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Notes: Using an antibody that recognizes the products of all known members of the fos family of immediate early genes, it was demonstrated that destruction of the nigrostriatal pathway by 6-hydroxydopamine (6-OHDA) lesions of the medial forebrain bundle produces a prolonged (〉3 months) elevation of Fos-like immunoreactivity in the striatum. Using retrograde tract tracing techniques, we have previously shown that this increase in Foslike immunoreactivity is located predominantly in striatal neurons that project to the globus pallidus. In the present study, Western blots were performed on nuclear extracts from the intact and denervated striatum of 6-OHDA-lesioned rats to determine the nature of Fos-immunoreactive protein(s) responsible for this increase. Approximately 6 weeks after the 6-OHDA lesion, expression of two Fos-related antigens with apparent molecular masses of 43 and 45 kDa was enhanced in the denervated striatum. Chronic haloperidol administration also selectively elevated expression of these Fos-related antigens, suggesting that their induction after dopaminergic denervation is mediated by reduced activation of D2-like dopamine receptors. Western blot immunostaining using an antibody which recognizes the N-terminus of FosB indicated that the 43 and 45 kDa Fos-related antigens induced by dopaminergic denervation and chronic haloperidol administration may be related to a truncated from of FosB known as ΔFosB. Consistent with this proposal, retrograde tracing experiments confirmed that ΔFosB-like immunoreactivity in the deafferented striatum was located predominantly in striatopallidal neurons. Gel shift experiments demonstrated that elevated AP-1 binding activity in denervated striata contained FosB-like protein(s), suggesting that enhanced ΔFosB levels may mediate some of the effects of prolonged dopamine depletion on AP-1-regulated genes in striatopallidal neurons. In contrast, chronic administration of the D1-like receptor agonist CY 208–243 to 6-OHDA-lesioned rats dramatically enhanced ΔFosB-like immunoreactivity in striatal neurons projecting to the substantia nigra. Western blot immunostaining revealed that ΔFosB and, to a lesser extent, FosB are elevated by chronic D1-like agonist administration. Both the quantitative reverse transcriptase-polymerase chain reaction and the ribonuclease protection assay demonstrated that Δfos B mRNA levels were substantially enhanced in the denervated striatum by chronic D1-like agonist administration. Lastly, we examined the effects of chronic administration of D1-like and D2-like dopamine receptor agonists on striatal ΔFosB expression in the 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) primate model of Parkinson's disease. In monkeys rendered Parkinsonian by MPTP, there was a modest increase in ΔFosB-like protein(s), while the development of dyskinesia produced by chronic D1-like agonist administration was accompanied by large increases in ΔFosB-like protein(s). In contrast, administration of the long-acting D2-like agonist cabergoline, which alleviated Parkinsonian symptoms without producing dyskinesia reduced ΔFosB levels to near normal. Taken together, these results demonstrate that chronic alterations in dopaminergic neurotransmission produce a persistent elevation of ΔFosB-like protein(s) in both the rodent and primate striatum.

Notes: Summary In animal models of Parkinson's disease (PD), glutamate antagonists diminish levodopa (LD)-associated motor fluctuations and dyskinesias. We sought to investigate if these preclinical observations can be extended to the human disease, by evaluating the effects of three non-competitive NMDA antagonists (dextrorphan, dextromethorphan and amantadine) on the motor response to LD in patients with advanced PD. In four separate trials, adjuvant therapy with these drugs reduced LD-induced dyskinesias and motor fluctuations. These findings support the view that drugs acting to inhibit glutamatergic transmission at the NMDA receptor can ameliorate LD associated motor response complications.

Notes: Abstract  Vascular endothelial growth factor (VEGF) is an angiogenic factor that may be involved in tumor growth and metastasis. Only a few data concerning the role of VEGF in renal cell carcinomas (RCCs) are available, and no studies have yet evaluated its prognostic value. The aim of the present study was to assess VEGF expression in a large series of renal tumors with a long follow-up, correlated with the usual histoprognostic factors and survival. VEGF immunostaining was performed on formalin-fixed, paraffin-embedded archival tissue from 74 renal carcinomas (62 conventional renal cell and 12 papillary carcinomas). Positivity of immunostaining was semi-quantitatively scored by two pathologists. Angiogenesis was evaluated by immunostaining with anti-CD34 antibodies on serial sections. Cytoplasmic VEGF expression was detected in tumor cells in 35% (26/74) of RCCs, including 18 out of the 62 (29%) conventional RCCs and 8 out of the 12 (67%) papillary carcinomas (P=0.02). In the group of conventional RCCs, VEGF expression was positively correlated with both nuclear grade (P=0.05) and size of the tumor (P=0.05). Furthermore, a significant correlation was observed between VEGF expression and microvascular count (P=0.04). Finally, cumulative survival rate was significantly lower in the group of patients with conventional RCCs expressing VEGF (log rank test, P=0.01). In the Cox model, VEGF expression was a significant independent predictor of outcome, as well as stage and nuclear grade. This study suggests that VEGF is involved in angiogenesis in conventional RCCs and appears to be a potential prognostic factor in these tumors.

Notes: Summary  The disposal of bark residues is an important problem for the forest industry. An important proportion of the bark produced by the paper and lumber industries is used for energy production, but a significant amount of bark is still unused. The objective of this study was to determine the technical feasibility of making particleboards from black spruce bark residues bonded with urea formaldehyde resin and meeting the indoor performance requirements for wood particleboards. In the positive case, this would define a new use for black spruce bark residues. Fresh black spruce bark residues were obtained from a sawmill located in the northeast part of the province of Quebec, Canada. The bark was kiln-dried at 60 °C, the particles were generated from a hammermill and sieved. Particles from 0.02 to 2.0 mm were used in the surface layers and particles from 2.0 to 6.0 mm were used in the core layer. Particleboards of 540 × 560 × 16 mm were made with a laboratory hot press following a factorial design with two manufacturing variables at three levels: (1) wood particles content of the surface layers (0, 25, 50 percent); and (2) UF resin content of the surface layers (12, 14 and 16 percent) with a UF resin content in the core of 8 percent. This resulted in a factorial design of 9 different combinations repeated 3 times for a total of 27 boards. It was observed that the heating kinetics varied according to the wood particles content in the surface layers. The compression ratio of the mat and the board internal bond, modulus of elasticity, modulus of rupture, linear expansion and thickness swell were determined. The results show that it is technically possible to make particleboard from bark residues meeting the American National Standard Institute indoor requirement for wood particleboard under certain conditions. The modulus of rupture of the boards was the most critical property in this study. The best mechanical properties were obtained with a 50 percent wood content and 14 percent resin content in the surface layers. The particleboards produced in this study did not meet the minimal requirements for linear expansion. The temperature measurements performed in the core of the mat during hot pressing show that heat transfer improves with an increase in wood particles content in the surface layers.