Ionogels Derived from Fluorinated Ionic Liquids to Enhance Aqueous Drug Solubility for Local Drug Administration.

Gelatin is a popular biopolymer for biomedical applications due to its harmless impact with a negligible inflammatory response in the host organism. Gelatin interacts with soluble molecules in aqueous media as ionic counterparts such as ionic liquids (ILs) to be used as cosolvents to generate the so-called Ionogels. The perfluorinated IL (FIL), 1-ethyl-3-methylpyridinium perfluorobutanesulfonate, has been selected as co-hydrosolvent for fish gelatin due to its low cytotoxicity and hydrophobicity aprotic polar structure to improve the drug aqueous solubility. A series of FIL/water emulsions with different FIL content and their corresponding shark gelatin/FIL Ionogel has been designed to enhance the drug solubility whilst retaining the mechanical structure and their nanostructure was probed by simultaneous SAXS/WAXS, FTIR and Raman spectroscopy, DSC and rheological experiments. Likewise, the FIL assisted the solubility of the antitumoural Doxorubicin whilst retaining the performing mechanical properties of the drug delivery system network for the drug storage as well as the local administration by a syringe. In addition, the different controlled release mechanisms of two different antitumoral such as Doxorubicin and Mithramycin from two different Ionogels formulations were compared to previous gelatin hydrogels which proved the key structure correlation required to attain specific therapeutic dosages.

A time-course comparative clinical and immune response evaluation study between the human pathogenic Orientia tsutsugamushi strains: Karp and Gilliam in a rhesus macaque (Macaca mulatta) model.

BACKGROUND: Scrub typhus is a vector-borne febrile illness caused by Orientia tsutsugamushi transmitted by the bite of Trombiculid mites. O. tsutsugamushi has a high genetic diversity and is increasingly recognized to have a wider global distribution than previously assumed. METHODOLOGY/PRINCIPLE FINDINGS: We evaluated the clinical outcomes and host immune responses of the two most relevant human pathogenic strains of O. tsutsugamushi; Karp (n = 4) and Gilliam (n = 4) in a time-course study over 80 days post infection (dpi) in a standardized scrub typhus non-human primate rhesus macaque model. We observed distinct features in clinical progression and immune response between the two strains; Gilliam-infected macaques developed more pronounced systemic infection characterized by an earlier onset of bacteremia, lymph node enlargement, eschar lesions and higher inflammatory markers during the acute phase of infection, when compared to the Karp strain. C-reactive protein (CRP) plasma levels, interferon gamma (IFN-γ, interleukin-1 receptor antagonist (IL-1ra), IL-15 serum concentrations, CRP/IL10- and IFN-γ/IL-10 ratios correlated positively with bacterial load in blood, implying activation of the innate immune response and preferential development of a T helper-type 1 immune response. The O. tsutsugamushi-specific immune memory responses in cells isolated from skin and lymph nodes at 80 dpi were more markedly elevated in the Gilliam-infected macaques than in the Karp-infected group. The comparative cytokine response dynamics of both strains revealed significant up-regulation of IFN-γ, tumor necrosis factor (TNF), IL-15, IL-6, IL-18, regulatory IL-1ra, IL-10, IL-8 and granulocyte-colony-stimulating factor (G-CSF). These data suggest that the clinical outcomes and host immune responses to scrub typhus could be associated with counter balancing effects of pro- and anti-inflammatory cytokine-mediated responses. Currently, no data on characterized time-course comparisons of O. tsutsugamushi strains regarding measures of disease severity and immune response is available. Our study provides evidence for the strain-specificity of host responses in scrub typhus, which supports our understanding of processes at the initial inoculation site (eschar), systemic disease progression, protective and/or pathogenic host immune mechanisms and cellular immune memory function. CONCLUSIONS/SIGNIFICANCE: This study characterised an improved intradermal rhesus macaque challenge model for scrub typhus, whereby the Gilliam strain infection associated with higher disease severity in the rhesus macaque model than the previous Karp strain infection. Difficulties associated with inoculum quantitation for obligate-intracellular bacteria were overcome by using functional inoculum titrations in outbred mice. The Gilliam-based rhesus macaque model provides improved endpoint measurements and contributes towards the identification of correlates of protection for future vaccine development.

Characterization of Tuna Gelatin-Based Hydrogels as a Matrix for Drug Delivery.

