Muscle and brain changes of calcitonin gene-related peptide in experimentally induced unilateral rat masseter myositis

AIMS: To investigate changes in calcitonin gene-related peptide (CGRP)-like immunoreactivity (CGRP-LI) in the rat masseter muscle and brain after the unilateral experimental induction of masseter myositis. METHODS: Ipsilateral and contralateral changes of the CGRP were examined in rat masseter muscle after the induction of unilateral myositis on the right side with an intramuscular injection of 0.01 mL Freund's adjuvant. The left masseter, and left and right masseters of control rats, were injected with 0.01 mL saline (0.9%). After 21 days, tissue samples from the masseter muscles and the hypothalamic-pituitary-adrenal (HPA) axis were analyzed for the presence of CGRP by immunohistochemistry, radioactive immunoassay, and high performance liquid chromatography. Hematoxylin-eosin staining was used to confirm inflammation in the masseter muscles. RESULTS: Elevated CGRP-LI was detected bilaterally in the masseter muscles (P < .001) in the myositis group. CGRP-immunoreactive nerve fibers were mainly detected in close proximity to muscle cells and in the walls of the blood vessels. Compared to the control rats, a significant difference in scratching behavior was seen in the myositis group from day 9 until day 21. In the myositis group, CGRP-LI was increased in the pituitary gland concomitant with the increase in CGRP-LI in the masseter muscles but was decreased in the hypothalamus. A possible explanation for these changes could be that rats with chronic myositis develop an abnormal function of the HPA axis triggered by masseter muscle inflammation. CONCLUSION: The results of this study demonstrate that CGRP may play an important role both peripherally and centrally in masseter muscle myositis in association with presumed nociceptive behavior.     

Practical wisdom: competencies required in alleviating suffering in palliative care

The aim of this article is to reflect upon the competencies required to alleviate suffering in palliative care. The knowledge to prudently and wisely act in a situation involving human relationships can be defined in terms of practical abilities and contextual skills. In the setting of the care of the very ill and dying, practical wisdom such as the carer's ability to meet the suffering person and to act with sensitivity and openness, becomes important. From this, learning to alleviate suffering emerges as receiving insight and wisdom from the suffering person's experience of suffering. This means that the testimony of suffering persons--what they have endured, given up and experienced--becomes as significant as theoretical and practical knowledge of suffering. The professional carer needs to learn how to be open to and interpret what the suffering person, living with suffering and death in the midst of life, can teach.     

Could sound be used as a strategy for reducing symptoms of perceived motion sickness?

Background  

Working while exposed to motions, physically and psychologically affects a person. Traditionally, motion sickness symptom reduction has implied use of medication, which can lead to detrimental effects on performance. Non-pharmaceutical strategies, in turn, often require cognitive and perceptual attention. Hence, for people working in high demand environments where it is impossible to reallocate focus of attention, other strategies are called upon. The aim of the study was to investigate possible impact of a mitigation strategy on perceived motion sickness and psychophysiological responses, based on an artificial sound horizon compared with a non-positioned sound source.     

Violation of dignity in care-related situations

This study seeks to explore narratives of care-related violations for patients with life-threatening illness receiving palliative care. Narratives told in dialogues with the researcher were processed phenomenologically hermeneutically. Four structures of meanings are described: focal points in recalling the experiences, experienced consequences of being violated, relationships causing violation, and personal struggling. The phenomenon of care-related violations means a complex experience of suffering as being abandoned, confronted with hopelessness, and further wounded. This experience may be directed toward readiness to share, introspectiveness, willingness to comprehend the incomprehensible, the riskiness of facing others, and attentiveness to acts of caring. It can be experienced in various relationships to professionals, family members and friends, to the mass media, and to welfare systems. Care-related violating episodes reveal the vulnerability of the person who is already suffering and makes him or her still more wounded, when actually comfort is expected. To receive affirmation in the state of fragility with increased suffering provoked by care-related violations can contribute to a transformation from human degradation into dignity, finding meaning, or reaching reconciliation in suffering.     

The point of transition on the dose‐effect curve as a reference point in the evaluation of in vitro toxicity data

Dose‐effect evaluation is an increasingly important step of health risk assessment. The foreseen increase of in vitro methods argues for the development and evaluation of a clearly defined reference points for dose‐effect modelling of in vitro data. In the present study, the traditional use of a concentration corresponding to 10% or 50% of the maximal effect (EC₁₀ or EC₅₀) is compared with a strategy, under which, a reference point (Benchmark dose, BMD_T) is calculated that represents the dose where the slope of the dose‐effect curve changes the most (per unit log‐dose) in the low dose region. To illustrate the importance of the reference point, dose‐effect data on CYP1A1 enzyme activity for 30 polychlorinated biphenyl (PCB) congeners were evaluated in order to calculate relative potencies, in relation to 2,3,7,8‐TCDD, with confidence intervals (CIs). The present study shows that the interpretation of the results as potency and rank orders potentially depends on the choice and definition of the reference point (BMD_T, EC₁₀ or EC₅₀). This is important as potency ranking may be used as a method for screening and prioritization, in research, in policy development or in pharmaceutical development. The use of the BMD_T implies a focus on the change of structure in the parameter's dose–response rather than a particular percentage change in the response in such a parameter. In conclusion, the BMD_T may be used as an alternative base for evaluation of dose‐effect relationships in vitro. It offers an objective geometrical definition of a reference point in the low‐dose region of the dose‐effect curve. Copyright © 2012 John Wiley & Sons, Ltd.     

