Decreased cytogenesis in the granule cell layer of the hippocampus and impaired place learning after irradiation of the young mouse brain evaluated using the IntelliCage platform

Radiation therapy is used to treat malignant tumors in the brain and central nervous system involvement of leukemia and lymphomas in children. However, ionizing radiation causes a number of adverse long-term side effects in the brain, including cognitive impairment. Hippocampal neurogenesis is important for place learning and has been shown to be decreased by irradiation (IR) in rats and mice. In the present study, 10-day-old male mice received 6-Gy IR to the brain on postnatal day 10. We used BrdU labeling of the granule cell layer (GCL) of the hippocampus to evaluate cell proliferation and survival. An unbiased, automated platform for monitoring of behavior in a group housing environment (IntelliCage) was used to evaluate place learning 2 months after IR. We show that cranial IR impaired place learning and reduced BrdU labeling by 50% in the GCL. Cranial IR also reduced whole body weight gain 5%. We conclude that this experimental paradigm provides a novel and time-saving model to detect differences in place learning in mice subjected to IR. This method of detecting behavioral differences can be used for further studies of adverse effects of IR on hippocampal neurogenesis and possible new strategies to ameliorate the negative effects of IR on cognition.     

Focus groups in Swedish psoriatic patients with pruritus

Pruritus is a common complaint among patients of psoriasis vulgaris of the chronic plaque type. Despite a high prevalence of pruritus in psoriasis, limited information is available on this subject. The aim was to assess patients' perspective of pruritus in psoriasis vulgaris of plaque type, by using focus groups. A total of 20 patients with chronic plaque psoriasis participated in focus group discussions and were divided into five groups, on different occasions. Themes for the discussion were introduced and moderated by the investigators. The focus groups created a proper atmosphere for discussion on different aspects of pruritus in psoriasis. The patients regarded themselves able to discriminate between pruritus and pain. Pruritus was most common on the lower back and legs. Stress, cold weather and skin dryness were seen as the most common worsening factors for pruritus. Sunbathing and application of emollients with or without steroids and calcipotriol cream were suggested as factors that relieved pruritus. Quality of life was affected in some patients, for instance they were reluctant to participate in social activities. Patients' perspectives on pruritus in psoriasis were important for a better understanding of this sensation. The information collected from the focus group discussions might be useful for further study in this area.     

Intraischemic mild hypothermia prevents neuronal cell death and tissue loss after neonatal cerebral hypoxia-ischemia

The effectiveness of hypothermia in preventing ischemic brain damage depends on when it is started. The purpose of this study was to investigate the effects of temperature reduction during a hypoxic-ischemic (HI) insult on brain injury and signalling pathways of neuronal cell death and survival. Seven-day-old mice were subjected to left common carotid artery ligation and hypoxia (10% oxygen) at different temperatures (37, 36 or 34 degrees C) for 50 min. Brain injury at 7 days post-HI was significantly reduced from 67.4% at 37 degrees C to 31.6% at 36 degrees C and 10% at 34 degrees C, with no observable injury in the cortex of the 34 degrees C group. Cytochrome c release, caspase-3 activation and apoptosis-inducing factor translocation from mitochondria to nuclei were all significantly inhibited after intraischemic temperature reduction. Concurrently, the cell survival signalling pathway involving Akt was significantly sustained (the phosphorylated form of Akt was maintained) when the hypoxia temperature was decreased. These results indicate that intraischemic hypothermia diminished apoptosis through inhibition of both caspase-dependent and caspase-independent neuronal cell death pathways and promoted cell survival by inhibition of phosphorylated Akt dephosphorylation in the neonatal brain, thereby preventing neuronal cell death.     

