A Galactooligosaccharide Product Decreases the Rotavirus Infection in Suckling Rats.

The leading cause of gastroenteritis among young children worldwide is the Group A rotaviruses (RV), which produce a wide range of symptoms, from a limited diarrhea to severe dehydration and even death. After an RV infection, immunity is not complete and less severe re-infections usually occur. These infections could be ameliorated by nutritional interventions with bioactive compounds, such as prebiotics. The aim of this research was to study the impact of a particular galactooligosaccharide (B-GOS) on the RV symptomatology and immune response during two consecutive infections. Lewis neonatal rats were inoculated with SA11 (first RV infection) on day 6 of life and with EDIM (second RV infection) on day 17 of life. B-GOS group was administered by oral gavage with a daily dose of B-GOS between days three to nine of life. Clinical and immunological variables were assessed during both infective processes. In the first infection, after the prebiotic intervention with B-GOS, a lower incidence, duration, and overall severity of the diarrhea (p < 0.05) was observed. In addition, it improved another severity indicator, the fecal weight output, during the diarrhea period (p < 0.05). The second RV infection failed in provoking diarrhea in the groups studied. The immune response during first infection with SA11 was not affected by B-GOS administration and had no impact on second infection, but the prebiotic intervention significantly increased IFN-γ and TNF-α intestinal production after the second infection (p < 0.05). In summary, B-GOS supplementation is able to reduce the incidence and severity of the RV-associated diarrhea and to influence the immune response against RV infections.

Novel techniques for drug loading quantification in mesoporous SBA-15 using chemometric-assisted UV and FT-IR data.

Albendazole is a crystalline drug that is poorly soluble in water, thus the dissolution rate in gastrointestinal fluids is limited. Mesoporous materials loaded with poorly water-soluble drugs become an interesting strategy to increase their solubility/dissolution rate as the drug state changes from crystalline to amorphous. In order to determine the drug loading content into mesoporous materials analytical methods such as elemental analysis, UV and HPLC are commonly used. However, elemental analysis and HPLC are destructive and relatively expensive. In addition, UV is time consuming. Moreover, UV and HPLC require the drug release from the mesoporous material before the quantification step. Therefore, the aim of this work was to develop quantifications techniques based on chemometric models combined with UV and FT-IR spectra without needing the drug release from the mesoporous material. Partial least squares regression (PLSR) was used as chemometric regression method. Albendazole content in the SBA-15 powders was first quantified by elemental analysis as reference measurement for multivariate calibration. The excellent drug loading predictions prove that robust calibration models can be obtained from both techniques (i.e., 0.999 and 0.998 adjusted correlation coefficient for UV and FT-IR, respectively). Additionally, the adjusted correlation coefficients determined from the validation models for UV and FT-IR are 0.963 and 0.930, respectively. It is important to highlight that the prediction adjustment of the FT-IR model (root-mean-square error of prediction=2.196%) presented lower error than the UV model (root-mean-square error of prediction=3.553%). Therefore, this development contributes to improve the overall time and cost of drug loading determination into mesoporous materials.

Synthesis and characterization of mesoporous SBA-15 and SBA-16 as carriers to improve albendazole dissolution rate.

Albendazole (ABZ, anti-parasitic active pharmaceutical ingredient) is a crystalline low water-soluble drug, thus the dissolution rate in gastrointestinal fluids is limited. Consequently, the improvement of the water solubility and dissolution rate of ABZ implies a great challenge for a more efficient treatment of hydatidosis. In this context, SBA-15 and SBA-16 ordered mesoporous silica materials were synthetized and loaded with ABZ. X-ray diffraction, FT-IR spectroscopy, nitrogen physisorption manometry, particle size distribution and scanning electronic microscopy were used to characterize unloaded and loaded materials (ABZ/SBA-15 and ABZ/SBA-16). The loaded ABZ amount in the carriers was estimated by elemental analysis. For the loaded materials, the drug solubility and release profile were evaluated. In addition, mathematical models were compared to explain the dissolution kinetics of ABZ from mesoporous solids. ABZ was successfully loaded into the mesopores. The amorphous state of the adsorbed ABZ was confirmed by differential scanning calorimetry that resulted in a notable increment in the dissolution rate compared to crystalline ABZ. Drug release behaviors were well simulated by the Weibull model for ABZ/SBA-15 and by the Gompertz function for pure ABZ and ABZ/SBA-16. The SBA-15 carrier exhibited the highest drug loading and dissolution rate becoming a promising material to improve ABZ bioavailability.

Prevention of Rotavirus Diarrhea in Suckling Rats by a Specific Fermented Milk Concentrate with Prebiotic Mixture.

