Perinatal undernutrition facilitates morphine sensitization and cross-sensitization to cocaine in adult rats: a behavioral and neurochemical study

The development of sensitization to the locomotor effects of morphine and cross-sensitization between morphine and cocaine were evaluated in adult rats submitted to a protein malnutrition schedule from the 14th day of gestation up to 30 days of age (D-rats), and compared with well-nourished animals (C-rats). Dose-response curves to morphine-induced locomotor activity (5, 7.5, 10 or 15 mg/kg, i.p., every other day for 5 days) revealed a shift to the left in D-rats compared to C-rats. This implies that D-rats showed behavioral sensitization to the lower dose of morphine used (5 mg/kg), which was ineffective in C-rats. Furthermore, when a cocaine challenge (10 mg/kg, i.p) was given 48 h after the last morphine administration, only D-rats exhibited cross-sensitization in morphine-pretreated animals (7.5 and 10 mg/kg). In order to correlate the differential response observed with the functioning of the mesocorticolimbic dopaminergic system, extracellular dopamine (DA) levels were measured in the nucleus accumbens (core and shell) and the dorsal caudate-putamen. A challenge with cocaine in morphine pre-exposed animals produced an increase in DA release, but only in the nucleus accumbens “core” of D-rats. Similar DA levels were found in the nucleus accumbens “shell” and in the dorsal caudate-putamen of both groups. Finally, these results demonstrate that D-rats had a lower threshold for developing both a progressive behavioral sensitization to morphine and a cross-sensitization to cocaine. In accordance with these behavioral findings, a higher responsiveness of the nucleus accumbens core, expressed by increased DA levels, both basal and after cocaine challenge, was observed in D-rats.     

Neurolytic Blocks of the Sympathetic Axis for the Treatment of Visceral Pain in Cancer

Pain due to cancer is frequently visceral, and neurolysis of the sympathetic axis has been shown to be an effective and safe method for treating this visceral pain. Several studies have documented the efficacy of neurolytic blocks both by a reduction in the intensity of pain and by a decrease in opioid consumption. Neurolysis of the sympathetic axis should be incorporated into the pain specialist's arsenal as an adjuvant to oral pharmacologic therapy.     

Locus coeruleus activity in perinatally protein-deprived rats: effects of fluoxetine administration

We have previously described an increased locus coeruleus activity in perinatally protein-deprived rats. Since locus coeruleus dysfunction has been involved in different types of anxiety disorders and considering the modulating action of serotonergic transmission on locus coeruleus activity, we assessed the effect of fluoxetine, a selective serotonin reuptake inhibitor (SSRI), on locus coeruleus activity as measured by the firing rate and the number of spontaneously active cells/track. Repeated fluoxetine administration reduced locus coeruleus activity in both control and protein-deprived rats, although the reduction was greater in protein-deprived rats. Dose-response curves for the inhibitory effect of clonidine showed subsensitivity of alpha2-adrenergic autoreceptors in protein-deprived rats, a phenomenon reversed by fluoxetine treatment. Dose-response curves for the inhibitory effect of 2,5-dimethoxy-4-iodoamphetamine (DOI) were similar in both groups of rats. Following fluoxetine administration, subsensitivity to this effect developed in control but not in protein-deprived rats. Extracellular noradrenaline level in the prefrontal cortex, as measured by microdialysis procedure, was higher in protein-deprived rats compared to controls, and this difference was reduced after fluoxetine administration. A challenge with yohimbine increased the extracellular noradrenaline level in control but not in protein-deprived rats, suggesting subsensitivity of alpha2-adrenergic autoreceptors in early protein malnourished animals. These results stress the complexity of plastic changes induced by early protein malnutrition and sustain the hypothesis that perinatally protein-deprived rats may represent a useful animal model for screening antipanic agents.     