The skin of yellowfin tuna is one of the fishery industry solid residues with the greatest potential to add extra value to its circular economy that remains yet unexploited. Particularly, the high collagen content of fish skin allows generating gelatin by hydrolysis, which is ideal for forming hydrogels due to its biocompatibility and gelling capability. Hydrogels have been used as drug carriers for local administration due to their mechanical properties and drug loading capacity. Herein, novel tuna gelatin hydrogels were designed as drug vehicles with two structurally different antitumoral model compounds such as Doxorubicin and Crocin to be administrated locally in tissues with complex human anatomies after surgical resection. The characterization by gel permeation chromatography (GPC) of purified gelatin confirmed their heterogeneity composition, exhibiting three major bands that correspond to the ß and α chains along with high molecular weight species. In addition, the Fourier Transform Infrared (FT-IR) spectra of gelatin probed the secondary structure of the gelatin showing the simultaneous existence of α helix, ß sheet, and random coil structures. Morphological studies at different length scales were performed by a multi-technique approach using SAXS/WAXS, AFM and cryo-SEM that revealed the porous network formed by the interaction of gelatin planar aggregates. In addition, the sol-gel transition, as well as the gelation point and the hydrogel strength, were studied using dynamic rheology and differential scanning calorimetry. Likewise, the loading and release profiles followed by UV-visible spectroscopy indicated that the novel gelatin hydrogels improve the drug release of Doxorubicin and Crocin in a sustained fashion, indicating the structure-function importance in the material composition.

NePCM Based on Silver Dispersions in Poly(Ethylene Glycol) as a Stable Solution for Thermal Storage.

The main objective of this study is to design and characterize silver suspensions based on poly(ethylene glycol) PEG400, Ag/PEG400, as energy storage media for low-temperature applications. A polyvinylpyrrolidone (PVP) treatment was applied to ~22 nm silver nanoparticles to ensure good stability in poly(ethylene glycol). An array of different experimental techniques was utilized to analyze the molecular mass and purity of base poly(ethylene glycol), morphology of dry PVP-capped Ag nanoparticles, hydrodynamic average size of dispersed Ag particles, as well as thermal stability of PEG400 and Ag/PEG400 dispersions. Samples exhibited good temporal stabilities with average hydrodynamic diameter around 50 nm according to dynamic light scattering analyses. Melting and solidification transitions were investigated in terms of temperature and enthalpy from differential scanning calorimeter (DSC) thermograms. The thermophysical characterization was completed with thermal conductivity (k), dynamic viscosity (η), isobaric heat capacity (Cp), density (ρ), and surface tension (σ) measurements of designed materials using a Hot Disk thermal conductivimeter, a rotational rheometer, a DSC calorimeter working with a quasi-isothermal modulated method, a U-tube densimeter and a drop shape analyzer, respectively. For a nanoparticle loading of only 1.1% in mass, sub-cooling reduced by 7.1% and thermal conductive improved by 3.9%, with almost no penalization in dynamic viscosity (less than 5.4% of increase). Maximum modifications in Cp, ρ, and σ were 0.9%, 2.2%, and 2.2%, respectively. Experimental results were compared with the values provided by using different theoretical or semi-empirical equations. In particular, good descriptions of dynamic viscosity as functions of temperature and nanoparticle volume concentration were obtained by using the Vogel-Fulcher-Tammann equation and a first-order polynomial η( ϕ v , n p ) correlation, with absolute average deviations of 2.2% and 0.55%, respectively.

Cruciferous Vegetables as Antioxidative, Chemopreventive and Antineoplasic Functional Foods: Preclinical and Clinical Evidences of Sulforaphane Against Prostate Cancers.

BACKGROUND: Sulforaphane (SF, 1-isothiocyanato-4-(methyl-sulfinyl)-butane) is found in broccoli, cabbage and cauliflower. METHODS: we performed a critical review on the antioxidative, chemopreventive and antitumor effects of SF from cruciferous vegetables against prostate cancers and molecular pathways. For a complete and reliable review, primary and secondary resources were used, including original and review articles, books and government documents published until March 2018. Articles that are in duplicity and disconnected are not considered for review. SF is derived from glucoraphanin (4-methyl-sulfinyl-butyl-glucosinate), being one of the most commonly found isothiocyanates in vegetables from Brassica spp., especially in broccoli samples. In vitro studies indicate that SF induces apoptosis in a dependent or non-dependent method of androgens by transcription of tumor suppressor genes, oxidation response and higher expression of phase II enzymes in prostate cancer cells. Sulforaphane also decreases transcription of the nuclear factor kB and antiapoptotic proteins, expression of cyclin D2 and survivin and DNA synthesis, increases Nrf2 gene activity, interferes with genome compacting by inhibition of histone deacetylases and disrupts Hsp90 complexes, which cause cell cycle arrest, mitosis interruption, activation of caspases and mitochondria depolarization. CONCLUSION: SF and cruciferous vegetables play antioxidative and chemopreventive role, delaying or blocking in vivo carcinogenesis, causing biochemical and epigenetic changes, preventing, delaying, or reversing preneoplastic or advanced prostate lesions, and frequently activating tumor cell death by intrinsic methods of apoptosis. These outcomes encourage the consumption of Brassica specimens, which could be easily achieved by the incorporation of food and vegetables rich in cruciferous isothiocyanates in the diet.

