Povećanje oslobađanja gliklazida iz smjesa dobivenih geometrijskim miješanjem

The poorly water soluble antidiabetic drug gliclazide was selected to study the effect of excipients on dissolution rate enhancement. Ordered mixtures of micronized gliclazide with lactose, mannitol, sorbitol, maltitol and sodium chloride were prepared by manual shaking of glass vials containing the drug and excipient(s). Different water soluble excipients, addition of surfactant and superdisintegrant, drug concentration and carrier particle size influenced the dissolution rate of the drug. Dissolution rate studies of the prepared ordered mixtures revealed an increase in drug dissolution with all water soluble excipients. The order of dissolution rate improvement for gliclazide was mannitol > lactose > maltitol > sorbitol > sodium chloride. Composite granules of the particle size range 355-710 µm were superior in increasing the drug dissolution rate from ordered mixtures. Reducing the carrier particle size decreased the dissolution rate of the drug, as well as the increase in drug concentration. Kinetic modeling of drug release data fitted best the Hixson-Crowell model, which indicates that all the ordered mixture formulations followed the cube root law fairly well.Teško topljivi antidijabetik gliklazid izabran je za proučavanje utjecaja pomoćnih tvari na povećanje oslobađanja. Homogene smjese mikroniziranog gliklazida s laktozom, manitolom, sorbitolom, maltitolom i natrijevim kloridom pripravljene su ručnim tresenjem staklenih bočica s lijekom i pomoćnom tvari/tvarima. Na oslobađanje lijeka utjecali su vrsta vodotopljivog ekscipijensa, dodatak surfaktanta i superdezintegratora, udio lijeka i veličina čestica punila. Sve vodotopljive pomoćne tvari povećavale su oslobađanje ljekovite tvari i to sljedećim redom: manitol > laktoza > maltitol > sorbitol > natrijev klorid. Najbolje oslobađanje lijeka bilo je iz kompozitnih granula veličine 355 do 710 µm. Iz smjesa s manjom veličinom čestica punila i većim udjelom lijeka oslobađanje lijeka bilo je manje. Kinetičko modeliranje oslobađanja najbolje je odgovaralo Hixson-Crowellovom modelu, što ukazuje na to da sve formulacije prilično dobro slijede zakon trećeg korijena

MusMorph, a database of standardized mouse morphology data for morphometric meta-analyses.

Complex morphological traits are the product of many genes with transient or lasting developmental effects that interact in anatomical context. Mouse models are a key resource for disentangling such effects, because they offer myriad tools for manipulating the genome in a controlled environment. Unfortunately, phenotypic data are often obtained using laboratory-specific protocols, resulting in self-contained datasets that are difficult to relate to one another for larger scale analyses. To enable meta-analyses of morphological variation, particularly in the craniofacial complex and brain, we created MusMorph, a database of standardized mouse morphology data spanning numerous genotypes and developmental stages, including E10.5, E11.5, E14.5, E15.5, E18.5, and adulthood. To standardize data collection, we implemented an atlas-based phenotyping pipeline that combines techniques from image registration, deep learning, and morphometrics. Alongside stage-specific atlases, we provide aligned micro-computed tomography images, dense anatomical landmarks, and segmentations (if available) for each specimen (N = 10,056). Our workflow is open-source to encourage transparency and reproducible data collection. The MusMorph data and scripts are available on FaceBase ( www.facebase.org , https://doi.org/10.25550/3-HXMC ) and GitHub ( https://github.com/jaydevine/MusMorph )

Visual Personal Familiarity in Amnestic Mild Cognitive Impairment

BACKGROUND: Patients with amnestic mild cognitive impairment are at high risk for developing Alzheimer's disease. Besides episodic memory dysfunction they show deficits in accessing contextual knowledge that further specifies a general concept or helps to identify an object or a person. METHODOLOGY/PRINCIPAL FINDINGS: Using functional magnetic resonance imaging, we investigated the neural networks associated with the perception of personal familiar faces and places in patients with amnestic mild cognitive impairment and healthy control subjects. Irrespective of stimulus type, patients compared to control subjects showed lower activity in right prefrontal brain regions when perceiving personally familiar versus unfamiliar faces and places. Both groups did not show different neural activity when perceiving faces or places irrespective of familiarity. CONCLUSIONS/SIGNIFICANCE: Our data highlight changes in a frontal cortical network associated with knowledge-based personal familiarity among patients with amnestic mild cognitive impairment. These changes could contribute to deficits in social cognition and may reduce the patients' ability to transition from basic to complex situations and tasks

Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes

BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P = 0.98). There were no significant between-group differences in rates of acute pancreatitis (P = 0.07) or pancreatic cancer (P = 0.32). CONCLUSIONS: Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events

Do herpes e suas implicações audiológicas: uma revisao de literatura Herpes and its hearing implications: a literature review

TEMA: herpes e audiologia. OBJETIVO: realizar revisão teórica principalmente sobre os vírus herpes simples tipo 1, herpes simples tipo 2 e varicela-zoster, bem como sobre seus efeitos na audição humana. Esses se constituem nos tipos de vírus herpéticos humanos de maior relevância para a área da Audiologia dentro da ciência da Fonoaudiologia e, no entanto, são pouco conhecidos e estudados, especialmente no Brasil. MÉTODOS: realizou-se pesquisa em bases de dados eletrônicas nacionais e internacionais, incluindo SciELO, MEDLINE e LILACS, a partir da seguinte combinação de descritores: herpes simplex/zoster X hearing loss ou deafness. Foram selecionados estudos publicados desde a década de 90 até os dias atuais, relevando-se aqueles que contivessem maior valor informativo, contribuindo para os objetivos do presente trabalho. CONCLUSÃO: os vírus herpéticos estudados apresentam estreita relação com distúrbios auditivos, independentemente da idade em que o sujeito é acometido.<br>BACKGROUND: herpes and audiology. PURPOSE: to promote a theoretical approach mainly on herpes simplex virus type 1, herpes simplex virus type 2 and varicella zoster virus, and their effects on human hearing. Although representing the most relevant human herpetic viruses for the area of Audiology within the Speech and Language Pathology Science, these viruses are little studied and known, especially in Brazil. METHODS: a research was carried out in national and international electronic databases, including SciELO, MEDLINE and LILACS, and using the following keyword combinations: herpes simplex/zoster X hearing loss or deafness. Studies published from the 90's until today were selected, revealing those that would contain the highest informative value, which would thus contribute for the objectives of this work. CONCLUSION: the studied herpetic viruses show strict relation with hearing disorders, regardless of the age in which the patient is affected