Interactive role of adenosine and dopamine in the opiate withdrawal syndrome

Adenosine reduces opioid withdrawal symptoms by activating A₁ adenosine receptors, probably by inhibiting excitatory amino acid release. Since blockade of A_2A adenosine receptors seems to enhance dopaminergic striatopallidal transmission, we evaluated the role of the purinergic system in the opiate withdrawal syndrome by using two A₁ receptor agonists [N⁶-cyclohexyladenosine, CHA and 2-chloro-N⁶-cyclopentyladenosine, CCPA], and two A_2A receptor antagonists (SCH 58261 and 8-(3-chlorostyryl)caffeine, CSC).Male adult rats received increasing doses of morphine sulphate suspended in 5 ml/kg of a sustained release preparation (40–100 mg/kg s.c.) daily for 4 days and 20 h after the last administration, the withdrawal syndrome was evoked by naloxone (5 mg/kg i.p.). Animals were observed for 30 min for signs of opiate withdrawal. Other groups of rats were implanted with concentric probes for microdialysis and dopamine levels were measured in the nucleus accumbens. CHA and CCPA (0.05, 0.1 or 0.5 mg/kg i.p.) significantly reduced "wet-dog" shakes, diarrhoea, teeth chattering, jumping and writhing. SCH 58261 and CSC (0.1, 0.5 or 1 mg/kg i.p.), given 10 min before naloxone, also reduced signs of opiate withdrawal. CHA plus SCH 58261 and CCPA plus CSC greatly enhanced the reduction of withdrawal signs observed with CHA and CCPA or CSC and SCH 58261 alone. In vivo microdialysis showed that naloxone significantly decreased DA release; this effect was prevented by pretreatment with systemic SCH 58261 and CSC, but not with CHA and CCPA. Our results demonstrate that A₁ and A_2A adenosine receptors mediate the effect induced by adenosine in opiate withdrawal syndrome and suggest that adenosine A₁ agonists and adenosine A_2A antagonists may be beneficial in the treatment of this syndrome.L. Stella and V. de Novellis share first authorship     

Outcome of orthotopic liver transplantation in autoimmune hepatitis according to subtypes

The relevance of autoimmune hepatitis (AIH) classification for clinical purposes is controversial. We analyzed the outcome after orthotopic liver transplantation (OLT) of nine type I and seven type II AIH patients. Type II patients had a significantly higher incidence of cirrhosis at the time of diagnosis, more resistance to steroid therapy, and a higher Child-Pugh score at the time of OLT. OLT was performed in emergency in three type II patients and electively in all type I patients. Four type II and one type I patients died in the postoperative period. There was no difference regarding the incidence of post-OLT infection and rejection between the two types. No recurrence of AIH was observed. The 6-year actuarial survival rates for type I and type II patients were 76% and 43%, respectively. Type II AIH patients who have a poor response to medical therapy should be considered for OLT with a shortened delay.     

Pain evaluation and management: a survey of Italian radiotherapists

Goals The objective of this study was to assess the knowledge possessed and the attitudes held by Italian radiotherapists regarding evaluation and treatment of pain.Methods One hundred and twenty-six radiotherapists completed a 16-item questionnaire that was specifically designed to investigate three main topics: the attention paid to pain, the use of analgesics, and pain in children. Chi-square or Fishers exact text was employed to evaluate differences based on position (staff/resident), age (<35/>35 years old), availability of consultants in pain therapy and/or palliative care, colleagues with main interest in palliative care among their own staff, and region of residence (north/center/south of Italy).Results Overall percentage of correct answers was 76.6% (range 34.9–94.4%). Correct answers by groups of items were: attention paid to pain 77.3%, use of analgesics 81.5%, and pain in children 63.7%.Conclusion Results of the survey demonstrate that knowledge and attitudes of Italian radiotherapists towards the approach to and treatment of pain can be considered satisfactory.     

Oligoclonal banding detected by urinary protein electrophoresis and immunofixation in two patients with the acquired immune deficiency syndrome and proteinuria

Monoclonal and oligoclonal banding has been observed in electrophoretograms of serum, cerebrospinal fluid, and urinary protein from patients infected with the human immunodeficiency virus (HIV). This is the first report of kappa oligoclonal banding in the protein electrophoretograms for urine but not for serum of two patients with the acquired immune deficiency syndrome (AIDS). Both patients had proteinuria, but only one had the nephrotic syndrome and renal failure. Serum oligoclonal banding in HIV-infected patients occurs much more frequently than in age-matched controls and may be detected before AIDS or lymphadenopathy syndrome evolves. The use of oligoclonal banding as a marker for HIV infection is currently under investigation. Urine as well as serum samples should be included in this research.     

Intravenous Immunoglobulins as a new opportunity to treat discoid lupus erythematosus: A case report and review of the literature

Discoid lupus erythematosus (DLE) is a chronic dermatological disease that can lead to scarring, alopecia and dyspigmentation, if not properly treated. Actually, no drugs are specifically approved for the treatment of CLE, although the first-line therapy usually consists of photoprotection associated to topical or oral steroids, topical calcineurin inhibitors and hydroxychloroquine (HCQ). In cases of DLE refractory to these medications, many other agents have been employed, such as dapsone, methotrexate, azathioprine, cyclophosphamide, biologic drugs and Intravenous Immunoglobulin (IVIG).We described the case of a DLE patient resistant to combination therapy with steroid and HCQ who was successfully treated with cyclical IVIG therapy. The treatment with IVIG resulted rapidly effective with persistent efficacy and low rates of relapses, although more cycles of IVIG are needed to achieve a stable clinical remission.We also discussed the beneficial and promising effects of IVIG in patients with Cutaneous Lupus reporting the previously published data.     

