The R7 subfamily of RGS proteins assists tachyphylaxis and acute tolerance at mu-opioid receptors.

Members of the R7 subfamily of regulators of G-protein signaling (RGS) proteins (RGS6, RGS7, RGS9-2, and RGS11) are found in the mouse CNS. The expression of these proteins was effectively reduced in different neural structures by blocking their mRNA with antisense oligodeoxynucleotides (ODNs). This was achieved without noticeable changes in the binding characteristics of labeled beta-endorphin to opioid receptors. Knockdown of R7 proteins enhanced the potency of antinociception promoted by morphine and [D-Ala(2), N-MePhe(4), Gly-ol(5)]-enkephalin (DAMGO)-both agonists at mu-opioid receptors. The duration of morphine analgesia was greatly increased in RGS9-2 and in RGS11 knockdown mice. The impairment of R7 proteins brought about different changes in the analgesic activity of selective delta agonists. Knockdown of RGS11 reduced [D-Ala(2)]deltorphin II analgesic effects. Those of RGS6 and RGS9-2 proteins caused [D-Ala(2)]deltorphin II to produce a smoothened time-course curve-the peak effect blunted and analgesia extended during the declining phase. RGS9-2 impairment also promoted a similar pattern of change for [D-Pen(2,5)]-enkephalin (DPDPE). RGS7-deficient mice showed an increased response to both [D-Ala(2)]deltorphin II and DPDPE analgesic effects. A single intracerebroventricular (i.c.v.) ED(80) analgesic dose of morphine gave rise to acute tolerance in control mice, but did not promote tolerance in RGS6, RGS7, RGS9-2, or RGS11 knockdown animals. Thus, R7 proteins play a critical role in agonist tachyphylaxis and acute tolerance at mu-opioid receptors, and show differences in their modulation of delta-opioid receptors.     

Lung Cancer and COPD: a Common Combination

Background and objectiveTo analyse frequency, characteristics and patient survival with lung cancer (LC) and Common Obstructive Pulmonary Disease (COPD), comparing them with patients that do not have COPD.Material and methodsA retrospective study, of patients diagnosed by means of cytohistology. Survival was estimated by the Kaplan-Meier method. Statistical analysis was carried out using SPSS 15.0.ResultsA total of 996 patients were diagnosed, 39.8% with COPD. Mean age70±9.19 years. GOLD stages: I 18.2%, II 53.6%, III 24%, IV 4.2%. The histological types: squamous cell carcinoma 48.2%, adenocarcinoma 22%, and small cell carcinoma 22.5%. Survival was longer in the COPD group.ConclusionsLC and COPD are combined in 39.8%. Squamous cell type is more frequent and survival was longer in the COPD group.     

Composite prostheses for the repair of abdominal wall defects: effect of the structure of the adhesion barrier component

The component of a composite prosthesis, which makes contact with the visceral peritoneum, can be reabsorbable or non-reabsorbable, and laminar or reticular. This study was designed to determine whether the composition of this second, barrier component could improve its behavior at this interface. Abdominal wall defects in rabbits were repaired using a polypropylene prosthesis (PP), or the composites Sepramesh (PP+h) or Vicryl (PP+v). Fourteen days after surgery, the implants were evaluated by light and scanning electron microscopy, and immunohistochemistry. Prosthetic areas occupied by adhesions (PP: 71.08±5.09, PP+h: 18.55±4.96, P+v: 69.69±16.81%), neoperitoneal thickness (PP: 256.17±21.68, PP+h: 83.11±19.63, PP+v:213.72±35.90 μm) and macrophage counts (PP: 8.73±1.16, PP+h: 27.33±4.13, PP+v: 31.24±3.08%) showed significant differences (P<0.05). The tested biomaterials induced an optimal recipient tissue infiltration. Least adhesion formation was observed on the PP+h implants. This suggests that the second component, although reabsorbable, should be smooth in structure.     

The incidence of endocarditis caused by a prosthetic valve and its risk factors

To study the incidence and risk factors of prosthetic valve endocarditis (PVE) we followed 99.5% of 912 patients who had valve replacement from January 1, 1981 through December 31, 1985, for 1 to 6 (mean 3) years. PVE occurred in 27 patients (2.96% or 0.98% per patient-year). The incidence of PVE in the aortic position (3.9%) was significantly higher than in the mitral position (1.5%): p less than 0.25. PVE developed in 19 out of 329 patients with bioprostheses (5.8%) and in 8 out of 583 patients with mechanical valves (1.4%): p less than 0.005. Actuarially at 5 years follow-up 90.7% of the bioprosthetic group and 98.4% of the mechanical valve group was free of PVE (p less than 0.01). Bioprosthetic valve replacement in infective endocarditis further increased the risk of PVE compared to valve replacement by mechanical prostheses. In conclusion: in order of importance antecedent endocarditis, bioprostheses, male sex and aortic position are risk factors in the development of PVE. In patients requiring operation for infective endocarditis, mechanical valves are recommended. As the outcome of PVE is still very grave, authors stress the importance of prophylaxis, early diagnosis and timely operation.