Developing paediatric medicines: identifying the needs and recognizing the challenges.

There is a significant need for research and development into paediatric medicines. Only a small fraction of the drugs marketed and utilized as therapeutic agents in children have been clinically evaluated. The majority of marketed drugs are either not labelled, or inadequately labelled, for use in paediatric patients.

Effect of polymer molecular weight on the production of drug nanoparticles.

Stable, polymer-coated nanoparticles of two hydrophobic drugs, namely nabumetone and halofantrine, have been prepared by a wet-bead milling process performed in the presence of a stabilizing homopolymer, either hydroxypropylmethylcellulose (HPMC) or polyvinylpyrrolidone (PVP), of differing molecular weights and concentrations. Although nabumetone nanoparticles could only be produced when HPMC was used as stabilizing polymer, halofantrine nanoparticles could be prepared using either HPMC or PVP. Stable nanoparticles of nabumetone could be produced using a HPMC solution of viscosity average molecular weight, M(v), of 5 kg/mol over an approximate four fold polymer concentration range (0.

Effects of parathyroidectomy on bone remodeling markers and vitamin D status in patients with chronic kidney disease-mineral and bone disorder.

Background/aims: Chronic renal failure (CRF) is often associated with bone disorders including chronic kidney disease-mineral and bone disorder (CKD-MBD). Parathyroid hormone (PTH) has a relationship to bone remodeling, and so this study was undertaken to evaluate changes in bone remodeling markers after parathyroidectomy (PTX).

Methods: Twelve adult patients, mean age 43.

Naturally occurring compounds affect glutamatergic neurotransmission in rat brain.

Natural products, including those derived from plants, have largely contributed to the development of therapeutic drugs. Glutamate is the main excitatory neurotransmitter in the central nervous system and it is also considered a nociceptive neurotransmitter, by acting on peripheral nervous system. For this reason, in this study we investigated the effects of the hydroalcoholic extracts from Drymis winteri (polygodial and drimanial), Phyllanthus (rutin and quercetine), Jathopha elliptica (jatrophone), Hedyosmum brasiliense (13HDS), Ocotea suaveolens (Tormentic acid), Protium kleinii (alphabeta-amyrin), Citrus paradise (naringin), soybean (genistein) and Crataeva nurvala (lupeol), described as having antinociceptive effects, on glutamatergic transmission parameters, such as [(3)H]glutamate binding, [(3)H]glutamate uptake by synaptic vesicles and astrocyte cultures, and synaptosomal [(3)H]glutamate release.

Surgical approach to concealed penis: technical refinements and outcome.

Objectives: A concealed penis is defined as a phallus of normal size buried in prepubic tissue (buried penis), enclosed in scrotal tissue (webbed penis), or trapped by scar tissue after penile surgery (trapped penis). We report our results using a standardized surgical approach that was highly effective in both functional and cosmetic terms.

Methods: From January 2002 to December 2005, 56 patients (median age 7 years) underwent surgery for a buried penis, 11 (median age 5 years) for a webbed penis, and 20 (median age 8 years) for a trapped penis.

Ipsilateral right testicular metastasis from renal cell carcinoma in a responder patient to interleukine-2 treatment.

We present a case of metastatic spreading to the testicle in a 46-year-old patient with renal cell carcinoma, "clear-cell" type, during interleukin-2 combined subcutaneous plus aerosol treatment. Testicular metastasis occurred while the patient showed a response to the treatment with disappearance of lung lesions and reduction of lymph-nodes lesions. After orchiectomy with spermatic cord resection and disease re-evaluation confirming the previous response, the patient re-started immunotherapy.

A molecular basis of analgesic tolerance to cannabinoids.

Clinical usage of cannabinoids in chronic pain states is limited by their central side effects and the pharmacodynamic tolerance that sets in after repeated dosage. Analgesic tolerance to cannabinoids in vivo could be caused by agonist-induced downregulation and intracellular trafficking of cannabinoid receptors, but little is known about the molecular mechanisms involved. We show here that the type 1 cannabinoid receptor (CB1) interacts physically with G-protein-associated sorting protein 1 (GASP1), a protein that sorts receptors in lysosomal compartments destined for degradation.

Relationship between diet and anticoagulant response to warfarin: a factor analysis.

