Long live the Liver!

International Journal of Diabetes in Developing Countries -     

PMP22 Gene–Associated Neuropathies: Phenotypic Spectrum in a Cohort from India

Journal of Molecular Neuroscience - Reports of spectrum of clinical manifestations in PMP22 gene–associated neuropathies (duplication/mutations) are scarce. To identify the frequency of PMP22...     

Pharmacokinetics of Piperaquine Transfer into the Breast Milk of Melanesian Mothers

Transfer of piperaquine (PQ) into breast milk was examined in 27 Papua New Guinean women given a 3-day course of dihydroartemisinin-PQ or sulfadoxine-pyrimethamine-PQ during the second/third trimester. Breast milk was sampled on days 1, 2, 3 to 5, 7 to 11, and 14 to 17 postdelivery, a median of 70 days postdose (range, 6 to 145 days). A blood sample was taken at delivery, and additional serial samples were available from 9 women who delivered within 42 days of dosing. Milk and plasma PQ were assayed by high-performance liquid chromatography. A population-based approach was used to model the log_e(plasma) and milk concentration-time data. A sigmoid E_max model best described PQ breast milk transfer. The population average milk:plasma PQ ratio was 0.58, with a peak of 2.5 at delivery. The model-derived maximum milk intake (148 ml/kg of body weight/day) was similar to the accepted value of 150 ml/kg/day. The median estimated absolute and relative cumulative infant PQ doses were 22 μg and 0.07%, respectively, corresponding to absolute and relative daily doses of 0.41 μg/kg and 0.004%. Model-based simulations for PQ treatment regimens given at birth, 1 week postdelivery, and 6 weeks postdelivery showed that the highest median estimated relative total infant dose (0.36%; median absolute total dose of 101 μg/kg) was seen after maternal PQ treatment 6 weeks postpartum. The maximum simulated relative total and daily doses from any scenario were 4.3% and 2.5%, respectively, which were lower than the recommended 10% upper limit. Piperaquine is transferred into breast milk after maternal treatment doses, but PQ exposure for suckling infants appears safe.     

Fetuin-A levels are increased in the adipose tissue of diabetic obese humans but not in circulation

Background

The hepatokine fetuin-A is linked to obesity and type 2 diabetes, but its presence and expression in adipose tissue remain unclear. In this study, we aimed to assess the circulating levels of fetuin-A and its expression in subcutaneous adipose tissue (SAT) from diabetic and non-diabetic obese subjects and their modulation by exercise.

Methods

SAT and blood were obtained from adults obese (diabetic, n=118 and non-diabetic, n=166) before and after a 3-month exercise program (diabetic, n=40 and non-diabetic, n=36, respectively). Plasma fetuin-A was assayed using ELISA. The presence and expression of fetuin-A in SAT, peripheral blood mononuclear cells (PBMCs) and cell lines (3T3-L1, THP-1, HepG2, RAW 264.7) were analysed using confocal microscopy, immunoblotting and qRT-PCR.

Results

Plasma fetuin-A level did not significantly differ between diabetic and non-diabetic obese subjects. However, when the non-diabetic group was divided into metabolically healthy and unhealthy phenotypes, significantly higher fetuin-A level was observed in the unhealthy sub-group. Circulating fetuin-A was mainly associated with glycaemic markers. In SAT, fetuin-A protein level was significantly higher in the diabetic obese subjects but its mRNA was not detected. Similarly, fetuin-A protein was detected in PBMCs, but its mRNA was not. In line with this, the use of various cell lines and culture media indicated that the presence of fetuin-A in SAT and PBMCs was due to its uptake from circulation rather than its endogenous expression. Finally, physical exercise decreased fetuin-A levels in both plasma and SAT in both groups.

Conclusions

Fetuin-A levels increased in association with diabetes in SAT but not in circulation in the obese subjects. Moreover, physical exercise decreased fetuin-A level. Fetuin-A potentially acts as a hepatokine taken up by other tissues, such as adipose tissue.

     

Interplay between fluoride and abrasivity of dentifrices on dental erosion–abrasion

Objectives

Eroded teeth are more susceptible to toothbrushing wear than sound teeth. We tested the hypothesis that fluoride and abrasivity of dentifrices can interact, modulating the development of erosive–abrasive lesions.

