Granulomatous mastitis: a report of seven cases

The clinical history and histological features of seven cases of granulomatous mastitis are presented. The lesion occurs in young parous women as a tender extra-areolar breast lump. Histologically, non-caseating discrete granulomas are present, confined to breast lobules with, in three cases, coalescence of the granulomas and microabscess formation. Pathogenesis of the changes is discussed. It is thought that granulomatous mastitis is an entity morphologically distinct from duct ectasia/plasma cell mastitis and the commoner forms of granulomatous breast diseases.     

The inositol monophosphatase inhibitor L-690,330 affects pilocarpine-behavior and the forced swim test

Rationale

Lithium has been a standard pharmacological treatment for bipolar disorder over the last 60 years; however, the molecular targets through which lithium exerts its therapeutic effects are still not defined. Attenuation of the phosphatidylinositol signal transduction pathway as a consequence of inhibition of inositol monophosphatase (IMPase) has been proposed as one of the possible mechanisms for lithium-induced mood stabilization.

Objectives

The objective was to study the behavioral effect of the specific competitive IMPase inhibitor L-690,330 in mice in the lithium-sensitive pilocarpine-induced seizures paradigm and the forced swim test (FST).

Methods

The inhibitor was administered intracerebroventricularly in liposomes.

Results

L-690,330 increased the sensitivity to subconvulsive doses of pilocarpine and decreased immobility time in the FST.

Conclusions

It is possible that the behavioral effects of lithium in the pilocarpine-induced seizures and in the FST are mediated through the inhibition of IMPase, but reversal of the inhibitor’s effect with intracerebroventricular inositol would be an important further step in proof.     

Quantification of Anthocyanins in Elderberry and Chokeberry Dietary Supplements

Elderberry and chokeberry food supplements may be ‘functional food’ in patients with metabolic syndrome or influenza but, for this, adequate amounts of co‐active ingredients must be consumed in the daily dose. This study aimed to quantify the anthocyanin content in three elderberry and six chokeberry products to assess their usefulness as functional food. Analyses were carried out using an established HPLC procedure. The minimum anthocyanin doses for the treatment of metabolic syndrome disorders were estimated as 110 mg per day and 3.5 g per day for influenza. Three products were inappropriate for clinical use. The lowest liquid supplies were achieved with a proprietary elderberry concentrate (11 mL) and a proprietary chokeberry mother juice (100 mL). Clinical studies are now required to prove the effectiveness and adapt the doses according to the clinical symptoms. Copyright © 2015 John Wiley & Sons, Ltd.     

Fish oil stabilisation by microencapsulation with modified cellulose

Fish oil is the richest dietary source of long-chain omega-3 polyunsaturated fatty acids (PUFA). Stabilisation of omega-3 PUFA against oxidation is an important task in food processing. The ability of modified celluloses to act as microencapsulating agents for fish oil was investigated. Fish oil microcapsules were produced by spray-drying of homogenised emulsions containing modified celluloses and maltodextrin as coating materials. The quality of microcapsules was evaluated by scanning electron microscopy, determination of encapsulation efficiency, peroxide value during storage and solubility in water. Methylocellulose (MC) and hydroxypropyl methylocellulose (HPMC) showed good emulsifying properties. Homogenisation of emulsions resulted in creation of high amount of stable foam. More damage occurred in the powders coated with HPMC. The oil retention level was very high, 98.5% (i.e. up to 400.0 g/kg ready powder). Samples with fish oil content of approximately 500.0 g/kg exhibited more structural damage impairing the stabilisation effect. This study indicates that the use of modified cellulose, especially MC, as a coating material for the preparation of spray-dried fish oil microcapsules improves the stability and the concentration of fish oil in the powder.     

Expression pattern of gastrointestinal selenoproteins— targets for selenium supplementation

There is experimental and epidemiological evidence for an association between low selenium levels and gastrointestinal cancer incidence, prevalence, and mortality. To identify targets for selenium supplementation in the human digestive tract, we examined mRNA expression of various selenocysteine‐containing proteins in normal mucosa biopsy specimens. Tissue samples from the esophagus and from different sites of the stomach, small bowel, and colon were obtained during endoscopies of the upper and lower gastrointestinal tract. Northern blot analyses revealed a lack of cytosolic glutathione peroxidase mRNA but a differential mRNA expression pattern of gastrointestinal and plasma glutathione peroxidase, selenoprotein P, and thioredoxin reductase. Glutathione peroxidase and thioredoxin reducíase activities were detected in the mucosa of all biopsies, but the differential pattern did not reflect the differential mRNA steady‐state levels. In addition to gastrointestinal glutathione peroxidase, which was found to play a role in colon cancer resistance, we identified further gastrointestinal selenoproteins, which may be involved in gastrointestinal cell defense and cell differentiation.     

Use of a food frequency questionnaire in American Indian and Caucasian pregnant women: a validation study

Background  

Food frequency questionnaires (FFQs) have been validated in pregnant women, but few studies have focused specifically on low-income women and minorities. The purpose of this study was to examine the validity of the Harvard Service FFQ (HSFFQ) among low-income American Indian and Caucasian pregnant women.     

Pharmacokinetics of Coadministration of Guanfacine Extended Release and Methylphenidate Extended Release

Background

α₂-Adrenoceptor agonists are used adjunctively to psychostimulants in treating attention-deficit/hyperactivity disorder (ADHD) when psychostimulants alone do not sufficiently reduce symptoms. However, data on the pharmacokinetic profiles and safety of combination treatments in ADHD are needed.

Objective

The primary objective of this study was to evaluate the pharmacokinetic profiles of guanfacine extended release (GXR) and methylphenidate hydrochloride (MPH) extended release, alone and in combination.

Study Design

This was an open-label, randomized, three-period crossover, drug–drug interaction study.

Setting

The study was conducted at a single clinical research center.

Participants

Thirty-eight healthy adults were randomized in this study.

Interventions

Subjects were administered single oral doses of GXR (Intuniv^®; Shire Development LLC, Wayne, PA, USA) 4 mg, MPH (Concerta^®; McNeil Pediatrics, Titusville, NJ, USA) 36 mg, or GXR and MPH combined.

Main Outcome Measures

Guanfacine, dexmethylphenidate (d-MPH), and l-methylphenidate (l-MPH) levels were measured with blood samples collected predose and up to 72 h postdose. Safety evaluations included treatment-emergent adverse events (TEAEs), vital signs, and electrocardiograms (ECGs).

Results

Thirty-five subjects completed the study. Analyses of the 90 % confidence intervals (CIs) for the geometric mean ratios of the maximum plasma concentration (C_max) and area under the concentration–time curve extrapolated to infinity (AUC_∞) values for guanfacine and d-MPH following administration of GXR or MPH alone or combined met strict bioequivalence criteria (90 % CIs within the interval of 0.80–1.25). Overall, combining GXR and MPH did not alter the pharmacokinetic parameters of either medication. Sixteen subjects (42.1 %) had at least one TEAE. The most commonly reported TEAEs included headache and dizziness following GXR, MPH, and GXR and MPH combined. Two subjects had clinically significant abnormalities in ECG results following coadministration: both events were mild and resolved the same day.

Conclusions

In this short-term, open-label study of healthy adults, coadministration of GXR and MPH did not result in significant pharmacokinetic drug–drug interactions. No unique TEAEs were observed with coadministration of GXR and MPH compared with either treatment alone.