Treatment of experimental renal osteodystrophy with pamidronate

We evaluated the effects of the bisphosphonate pamidronate on bone histomorphometry, structure and strength in male rats with uninephrectomy or with chronic renal disease induced by 5/6 nephrectomy. In rats with chronic renal disease the plasma urea, phosphate and parathyroid hormone levels were significantly increased compared to rats with a uninephroctomy and none of these parameters was affected by pamidronate treatment. In the femoral midshaft, chronic renal disease reduced cortical bone mineral density and content. No difference was observed in the breaking load of the femoral midshaft. In the distal femur, a high-turnover renal osteodystrophy was found but pamidronate suppressed this bone turnover and increased bone mineral content. Treatment had no effect on chronic disease-induced augmentation of osteoid volume or fibroblast surface. These studies show that in this model of stage 3 renal disease, pamidronate increased mineral content in the femoral midshaft and distal metaphysis primarily by adding bone to endocortical and trabecular surfaces but did not reduce osteitis fibrosa.     

Modifying drug release and tablet properties of starch acetate tablets by dry powder agglomeration

In this study three model drugs (N-acetyl-D-glucosamine (NAG), anhydrous caffeine, and propranolol hydrochloride) were agglomerated with starch acetate (SA) by mixing the binary powders on a stainless steel (SS) plate. Agglomeration was induced by triboelectrification of the particles during mixing, and it was evaluated as a method to achieve controlled drug release rate. These agglomerates, mixed with different amounts of a disintegrant, were compressed into tablets whose dissolution characteristics were determined. Triboelectric measurements showed that when the drugs were in contact with SS, charges of the opposite polarity were generated to SA (+) and caffeine and NAG (-) promoting adhesion. Instead, propranolol HCl was charged with the same polarity as SA. SEM micrographs showed that smaller caffeine particles, in spite of their larger negative charge, agglomerated less efficiently with SA than larger NAG particles. This emphasizes the importance of particle size in the agglomeration process. Propranolol HCl did not form agglomerates with SA since their particle sizes and charges were identical. As a result, agglomeration of powders prior to tablet compression allows for modification and control of the release rate of the drugs from the SA matrix tablets as well as the tensile strength of the tablets.     

Prolonged unloading in growing rats reduces cortical osteocyte lacunar density and volume in the distal tibia

Bone dynamically adapts its structure to the environmental demands placed upon it. Load-related stimuli play an important role in this adaptation. It has been postulated that osteocytes sense changes in these stimuli and initiate adaptive responses, across a number of scales, through a process known as mechanotransduction. While much research has focused on gross and tissue-level adaptation, relatively little is known regarding the relation between cellular-level features (e.g. osteocyte lacunar density, volume and shape) and loading. The increasing availability of high resolution 3D imaging modalities, including synchrotron-based techniques, has made studying 3D cellular-level features feasible on a scale not previously possible. The primary objective of this study was to test the hypothesis that unloading (sciatic neurectomy) during growth results in altered osteocyte lacunar density in the tibial diaphysis of the rat. Secondarily, we explored a potential effect of unloading on mean lacunar volume. Lacunar density was significantly (p < 0.05) lower in immobilized bones (49,642 ± 11,955 lacunae per mm³; n = 6) than in control bones (63,138 ± 1956 lacunae per mm³; n = 6). Mean lacunar volume for immobilized bones (209 ± 72 μm³; n = 6) was significantly smaller (p < 0.05) than that for the control bones (284 ± 28 μm³; n = 6). Our results demonstrate that extreme differences in loading conditions, such as those created by paralysis, do indeed result in changes in osteocyte lacunar density and volume. Further investigation is warranted to examine relations between these measures and more subtle variation in loading as well as pathological states, which have been linked to alterations in mechanotransduction.     