Methods

Human enamel and root dentin specimens were submitted to cycles of demineralization, remineralization and toothbrushing using six dentifrices formulated with three different abrasivity levels: low (L), medium (M) and high (H); with (+F) and without (−F) fluoride. Surface loss was quantified by optical profilometry and compared among groups (α = 0.05).

Results

In dentin, it was ranked: L < M < H, for both +F and −F dentifrices. In enamel, +F dentifrices had similar results; however for −F formulations, M and H did not differ. Fluoride reduced surface loss in enamel, at all abrasive levels. In dentin, the same fluoride effect was observed but only for the low abrasive formulation.

Conclusions

Both fluoride and abrasivity were important modulators of enamel surface loss, while abrasivity had a higher impact than fluoride on dentin.     

A Novel Prefabricated Grid for Guided Endodontic Microsurgery

Introduction

This study aimed to introduce a novel method using cone-beam computed tomographic (CBCT) imaging and prefabricated grids to guide apical access during endodontic microsurgery and to compare its accuracy with that of the nonguided method.

Current oscillatory phenomena based on electrogenerated superoxide ion at the HMDE in dimethylsulfoxide

A study on the current oscillation based on the electrogenerated superoxide ion $({\mathrm{O}}_2^{\text{<mglyph src="https://sdfestaticassets-us-east-1.sciencedirectassets.com/shared-assets/16/entities/rad"></mglyph>}-})$ at a hanging mercury drop electrode (HMDE) in dimethylsulfoxide solution containing tetra-n-alkylammonium perchlorate as the electrolyte was carried out. Cyclic voltammetric, potential step chronoamperometric, normal and reverse pulse voltammetric techniques were employed in this study. A bare glassy carbon electrode, a liquid hemispherical mercury (Hg) drop-coated gold (Au) electrode and a Hg film-coated Au electrode were also used as working electrodes to understand the mechanism of the current oscillation. The experimental conditions were optimized for a simple, regular and reproducible current oscillation. The specific adsorption phenomenon of iodide ion and the adsorption of the alkyl chain of the supporting electrolyte on the HMDE surface were also considered to clarify the experimental factors governing the current oscillation phenomenon. It has been concluded that the oscillation is mainly due to the promoted oxidation (dissolution) of the HMDE itself by the adsorption of ${\mathrm{O}}_2^{\text{<mglyph src="https://sdfestaticassets-us-east-1.sciencedirectassets.com/shared-assets/16/entities/rad"></mglyph>}-}$, resulting in the formation–destruction of a passive film such as ${\mathrm{Hg}}_2({\mathrm{O}}_2^{\text{<mglyph src="https://sdfestaticassets-us-east-1.sciencedirectassets.com/shared-assets/16/entities/rad"></mglyph>}-}{)}_2$ on the electrode surface. A probable mechanism for the observed current oscillation is discussed.     

Relationship between nocturnal intraocular pressure-related peak recorded by contact lens sensor and disease progression in treated glaucomatous eyes

Purpose:The aim of this study is to study the association between Nocturnal Intraocular Pressure (IOP) related Peak recorded by a Contact Lens Sensor (CLS) and glaucoma progression in treated glaucomatous eyes.Methods:Institutional study in which forty glaucoma patients were recruited from glaucoma clinic. A total of 19 patients were labeled as progressors on current anti-glaucoma treatment despite controlled day time IOP whereas twenty one patients were clinically stable showing no progression. Worse eye of each patient was selected for placement of CLS. The timing of the highest signal (IOP related peak) was noted in 24 hour CLS graph and if it fell within the time frame of 11 pm to 5 am, it was labeled as ''nocturnal IOP related peak''.Results:Progressors were found to be significantly more prone to night spike than Non Progressors (χ² = 6.812; n = 40; P = 0.009), thus, showing a definite association between the two. Association between Nocturnal IOP related peak and various other variables like age, gender, mean daytime IOP and systemic illness was studied. A positive correlation was established between female gender and Nocturnal IOP related spike with a significantly higher proportion of females showing night spike than their male counterparts (χ² = 5.763; n = 40; P = 0.016). Other parameters did not show any significant relationship with Nocturnal IOP related spike.Conclusion:Dynamic 24 hour recording by CLS is beneficial in detecting nocturnal IOP-related peak, and thus, can potentially improve the clinical care of glaucoma patients, especially those showing progression.