Enhanced analgesic effects of tramadol and common trace element coadministration in mice

Chronic pain is managed mostly by the daily administration of analgesics. Tramadol is one of the most commonly used drugs, marketed in combination with coanalgesics for enhanced effect. Trace elements are frequent ingredients in dietary supplements and may enhance tramadol's analgesic effect either through synergic mechanisms or through analgesic effects of their own. Swiss Weber male mice were divided into nine groups and were treated with a combination of the trace elements Mg, Mn, and Zn in three different doses and a fixed dose of tramadol. Two groups served as positive (tramadol alone) and negative (saline) controls. Nociceptive assessment by tail‐flick (TF) and hot‐plate (HP) tests was performed at baseline and at 15, 30, 45, and 60 min after intraperitoneal administration. Response latencies were recorded and compared with the aid of ANOVA testing. All three trace elements enhanced tramadol's analgesic effect, as assessed by TF and HP test latencies. Coadministration of these trace elements led to an increase of approximately 30% in the average pain inhibition compared with the tramadol‐alone group. The most effective doses were 0.6 mg/kg b.w. for Zn, 75 mg/kg b.w. for Mg, and 7.2 mg/kg b.w. for Mn. Associating trace elements such as Zn, Mg, and Mn with the standard administration of tramadol increases the drug's analgesic effect, most likely a consequence of their synergic action. These findings impact current analgesic treatment because the addition of these trace elements may reduce the tramadol dose required to obtain analgesia. © 2015 Wiley Periodicals, Inc.     

Hepatitis C infection and hepatocellular carcinoma in liver transplantation: a 20-year experience

Background: Hepatitis C infection (HCV) and hepatocellular carcinoma (HCC), the two main causes of liver transplantation (LT), have reduced survival post-LT. The impact of HCV, HCC and their coexistence on post-LT survival were assessed.Methodology: All 601 LT patients from 1992 to 2011 were reviewed. Those deceased within 30 days (n = 69) and re-transplants (n = 49) were excluded. Recipients were divided into four groups: (a) HCC-/HCV-(n = 252) (b) HCC+/HCV-(n = 58), (c) HCC-/HCV+ (n = 106) and (d) HCC+/HCV+ (n = 67). Demographics, the donor risk index (DRI), Model for End-Stage Liver Disease (MELD) score, survival, complications and tumour characteristics were collected. Statistical analysis included anova, chi-square, Fisher''s exact tests and Cox and Kaplan–Meier for overall survival.Results: Groups were comparable with regards to baseline characteristics, but HCC patients were older. After adjusting for age, MELD, gender and the donor risk index (DRI), survival was lower in the HCC+/HCV+ group (59.5% at 5 yrs) and the hazard ratio (HR) was 1.90 [95% confidence interval (CI),1.24–2.95, P = 0.003] and 1.45 (95% CI, 0.99–2.12, P = 0.054) for HCC-/HCV+. HCC survival was similar to controls (HR 1.18, 95% CI, 0.71–1.93, P = 0.508). HCC+/HCV-patients exceeded the Milan criteria (50% versus 31%, P < 0.04) and had more micro-vascular invasion (37.5% versus 20.6%, P = 0.042). HCC+/HCV+ versus HCC+/HCV-survival remained lower (HR 1.94, 95% CI, 1.06–3.81, P = 0.041) after correcting for tumour characteristics and treatment.Conclusion: HCV patients had lower survival post-LT. HCC alone had no impact on survival. Patient survival decreased in the HCC+/HCV+ group and this appears to be as a consequence of HCV recurrence.     

What is Recovery? Functioning and Recovery Stories of Self-Identified People in Recovery in a Services User Group and Their Peer Networks in Birmingham England

The study was based on a peer snowballing method involving members of a service users group in Birmingham, United Kingdom, who were asked to identify and interview members of their peer networks who had achieved “sustained recovery” of one year. Two hundred and nineteen individuals were recruited who defined themselves as being in recovery, consisting of 132 individuals in medication maintained recovery and 87 in abstinent recovery. Those in maintained recovery were more anxious about using heroin and had lower self-efficacy, worse physical health, poorer quality of life, and more peer group members still using. Being older was associated with greater quality of life (rather than time since last use) supporting a “maturing out” hypothesis.     

Predictive value of diagnostic tests in polytrauma patients with abdominal and craniocerebral injuries

In a study on 1024 polytrauma patients with craniocerebral injury, abdominal injury was present in 206 (20.11%) of them. In order to identify the intraabdominal organs injury, physical examination and specific diagnostic tests will be used. Their value was calculated by means of informational indices. The main indices, sensitivity, positive predictive value and accuracy were: for physical examination = 81.06%, 90.3%, 94.72%; for peritoneal lavage = 94.17%, 95.12%, 97.94%; for abdominal computed tomography = 98.44%, 97.65% and 99.25%. As one might expect the abdominal computed tomography is the most accurate method for the diagnosis of intraabdominal organs injuries.     

MDMA (ecstasy): neuroendocrine and behavioral features

Long lasting 5HT system impairment has been demonstrated in experimental animals exposed to ecstasy use; MDMA seems to be able to induce behavioral conditioning and reiterated use because of its dopaminergic action. Among behavioral aspects of ecstasy users mood disorders, irritability and difficult in relationships, interpersonal difficulties, high levels of impulsiveness and hostility, high sensation seeking, cognitive and attentive deficit have been reported. A derangement of serotonin system function was reported also in humans exposed to ecstasy, as confirmed by neuroendocrine challenges and brain imaging techniques. Recent researches suggest functional changes in dopaminergic system too. The persistence of behavioral and neuroendocrine changes many months after MDMA's discontinuation, indicate a lack of reversibility in the dysfunction induced by ecstasy, or the persistence of psychobiological traits that could preexist to MDMA exposure, possibly involved in substance abuse vulnerability.     

Both apoptosis and complement membrane attack complex deposition are major features of murine acute graft-vs.-host disease

The parent-into-F1 mouse model (P-->F1) of acute graft-vs.-host disease (GVHD) is a useful model of human acute GVHD because it allows the study of the T cell contribution to pathology without the complicating effects of conditioning regimens. To determine the similarity of this model to human GVHD, we assessed injury in organs typically involved in human acute GVHD (skin, liver) and less typically involved organs (spleen, kidney, lung). Mice were assessed histologically at early (2 weeks), intermediate (3 months) and late (6 month) time points. Based on the emerging roles of Fas ligand killing and complement deposition in allograft rejection, we correlated the amount of tissue specific TUNEL positive apoptosis and deposition of complement (C5b-9) with histopathologic changes. Our results indicate a striking similarity histologically between acute GVHD occurring in this model and in humans following bone marrow transplant. Moreover, C5b-9 deposition and apoptotic cell accumulation were found to parallel tissue injury in major organs of acute GVHD mice, although not all organs exhibited the same kinetic pattern. These results indicate a role for both adaptive immunity and innate immunity in this model of GVHD and support its use in modeling human acute GVHD in the nonmyeloablative setting.