Development and evaluation of a quality control system based on transdermal electrical resistance for skin barrier function in vitro.

Background: In vitro skin permeation experiments are highly relevant for pharmaceutical, cosmetic, agricultural developments, and regulatory evaluation. A key requirement is the skin barrier integrity, that is accompanied by an intact stratum corneum (SC) which implements high skin quality. A variety of integrity tests are currently available, for example, measurement of transepidermal water loss, monitoring the permeation of tritiated water and the measurement of transdermal electrical resistance (TER).

Treatment of postmenopausal osteoporosis with delayed-release risedronate 35 mg weekly for 2 years.

Unlabelled: Bone mineral density response to once weekly delayed-release formulation of risedronate, given before or following breakfast, was non-inferior to that seen with traditional immediate-release risedronate given daily before breakfast. Delayed-release risedronate is a convenient dosing regimen for oral bisphosphonate therapy that might avoid poor compliance.

Introduction: This 2-year, randomized, controlled, non-inferiority study assessed the efficacy and safety of a delayed-release (DR) 35-mg weekly oral formulation of risedronate that allows subjects to take their weekly risedronate dose before or immediately after breakfast.

Efficacy and safety of risedronate 150-mg once a month in the treatment of postmenopausal osteoporosis: 2-year data.

Unlabelled: This study showed that risedronate 150-mg once a month provides similar efficacy and safety at 2 years compared with risedronate 5-mg daily for the treatment of postmenopausal osteoporosis. This adds to the range of risedronate dosing options and provides an alternative for patients who prefer once-a-month dosing.

Introduction: Risedronate is effective in the treatment of postmenopausal osteoporosis in oral daily, weekly, or on two consecutive days per month doses.

Efficacy and safety of a novel delayed-release risedronate 35 mg once-a-week tablet.

Unlabelled: Dosing regimens of oral bisphosphonates are inconvenient and contribute to poor compliance. The bone mineral density response to a once weekly delayed-release formulation of risedronate given before or following breakfast was non-inferior to traditional immediate-release risedronate given daily before breakfast. Delayed-release risedronate is a convenient regimen for oral bisphosphonate therapy.

Comparison of the effects of once-monthly versus once-daily risedronate in postmenopausal osteoporosis: a phase II, 6-month, multicenter, randomized, double-blind, active-controlled, dose-ranging study.

Background: Risedronate 5 mg/d is approved by the US Food and Drug Administration for the treatment and prevention of postmenopausal osteoporosis. Once-monthly dosing options might increase treatment compliance and persistence.

Objective: The aim of this study was to compare the tolerability and efficacy of 3 once-monthly risedronate dosing regimens with those of risedronate 5 mg/d.

Characterization of human hair melanin and its degradation products by means of magnetic resonance techniques.

Melanin granules (MGs) have been extracted from human Chinese black hairs by either acid hydrolysis (CH-type MGs) or enzymatic digestion (CP-type MGs), and their chemical structure investigated at the solid state by means of (13)C cross polarization magic angle spinning (CPMAS NMR) and EPR spectroscopy. Both types of MGs contain a large amount of protein that is tightly bound to the true melanin polymer, with CP-type MGs having a larger protein content than CH-type ones. Moreover, MGs may also contain variable amounts of lipid-like material.

Synthesis and characterization of a Gd(III) based contrast agent responsive to thiol containing compounds.

A novel Gd(III) complex with a modified DO3A-like chelating cage has been synthesized and characterized as a candidate contrast agent responsive to the concentration of free thiols in tissues (essentially represented by reduced glutathione, GSH). The novel compound (called Gd-DO3AS-Act) bears a flexible linker ending with a 2-pyridyl-dithio group, that can promptly react with free thiols (XSH) to form mixed disulfides of the form Gd-DO3AS-SX. Compound Gd-DO3AS-Act is characterized by a millimolar relaxivity as high as 8.

Monthly dosing with risedronate 50 mg on three consecutive days a month compared with daily dosing with risedronate 5 mg: a 6-month pilot study.