Chronic maternal morphine alters calbindin D‐28k expression pattern in postnatal mouse brain

The distribution pattern of calbindin (CB)‐D28k‐expressing neurons results to be altered in several brain regions of chronic morphine exposed adult mice. In this study, the influence of chronic maternal exposure to morphine on the distribution pattern of CB‐D28k‐expressing neurons in the brain of mouse offspring was investigated. Females of CD‐1 mice were daily administered with saline or morphine for 7 days before mating, during the whole gestation period, and until 21 day post‐partum. Their offspring were sacrificed on postnatal day 18, and the brains were examined by histology using cresyl violet and by immunohistochemistry using a rabbit polyclonal anti‐CB‐D28k antibody. Histology revealed no significant differences in the distribution pattern and the number of neurons between the offspring forebrain of the control group of mice and the two groups of mice treated with different doses of morphine. However, immunohistochemical analysis revealed that the number of CB‐D28k‐immunoreactive neurons remarkably decreased in the cingulate cortex, in the layers II–IV of the parietal cortex and in all regions of the hippocampus, while it increased in the layers V–VI of the parietal cortex and in the subicular region of the offspring brain of morphine treated mice. Overall, our findings demonstrate that maternal exposure to morphine alters the pattern of CB‐D28k‐expressing neuron pattern in specific regions of murine developing brain, in a layer‐ and dose‐dependent way, thus suggesting that these alterations might represent a mechanism by which morphine modifies the functional aspects of developing brain. Synapse 70:15–23, 2016. © 2015 Wiley Periodicals, Inc.     

Chromosomal evolution in Rattini (Muridae, Rodentia)

The Rattini (Muridae, Murinae) includes the biologically important model species Rattus norvegicus (RNO) and represents a group of rodents that are of clinical, agricultural and epidemiological importance. We present a comparative molecular cytogenetic investigation of ten Rattini species representative of the genera Maxomys, Leopoldamys, Niviventer, Berylmys, Bandicota and Rattus using chromosome banding, cross-species painting (Zoo-fluorescent in situ hybridization or FISH) and BAC-FISH mapping. Our results show that these taxa are characterised by slow to moderate rates of chromosome evolution that contrasts with the extensive chromosome restructuring identified in most other murid rodents, particularly the mouse lineage. This extends to genomic features such as NOR location (for example, NORs on RNO 3 are present on the corresponding chromosomes in all species except Bandicota savilei and Niviventer fulvescens, and the NORs on RNO 10 are conserved in all Rattini with the exception of Rattus). The satellite I DNA family detected and characterised herein appears to be taxon (Rattus) specific, and of recent origin (consistent with a feedback model of satellite evolution). BAC-mapping using clones that span regions responsible for the morphological variability exhibited by RNO 1, 12 and 13 (acrocentric/submetacentric) and their orthologues in Rattus species, demonstrated that the differences are most likely due to pericentric inversions as exemplified by data on Rattus tanezumi. Chromosomal characters detected using R. norvegicus and Maxomys surifer whole chromosome painting probes were mapped to a consensus sequence-based phylogenetic tree thus allowing an objective assessment of ancestral states for the reconstruction of the putative Rattini ancestral karyotype. This is thought to have comprised 46 chromosomes that, with the exception of a single pair of metacentric autosomes, were acrocentric in morphology.     

VGF: an inducible gene product, precursor of a diverse array of neuro-endocrine peptides and tissue-specific disease biomarkers

The vgf gene (non-acronymic) is induced in vivo by neurotrophins including Nerve Growth Factor (NGF), Brain Derived Growth Factor (BDNF) and Glial Derived Growth Factor (GDNF), by synaptic activity and by homeostatic and other stimuli. Post-translational processing of a single VGF precursor gives raise to a varied multiplicity of neuro-endocrine peptides, some of which are secreted upon stimulation both in vitro and in vivo. Several VGF peptides, accounting for ～20% of the VGF precursor sequence, have shown biological roles including regulation of food intake, energy balance, reproductive and homeostatic mechanisms, synaptic strengthening, long-term potentiation (LTP) and anti-depressant activity. From a further ～50% of VGF derive multiple "fragments", largely identified in the human cerebro-spinal fluid by proteomic studies searching for disease biomarkers. These represent an important starting point for discovery of further VGF products relevant to neuronal brain functions, as well as to neurodegenerative and psychiatric disease conditions. A distinct feature of VGF peptides is their cell type specific diversity in all neuroendocrine organs studied so far. Selective differential profiles are found across the cell populations of pituitary, adrenal medulla and pancreatic islets, and in gastric neuroendocrine as well as some further mucosal cells, and are yet to be investigated in neuronal systems. At the same time, specific VGF peptide/s undergo selective modulation in response to organ or cell population relevant stimuli. Such pattern argues for a multiplicity of roles for VGF peptides, including endocrine functions, local intercellular communication, as well as the possible mediation of intracellular mechanisms.     

Intermittent Pringle Maneuver and Hepatic Function: Perioperative Monitoring by Noninvasive ICG-Clearance

Background  

Intermittent Pringle maneuver or selective portal clamping often are used to control inflow during parenchymal liver transection. This study was designed to determinate whether these maneuvers are associated with adverse hepatic function.