Chronic mild stress modulates 5-HT1A and 5-HT2A receptor expression in the cerebellar cortex of NC/Nga atopic-like mice

Atopic eczema symptoms may worsen due to stress. In the present study, the cerebellar cortex of the atopic-like mouse NC/Nga was studied regarding the effect of chronic mild stress on expression of two well-characterized serotonergic receptors (R), 5-HT1A and 5-HT2A. In total 24 mice were used. Sixteen of these mice were subjected to unpredictable stressors for 12 weeks, and 8 mice were used as controls. In order to evoke an eczema, a mite antigen was applied to 16 mice from week 9 of the experiment. Thus, three groups of mice, stressed eczematous (SE), non-stressed eczematous (NSE) and stressed control (SC), respectively, were obtained. The expression of the 5-HT1AR was analyzed using quantitative immunohistochemistry. For evaluation of 5-HT2AR a semi-quantitative technique was used, the cell density and signal intensity being measured. The highest average value for 5-HT1AR expression, in the Purkinje cells, was recorded in the NSE group, while the lowest average was in the SC group. 5-HT1AR expression differed significantly between the groups. The highest average value for density of 5-HT2AR positive Purkinje cells was evident in the SE group, while the lowest was in the SC group, this difference between groups also being statistically significant. In addition, the signal intensity was highest in the SE group, with a difference compared to the other groups. In conclusion, chronic mild stress modulates serotonergic receptor expressions in the cerebellar cortex of atopic-like mice.     

Serotonin transporter protein overexpression and association to Th 17 and T regulatory cells in lupoid leishmaniasis

The immunopathogenesis of chronic non-healing Old World cutaneous leishmaniasis is challenging. There is a bidirectional communication between the nervous and immune systems, serotonin being an important mediator in this respect. Our aim was to study the role of the serotonin transporter protein (SERT) and its relation to T cell-related immune responses in lupoid leishmaniasis. Paraffin-embedded skin biopsies of 12 cases of lupoid and 12 cases of usual types of cutaneous leishmaniasis were investigated using immunohistochemistry regarding expression of SERT, Th1, Th2, Th17 and T regulatory cell (Treg) markers. SERT as well as Tregs and interleukin (IL)-17 positive cells were more prevalent while IL-5 (Th2) and interferon (IFN)-γ (Th1) expressing cells were less numerous in the lupoid tissue compared to those from the usual type of leishmaniasis. The majority of the SERT⁺ cells were also tryptase⁺ (mast cells). There was a positive correlation between a higher number of SERT⁺ and IL-17⁺ cells in the lupoid type, while lower numbers of SERT⁺ cells were significantly related to lower percentages of CD25⁺ cells in the usual type of leishmaniasis. These results might indicate a role for SERT, Th17 and Tregs in the pathogenesis of lupoid leishmaniasis.     

Role of genetic and epigenetic changes in Burkitt lymphoma

All Burkitt lymphomas (BLs) carry reciprocal chromosomal translocations that activate the c-myc oncogene through juxtaposition to one of the immunoglobulin (Ig) loci. Many BL carry point mutation in the p53 tumor suppressor gene or other defects in the p14ARF-MDM2-p53 pathway, and inactivation of the p16INK4a gene by promoter methylation or homozygous deletion. This indicates that disruption of both the pRb and p53 tumor suppressor pathways is critical for BL development. Alterations of other genes, including Bax, p73, and BCL-6, may provide further growth stimulation and apoptosis protection. Thus, BL development involves multiple genetic and epigenetic changes that drive cell cycle progression and avert cell death by apoptosis.     

Dose effects of continuous vinblastine chemotherapy on mammalian angiogenesis mediated by VEGF-A