Objective: Risedronate 5 mg daily significantly reduces the incidence of vertebral and non-vertebral osteoporotic fractures in postmenopausal women. We compared the efficacy and tolerability of risedronate 50 mg administered on 3 consecutive days per month, with and without a loading dose, with those of risedronate 5 mg daily in a randomized, double-blind study.

Methods: Subjects were postmenopausal women 65-80 years old with low bone mineral density (BMD) (T-score < or = -2).

Efficacy and safety of risedronate 150 mg once a month in the treatment of postmenopausal osteoporosis.

Introduction: Risedronate has been shown to be effective in the treatment of postmenopausal osteoporosis when given orally in daily or weekly doses or on 2 consecutive days per month. This randomized, double-blind, multi-center study was designed to assess the efficacy and safety of a single 150 mg risedronate once-a-month oral dose compared with the 5 mg daily regimen.

Methods: Women with postmenopausal osteoporosis were randomly assigned to receive risedronate 5 mg daily (n=642) or 150 mg once a month (followed by daily placebo) (n=650) in a double-blind fashion for 2 years.

Functional outcomes of the retromaxillary-infratemporal fossa dissection for advanced head and neck/skull base lesions.

The retromaxillary-infratemporal fossa (RM-ITF) dissection, using a preauricular incision, was initially popularized for the treatment of temporomandibular joint disorders, facial fractures, and orbital tumors. This approach has been expanded for the treatment of advanced head and neck and skull base tumors extending into the infratemporal fossa. We studied prospectively eight consecutive patients requiring a RM-ITF dissection.

Safety and efficacy of risedronate in patients with age-related reduced renal function as estimated by the Cockcroft and Gault method: a pooled analysis of nine clinical trials.

Unlabelled: The incidences of osteoporosis and renal insufficiency increase with age. We studied the influence of renal function on the safety and efficacy of risedronate 5 mg daily in osteoporotic women. Risedronate was safe and effective in osteoporotic women with mild, moderate, or severe age-related renal impairment.

WR-2721 (Amifostine) ameliorates cisplatin-induced hearing loss but causes neurotoxicity in hamsters: dose-dependent effects.

Chemoprotective agents reduce the toxic side effects of chemotherapy agents such as cisplatin. The conventional belief is that the chemoprotective agent WR-2721 (Amifostine), while protecting against most cisplatin-induced side effects, does not protect against cisplatin-induced ototoxicity (i.e.

Titanium mesh repair of the severely comminuted frontal sinus fracture.

Background: Severely comminuted frontal sinus fractures are difficult to contour and immobilize. Frequently, plates or wires are inadequate in fixating all fragments together, resulting in less than optimal outcomes. Advancements in the development of biomaterials have now made titanium mesh a new option for the repair of severely comminuted fractures.

Evaluation of hydroxyapatite ossicular chain prostheses.

Hydroxyapatite (HA) middle ear prostheses have gained popularity as an alternative to human autografts and homografts. This study reports on 3 HA prostheses types: total ossicular chain prostheses, used for grafting the stapes footplate to the tympanic membrane; partial ossicular chain prostheses, used for grafting the stapes superstructure to the tympanic membrane; and Kartush incus struts (Smith & Nephew Richards Inc), used for grafting the stapes superstructure to the undersurface of the malleus. This single-surgeon study of 33 consecutive cases revealed a statistically significant difference in mean postoperative air-bone gap and airbone gap closure between incus struts (14/26 dB) or partial (22/11 dB) or total (25/10 dB) ossicular chain prostheses (t test: P<0.

Measurement of peripheral vestibular blood flow in a gerbil model of endolymphatic hydrops.

Presently, many investigators believe that the dysfunction of microcirculatory mechanisms may be responsible for vestibular symptoms in Meniere's disease. This study, using intravital microscopy (IVM), a technique that provides in vivo microcirculatory measures, was designed to determine whether impaired vestibular blood flow exists in endolymphatic hydrops. Hydrops was induced in the gerbil model by obliteration of the vestibular aqueduct and was confirmed histologically after IVM.

Cisplatin-induced increases in spontaneous neural activity in the dorsal cochlear nucleus and associated outer hair cell loss.