Rheological and volumetric properties of TiO2-ethylene glycol nanofluids.

Homogeneous stable suspensions obtained by dispersing dry TiO2 nanoparticles in pure ethylene glycol were prepared and studied. Two types of nanocrystalline structure were analyzed, namely anatase and rutile phases, which have been characterized by scanning electron microscopy. The rheological behavior was determined for both nanofluids at nanoparticle mass concentrations up to 25%, including flow curves and frequency-dependent storage and loss moduli, using a cone-plate rotational rheometer. The effect of temperature over these flow curve tests at the highest concentration was also analyzed from 283.15 to 323.15 K. Furthermore, the influence of temperature, pressure, nanocrystalline structure, and concentration on the volumetric properties, including densities and isobaric thermal expansivities, were also analyzed.

Rheological non-Newtonian behaviour of ethylene glycol-based Fe2O3 nanofluids.

The rheological behaviour of ethylene glycol-based nanofluids containing hexagonal scalenohedral-shaped α-Fe2O3 (hematite) nanoparticles at 303.15 K and particle weight concentrations up to 25% has been carried out using a cone-plate Physica MCR rheometer. The tests performed show that the studied nanofluids present non-Newtonian shear-thinning behaviour. In addition, the viscosity at a given shear rate is time dependent, i.e. the fluid is thixotropic. Finally, using strain sweep and frequency sweep tests, the storage modulus G', loss modulus G″ and damping factor were determined as a function of the frequency showing viscoelastic behaviour for all samples.

Thermal conductivity and viscosity measurements of ethylene glycol-based Al2O3 nanofluids.

The dispersion and stability of nanofluids obtained by dispersing Al2O3 nanoparticles in ethylene glycol have been analyzed at several concentrations up to 25% in mass fraction. The thermal conductivity and viscosity were experimentally determined at temperatures ranging from 283.15 K to 323.15 K using an apparatus based on the hot-wire method and a rotational viscometer, respectively. It has been found that both thermal conductivity and viscosity increase with the concentration of nanoparticles, whereas when the temperature increases the viscosity diminishes and the thermal conductivity rises. Measured enhancements on thermal conductivity (up to 19%) compare well with literature values when available. New viscosity experimental data yield values more than twice larger than the base fluid. The influence of particle size on viscosity has been also studied, finding large differences that must be taken into account for any practical application. These experimental results were compared with some theoretical models, as those of Maxwell-Hamilton and Crosser for thermal conductivity and Krieger and Dougherty for viscosity.

Prevalence of diabetes and patterns of health services utilization: a comparative analysis between a private and a health reform group of insured, 1997-1998

OBJECTIVE: To compare the prevalence and health services utilization patterns of diabetes mellitus in a group of insured under the Puerto Rico Health Reform Act and the private sector of the same insurance company. METHODS: The medical claims of the public sector insured whose main diagnosis was diabetes mellitus (ICD9-250.0-9) were selected for analysis. Prevalence and medical utilization rates were estimated. General characteristics and services utilization were compared by age and sex using the chi-square distribution. RESULTS: A total of 38,139 diabetic cases were identified during the study period. Overall prevalence was 6.23 (95 CI: 6.17-6.29); 5.22 among males (95 CI: 5.14-5.30) and 7.09 among females (95 CI: 7.00-7.18). The proportion of cases was larger in persons aged 65 years or more (60.3) and females (61.6). Overall, 84.7 of insured diabetics had medical office visits, while 7.8 had emergency room services and 1.3 had hospital admissions. Female cases had more physician office visits (62) and insulin prescriptions (65) compared to males (p < 0.05). The most reported complication was cerebrovascular accident (4.4). The prevalence of diabetes was higher in the public sector (6.23) when compared to the private sector (4.73) (p < 0.01). The mean number of oral hypoglycemic (32.77 +/- 0.40) and insulin (40.99 +/- 0.54) prescriptions were higher in the public sector (p < 0.01). Emergency room utilization rate was larger among males in the younger age groups of the private sector. However, hospital admissions were larger in both sexes of the younger age group of the public sector when compared with the private sector. CONCLUSIONS: A higher prevalence of diabetes and mean service utilization was observed in the public sector. An in-depth analysis of the health care of patients with diabetes in the public sector is needed.

