Importance of high pKA acids in cariogenic potential of plaque

Through the use of computer simulation, it is shown that anions of high pKA acids (e.g., acetic, propionic, butyric), present in resting plaque fluid, act as effective buffers during the production of stronger acids (e.g., lactic) by oral micro-organisms. Using reported organic acid compositions for plaque, obtained from caries-resistant and caries-susceptible individuals, analyzed at various times following sucrose exposure, it is shown that the calculated pH values of the aqueous phase of plaque describe typical Stephan curves. Furthermore, it is shown that for higher acid anion contents in resting plaque, a higher degree of saturation of the aqueous plaque phase with respect to enamel is maintained during acid production, resulting in a lower demineralization potential of plaque. Enamel demineralization experiments conducted in vitro confirmed the significance of the results of the computer simulations, thus providing evidence for a correlation between the known metabolic activity of plaque (organic acid composition), physical chemistry of plaque, and caries susceptibility.     

Enhanced enamel remineralization under acidic conditions in vitro

We conducted this study to test the hypothesis that acidic solutions undersaturated with respect to enamel and supersaturated with respect to fluorapatite can enhance enamel remineralization by reducing preferential remineralization of the outer lesion and promoting mineral ion penetration. We used quantitative microradiography to assess mineral changes in artificial surface-softened and subsurface lesions in human enamel in vitro, induced by such an acidic solution and by a neutral remineralizing solution. For surface-softened lesions, the extent of remineralization was similar for both solutions, although preferential remineralization of the outer lesion was observed with the neutral solution. For subsurface lesions, preferential remineralization of the outer lesion was not observed with either solution. However, the extent of subsurface lesion remineralization by the acidic solution was significantly greater than that observed with the neutral solution. Results obtained are noted to reflect inherent differences in lesion type and the properties of the solutions studied.     

Improvement in insulin sensitivity and dyslipidemia in protease inhibitor-treated adult male patients after switch to atazanavir/ritonavir.

BACKGROUND: Treatment of human immunodeficiency virus (HIV) with protease inhibitors (PIs) is associated with insulin resistance, triglyceride-rich dyslipidemia, and fat redistribution. Atazanavir (ATV), a potent once-daily PI, has been recognized for its convenience to patients, and some studies describe improved lipid metabolism. However, its effects on insulin sensitivity have not been elucidated. We conducted this study to test the hypothesis that ATV improves insulin resistance and dyslipidemia. METHODS: We prospectively studied 9 HIV-infected men with dyslipidemia (median age, 53 years; baseline triglyceride level, >200 mg/dL) on stable PI-containing antiretroviral therapy who elected to change PI therapy to ritonavir-boosted ATV therapy, dose of 300/100 mg. We measured insulin resistance at baseline and after 12 weeks of therapy using a hyperinsulinemic euglycemic clamp (insulin dose, 200 mU/m minute). Fasting lipid profiles and body composition (whole-body dual energy x-ray absorptiometry) were also measured at baseline and after 12 weeks. RESULTS: All 9 patients completed the study and maintained undetectable viral loads (<50 copies/mL) and stable CD4 counts. After 12 weeks, insulin sensitivity significantly improved (+28%; P = 0.008) in all patients. Triglyceride levels also improved. CONCLUSIONS: Using the gold-standard euglycemic clamp, ritonavir-boosted ATV therapy improved PI-induced insulin resistance among dyslipidemic HIV-infected men on PI-based antiretroviral therapy. These findings were not attributable to a change in body weight and provide further evidence for ATV's unique metabolic profile among the PIs.     

Health literacy and diabetic foot ulcer healing

The adherence by patients to diabetic foot ulcer therapy is often difficult. The goal of this study was to begin to understand how a patient's health literacy affects their foot ulcer management decisions. Initially using a cross‐sectional study design, we evaluated diabetics with foot ulcers within 4 weeks of being asked to participate in a longitudinal study. We assessed health literacy using measures of general health literacy, diabetes health literacy, diabetes self‐efficacy, and diabetes numeracy. Individuals enrolled in the study had higher health literacy based on the Short Test of Functional Health Literacy in Adults [33.8 (SD 2.3) versus 27.3 (SD 9.6); p = 0.009] as compared to individuals who previously declined an invitation to enroll in the study. Furthermore, patients with lower Short Test of Functional Health Literacy in Adults scores had larger (p = 0.04) and older (p = 0.125) wounds (markers for poorer prognosis). Other measures of literacy showed similar results. In conclusion, those with diminished health literacy were less likely to enroll in an investigational study and had wounds that were less likely to heal.     

Human neutrophil annexin I promotes granule aggregation and modulates Ca(2+)-dependent membrane fusion.

The mechanism and cofactor requirements of exocytotic membrane fusion in neutrophils are unknown. Cytosolic proteins have been implicated in membrane fusion events. We assessed neutrophil cytosol for the presence of fusogenic proteins using a liposome fusion assay (lipid mixing). A fusogenic 36-kD protein containing amino acid sequence homology with human annexin I was purified from the cytosol of human neutrophils. This protein also shared functional characteristics with annexin I: it associated with and promoted lipid mixing of liposomes in a Ca(2+)-dependent manner at micromolar Ca2+ concentrations. The 36-kD protein required diacylglycerol to promote true fusion (contents mixing) at the same Ca2+ concentrations used for lipid mixing. The 36-kD protein exhibited a biphasic dose-response curve, by both promoting and inhibiting Ca(2+)-dependent lipid-mixing between liposomes and a plasma membrane fraction. The 36-kD protein also promoted Ca(2+)-dependent increases in aggregation of a specific granule fraction, as measured by a turbidity increase. Antiannexin I antibodies depleted the 36-kD protein from the cytosol by greater than 70% and diminished its ability to promote lipid mixing. Antiannexin I antibodies also decreased by greater than 75% the ability of neutrophil cytosol to promote Ca(2+)-dependent aggregation of the specific granules. These data suggest that annexin I may be involved in aggregation and fusion events in neutrophils.     

FDA批准大麻二酚用于治疗难治性癫痫的审评思路分析

FDA于2018年6月25日批准Epidiolex口服溶液用于治疗难治性癫痫,其活性成分是来源于大麻的高纯度原料大麻二酚。本文通过对FDA关于Epidiolex的审评过程进行分析,结合其审评制度探索FDA在人用经验、化学制造和控制(chemistry,manufacturing,and control,CMC)、非临床、临床等方面的审评思路。同时对FDA关于植物来源高纯度药物审评的重点及特点进行阐述,目的是为我国天然药物研究和技术审评提供有益的参考。     

功能性便秘与情感障碍相关性分析

功能性便秘是一种常见的功能性肠病,焦虑抑郁等情感障碍与功能性便秘是相互影响的。该文从三个方面阐述功能性便秘与焦虑抑郁等情感障碍的相关性。