D2 autoreceptor switches CB2 receptor effects on [3H]-dopamine release in the striatum

CB₂ receptors (CB₂R) are expressed in midbrain neurons. To evidence the control of dopamine release in dorsal striatum by CB₂R, we performed experiments of [³H]-dopamine release in dorsal striatal slices. We found a paradoxical increase in K⁺-induced [³H]-dopamine release by CB₂R activation with GW 833972A and JWH 133 two selective agonist. To understand the mechanism involved, we tested for a role of the D₂ autoreceptor in this effect; because in pallidal structures, the inhibitory effect of CB₁ receptors (CB₁R) on GABA release is switched to a stimulatory effect by D₂ receptors (D₂R). We found that the blockade of D₂ autoreceptors with sulpiride prevented the stimulatory effect of CB₂R activation; in fact, under this condition, CB₂R decreased dopamine release, indicating the role of the D₂ autoreceptor in the paradoxical increase. We also found that the effect occurs in nigrostriatal terminals, since lesions with 6-OH dopamine in the middle forebrain bundle prevented CB₂R effects on release. In addition, D₂–CB₂R interaction promoted cAMP accumulation, and the increase in [³H]-dopamine release was prevented by PKA blockade. D₂–CB₂R coprecipitation and proximity ligation assay studies indicated a close interaction of receptors that could participate in the observed effects. Finally, intrastriatal injection of CB₂R agonist induced contralateral turning in amphetamine-treated rats, which was prevented by sulpiride, indicating the role of the interaction in motor behavior. Thus, these data indicate that the D₂ autoreceptor switches, from inhibitory to stimulatory, the CB₂R effects on dopamine release, involving the cAMP → PKA pathway in nigrostriatal terminals.     

Increased lipid and protein oxidation and lowered anti-oxidant defenses in systemic lupus erythematosus are associated with severity of illness,autoimmunity, increased adhesion molecules,and Th1 and Th17 immune shift

This study investigated nitro-oxidative stress in patients with systemic lupus erythematosus (SLE) in association with disease activity, immune-inflammatory biomarkers, and adhesion molecules. Two-hundred-four patients with SLE and 256 healthy volunteers were enrolled in this case-control study, which measured nitro-oxidative stress biomarkers, including lipid peroxides (LOOH), advanced oxidation protein products (AOPPs), nitric oxide metabolites (NO_x), sulfhydryl (?SH) groups, products of deoxyribonucleic acid (DNA)/ribonucleic acid (RNA) oxidative degradation, and total radical-trapping anti-oxidant parameter (TRAP). Also measured were anti-nuclear antibodies (ANAs), antibodies against double-stranded DNA (dsDNA), plasma levels of diverse cytokines, C-reactive protein, and adhesion molecules. LOOH (p < 0.001) and AOPP (p < 0.001) were significantly higher, while TRAP was significantly lower (p < 0.001) in SLE patients than in controls. AOPP and LOOH were significantly and positively associated with SLE disease activity index (SLEDAI) scores, anti-nuclear antibodies, and antibodies against double-stranded DNA (anti-dsDNA) levels, while TRAP was significantly and inversely correlated with SLEDAI, ANA, and dsDNA antibody levels. There were significant positive associations between AOPP and LOOH and immune-inflammatory markers, indicating T helper (Th)-17 and Th1 bias and Th1 + Th17/Th2 ratio (p = 0.002 and p = 0.001, respectively). AOPP and LOOH (positively) and TRAP (inversely) were associated with adhesion molecule expression. A model predicting SLE was computed showing that, using LOOH, AOPP, NO_x, adhesion molecules, and body mass index, 94.2% of the patients were correctly classified with a specificity of 91.5%. Increased nitro-oxidative stress takes part in the (auto)immune pathophysiology of SLE and modulates severity of illness and adhesion molecule expression.     

Metal presence in hair after metal‐on‐metal resurfacing arthroplasty

The elevation of metal levels in serum and urine during post‐operative follow‐up is a frequent find following the implantation of certain models of metal‐on‐metal hip prostheses. Among 45 patients with the same resurfacing prostheses, chromium (Cr) and cobalt (Co) levels in serum and urine were determined at 3, 4, 5, and 6 years after surgery. In the same period, levels of Cr, Co and molibdene (Mo) in scalp hair were also measured. Mean Cr and Co levels in serum were 8.29 µg/L (SD 17.97) and 8.38 µg/L (SD 21.97), respectively, whereas in urine levels were 16.20 µg/L (SD SD 32.55) and 75.40 µg/L (SD 190.86), respectively. In hair, mean Cr level were 163.27 µg/g (SD 300.62), mean Co level 61.98 µg/g (SD 126.48), and Mo 31.36 µg/g (SD 37.86). A high concordance was observed between chromium‐urine and chromium‐serum and between cobalt‐urine and cobalt‐hair. A moderate concordance was present between cobalt‐urine and cobalt‐serum, and between cobalt‐hair and cobalt‐serum. Eleven patients required revision surgery, five of them due to metallosis and periarticular cyst. At 1 year after reintervention, analytics were performed again and the following decrease rates were found: 42.8% in Cr levels, 51.1% in Mo levels, and 90.3% in Co levels. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31:2025–2031, 2013     

Elasticity of the smallest noncapillary pulmonary blood vessels in the cat

We have previously described the compliance behavior of the pulmonary interalveolar capillary blood vessels in the cat and now characterize the compliance coefficient of the pulmonary arterioles and venules less than 50 μm in diameter in that species. These observations are unclassified with respect to arterioles and venules. Our method of silicone rubber microvascular casting under 0 to 23.75 cm H₂O pressures was used and diameter measurements were made from histological slides. Since the exact position of the vessels in branching hierarchy was not known, we called these vessels juxta-alveolar. The diameters of the smallest noncapillary blood vessels were measured and were analyzed by extreme-value statistics. We obtain a compliance coefficient, α, of 0.274 μm/cm H₂O over the pressure range measured, and a mean diameter of 14.5 μm for the smallest noncapillary blood vessels, 0Δp. These vessels are compliant.     

Liver biopsy complications monitored by ultrasound

Ultrasound (US) was performed in 96 patients (on 108 occasions) 2-4 h after diagnostic liver puncture with a modified Menghini needle. Serious complications (major haemorrhages: one intraparenchymal and one into the abdominal cavity) were seen in two patients, while seven presented with minor bleedings though without any registered clinical abnormality (slight pain in one). On 11 occasions (10 patients) slight to moderate pain was observed though in combination with a normal US. Findings on US and clinical observations showed poor correlation and the number of bleeding complications discovered by US examination seems to depend upon when the study is performed. US does not replace the clinical follow-up but may be helpful in the presence of adverse clinical reactions in order to establish the type of lesion: profuse parenchymal haemorrhage versus bleeding into the abdominal cavity. This information may be helpful in the choice between conservative and surgical therapy.