Lymphoid stromal cells - potential implications for the pathogenesis of CVID.

Non-hematopoietic lymphoid stromal cells (LSC) maintain lymph node architecture and form niches allowing the migration, activation, and survival of immune cells. Depending on their localization in the lymph node, these cells display heterogeneous properties and secrete various factors supporting the different activities of the adaptive immune response. LSCs participate in the transport of antigen from the afferent lymph as well as in its delivery into the T and B cell zones and organize cell migration via niche-specific chemokines. While marginal reticular cells (MRC) are equipped for initial B-cell priming and T zone reticular cells (TRC) provide the matrix for T cell-dendritic cell interactions within the paracortex, germinal centers (GC) only form when both T- and B cells successfully interact at the T-B border and migrate within the B-cell follicle containing the follicular dendritic cell (FDC) network. Unlike most other LSCs, FDCs are capable of presenting antigen via complement receptors to B cells, which then differentiate within this niche and in proximity to T follicular helper (TFH) cells into memory and plasma cells. LSCs are also implicated in maintenance of peripheral immune tolerance. In mice, TRCs induce the alternative induction of regulatory T cells instead of TFH cells by presenting tissue-restricted self-antigens to naïve CD4 T cells via MHC-II expression. This review explores potential implications of our current knowledge of LSC populations regarding the pathogenesis of humoral immunodeficiency and autoimmunity in patients with autoimmune disorders or common variable immunodeficiency (CVID), the most common form of primary immunodeficiency in humans.

Inhibition of human serum and rabbit muscle cholinesterase by local anesthetics.

The effects of tertiary amine local anesthetics (procaine, mepivacaine, lidocaine, tetracaine, dibucaine, and bupivacaine) and chlorpromazine were investigated for rabbit muscle acetylcholinesterase and human serum cholinesterase. The muscle enzyme was poorly inhibited by local anesthetics containing an amide linkage. The serum cholinesterase was inhibited by all those compounds, their relative potencies being proportional to their octanol/water partition coefficients. The dissociation constants of tetracaine and procaine, ester anesthetics, were 1000-fold and 100-fold, respectively, that which would be expected from their partition coefficient basis respective to the other amide anesthetics. Procaine showed competitive inhibition of serum cholinesterase, whereas for most anesthetics a mixed type of inhibition was observed. Procaine probably binds at the main anionic site, while the other positively charged anesthetics bind to either the catalytic centre or to the peripheral or modulator anionic site, modifying the kinetic behaviour of cholinesterase as has been demonstrated by the appearance of negative cooperativity for binding to the substrate.

[Use of vecuronium and atracurium in continuous infusion. A comparative study using electromyography and accelerometry]. / Utilización del vecuronio y atracurio en infusión continua. Estudio comparativo con electromiografía y acelerometría.

Vecuronium and atracurium, muscle relaxant agents of intermediate action, were administered in continuous infusion to 175 patients undergoing prolonged surgical operations with the purpose of achieving serum concentrations inducing maintained blocking of neuromuscular function. We used a 0.08 mg/kg or 0.5 mg/kg bolus intubation dose followed by a continuous infusion of vecuronium (72 patients) or atracurium (103 patients) 10 minutes after, at the necessary pace to maintain inhibition of neuromuscular transmission over 90%. Monitoring of relaxation was done by means of four supramaximal stimuli trains which were repeated every 20 seconds and applied to the cubital nerve. Composite electromyogram (electromyography) and thumb acceleration (mechanomyography-accelerometry) were simultaneously recorded. Infusion was interrupted 15 minutes before ending the operation; reversion occurred spontaneously in 143 patients and 32 patients had to be reversed with neostigmine. Beginning of action, total duration of infusion, infusion speed, and 25-75 spontaneous and after decurarization recovery index were measured. Initial dose allowed an easy tracheal intubation and the constant relaxation achieved with 0.068 mg/kg/h and 0.46 mg/kg/h infusion of vecuronium and atracurium was adequate for all operations. Spontaneous recovery is often adequate at the end of operations in carefully monitored patients. Both monitoring methods are useful for clinical evaluation of neuromuscular transmission.

[A tiapride and ketamine combination in short duration anesthesia]. / Asociación de tiapride y ketamina en anestesia de corta duración.

Tiapride was used as premedication on a series of 16 patients subsequently submitted to general anesthesia with ketamine. In order to compare the effects of tiapride on the incidence of visionary dreams, hallucinations and dyslepsic syndrome brought about by, this series was compared with 2 further series of patients premedicated with dihydrobenzoperidol plus fentanyl (15 patients) and diazepam plus haloperidol (11 patients). Effectiveness was evaluated by means of a 10 point recovery scale (1: rate of sedation; 2: anterior amnesia; 3: comprehensiveness and collaboration test; 4: space sense and time orientation; 5: Bender test; 6: dysleptic syndrome; 7: sick feeling and vomit; 8: subjective status; 9: recovery quality; 10: dreams and hallucinations) at 15, 30 and 60 minutes after the administration of the different premedications. General tolerance was evaluated by continuous quantification of vital signs: pulse rate, EKG and systolic, diastolic and mean blood pressures. The effects were analysed with ANOVA one-way, Newman-Keuls and t-paired tests. Premedication with 7.5 mg/kg of tiapride significantly reduced the incidence of dreaming, provided the necessary sedation and appropiate postoperative analgesia and rapid recovery of psychomotor coordination with no obvious alterations in haemodynamic parameters attributable to the selective blocking action of the dopaminergic receptors. The association tiapride-ketamine may be useful in anesthesia for day-case surgery.

Influence of NaCl on the kinetic behaviour of mammalian muscle acetylcholinesterase.

Acetylcholinesterase was solubilized from rabbit white muscle by means of dilute buffer and Triton X-100 (0.5%). About 50% of total activity was brought into solution with buffer, the rest being solubilized by extracting the tissue with buffer and Triton X-100. The enzyme activity recovered in the supernatants was 170% of that found in the homogenate in the absence of Triton X-100 indicating that, to some extent, the enzyme could be found in an occluded form in muscle. At suboptimum substrate concentration the Triton-solubilized acetylcholinesterase displayed a negative cooperativity, this phenomenon being greatly modified in the presence of NaCl. As the salt concentration increased (0-400 mM) the enzyme activity decreased, the Km values being linearly-dependent on the NaCl concentration in the assay medium. We propose a kinetic pattern to explain both the negative cooperativity produced by the substrate and the effect of NaCl on the kinetic behaviour on this enzyme. Our data are consistent with the hypothesis of binding of substrate to both the catalytic anionic site and a peripheral anionic site, the salt showing the capacity to compete with the substrate for these two binding sites.

Prolonged suxamethonium-induced neuromuscular blockade associated with organophosphate poisoning.

We report a patient, exposed to Malathion during agricultural work, who suffered a prolonged apnoea after the administration of suxamethonium. He had a normal phenotype (E1u E1u), but an extremely low plasma cholinesterase activity. The diagnosis was made by assaying cholinesterase activity and analysing the enzymic components by electrophoresis on polyacrylamide gel slabs. The results indicated that the apnoea was a result of the low activity of plasma cholinesterase induced by Malathion.