Low-dose continuous or metronomic chemotherapy with several agents can exert significant antiangiogenic effects, as shown in preclinical studies. Therapy of this kind is generally well tolerated compared with conventional chemotherapy with high, temporally spaced out bolus doses. A critical point emerges when the effects on angiogenesis of low-toxic metronomic doses of chemotherapeutics in preclinical studies are to be transferred to clinical protocols, as there is a risk that a virtually non-toxic dose might also be ineffective; clearly, dose-effect data are important. We therefore sought to investigate whether a dose-dependent response exists in metronomic vinblastine chemotherapy. The surrogate tumor-free rat mesentery model, allowing the study of antiangiogenic effects per se, was used. Following systemically administered metronomic chemotherapy, it closely reflects the indirectly assessed antiangiogenic and growth-retarding effects in a syngenic cancer model. VEGF-A, which is a central proangiogenic factor in most tumors, was administered i.p. to induce angiogenesis in the mesenteric test tissue and, using morphometry, the angiogenesis-modulating effects of vinblastine were assessed in terms of objective quantitative variables. We report that continuous vinblastine treatment with an apparently non-toxic dose (1.0 mg/kg/week or 0.143 mg/kg/day) for 10 days, and a dose that substantially inhibited the physiologic body-weight gain (2.0 mg/kg/week or 0.286 mg/kg/day) for 6 days, demonstrates a dose-response relationship; the high dose significantly suppresses angiogenesis. To our knowledge, no previous study has reported on a dose-dependent antiangiogenic effect by continuous or metronomic vinblastine treatment in a mammalian in vivo model.     

Cutaneous human papillomavirus 88: remarkable differences in viral load

A human papillomavirus (HPV) was cloned from a patient with multiple squamous cell carcinomas (SCCs) and identified as HPV88, recently categorized into a new species within the genus Gamma. The HPV88 viral load in an SCC of the index patient exceeded 1 million copies/cell. By contrast, a survey of 447 skin lesions (79 actinic keratoses, 73 seborrhoeic keratoses, 169 basal cell carcinomas and 126 SCCs) and 362 healthy skin biopsies found detectable HPV88 DNA in only 7 specimens. All these had very low viral loads (<1 copy/10(3) cells) implying extreme biological variability in viral load.     

Item development for a questionnaire investigating patient self reported perception,satisfaction and outcomes of a single osteopathy in the cranial field (OCF) treatment

BackgroundOsteopathy in the Cranial Field (OCF) is a treatment approach used by osteopaths in the management of a wide variety of complaints. OCF is based on the premise that the bones of the skull are mobile and that changes in the flow of cerebrospinal fluid can affect the function of the body. There are only a few studies assessing the effectiveness of OCF and there is no published research investigating patients' perception of what happens during and post an OCF treatment.ObjectiveTo develop items for a patient self-reported questionnaire that assesses patients' own perceptions of one OCF treatment.DesignSystematic literature search, item development and face validity testing.MethodsA systematic search of the literature was undertaken to identify a measure or measures that may be suitable to assess patient perceptions of OCF. No measure of patient perception of OCF was located. Measures of patient ratings of satisfaction, efficacy and outcomes of physical therapy treatment were located and reviewed. From these published measures, items that were appropriate for a measure of OCF were identified and considered as possible items to include in a new measure of patient perception of OCF. Items were developed and face validity was investigated.ParticipantsSix osteopaths who were familiar with or use OCF as part of their treatment approach, 2 patients who had previously been treated by osteopaths who used OCF exclusively, and 2 patients who had not previously received any OCF treatment as part of their osteopathic treatment.ResultsA systematic literature search was conducted. Appropriate items were extracted from 7 articles in the ‘osteopathy’ search and 4 additional articles from the ‘manual therapy’ search. Items were reworded, where appropriate, to ensure they reflected the OCF approach. Consideration of face validity identified a number of changes that were required to some of the items.ConclusionsThe Patient Perception Measure of Osteopathy in the Cranial Field (PPM-OCF) was developed to assess patient perceptions of the OCF treatment approach. Six domains of patient perception of treatment were identified and 37 items were developed within these 6 domains. Further psychometric testing of the PPM-OCF is required prior to its application in the clinical and research settings.     

Immediate diagnosis of ventriculits: evaluation of parameters independent of microbiological culture

Background  

Generally accepted reference values in CSF diagnostics are not valid in cerebrospinal fluid (CSF) containing large amounts of blood. Residual blood may obscure ventriculitis as diagnostics largely depend on parameters such as cell count, lactic acid and total protein measurement. We sought to improve the diagnostics by evaluating a cytokine panel and soluble CD62L as markers of ventriculitis. In addition, we tested an algorithm of established parameters to predict ventriculitis in a specific patient collective.