Background: Diet composition is one of the factors that may contribute to intraindividual variability in the anticoagulant response to warfarin.

Aim Of The Study: To determine the associations between food pattern and anticoagulant response to warfarin in a group of Brazilian patients with vascular disease.

Methods: Recent and usual food intakes were assessed in 115 patients receiving warfarin; and corresponding plasma phylloquinone (vitamin K(1)), serum triglyceride concentrations, prothrombin time (PT), and International Normalized Ratio (INR) were determined.

Ligand-induced down-regulation of the cannabinoid 1 receptor is mediated by the G-protein-coupled receptor-associated sorting protein GASP1.

The cannabinoid 1 receptor (CB1R) is one of the most abundant seven transmembrane (7TM) spanning/G-protein-coupled receptors in the central nervous system and plays an important role in pain transmission, feeding, and the rewarding effects of cannabis. Tolerance to cannabinoids has been widely observed after long-term use, with concomitant receptor desensitization and/or down-regulation depending on the brain region studied. Several CB1R agonists promote receptor internalization after activation, but the postendocytic sorting of the receptor has not been studied in detail.

Vitamin D status and the metabolic syndrome.

The identification of vitamin D receptor expression in different tissues suggests a widespread role for vitamin D action beyond its classical function in bone and mineral metabolism. Recently, the importance of vitamin D status as a risk factor in the development of metabolic syndrome has been the focus of several studies.

Surgical approach to the congenital megaprepuce.

The megaprepuce (MP) is a very rare malformation of unknown aetiology, with anatomical findings similar to those observed in the congenital buried penis (BP). The aspect of this entity and the symptoms are rather typical: the penis is totally buried and before micturition an evident pubic and scrotal swelling denounces the urine collection in an abnormal preputial cavity surrounding the entire shaft. Early surgery is recommended, in order to deal with functional and cosmetic aspects.

Early effects of extracorporeal shock wave treatment on osteoblast-like cells: a comparative study between electromagnetic and electrohydraulic devices.

Background: Extracorporeal shockwave therapy (ESWT) has been increasingly applied to treat orthopedic and musculoskeletal pathologies. ESWT involves mechanical perturbations that, as with other physical therapies, can result in mechanical stimuli to a large number of cells, including bone cells. The aim of this study was to evaluate the effects of shock waves on osteoblast-like cells (MG63) when using two different generators of shock waves (electrohydraulic and electromagnetic devices), in terms of cell damage, cell viability, osteogenic phenotype expression, and cytokine production.

Influence of ethanol on aspirin release from hypromellose matrices.

Release profiles of aspirin from hypromellose matrices in hydro-ethanolic media were studied. Percent aspirin released increased with increasing levels of ethanol in the dissolution media, correlating with the drug's solubility, however, dose dumping of aspirin did not occur. An initial rapid release was observed in media comprising 40% ethanol.

Using ultrasonic technology to manufacture products.

The use of ultrasonics in medical device manufacturing is gaining momentum as designers and engineers take advantage of the benefits it offers. A number of example medical applications are described that demonstrate the utility of ultrasonic processing in their manufacturer.

Dermatitis in the mining industry: incidence, sources, and time loss.

Occupational skin diseases and disorders are the most commonly reported nontrauma-related category of occupational illness in the United States, and mining has one of the highest incidence rates among all industries. The authors' objective in this study was to describe mining industry dermatitis incidence, sources of exposure, and resultant time lost from work. The authors reviewed Mine Accident, Injury and Illness Reports.

Aggregation and proteasome: the case of elongated polyglutamine aggregation in spinal and bulbar muscular atrophy.

Aggregates, a hallmark of most neurodegenerative diseases, may have different properties, and possibly different roles in neurodegeneration. We analysed ubiquitin-proteasome pathway functions during cytoplasmic aggregation in polyglutamine (polyQ) diseases, using a unique model of motor neuron disease, the SpinoBulbar Muscular Atrophy. The disease, which is linked to a polyQ tract elongation in the androgen receptor (ARpolyQ), has the interesting feature that ARpolyQ aggregation is triggered by the AR ligand, testosterone.

The sesquiterpenes polygodial and drimanial in vitro affect glutamatergic transport in rat brain.