A prospective,randomized, pragmatic,health outcomes trial evaluating the incorporation of hylan G-F 20 into the treatment paradigm for patients with knee osteoarthritis (Part 2 of 2): economic results

OBJECTIVE: Viscosupplementation with hylan G-F 20 has recently become registered for treatment of patients with osteoarthritis (OA) of the knee in most parts of the world. The cost effectiveness and cost utility of this new therapeutic modality were determined as part of a Canadian prospective, randomized, 1-year, open-label, multicentered trial. DESIGN: A total of 255 patients were randomized to 'Appropriate care with hylan G-F 20' (AC+H) or 'Appropriate care without hylan G-F 20' (AC). Costs (1999 Canadian dollars) were collected from the societal viewpoint and included all costs related to OA of the knee and OA in all joints. Patients completed a number of outcomes questionnaires including the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the Health Utilities Index Mark 3 (HUI3). Data were collected at clinic visits (baseline, 12 months) and by telephone (1, 2, 4, 6, 8, 10, and 12 months). RESULTS: The AC+H group over the year had higher costs ($2125-$1415=$710, P< 0.05), more patients improved (69%-40%=29%,P =0.0001), greater increases in HUI3 (0.13-0.03=0.10, P< 0.0001) and increased quality-adjusted life years (QALYs) (0.071, P< 0.05). The incremental cost-effectiveness ratio was $2505/patient improved. The incremental cost-utility ratio was $10000/QALY gained. Sensitivity analyses and a second cost perspective gave similar results. CONCLUSION: The cost-utility ratio is below the suggested Canadian adoption threshold. The results provide strong evidence for adoption of treatment with hylan G-F 20 in the patients and settings studied in the trial.     

Oral infectious diseases: a potential risk factor for HIV virus recrudescence?

As the highly active antiretroviral therapy (HAART) has transitioned human immunodeficiency virus (HIV) infection into a 'chronic disease' management strategy, there is growing evidence that infection with non-HIV pathogens in HIV+ patients may have important public health implications in undermining HAART success and acquired immunodeficiency syndrome progression. Several bacterial and host cell products during infections with non-HIV pathogens have shown the capacity to regulate HIV replication in latently infected cells. A high prevalence of oral infections caused by bacteria, viruses and fungi has been described in HIV+ patients, including periodontal disease. The oral cavity appears to be a site of HIV pathogenesis and potential reservoir for the disease as HIV RNA and DNA forms are present in saliva as well as in gingival crevicular fluid, and oral epithelial cells are susceptible to either cell free or cell-associated HIV infection. The clinical and biological bases of potential associations between chronic oral inflammatory disorders, such as periodontal disease, and exacerbation of HIV viraemia have received little attention. This review attempts to evaluate the current understanding of HIV reactivation as a result of co-infection and/or inflammation induced by non-HIV pathogens in HIV-infected patients, and presents a hypothetic model about the potential role of periodontitis as a global oral infection that potentially contributes to HIV recrudescence.     

Anterior cruciate ligament allograft transplantation for intraarticular ligamentous reconstruction

Summary A multiplicity of surgical operations have been developed in an attempt to achieve satisfactory function after anterior cruciate ligament (ACL) repair. None of these procedures have been able to reproduce the fiber organization anatomy of attachment site, vascularity, or function of the ACL. Twenty-nine foxhounds received a deep-frozen bone-ACL-bone allograft and a ligament augmentation device (LAD). Biomechanical, microvascular, and histological changes were evaluated 3, 6, and 12 months following implantation. The maximum loads of the allograft/LADs were 34.3% (387.2N) after 3 months, 49.3% (556.6N) after 6 months, and 61.1% (698.8N) after a year. The maximum load was 69.1% (780 N). In general, after 6 months the allografts showed normal collagen orientation. The allografts demonstrated no evidence of infection or immune reaction. No bone ingrowth into the LAD was observed. Polarized light microscopy and periodic acid-schiff staining showed that the new bone-ligament substance interface had intact fiber orientation at the area of the ligament insertion. Microvascular examination using the Spalteholtz technique revealed revascularization and the importance of an infrapatellar fat pad for the nourishment of ACL allografts.