Tinnitus is one of the consequences of cisplatin chemotherapy, but its underlying mechanisms are not well understood. Since it has been shown that cisplatin causes outer hair cell loss, it is possible that loss of these cells might induce tinnitus by increasing spontaneous activity in the central auditory system. To test this possibility, the present study examined the effects of cisplatin treatment on cochlear hair cells and on spontaneous neural activity in the dorsal cochlear nucleus of hamsters.

Magnetic resonance imaging of the facial nerve in children with idiopathic facial paralysis.

The role of gadolinium-enhanced MRI (Gd-MRI) in the diagnosis of idiopathic facial paralysis (IFP) in children is not well defined. Fourteen children with IFP were evaluated to assess the use of Gd-MRI for the presence and pattern of enhancement and its usefulness in predicting the recovery of facial function. Six of 14 children had enhancement of the facial nerve on Gd-MRI, whereas 8 had none.

Nasal alar reconstruction: a critical analysis using melolabial island and paramedian forehead flaps.

Objectives: To qualitatively and quantitatively describe aesthetic and functional outcomes following Mohs ablative surgery involving the alar subunit, using a paramedian or subcutaneous melolabial island flap.

Study Design: Retrospective review.

Methods: A single surgeon's results in 38 consecutive patients were analyzed.

Inhibition of brain choline uptake by isoarecolone and lobeline derivatives: implications for potential vector-mediated brain drug delivery.

Delivery of certain compounds to brain is restricted by the nature of the blood-brain barrier (BBB). Many valuable pharmaceuticals are excluded from the CNS due to hydrophilicity or charge. These limitations have been overcome by numerous methods.

Effects of P-glycoprotein modulators on etoposide elimination and central nervous system distribution.

In this study, P-glycoprotein modulator effects on pharmacokinetics and central nervous system distribution of the chemotherapeutic agent etoposide were evaluated. The multidrug resistance transporter P-glycoprotein is expressed in normal tissues, and its physiological function is thought to be an excretory and/or protective one. To examine this further, we evaluated etoposide under steady-state and bolus dose conditions.

16-Epiestriol, a novel anti-inflammatory nonglycogenic steroid, does not inhibit IFN-gamma production by murine splenocytes.

All the steroidal anti-inflammatory drugs currently available are glucocorticoids. The desired anti-inflammatory activities of glucocorticoids frequently are accompanied by adverse side effects, notably glycogenic activities and profound immunosuppression, that can limit clinical use. We recently identified 16-epiestriol, a naturally occurring steroid, as exhibiting significant anti-inflammatory activity without glycogenic activity.

The effects of flunarizine and pentoxifylline on vestibular blood flow in the guinea pig.

Several authors have proposed that complications arising from vestibular disorders are the result of compromised circulation. The purpose of the current study was to assess the ability of flunarizine and pentoxifylline to increase peripheral vestibular blood flow (VBF), since flunarizine is a selective calcium-channel entry blocker that inhibits calcium-related contraction of smooth muscle, while pentoxifylline is a xanthine derivative that promotes microcirculation by affecting red blood cell malleability. Both of these treatment strategies have received considerable attention in clinics and laboratory, but their effects on blood flow are unclear.

Guinea pig vestibular blood flow in response to calcitonin-gene related peptide.

Little is known about the physiologic regulation of the vestibular end organ blood flow. The purpose of the current study was to examine posterior semicircular canal ampulla blood flow in addition to systemic factors during intravenous infusions of calcitonin-gene related peptide (CGRP), a factor involved in the tonic regulation of blood flow. Receptors for this factor are known to be available to the vascular supply of the vestibular organs.

Comparison of five agents in protecting the cochlea against the ototoxic effects of cisplatin in the hamster.

The purpose of this investigation was to study the ameliorating effects of four agents on cisplatin-induced ototoxicity. Hamsters were given a series of five cisplatin injections either alone or in combination with sodium thiosulfate (STS), diethyldihydrothiocarbamate (DDTC), and S-2(3-aminopropylamino) ethylphosphorothioic acid (WR-2721), or fosfomycin. Ototoxicity was assessed anatomically by quantifying the extent of cochlear damage with the scanning electron microscope and physiologically with measures of the auditory brain stem response.