Evaluation of the mass balance assumption with respect to the two-resistance model of intestinal absorption by using in situ single-pass intestinal perfusion of theophylline in rats.

Methods of analyzing drug absorption data from rat intestinal-perfusion experiments are discussed in terms of mass-transfer resistances, or reciprocal permeabilities, and mass balances. Typically, a two-resistance model is used to determine the dimensionless effective permeability (P*eff) by measuring the disappearance of drug from the perfusing solution. Unstated assumptions in two-resistance models are (1) the portal blood is under sink conditions and (2) complete transfer of drug occurs from the intestinal perfusate to the portal vein. The assumption of sink conditions is generally acceptable, because the drug concentration in portal blood is approximately two orders of magnitude less than in the perfusate. Single-pass intestinal-perfusion experiments were performed on rats with theophylline as a model compound. The drug mass leaving the intestinal perfusate was substantially less than the drug mass appearing in the portal plasma; that is, the assumption of complete transfer did not hold for theophylline in this experimental system. These data indicate that models based on the two-resistance theory can lead to overestimation of P*eff by the ratio of the drug mass leaving the perfusate to the drug mass appearing in the plasma. For compounds for which the assumption of complete transfer does not hold, a more accurate estimate of P*eff may be determined by dividing the value derived from perfusate data by the mass balance ratio (i.e., the drug mass leaving the perfusate divided by the drug mass appearing in the plasma).     

Calcium antagonists and multi-infarct dementia: A trial involving sequential NMR and psychometric assessment

A double-blind placebo-controlled trial of the calcium antagonist Nimodipine in 10 patients with multi-infarct dementia (MID) shows that there is no improvement when compared with 10 patients on placebo assessed by clinical ratings and sequential NMR imaging. The value of repeated NMR imaging in measuring changes in MID is described.     

The effect of Miglycol 812 oil on the oral absorption of propranolol in the rat

This work has examined the effect of Miglyol 812 oil and its composite fatty acids on the oral absorption of propranolol with reference to its intravenous (i.v.) pharmacokinetics. Propranolol hydrochloride, spiked with 4-(3) H labelled compound, was administered i.v. or orally to male Wistar rats and blood concentrations of parent material determined by liquid scintillation counting after extraction into toluene. An i.v. dose-linearity study indicated dose-independent pharmacokinetics for propranolol at 1-2 mg kg-1, with a mean Cls, Vss, MRTi.v. and t0.5 beta of 0.076 L min-1 kg-1, 4.74 L kg-1, 57.81 min and 47.10 min, respectively. At 5 mg kg-1, there was evidence of non-linearity with MRTi.v. increased by about 250%, Vss by 170% and t0.5 beta by 230% compared with the lower doses. After oral administration of propranolol (10 mg kg-1) in aqueous solution, with or without Tween 80 (6%), the mean absorption time (MAT) and terminal half-life were approximately 55 min and 86 min, respectively. The MAT for propranolol administered in a 50% octanoic and lauric acid (1:1 by weight) oil-in-water emulsion, stabilized with 6% Tween 80 (129-90 min), was significantly longer compared with that for a 50% Miglyol 812 oil-in-water emulsion containing the same surfactant (16.55 min). The terminal half-life of propranolol administered in the fatty acid formulation (128.96 min), unlike that for the Miglyol emulsion (54-37 min), was significantly longer compared with that observed after i.v. administration (t0.5 beta = 47 min).(ABSTRACT TRUNCATED AT 250 WORDS)     

Menopausal symptoms in women treated for breast cancer: the prevalence and severity of symptoms and their perceived effects on quality of life.

OBJECTIVES: To determine, first, the prevalence and severity of various symptoms related to estrogen deficiency in women within a few years of receiving treatment for breast cancer, second, how women perceive the effects of these symptoms on their quality of life and, third, what measures have been taken to relieve vasomotor symptoms. METHODS: Two hundred women (aged 29-65 years) who had received treatment for breast cancer within the last 5 years were included in this cross-sectional survey. Information was collected about their breast cancer treatment, menopausal symptoms (Menopausal Rating Scale), the perceived effects of menopausal symptoms on their and their partner's quality of life and any treatments they were receiving for hot flushes. RESULTS: All but one woman reported at least one symptom related to the menopause (95.9% vasomotor; 83.3% psychological; 89.7% somatic). Current treatment with tamoxifen or previous chemotherapy did not influence the prevalence or the severity of hot flushes. Current antidepressant treatment was, however, significantly associated with a higher prevalence and severity of most menopausal symptoms, including hot flushes and sweats (p = 0.008). The severity of hot flushes and sweats was significantly correlated with self-assessed effects on overall quality of life (r(s) = 0.47); 56.4% of the respondents believed that menopausal symptoms had affected their partner's quality of life, the strongest correlations being with severity of sexual symptoms (r(s) = 0.56) and vaginal dryness (r(s) = 0.5). Only 21% of women experiencing hot flushes were receiving any treatment for hot flushes, with most women describing no knowledge or poor knowledge of treatment options. CONCLUSIONS: The majority of women receiving treatment for breast cancer report menopausal symptoms, which negatively correlate, not only with their own, but also with their partner's quality of life. Most women experiencing hot flushes are not receiving treatment due to lack of both awareness and confidence in the existing treatment options.     