Several microbial modulatory concepts, such as certain probiotics and prebiotics, confer protection against gastrointestinal infections, among which is acute diarrhea caused by the rotavirus (RV). Other microbiota modulators, such as postbiotics, produced during fermentation, might also have the potential to counteract RV infection. In light of this, a fermented milk, made by using Bifidobacterium breve C50 (BbC50) and Streptococcus thermophilus 065 (St065) with a prebiotic mixture-short chain galactooligosaccharides/long chain fructooligosaccharides (scGOS/lcFOS 9:1)-with potential to impact the intestinal microbiota composition was tested. An RV infected rat model was used to evaluate the amelioration of the infectious process and the improvement of the immune response induced by the fermented milk with prebiotic mixture. The dietary intervention caused a reduction in the clinical symptoms of diarrhea, such as severity and incidence. Furthermore, a modulation of the immune response was observed, which might enhance the reduction of the associated diarrhea. In addition, the fermented milk with prebiotic mixture was able to bind the virus and reduce its clearance. In conclusion, the postbiotic components in the fermented milk in combination with the prebiotics used here showed protective properties against RV infection.

Rotavirus Double Infection Model to Study Preventive Dietary Interventions.

Rotaviruses are the main cause of acute diarrhea among young children worldwide with an increased frequency of reinfection. Several life style factors, such as dietary components, may influence such processes by affecting the outcome of the first rotavirus infection and therefore having a beneficial impact on the anti-rotavirus immune responses during any subsequent reinfections. The aim of this research was to develop a double-infection model in rat that mimics real-life clinical scenarios and would be useful in testing whether nutritional compounds can modulate the rotavirus-associated disease and immune response. Three experimental designs and a preventive dietary-like intervention were conducted in order to achieve a differential response in the double-infected animals compared to the single-infected ones and to study the potential action of a modulatory agent in early life. Diarrhea was only observed after the first infection, with a reduction of fecal pH and fever. After the second infection an increase in body temperature was also found. The immune response against the second infection was regulated by the preventive effect of the dietary-like intervention during the first infection in terms of specific antibodies and DTH. A rotavirus-double-infection rat model has been developed and is suitable for use in future preventive dietary intervention studies.

Preventive Effect of a Synbiotic Combination of Galacto- and Fructooligosaccharides Mixture With Bifidobacterium breve M-16V in a Model of Multiple Rotavirus Infections.

Rotavirus (RV) causes morbidity and mortality among infants worldwide, and there is evidence that probiotics and prebiotics can have a positive influence against infective processes such as that due to RV. The aim of this study was to evidence a preventive role of one prebiotic mixture (of short-chain galactooligosaccharide/long-chain fructooligosaccharide), the probiotic Bifidobacterium breve M-16V and the combination of the prebiotic and the probiotic, as a synbiotic, in a suckling rat double-RV infection model. Hyperimmune bovine colostrum was used as protection control. The first infection was induced with RV SA11 and the second one with EDIM. Clinical variables and immune response were evaluated after both infections. Dietary interventions ameliorated clinical symptoms after the first infection. The prebiotic and the synbiotic significantly reduced viral shedding after the first infection, but all the interventions showed higher viral load than in the RV group after the second infection. All interventions modulated ex vivo antibody and cytokine production, gut wash cytokine levels and small intestine gene expression after both infections. In conclusion, a daily supplement of the products tested in this preclinical model is highly effective in preventing RV-induced diarrhea but allowing the boost of the early immune response for a future immune response against reinfection, suggesting that these components may be potential agents for modulating RV infection in infants.

Green synthesis of nanocrystalline faujasite zeolite.

In this work, the synthesis of 28 and 38 nm Na-Y zeolite nanocrystals is reported. The process was performed via green synthesis without any organic structure directing agents (SDAs), at low temperature and applying ultrasound-assisted aging. The zeolite nanoparticles obtained were characterized by X ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and N2 adsorption - desorption isotherm at 77 K. A simple, fast, efficient and environmentally friendly procedure to synthetize nanocrystalline FAU zeolite is described in the present study. The sonochemical pretreatment was found to directly affect the Na-Y zeolite properties. The final product obtained via ultrasound pretreatment shows high phase purity and crystallinity degree with crystal size smaller than 38 nm and elevated surface area (SBET ∼ 950 m2 g-1). The hierarchical micro- and mesoporous FAU zeolites exhibit a pore volume of ∼0.4 cm3 g-1.

Preclinical Immunomodulation by the Probiotic Bifidobacterium breve M-16V in Early Life.