Health Care Students’ Differing Conceptions of Expertise: A Challenge for Inter-Professional Care

The aim of the study was to examine do health care students, who study at different programs, value similar expert qualities. To investigate this issue, a questionnaire was administered among health care students in a Finnish polytechnic (two cohorts, total n = 466), consisting of a scale for rating the importance of different expert qualities. The questionnaire resulted in the following dimensions of the conceptions of expertise: (1) social skills, (2) scientific skills, (3) innovativeness, (4) continuing self-development, and (5) problem-solving skills. Also the Inventory of General Study Orientations (IGSO) was applied to analyse possible motivational explanations for different conceptions of expertise. In addition to the scales, an open-ended writing task was used to explore in depth students’ conceptions of expertise. It appeared that study orientations were a minor factor in the study, while study environment (study programs) clearly differentiated students’ conceptions of expertise. Thus, the study argues that health care students’ conceptions of expertise are constituted mainly on domain-specific bases and that students who graduate from different programs may possess very diverse ideas about their profession. Consequently, different conceptions captured during the education form a major challenge for inter-professional care later in work-life. This phenomenon should be taken into account when organising health care education.     

Spinal NMDA-receptor dependent amplification of nociceptive transmission to rat primary somatosensory cortex (SI)

The role of NMDA mechanisms in spinal pathways mediating acute nociceptive input to the somatosensory cortex is not clear. In this study, the effect of NMDA-antagonists on nociceptive C fibre transmission to the primary somatosensory cortex (SI) was investigated. Cortical field potentials evoked by CO(2)-laser stimulation of the skin were recorded in the halothane/nitrous oxide anaesthetized rat. The SI nociceptive evoked potential (EP) amplitudes were dependent on the frequency of noxious heat stimulation. The amplitudes of SI potentials evoked by CO(2)-laser pulses (duration 15-20 ms, stimulation energy 21-28 mJ/mm(2)) delivered at a frequency of 0.1 Hz were approximately 40% of the amplitudes of potentials evoked by 1.0 Hz stimulation. After intrathecal lumbar application of either of the NMDA-antagonists CPP or MK-801, the amplitudes of nociceptive SI potentials, evoked by 1.0 Hz stimulation of the contralateral hindpaw, were reduced to approximately 40% of controls. By contrast, field potentials evoked by 0.1 Hz stimulation of the hindpaw were unaffected by MK-801. SI potentials evoked by 1.0 Hz stimulation of the contralateral forepaw did not change after lumbar application of CPP or MK-801, indicating that the depression of hindpaw EPs was due to a segmental effect in the spinal cord. It is concluded that spinal NMDA-receptor mechanisms amplify the acute transmission of nociceptive C fiber input to SI in a frequency-dependent way.     

Sleep disturbances in a community sample from preschool to school age

Objective To study the prevalence of various sleep problems at school age in a Finnish community sample and to evaluate the persistence of the sleep problems from the preschool age to school age in a 4‐year follow‐up. Methods Parents completed the Sleep Disturbance Scale for Children questionnaire on their child's sleep during the preschool years (3–6 years) and again during the school years (7–11 years). At follow‐up the parents also completed a questionnaire on family structure and socio‐economic status. Results The parents of 481 children completed the questionnaires during both the first study and the follow‐up (girls 49%, boys 51%; mean age 9, range 7–11). At the population level, sleep problems slightly declined from preschool to school age (P < 0.05). However, sleep problems at preschool age showed a strong persistence to school age. At the follow‐up, 35% of the children who were considered to have a sleep disorder at preschool age still suffered from it at school age. At the community level, this equates to 9% of the children. The children with no sleep problems at preschool age rarely developed sleep problems at school age. Conclusions This study showed that various types of sleep problems are common at school age. Sleep problems persisted from preschool to school age at the individual level. It is important to recognize all types of sleep problems, especially persistent ones. Persistent sleep problems in children may cause and exacerbate other somatic, cognitive and psychiatric problems. Therefore, more attention should be focused on sleep problems in paediatric health care with interventions aimed particularly at children with prolonged sleep problems.     

