhibited growth. Co-expression of fructose-1,6-bisphosphatase drastically alleviated the growth inhibition, but did not increase short-term sorbitol production. The NADPH/NADP+ ratio decreased during sorbitol production. Overexpression of a membrane-bound transhydrogenase for NADPH generation from NADH elevated the short-term sorbitol production, but only partly alleviated the growth inhibition. Notably, a strain overexpressing all three enzymes exhibited sustainable sorbitol production at 312 mg/L, which was nearly 27-fold higher than the yield of the initial S6PDH-overexpressing strain. We discuss these results in relation to the optimization of photosynthetic supply for sorbitol production in cyanobacteria.

Postharvest dehydration induces variable changes in the primary metabolism of grape berries.

Postharvest dehydration causes changes in texture, color, taste and nutritional value of food due to the high temperatures and long drying times required. In grape berries, a gradual dehydration process is normally utilized for raisin production and for making special wines. Here we applied a raisin industry-mimicking dehydration process for eleven days at 50°C to intact berry clusters from cv. Sémillon plants, and a set of molecular, cellular and biochemical analyses were performed to study the impact of postharvest dehydration in the primary metabolism. Transcriptional analyses by real time qPCR showed that several aquaporins (VvTIP1;2 and VvSIP1) and sugar transporters (VvHT1, VvSWEET11, VvSWEET15, VvTMT1, VvSUC12) genes were strongly upregulated. Moreover, the study of key enzymes of osmolytes metabolism, including mannitol dehydrogenase (VvMTD) and sorbitol dehydrogenase (VvSDH), at gene expression and protein activity level, together with the transcriptional analysis of the polyol transporter gene VvPLT1, showed an enhanced polyol biosynthesis capacity, which was supported by the detection of sorbitol in dehydrated grapes only. The metabolism of organic acids was also modulated, by the induction of transcriptional and biochemical activity modifications in malate dehydrogenases and malic enzymes that led to organic acid degradation, as demonstrated by HPLC analysis. Taken together, this study showed that primary metabolism of harvested berries was severely influenced in response to dehydration treatments towards lower organic acid and higher sorbitol concentrations, while sugar transporter and aquaporin genes were significantly upregulated.

Involvement of hyperglycemia in the development of platelet procoagulant response: the role of aldose reductase and platelet swelling.

: Rise in mean platelet volume (MPV) has been demonstrated to be associated with increased platelet reactivity. In diabetes patients, augmented MPV was proposed to contribute to increased risk of thrombotic complications. Therefore, the aim of this study was to investigate whether under hyperglycemic conditions, aldose reductase (AR)-mediated sorbitol formation and associated rise in cell volume, which subsequently results in platelet hyperactivation. Platelets were obtained from 30 healthy volunteers and 13 patients with diabetes. We evaluated changes in platelet size, their reactivity (measured as aggregation and secretion), and sorbitol content evoked by glucose. Measurement of procoagulant activity and thromboelastography were performed to assess how hyperglycemia affects coagulation. We have found that incubation of platelets with glucose (>10 mmol/l) leads to increased MPV, potentiation of collagen-evoked platelet aggregation, secretion, and procoagulant response (measured as platelet-dependent thrombin generation and phosphatidylserine expression). Glucose-treated platelets had higher sorbitol content and demonstrated enhanced tubulin polymerization. All the above-mentioned phenomena were reduced following the blocking of AR or by vincristine (microtubule destabilizing agent). Thromboelastography measurements demonstrated that hyperglycemia is associated with reduction of clotting time (R) and increase in the alpha angle (reflects platelet activation). Addition of sorbinil (AR inhibitor) or vincristine normalized R variable and alpha angle. The hyperglycemic conditions may accelerate platelet-related thrombin generation through the activation of polyol pathway, enhanced tubulin polymerization and associated with it rise in platelet volume.

Application of 13C NMR cross-polarization inversion recovery experiments for the analysis of solid dosage forms.

Solid-state nuclear magnetic resonance (ssNMR) is a powerful and unique method for analyzing solid forms of the active pharmaceutical ingredients (APIs) directly in their original formulations. Unfortunately, despite their wide range of application, the ssNMR experiments often suffer from low sensitivity and peaks overlapping between API and excipients. To overcome these limitations, the crosspolarization inversion recovery method was successfully used. The differences in the spin-lattice relaxation time constants for hydrogen atoms T1(H) between API and excipients were employed in order to separate and discriminate their peaks in ssNMR spectra as well as to increase the intensity of API signals in low-dose formulations. The versatility of this method was demonstrated by different examples, including the excipients mixture and commercial solid dosage forms (e.g. granules and tablets).

Exposure to sorbitol during lactation causes metabolic alterations and genotoxic effects in rat offspring.

Sorbitol is a polyol used by the food industry as a sweetener. Women are consuming diet and light products containing sorbitol during pregnancy and in the postnatal period to prevent themselves from excessive weight gain and maintain a slim body. Although there is no evidence for the genotoxicity of sorbitol in the perinatal period, this study focused on evaluating the effects of the maternal intake of sorbitol on the biochemical and toxicological parameters of lactating Wistar rat offspring after 14days of mother-to-offspring exposure. A dose-dependent reduction of offspring length was observed. An increase in sorbitol levels determined in the milk was also observed. However, we detected an inverse relationship between the exposition dose in milk fructose and triacylglycerols concentrations. There was an increase in the plasmatic levels of ALT, AST and LDLc and a decrease in proteins, cholesterol and glucose levels in the offspring. Sorbitol exposure caused hepatocyte genotoxicity, including micronuclei induction. Maternal sorbitol intake induced myelotoxicity and myelosuppression in their offspring. The Comet assay of the blood cells detected a dose-dependent genotoxic response within the sorbitol-exposed offspring. According to our results, sorbitol is able to induce important metabolic alterations and genotoxic responses in the exposed offspring.