This study aimed to investigate the effect of supplementation with the probiotic Bifidobacterium breve M-16V on the maturation of the intestinal and circulating immune system during suckling. In order to achieve this purpose, neonatal Lewis rats were supplemented with the probiotic strain from the 6th to the 18th day of life. The animals were weighed during the study, and faecal samples were obtained and evaluated daily. On day 19, rats were euthanized and intestinal wash samples, mesenteric lymph node (MLN) cells, splenocytes and intraepithelial lymphocytes (IEL) were obtained. The probiotic supplementation in early life did not modify the growth curve and did not enhance the systemic immune maturation. However, it increased the proportion of cells bearing TLR4 in the MLN and IEL, and enhanced the percentage of the integrin αEß7+ and CD62L+ cells in the MLN and that of the integrin αEß7+ cells in the IEL, suggesting an enhancement of the homing process of naïve T lymphocytes to the MLN, and the retention of activated lymphocytes in the intraepithelial compartment. Interestingly, B. breve M-16V enhanced the intestinal IgA synthesis. In conclusion, supplementation with the probiotic strain B. breve M-16V during suckling improves the development of mucosal immunity in early life.

Use of hydroponics culture to assess nutrient supply by treated wastewater.

The use of treated wastewater for irrigation is increasing, especially in those areas where water resources are limited. Treated wastewaters contain nutrients that are useful for plant growth and help to reduce fertilizers needs. Nutrient content of these waters depends on the treatment system. Nutrient supply by a treated wastewater from a conventional treatment plant (CWW) and a lagooned wastewater from the campus of the University of Balearic Islands (LWW) was tested in an experiment in hydroponics conditions. Half-strength Hoagland nutrient solution (HNS) was used as a control. Barley (Hordeum vulgare L.) seedlings were grown in 4 L containers filled with the three types of water. Four weeks after planting, barley was harvested and root and shoot biomass was measured. N, P, K, Ca, Mg, Na and Fe contents were determined in both tissues and heavy metal concentrations were analysed in shoots. N, P and K concentrations were lower in LWW than in CWW, while HNS had the highest nutrient concentration. Dry weight barley production was reduced in CWW and LWW treatments to 49% and 17%, respectively, comparing to HNS. However, to a lesser extent, reduction was found in shoot and root N content. Treated wastewater increased Na content in shoots and roots of barley and Ca and Cr content in shoots. However, heavy metals content was lower than toxic levels in all the cases. Although treated wastewater is an interesting water resource, additional fertilization is needed to maintain a high productivity in barley seedlings.

Chemical properties and biological activity in soils of Mallorca following twenty years of treated wastewater irrigation.

On the Mediterranean island of Mallorca, the use of secondary-treated municipal wastewater in irrigation was introduced with the construction of the first wastewater treatment plants in the 1970s. In this study, the chemical properties and biological activity of 21 arable soils, irrigated for more than 20 years with secondary-treated wastewater, were tested in order to assess their quality. Soil quality was evaluated by measuring cation exchange capacity, pH, calcium carbonate equivalent, soil organic matter, total nitrogen, available phosphorus, water-soluble organic carbon, soil microbial biomass, soil basal respiration, and the activities of the enzymes dehydrogenase, ß-glucosidase and alkaline phosphatase. No negative effects of the irrigation treatment were observed on the measured soil parameters. Indeed, soil water-soluble organic carbon, soil microbial biomass and ß-glucosidase and alkaline phosphatase activities increased under treated wastewater irrigation. Biological activity of soils irrigated with treated wastewater was affected mainly by soil organic matter content. Although the typical crop management of alfalfa, and other forage crops associated with treated wastewater irrigation, may have contributed to the increase of these parameters, the results suggest that irrigation with treated wastewater is a strategy with many benefits to agricultural land management.

Disposition of instilled versus nebulized tobramycin and imipenem in ventilated intensive care unit (ICU) patients.

BACKGROUND: Delivery of antibiotics to the lower respiratory tract could potentially achieve antimicrobial bronchial drug concentrations without toxicity. AIM: To assess bronchial and serum concentrations of imipenem or tobramycin obtained by nebulization or instillation in critically ill mechanically ventilated patients. METHODS: Prospective randomized open trial. Eighteen patients ventilated for more than 48 h were included. Two doses of imipenem/cilastatin (1000/500 mg) separated by 8 h, or two doses of tobramycin 200 mg separated by 12 h were randomly nebulized or instilled into the tracheal tube. Five bronchoaspirates (two bronchoscopic, three blind) and five blood samples were collected on a timed schedule after the second dose. Respiratory and serum samples were analysed by HPLC, and a subset of blood samples was also evaluated by enzyme-immunoassay. RESULTS: When instilled, imipenem/cilastatin obtained higher concentrations in respiratory secretions than when nebulized (P=0.022, 1 h after the last dose; P=0.029, 2 h after the last dose). Tobramycin showed equally high concentrations when nebulized or instilled. Instillation of tobramycin may result in significant accumulation in patients with renal failure. CONCLUSIONS: High bronchial concentrations of imipenem could only be achieved by instillation, whereas tobramycin seems suitable for both modes of administration. Instillation of these antibiotics is a safe procedure that achieves high drug concentrations in respiratory secretions.