Prevalence of diabetes mellitus among insured of a health insurance company in Puerto Rico: 1997-1998

OBJECTIVE: The purpose of this study was to determine the prevalence of diabetes mellitus in persons covered by a health insurance company. METHODS: The medical claims of persons insured with Triple S Health Insurance Co. of Puerto Rico, whose main diagnosis was diabetes (ICD9-250.0-9), were selected for analysis. Prevalence and medical utilization rates were estimated. General characteristics and services utilization were compared by age and sex using the chi-square distribution. RESULTS: Overall prevalence was 4.73. Prevalence in the male population (5.07) was higher than that of females (4.43) in all age groups, but the difference was not statistically significant (p > 0.05). The proportion of diabetic cases was larger in the > 60 age group. 64 of the cases had 1 or more visits to a physician office, 2 were hospitalized, and almost 3 had emergency room visits. 29 of the cases had insulin prescriptions while 59 had oral prescriptions. The younger age group (< or = 44 years) had a larger utilization rate of emergency room and hospital admissions. Health service utilization varied by age and sex, however, the only significant difference was observed in glucose test services utilization (p < 0.05). CONCLUSIONS: The prevalence of diabetes in this group was lower than the prevalence reported in the Behavioral Risk Factor Surveillance System. This may be partially explained by the fact that the study group did not represent the composition of the Puerto Rican population. Prevalence studies using other groups will be helpful to determine the prevalence of diabetes in Puerto Rico.

The public health burden of diabetes: a comprehensive review

The review of several diabetes epidemiological studies confirms that diabetes is one of the most prevalent non-communicable diseases globally, and it is the fourth or fifth leading cause of death in most developed countries. Diabetes prevalence ranges from nearly 0 in New Guinea to 50 in the Indians of Arizona. No modifiable risk factors have been clearly established in persons with type 1 diabetes, but major environmental determinants have been suggested. Impaired glucose tolerance, gestational diabetes, insulin resistance, obesity and lack of physical activity have been consistently identified as risk factors for type 2 diabetes. The prevalence of diabetes increases with age, but a sex-specific tendency has not been consistent. In addition, the prevalence of diabetes is higher in African-Americans and Hispanics when compared to other ethnic groups. Diabetes affects almost all organs of the body and is the leading cause of blindness and amputations of legs, imposing both clinical and economic costs to patients and society.

Factores de riesgo relacionados al cancer de estomágo en el Hospital Escuela Oscar Danilo Rosales: julio 1997-diciembre 1999

Se logró analizar un caso de Cáncer Gástrico cada uno a 2 meses según lo esperado de acuerdo al comportamiento de los mismos en los últimos años, rehabilitandose un total de 26. La distribución por grupo etáreo fue de un (20) porciento como para los grupos menores de 40 años, cuatro con 15 porciento entre los 41 a 50 años y como 19.2 porciento entre 51 a 50 añosrespectivamente, registrándose una incidencia de 42.3 porciento 11 casos en mayores de 60 años. Estas edades oscilan entre 25 a 83 años con un promedio de 54.9 años, se observó una mayor frecuencia en la población urbana que en la rural en relación 2:1, siendo más frecuente en el primer grupo ocupacional 21 casos que en otro tipo de trabajar. De los 26 casos estudiados, 9 (34.6 porciento) presentaban antecedenes de ingesta rica de cloruro de sodio (sal común), 11 pacientes 42.1 porciento infirierón tener una dieta rica en almidón, 23 88.46 porciento son grandes tomadores de leche de por lo menos medio litro diario. Sin embargo, la dieta de estos pacientes ha sido pobre en vitamina C y verduras frescas. En menos frecuencia la ingesta de carne ahumada y arroz caliente se relacionó a cáncer de estómago 22.92 porciento y 23 por ciento respectivamente. De todos los pacientes estudiados 11 en total para un 42 porciento han sido tratados en algún momento de su vida por úlcera gástrica crónica y sólo un 3.8 porciento de ellos tenían antecedentes familiares de cáncer gástrico en línea directa. A los pacientes ingresados se les realizó endoscopía, clasificándose la lesión según Banman, encontrándose 11 (42 porciento) con el grado IV, 9 (34.6 porciento) grado III, cinco de ellos (19.2 por ciento) en grado II y sólo un caso en grado. A demás se le tomarón muestra para cultivo a 16 de estos pacientes, cuyo estudio microbiológico para Helicobacter P, fue en 7 casos para un 43.74 porciento