Toxicity of fullerene (C(60) ) to sediment-dwelling invertebrate Chironomus riparius larvae

An environmentally realistic method to test fullerene (C(60) ) toxicity to the benthic organism Chironomus riparius was created by allowing suspended fullerenes to settle down, making a layer on top of the sediment. To test the hypothesis that higher food concentrations will reduce toxic responses, two food concentrations were tested (0.5 and 0.8% Urtica sp.) in sediment containing fullerene masses of 0.36 to 0.55?mg/cm(2) using a 10-d chronic test. In the 0.5% food level treatments, there were significant differences in all growth-related endpoints compared with controls. Fewer effects were observed for the higher food treatment. Fullerene agglomerates were observed by electron microscopy in the gut, but no absorption into the gut epithelial cells was detected. In the organisms exposed to fullerenes, microvilli were damaged and were significantly shorter. The potential toxicity of fullerene to C. riparius appears to be caused by morphological changes, inhibiting larval growth. Environ. Toxicol. Chem. 2012; 31: 2108-2116. ? 2012 SETAC.     

Laminin isoform-specific promotion of adhesion and migration of human bone marrow progenitor cells

Laminins are alphabetagamma heterotrimeric extracellular proteins that regulate cellular functions by adhesion to integrin and nonintegrin receptors. Laminins containing alpha4 and alpha5 chains are expressed in bone marrow, but their interactions with hematopoietic progenitors are unknown. We studied human bone marrow cell adhesion to laminin-10/11 (alpha5beta1gamma1/alpha5beta2gamma1), laminin-8 (alpha4beta1gamma1), laminin-1 (alpha1beta1gamma1), and fibronectin. About 35% to 40% of CD34(+) and CD34(+)CD38(-) stem and progenitor cells adhered to laminin-10/11, and 45% to 50% adhered to fibronectin, whereas they adhered less to laminin-8 and laminin-1. Adhesion of CD34(+)CD38(-) cells to laminin-10/11 was maximal without integrin activation, whereas adhesion to other proteins was dependent on protein kinase C activation by 12-tetradecanoyl phorbol-13-acetate (TPA). Fluorescence-activated cell-sorting (FACS) analysis showed expression of integrin alpha6 chain on most CD34(+) and CD34(+)CD38(-) cells. Integrin alpha6 and beta1 chains were involved in binding of both cell fractions to laminin-10/11 and laminin-8. Laminin-10/11 was highly adhesive to lineage-committed myelomonocytic and erythroid progenitor cells and most lymphoid and myeloid cell lines studied, whereas laminin-8 was less adhesive. In functional assays, both laminin-8 and laminin-10/11 facilitated stromal-derived factor-1alpha (SDF-1alpha)-stimulated transmigration of CD34(+) cells, by an integrin alpha6 receptor-mediated mechanism. In conclusion, we demonstrate laminin isoform-specific adhesive interactions with human bone marrow stem, progenitor, and more differentiated cells. The cell-adhesive laminins affected migration of hematopoietic progenitors, suggesting a physiologic role for laminins during hematopoiesis.     

Sleep-related disorders in carpal tunnel syndrome

Introduction – Patients with carpal tunnel syndrome (CTS) often wake up at night due to pain and numbness of affected fingers and hand. We studied the sleep disorder caused by CTS. Subjects and methods – 34 consecutive patients referred for operative treatment of CTS answered to a sleep questionnaire and the results were compared to a stratified random sample of 1600 Finns aged 36–50 year, whose response rate to the mailed questionnaires was 75.2% (n=1186). Six CTS patients underwent a polygraphic sleep study before and after operative treatment of CTS. Results – CTS patients reported suffering from poor sleep quality, fragmentary sleep and daytime sleepiness more often than controls. Before operative treatment of CTS there were more nocturnal body movements (p<0.01) and awakenings lasted longer (p<0.05) than after operation. During preoperative sleep studies no drop in median nerve conduction was detected during awakenings. Conclusions – Patients with CTS suffer from fragmentary sleep. Although patients reported waking up for the pain or numbness of hands no impairment in median and ulnar nerve conduction could be observed during these awakenings. Operative treatment of hand entrapment significantly reduced the number of nocturnal movements.