Factors involved in inflammation-induced developmental white matter damage

Developmental white matter damage is a brain pathology associated with several long-term neurological disorders. An inflammatory insult has been suggested as the major instigating event. This study investigated the relative influence of inflammation, blood–brain barrier permeability and glial ontogeny in white matter damage. Systemic inflammation was induced in Monodelphis domestica (opossum) by serial intraperitoneal injections of lipopolysaccharide at different stages of brain development. Volume of white matter was estimated for the external capsule. Blood–brain barrier permeability was assessed immunocytochemically. Quantitative RT-PCR was used to measure relative levels of mRNA for IL-1β, IL-6 and COX-2. Developmental changes in numbers and appearance of microglia and astrocytes were estimated. Results showed that in response to systemic inflammation, white matter was reduced in the external capsule during a circumscribed period only. At the same developmental stage blood–brain barrier permeability was altered, cerebral inflammatory response was present and numbers of microglia increased. However, the periods of altered blood–brain barrier permeability and the cerebral inflammatory response were longer than the period of the external capsule's susceptibility to white matter damage, which coincided with the developmental increase in the number of astrocytes in this tract. Thus, the mechanism of white matter damage following systemic inflammation is multifactorial, including cerebral inflammation and breakdown of brain barriers occurring simultaneously at specific stages of glial cell development.     

Intraorally fast-dissolving particles of a poorly soluble drug: Preparation and in vitro characterization

In this study, the dissolution rate of a poorly soluble drug, perphenazine (PPZ) was improved by a solid dispersion technique to permit its usage in intraoral formulations. Dissolution of PPZ (4 mg) in a small liquid volume (3 ml, pH 6.8) within one minute was set as the objective. PVP K30 and PEG 8000 were selected for carriers according to the solubility parameter approach and their 5/1, 1/5 and 1/20 mixtures with PPZ (PPZ/polymer w/w) were prepared by freeze-drying from 0.1 N HCl solutions. The dissolution rate of PPZ was improved with all drug/polymer mixture ratios compared to crystalline or micronized PPZ. A major dissolution rate improvement was seen with 1/5 PPZ/PEG formulation, i.e. PPZ was dissolved completely within one minute. SAXS, DSC and XRPD measurements indicated that solid solutions of amorphous PPZ in amorphous PVP or in partly amorphous PEG were formed. DSC and FTIR studies suggested that PPZ dihydrochloride salt was formed and hydrogen bonding was occurred between PPZ and the polymers. It was concluded that molecular mixing together with salt formation promoted the dissolution of PPZ, especially in the case of the 1/5 PPZ/PEG dispersion, making it a promising candidate for use in intraoral formulations.     

Genetic mosaicism in basal cell carcinoma

Human basal cell cancer (BCC) shows unique growth characteristics, including a virtual inability to metastasize, absence of a precursor stage and lack of tumour progression. The clonal nature of BCC has long been a subject for debate because of the tumour growth pattern. Despite a morphologically multifocal appearance, genetic analysis and three-dimensional reconstructions of tumours have favoured a unicellular origin. We have utilized the X-chromosome inactivation assay in order to examine clonality in 13 cases of BCC. Four parts of each individual tumour plus isolated samples of stroma were analysed following laser-assisted microdissection. In 12/13 tumours, the epithelial component of the tumour showed a monoclonal pattern suggesting a unicellular origin. Surprisingly, one tumour showed evidence of being composed of at least two non-related monoclonal clones. This finding was supported by the analysis of the ptch and p53 gene. Clonality analysis of tumour stroma showed both mono- and polyclonal patterns. A prerequisite for this assay is that the extent of skewing is determined and compensated for in each case. Owing to the mosaic pattern of normal human epidermis, accurate coefficients are difficult to obtain; we, therefore, performed all analyses both with and without considering skewing. This study concludes that BCC are monoclonal neoplastic growths of epithelial cells, embedded in a connective tissue stroma at least in part of polyclonal origin. The study results show that what appears to be one tumour may occasionally constitute two or more independent tumours intermingled or adjacent to each other, possibly reflecting a local predisposition to malignant transformation.