Cancer morbidity of residents living near an oil refinery plant in North-West Italy

Cerano is a municipality of the Province of Novara (North-West Italy). To assess the morbidity associated to its proximity to a petrochemical plant, standardized incidence ratios (SIRs) of oncological pathologies in the period 2003–2009 were calculated based on age-sex specific rates for the district of the Local Health Authority of Novara (ASL13) and the main regional city of Turin. For all cancers combined, men showed a significant higher risk (SIR: 1.21; 95% CI: 1.02–1.40) compared to the ASL13 population; significantly lower risks for both men and women were observed in comparison to the Turin population. Among women, a significant excess of mesothelioma cancers was reported; a significantly higher risk for lympho-haematopoietic pathologies was also observed compared to the Turin population only. Several other cancers have significantly lower rates in Cerano for both men and women. Despite some studies’ limitations, these findings could suggest potential chemical risk factors and need further investigation.     

Inhibitory effects of Serenoa repens on the kinetic of pig prostatic microsomal 5α-reductase activity

The pathogenesis of benign prostatic hyperplasia is linked to the accumulation of dihydrotestosterone (DHT), the active form of testosterone (T), in prostatic tissue. We have defined characteristics of 5α-reductase enzyme which catalyzes the conversion of T into DHT in prostatic microsomes of growing pigs. Peaks for the 5α-reductase activity were found at pH 5.5 and 8.0, which indicates the presence of both type 1 and type 2 isozymes. Kinetic parameters of porcine 5α-reductase in the presence of Serenoa repens extracts revealed uncompetitive, noncompetitive, and mixed types of inhibitions. Our results show the inhibitory action of S. repens on prostate porcine microsomal 5α-reductase activity.     

Advances in light-curing units: four generations of LED lights and clinical implications for optimizing their use: Part 2. From present to future

The first part of this series of two described the history of light curing in dentistry and developments in LED lights since their introduction over 20 years ago. Current second- and third-generation LED light units have progressively replaced their halogen lamp predecessors because of their inherent advantages. The background to this, together with the clinical issues relating to light curing and the possible solutions, are outlined in the second part of this article. Finally, the innovative features of what may be seen as the first of a new fourth-generation of LED lights are described and guidance is given for the practitioner on what factors to consider when seeking to purchase a new LED light activation unit. Clinical Relevance: Adequate curing in depth is fundamental to clinical success with any light-activated restoration. To achieve this goal predictably, an appropriate light source needs to be combined with materials knowledge, requisite clinical skills and attention to detail throughout the entire restoration process. As dentists increasingly use light-cured direct composites to restore large posterior restorations they need to appreciate the issues central to effective and efficient light curing and to know what to look for when seeking to purchase a new light-curing unit.     

Reduced polymerization stress of MAPO-containing resin composites with increased curing speed,degree of conversion and mechanical properties

Objectives

The degree and rate of photopolymerization in resin-based dental composites will significantly affect polymer network formation and resultant material properties that may determine their clinical success. This study investigates the mechanical properties, the generation of stress from polymerization, tooth cusp deflection and marginal integrity of experimental resin composites that contain different photoinitiators.

Methods

Experimental light-activated resin composites (60 vol% particulate filled in 50/50 mass% bis-GMA/TEGDMA) were formulated using a monoacylphosphine oxide (MAPO) photoinitiator and compared with a conventional camphoroquinone (CQ)-based system. Similar radiant exposure was used (18 J cm⁻²) for polymerization of each material although the curing protocol was varied (400 mW cm⁻² for 45 s, 1500 mW cm⁻² for 12 s and 3000 mW cm⁻² for 6 s). Degree and rate of polymerization was calculated in real-time by near infrared spectroscopy and the generation of stress throughout polymerization measured using a cantilever beam method. Flexural strength and modulus were acquired by three-point bend tests. Standardized cavities in extract pre-molar teeth were restored with each material, the total cuspal deflection measured and post-placement marginal integrity between the tooth and restoration recorded.

Results

Generally, MAPO- exhibited a significantly higher degree of conversion (72 ± 0.8 to 82 ± 0.5%) compared with CQ-based materials (39 ± 0.7 to 65 ± 1.6%) regardless of curing protocol (p < 0.05) and MAPO-based materials exhibited less difference in conversion between curing protocols. CQ-based materials exhibited between ∼85 and 95% of the maximum rate of polymerization at <15% conversion, whereas MAPO-based RBCs did not approach the maximum rate until >50% conversion. Higher irradiance polymerization had a significant deleterious effect on the mechanical properties of CQ-based materials (p < 0.05) whereas MAPO-based materials exhibited increased strength and modulus and were less affected by the curing method. Total cuspal deflection in restored extracted teeth was higher for CQ- compared with MAPO-based materials cured at the lowest irradiance curing protocol (12.9 ± 4.0 and 8.3 ± 1.5 μm) and similar at 3000 mW cm⁻¹ for 6 s (10.1 ± 3.5 and 9.0 ± 1.5 μm). A significant decrease in marginal integrity was observed for CQ-based RBCs cured at high irradiance for short exposure time compared with that of the MAPO-based RBC cured using a similar protocol (p = 0.037).

Significance

Polymer network formation dictates the final properties of the set composite and the use MAPO photoinitiators may provide an effective restorative material that exhibits higher curing speeds, increased degree of conversion, strength and modulus without compromise in terms of polymerization stress and marginal integrity between tooth and restoration.