Noradrenergic and opioidergic alterations in neuropathy in different rat strains

The Fischer 344 (F344) rat strain differs from the Lewis strain in the response to neuropathic pain. Recently, we found that F344 rats totally recover from mechanical allodynia induced by chronic constriction injury (CCI) of the sciatic nerve 28 days after surgery whereas Lewis rats are initiating their recovery at this time point. Thus, the use of this neuropathic pain model in these different rat strains constitutes a good strategy to identify possible target genes involved in the development of neuropathic pain. Since differences between Lewis and F344 rats in their response to pain stimuli in acute pain models have been related to differences in the endogenous opioid and noradrenergic systems, we aimed to determine the levels of expression of key genes of both systems in the spinal cord and dorsal root ganglia (DRG) of both strains 28 days after CCI surgery. Real time RT-PCR revealed minimal changes in gene expression in the spinal cord after CCI despite the strain considered, but marked changes in DRG were observed. A significant upregulation of prodynorphin gene expression occurred only in injured DRG of F344 rats, the most resistant strain to neuropathic pain. In addition, we found a significant downregulation of tyrosine hydroxylase and proenkephalin gene expression levels in both strains whereas δ-opioid receptor was found to be significantly downregulated only in injured DRG of Lewis rats although the same trend was observed in F344 rats. The data strongly suggest that dynorphins could be involved in strain differences concerning CCI resistance.     

Different pattern of pleiotrophin and midkine expression in neuropathic pain: Correlation between changes in pleiotrophin gene expression and rat strain differences in neuropathic pain

Pleiotrophin (PTN) and midkine (MK) are two growth factors highly redundant in function that exhibit neurotrophic actions and are upregulated at sites of nerve injury, both properties being compatible with a potential involvement in the pathophysiological events that follow nerve damage (i.e. neuropathic pain). We have tested this hypothesis by comparatively studying PTN and MK gene expression in the spinal cord and dorsal root ganglia (DRG) of three rat strains known to differ in their behavioural responses to chronic constriction injury (CCI) of the sciatic nerve: Lewis, Fischer 344 (F344) and Sprague–Dawley (SD). Real time RT-PCR revealed minimal changes in PTN/MK gene expression in the spinal cord after CCI despite the strain considered, but marked changes were detected in DRG. A significant upregulation of PTN gene expression occurred in injured DRG of the F344 strain, the only strain that recovers from CCI-induced mechanical allodynia 28 days after surgery. In contrast, PTN was found to be downregulated in injured DRG of SD rats, the most sensitive strain in behavioural studies. These changes in PTN were not paralleled by concomitant modifications of MK gene expression. The results demonstrate previously unidentified differences between PTN and MK patterns of expression. Furthermore, the data suggest that upregulation of PTN, but not MK, could play an important role in the recovery from CCI.     

Efecto de la ortesis de tobillo pie en el control postural tras el accidente cerebrovascular: revisión sistemática

Introduction

Stroke is currently the main cause of permanent disability in adults. The impairments are a combination of sensory, motor, cognitive and emotional changes that result in restrictions on the ability to perform basic activities of daily living (BADL). Postural control is affected and causes problems with static and dynamic balance, thus increasing the risk of falls and secondary injuries. The purpose of this review was to compile the literature to date, and assess the impact of ankle-foot orthosis (AFO) on postural control and gait in individuals who have suffered a stroke.

Development

The review included randomised and controlled trials that examined the effects of AFO in stroke patients between 18 and 80 years old, with acute or chronic evolution. No search limits on the date of the studies were included, and the search lasted until April 2011. The following databases were used: Pubmed, Trip Database, Cochrane library, Embase, ISI Web Knowledge, CINHAL and PEDro. Intervention succeeded in improving some gait parameters, such as speed and cadence. However it is not clear if there was improvement in the symmetry, postural sway or balance.

Conclusions

Because of the limitations of this systematic review, due to the clinical diversity of the studies and the methodological limitations, 0these results should be considered with caution.     

