5-HYDROXYTRYPTAMINE-INDUCED CONTRACTION OF THE MARMOSET AORTA IS MEDIATED BY A 5-HT1-LIKE RECEPTOR

1. 5-Hydroxytryptamine (5-HT) exerts both contractile and relaxant effects in the marmoset isolated aorta, actions that are unaffected by the 5-HT₂ antagonist ketanserin. The aim of the present study was to define the receptors mediating the contractile activity of 5-HT in the marmoset aorta.
2. Contractile responses were elicited in aortic rings that were either: (i) precontracted submaximally with the thromboxane A₂ agonist U44069 in order to amplify the responses; or (ii) exposed to N ^ω-nitro- L -arginine (100 μmol/L) plus LY 53857 (0.1 μmol/L; a 5-HT₂ receptor antagonist shown previously to inhibit relaxation). The effect of 5-HT on adenosine 3',5'-cyclic monophosphate (cAMP) formation was also investigated.
3. The effects of agonists and antagonists comprised: (i) agonist potencies in the order 5-carboxamidotryptamine > 5-HT > sumatriptan > 8-hydroxy-2-(di- n -propylamino)tetralin; (ii) inhibition of contractile action of 5-HT by the 5-HT_1D antagonist GR 127935; (iii) a contractile response to methysergide; (iv) a lack of effect of tropisetron, an antagonist of 5-HT₃ and 5-HT₄ receptors; and (v) inhibition of forskolin-stimulated cAMP formation by 5-HT (in the presence of LY 53857), indicative of negative coupling to adenylate cyclase.
4. The above effects fulfil the criteria for a 5-HT₁-like receptor. In view of the previous finding that this contractile response is insensitive to ketanserin, it is concluded that the contractile effects of 5-HT in the marmoset aorta are mediated exclusively by a 5-HT₁-like receptor.     

The binding and processing of monoclonal human IgG1 by cells of a human macrophage-like cell line (U937)

The goal of these experiments was to assess the relationship between the binding and processing of IgG by Fc-receptor-bearing cells. Cells of the U937 human macrophage-like cell line were incubated with 125I- labeled monomers, dimers, oligomers (composed of 2-4 IgG1 subunits), and HP (heavy polymers composed of 5 or more subunits per polymer) of monoclonal human IgG1 in vitro. Binding was assessed by spinning cells through a layer of phthalate oils. Internalization of IgG1 was assessed by quantitating residual binding to cells after surface-bound IgG was removed by a brief treatment with a solution containing 0.25 M acetic acid and 0.5 M sodium chloride. Catabolism was assessed by measuring the release of radioactive fragments of IgG1, which were not precipitated by 10% trichloroacetic acid. Unstimulated U937 bound about 10,000 molecules per cell of IgG1 monomer, with an equilibrium binding constant (Ka) of 5 X 10(8) M-1. After stimulation with a conditioned medium in vitro, binding per cell was increased 3-7--fold, and the Ka was decreased 2-4--fold. Both unstimulated and stimulated cells internalized and catabolized labeled IgG1 HP, but stimulated cells internalized and digested much more IgG1 HP per cell than unstimulated cells. Both monomers and dimers of IgG1 were internalized and degraded very slowly by stimulated cells, even though both preparations readily bound to cells. In contrast, oligomers and (to an even greater extent) IgG1 HP were internalized and degraded much more rapidly. Internalization of IgG1 HP was markedly inhibited by incubation at 4 degrees C, but not by incubation with a variety of metabolic inhibitors. Catabolism was inhibited by chloroquine and monensin (inhibitors of lysosomal acidification) and by cytochalasin (an inhibitor of microfilament polymerization). Binding to the surface of cells was not markedly inhibited by any agent tested. The capacity of cells to bind labeled IgG1 was markedly reduced by prior incubation in the presence of unlabeled IgG1. This reduction was in part due to the steric blockade of receptors caused by the avid, but reversible, binding of IgG1. In addition, IgG1 oligomers or HP (but not IgG1 monomers or dimers) also caused an irreversible reduction in the number of Fc receptors by a process analogous to receptor down-regulation, as observed in other receptor--ligand systems.     

Possibility of selection against mtDNA mutations in tumors

Several studies of tumors have revealed substantial numbers of clonally expanded somatic mutations in mitochondrial DNA (mtDNA), not observed in adjacent intact tissues. These findings were interpreted as indicating the involvement of mtDNA mutations in tumorigenesis. Such comparisons, however, ignore an important confounding factor: the monoclonal origin of tumors as opposed to the highly polyclonal nature of normal tissues. Analysis of recently published data on the incidence of somatic mutations in nontumor monoclonal cells suggests that, contrary to the prevailing view, the process of tumorigenesis may be accompanied by active selection against detrimental mtDNA mutations.     

Oblique capsular shift in anterior and anteroinferior shoulder instability

Patients submitted to oblique capsular shift were followed-up; this is a personal method used to treat recurrent anterior and anteroinferior dislocation of the shoulder. A total of 186 patients were followed-up. The results were good as there were no recurrences, recovery of shoulder movement was early and ample, and the Constant score was about 81.2.     

Spigelian Hernia

We report on the evolution in concept and techniques that allowed us to improve the treatment of spigelian hernia, operable in day surgery in 90% of cases and through a preperitoneal and recently a preperitoneal and subfascial prosthetic repair (PHS). Background data. We propose an innovative use of the PHS mesh for spigelian hernia repair. With this new implementation, we confront the standard surgical technique and its postoperative period. Methods. From January 1992 to March 2004, we performed 2,500 hernia surgical operations, including 32 spigelian hernia repairs (1.3% of total case series). The first surgical approach used for 20 of these 32 patients (62.5% of total spigelian hernias), all electively operated on, was a classical preperitoneal repair (Wantz), performed when possible by size of defect and weight (Body Mass Index) of the patient, under local anesthesia and on a day-surgery basis. Our new modified technique takes place through the insertion of a PHS large-type mesh, whose bottom underlay portion lies flat in the preperitoneal space with the connector obliterating the hernial orifice and with the overlay portion lying on the internal oblique muscle, covered by the aponeurosis of the external oblique muscle. Results. Our modification to the classical technique consisted only in the application of a product, such as the PHS, in a hernia defect, which presented with an orifice of the size of the connector and, therefore, was easily repairable with the use of the PHS device. This approach is easier than the preperitoneal approach, its always suitable for local anaesthesia, and it gives a more comfortable postoperative period. The surgical approach may be performed completely in day surgery. Conclusions. We believe that spigelian hernia surgical repair should always be performed by means of a preperitoneal prosthesis under local anaesthesia when the patients clinical and physical conditions allow for it, always in day surgery, and using the PHS mesh when the hernia defect size fits with the connector diameter. This last possibility seems to be easier and more comfortable for the patient in the postoperative period.