Natural products including those derived from plants, have over the years greatly contributed to the development of therapeutic drugs. Polygodial and drimanial are sesquiterpenes isolated from the bark of the plant Drymis Winteri (Winteraceae) that exhibit antinociceptive properties. Since peripheral glutamate presents nociceptive actions, in this study it was investigated the effects of hydroalcooholic extracts from Drymis winteri (polygodial and drimanial) on the glutamatergic system in rat brain.

Relationship between calcium intake and body mass index in adolescents.

Epidemiologic and experimental data support thee possibility that dietary calcium intake plays a role in human body weight regulation. The aim of the present study was to evaluate calcium intake and its relationship with body mass index (BMI) in adolescents. Weight, height, 3-day food record and a food frequency questionnaire were collected among all adolescents participants at the Outpatient Clinic for Adolescents at the Federal University of Sao Paulo between 2001 and 2003.

Dietary phylloquinone depletion and repletion in postmenopausal women: effects on bone and mineral metabolism.

Introduction: Vitamin K has been implicated in increased bone fracture risk. Despite a potential role of vitamin K in bone, little is known about the effects of altered dietary phylloquinone intake on the underlying components of bone and mineral metabolism.

Methods: A 84-day in-house dietary phylloquinone (vitamin K) depletion-repletion study was undertaken in 21 postmenopausal women (mean age: 70 years) to assess the effects of altered vitamin K status on intestinal calcium (Ca) absorption, urinary and serum Ca and phosphorus (P), serum calcemic hormones, and serum biomarkers of bone turnover [osteocalcin and N-telopeptide type 1 collagen cross-links (NTx)] and the response to 1,25-dihydroxyvitamin D treatment (1 microg/dayx7 d).

Body composition changes in haemodialysis patients with secondary hyperparathyroidism after parathyroidectomy measured by conventional and vector bioimpedance analysis.

Considering the negative effects of secondary hyperparathyroidism (SHPT) in patients with chronic renal failure (CRF), the objective of the present study was to evaluate body composition changes using conventional and vector bioimpedance analysis in patients before and after parathyroidectomy (PTX). Twelve adult patients, mean age 43.4 (sd 12.

In vivo study on critical defects using the sheep model.

Bone grafting procedures are widely used to repair large defects successfully in humans, but new surgical therapies can be designed to improve allograft integration. The objective of this study was to investigate the best surgical procedure to study bone graft integration in a large animal model. An osteoperiosteal defect of 3 cm in the tibia or in the metatarsal was made in 15 adult crossbreed sheep to investigate osteo-integration of a homologous bone graft in an intercalary critical defect.

Reflections on the diseases linked to mutations of the androgen receptor.

This review summarizes the most recent information on two pathologies linked to mutations of the androgen receptor, namely, the complete androgen insensitivity syndrome (CAIS) and the spinal and bulbar muscular atrophy (SBMA or Kennedy's disease). Data on the clinical manifestations of the two diseases are presented, together with the most relevant findings on their physiopathology and genetics.

Citric acid prolongs the gastro-retention of a floating dosage form and increases bioavailability of riboflavin in the fasted state.

A floating dosage form based on calcium alginate beads has been developed. Riboflavin, was selected as the model drug and successfully incorporated into calcium alginate beads. The aims of the current study were to: (a) assess the influence of prolonged gastro-retention on the bioavailability of riboflavin from freeze dried calcium alginate beads administered under varying conditions of food intake and (b) to investigate the potential of citric acid to delay the gastric emptying of the calcium alginate beads.

The use of citric acid to prolong the in vivo gastro-retention of a floating dosage form in the fasted state.

Gastro-retentive dosage forms have the potential to improve local therapy and decrease the variation in bioavailability that is observed with a number of commercially available immediate and modified release preparations. In this study, a dosage form has been developed, utilising freeze-dried calcium alginate beads, designed to float on the surface of the stomach contents thus prolonging the retention time. The aim of the study was to also assess the in vivo behaviour of the radio-labelled calcium alginate beads when they were administered under fasting conditions with either water or an aqueous solution of citric acid, a potential gut transit delaying substance.

The power of ultrasonics.

This overview of ultrasonic technologies describes their effectiveness for a number of applications. Product examples illustrate use for welding, cutting and boring as well as atomising.