Clinical presentation of young people (10–24 years old) with brain tumors: results from the international MOBI-Kids study

Journal of Neuro-Oncology - We used data from MOBI-Kids, a 14-country international collaborative case–control study of brain tumors (BTs), to study clinical characteristics of the tumors in...     

Validity of the hospital discharge diagnosis in epidemiologic studies of biliopancreatic pathology

Background: The aim was to analyse the magnitude, direction and predictors of change in the main hospital discharge diagnosis (HDD) after a clinical expert review, among patients included in a multicentre molecular epidemiologic study of biliopancreatic diseases. Methods: A total of 602 patients with a suspicion diagnosis of pancreas cancer (PC), cancer of the extrahepatic biliary system (CEBS) or benign biliopancreatic pathologies (BPP) were prospectively recruited at five general hospitals. A structured form was used to collect information from medical records. A panel of experts revised all diagnostic information and established the main clinico-pathological diagnosis (CPD) by consensus. Results: Of the 204 cases with a HDD of PC, 176 (86%) were deemed to have a CPD of PC, eight of CEBS, twelve a neoplasm of different origin, four BPP and four syndromic diagnoses. Thus, 28 cases (14%) were false positives. Of the 129 patients with a HDD of CEBS, 15 (12%) were false positives. Nine of the 396 cases with a HDD of non-PC (2%) had a CPD of PC (false negatives), whilst 14 of 471 patients with a HDD of non-CEBS (3%) were deemed to have CEBS. Overall, sensitivity and specificity of HDD for PC were, respectively, 95 and 93%, and for CEBS, 89 and 97%. Cytohistological confirmation and laparotomy were independent predictors of diagnostic change. Conclusions: Validity of the HDD was high, but its association with some clinical variables suggests that sole reliance on HDD can significantly bias results, and highlights the need to review all HDDs. Alternatively, only patients at high risk of misdiagnosis could be reviewed: primarily, those lacking a cytohistological diagnosis or a laparotomy. No exclusions appear warranted solely on the basis of age, gender or tumour spread.     

Yohimbine prevents the effect of morphine on the redox status of neuroblastoma × glioma NG108-15 cells

The α₂-adrenoceptor antagonist yohimbine is known to interact with the effects of opioid receptor agonists in vivo, and thus could modulate the action of morphine-like analgesics. The focus of the present work was to further study these interactions in a cell culture endowed with opioid and α₂-adrenoceptors in order to know if they could happen at the cellular level. In a first step, incubation with morphine (10 μM) or the δ opioid agonist DPDPE (1 μM) for 6 h was shown to decrease the reduction of (4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium (MTT) by NG108-15 neuroblastoma × glioma hybrid cells in a naloxone-sensitive manner, thus showing that the opioids affect the redox status of the cells in a δ receptor-mediated way. Further experiments with 2–24 h incubation periods were subsequently performed with morphine 0.1 μM, 10 μM and 1 mM and several tests to confirm the effects on metabolism (MTT, Alamar Blue tests) to examine the potential toxic consequences (neutral red test, trypan blue exclusion assay, LDH test, caspase 3/7 activity) and to study the potential effect of yohimbine on morphine toxicity. These studies confirmed that incubation with morphine (0.1 μM and 10 μM) affected to a similar extent the redox status of the cells, an effect that did not translated into significant cell death and was transient since completely disappeared after 24 h of incubation. Morphine 1 mM was much more toxic than the lower concentrations. Yohimbine effectively prevented the effects of the lower concentrations of morphine when added to the incubation medium at 10 μM, a concentration devoid of significant toxicity. It seems that the exposure to pharmacologically relevant concentrations of morphine gives rise to short-term metabolic alterations of NG108-15 cells mediated by δ receptors and also sensitive to α₂-adrenoceptor blockade; therefore, the interactions previously described in vivo between opioid and α₂-adrenoceptor ligands do not necessarily require the presence of functional neuronal networks and they could happen at the cellular level.     

Measurement of urine pH for epidemiological studies on bladder cancer

Methods for efficiently identifying subjects with constantly acidic pH in epidemiological and clinical studies have not been assessed. We recruited 30 volunteers to estimate the minimum number of urine pH measurements using pH strips needed to identify subjects with "constantly acidic urine pH". Spearman's correlation coefficients between urine pH measured with a pH meter and with the four pH strips ranged from 0.94 to 0.95 (p < 0.001 for all four strips). Overall agreement within +/-0.5 pH units between the four strips and the pH meter ranged from 62.2% to 74.4%. When using a spot urine sample from a single morning to classify participants with respect to their urine pH, 80% of individuals fell into the acidic urine pH (pH equal to or lower than 6.0) group. When we required subjects to have urine pH equal to or lower than 6.0 in six consecutive AM spot urine samples and seven spot PM urine samples, only 20% of participants fulfilled this criterion. Measuring urine pH twice a day (early in the morning and early in the evening) during four consecutive days classified individuals in the same way as two daily measurements for one week. A single pH measurement from a spot urine sample is not reliable to identify individuals with constantly acidic pH. Morning and evening urine pH measurements with pH strips during four consecutive days identify individuals with constantly acidic urine pH individuals as well as one week of measurements, and thus might be useful to identify subjects with constantly acidic urine pH in epidemiological and clinical studies.     

Timing of blood extraction in epidemiologic and proteomic studies: results and proposals from the PANKRAS II Study

There are no consensus guidelines or standards for epidemiologic and ‘-omics’ studies using blood biomarkers on how to report the timing of extraction of blood samples. However, disease-induced changes in blood concentrations of exogenous and endogenous compounds may bias studies. The aim of the present report is to describe the timing of blood collection with respect to a variety of relevant clinical events in the PANKRAS II Study, and to suggest ways to display graphically the quantitative information. Subjects were 167 incident cases of exocrine pancreatic cancer prospectively recruited in five teaching hospitals in eastern Spain. Over 80% of patients had blood extracted during the first 6 months since onset of cancer symptoms, and 82% within the first month of admission to a study hospital. Over 80% of cases had blood drawn after an ultrasound, a CT scan or an ERCP, 25% after a laparotomy, and 37% after treatment onset. All three intervals from blood extraction to diagnosis, to treatment onset and to interview had a median of 0 days, and 88% of cases had blood drawn within 2 weeks of diagnosis. Over 72% of cases had concentrations of total lipids in the medium, normal range. Results suggest ways to report intervals involving blood biomarkers and may contribute to develop consensus guidelines and standards on the collection of blood samples in epidemiologic and ‘-omics’ research. PANKRAS II Study Group—Members of the Multicentre Prospective Study on the Role of K-ras and other Genetic Alterations in the Diagnosis, Prognosis and Etiology of Pancreatic and Biliary Diseases (PANKRAS II) Study Group are mentioned in previous publications. An erratum to this article can be found at     

Relapse to opiate use provokes biphasic changes of blood pressure in heroin-withdrawn addicts treated with clonidine.

The effect of relapse to opiate use on blood pressure and heart rate has been studied in heroin-withdrawn addicts treated with clonidine in an outpatient detoxification procedure. The daily dose of clonidine was established according to body weight and amount of heroin usually consumed at the onset of treatment. Patients who returned to heroin use were detected by increased urinary levels of opiates. Clonidine elicited significant reductions of blood pressure and heart rate reaching a plateau in the second day of treatment. Heroin consumption was found to provoke a further decrease of both systolic and diastolic pressure when the time interval between the relapse and the cardiovascular determinations was about 3 h as estimated by the patients. At longer intervals (16 h) this effect was reversed and both the hypotensive and the bradycardiac actions of clonidine seemed to be impaired. The possible impact of endogenous opioids and alpha-2 receptor sensitivity on these biphasic alterations is discussed.