Immunological profile of patients awaiting a renal transplant

BACKGROUND: A renal transplant is the best possible treatment for patients with terminal renal failure. Advances in the development of techniques of screening of pre-formed antibodies have contributed to a notable improvement in the results obtained with allogenic transplants. METHODS: The aim of the present work is to study the nature, class, isotype and specificity of antibodies detected in patients awaiting renal transplantation at Complejo Hospitalario Universitario Juan Canalejo, as well as their relation with the level of anti-human leucocyte antigen (HLA) sensitization. RESULTS: In all patient groups, there was a predominance of IgG. The distribution of anti-HLA antibody class showed that the most frequent pattern corresponded to a mixture of class I and class II antibodies for all groups. The study of specificity of anti-HLA antibody showed that of the patients with at least one previous transplant, 72% developed specific anti-HLA antibodies against some of the incompatible antigens of the donor, 12% against HLA antigens not related with the phenotype of the donor and in 16% it was not possible to determine their specificity. Most patients developed antibodies against antigens of locus B, probably because of that the number of incompatibilities contributed by the donors is also greater for locus B. CONCLUSIONS: The exhaustive study of sera of patients on a waiting list for transplantation with respect to the nature, isotype, class and specificity of the antibody is important since it is possible that different antibodies can bring about, in the transplant, events that will have different consequences for the survival of the graft.     

Involvement of bradykinin, cytokines, sympathetic amines and prostaglandins in formalin-induced orofacial nociception in rats

1. This study characterises some of the mechanisms and mediators involved in the orofacial nociception triggered by injection of formalin into the upper lip of the rat, by assessing the influence of various treatments on behavioural nociceptive responses (duration of facial rubbing) elicited either by a low subthreshold (i.e. non-nociceptive; 0.63%) or a higher concentration of the algogen (2.5%). 2. The kininase II inhibitor captopril (5 mg kg(-1), s.c.) and prostaglandin(PG) E(2) (100 ng lip(-1)) potentiated both phases of the response to 0.63% formalin, whereas tumour necrosis factor (TNF alpha; 5 pg lip(-1)), interleukin(IL)-1 beta (0.5 pg lip(-1)), IL-6 (2 ng lip(-1)) and IL-8 (200 pg lip(-1)), or the indirectly acting sympathomimetic drug tyramine (200 microg lip(-1)), each augmented only the second phase of nociception. 3. Conversely, both phases of nociception induced by 2.5% formalin were inhibited by the bradykinin (BK) B(2) receptor antagonist HOE140 (5 microg lip(-1)) or the selective beta(1)-adrenoceptor antagonist atenolol (100 microg lip(-1)). However, the BK B(1) receptor antagonist des-Arg(9)-Leu(8)-BK (1 and 2 microg lip(-1)), antibody and/or antiserum against each of the cytokines, the adrenergic neurone blocker guanethidine (30 mg kg(-1) day(-1), s.c., for 3 days) and the cyclooxygenase(COX)-2 inhibitor celecoxib (50 and 200 microg lip(-1), s.c.; or 1 and 3 mg kg(-1), i.p.) reduced only the second phase of the response. The nonselective COX inhibitor indomethacin and the 5-lipoxygenase activating protein inhibitor MK886 did not change formalin-induced nociception. 4. Our results indicate that BK, TNF-alpha, IL-1 beta, IL-6, IL-8, sympathetic amines and PGs (but not leukotrienes) contribute significantly to formalin-induced orofacial nociception in the rat and the response seems to be more susceptible to inhibition by B(2) receptor antagonist and selective COX-2 inhibitor than by B(1) receptor antagonist or nonselective COX inhibitor.     

A meiotic recombination in a new isolated familial somatotropinoma kindred

We report here the genetic findings of a new isolated familial somatotropinoma (IFS) kindred in which the mother (subject I:2) and one daughter (subject II:2) are affected; their ages at diagnosis were 25 and 14 years respectively. Additionally, patient I:2 developed virilization due to an androgen-secreting adrenocortical mass, presenting clinical and molecular features of sporadic adrenal carcinoma. To genotype this family and to narrow down the candidate interval of the putative IFS gene at 11q13, we performed haplotyping on the DNA from all five members of the family and allelotyping of one available somatotropinoma using polymorphic microsatellite markers from chromosome region 11q12.1-11q13.5. Results indicated that the disease haplotype, between markers D11S956 and D11S527, was transmitted from subject I:2 only to subject II:2. A meiotic recombination event was detected in the fraternal twin sister of II:2 (subject II:1), but her disease status is unknown. Since she is only 18 years old this genetic event cannot yet narrow down the area involved in the pathogenesis of IFS. Allelotyping of the somatotropinoma from II:2 revealed loss of the chromosome carrying the wild-type copy of the putative IFS gene inherited from her father. These results support the involvement of a tumor suppressor gene at 11q13.1-q13.3 in the pathogenesis of IFS.     

Theoretic rates of potential tissue donation in a university hospital

BACKGROUND: Catalonia and Spain have the highest rates of organ donation in the world. The National Transplant Organization studied the rates of potential and actual donors through the Quality Guarantee Program, but this research did not estimate potential tissue donation (PTD). The aim of this study was to define the theoretical rates of PTD at our university hospital in order to assess the main factors that exerted the greatest influence on tissue donation (TD). METHODS: We prospectively studied all deaths from May 1, of 2001 to May 31, of 2002 using a specific protocol. The selection of cornea, vessels, skin, and bone had been established by the recommendations of the Spanish Association of Tissue Banks (AEBT). We considered each deceased person as a PTD when there was no medical contraindication (MC), and obtained blood samples for serologic determinations. RESULTS: Among the 1960 deaths, 1444 (73.6%) displayed MC for TD. Only 516 (26.3%) patients were evaluated as PTD cases. Two hundred twenty-two cases (65%) were rejected due to lack of blood samples for serologic determination. The remaining 294 PTD cases were considered: family refusal of TD in 120 (40%) and consent in 174 (60%). All were corneal donors; 46 (26%) had been multitissue donors (20 vessels, 35 skin, and 30 bones) including 26 (56.5%) who were also organ donors. CONCLUSIONS: PTD cases at a university hospital represented about 25% of deaths but only 30% of PTDs actually became donors.     

Budesonide ameliorates early portal hypertension in the rat: possible antiexudative splanchnic action

Major portal pressure increase occurs on the second day post-stenosing–ligation of the portal vein in the rat and it is associated with pancreatic edema, intraperitoneal free exudate, hypoalbuminemia and hypoproteinemia. All this suggests the development of a regional exudative inflammatory response. In order to verify this hypothesis the steroid budesonide, whose antiinflammatory activity could prevent these alterations, was administered to rats with prehepatic portal hypertension. Wistar male rats were divided into the following groups: Control rats that were administered saline solution (CS; n = 10), Control rats that were administered budesonide (36 mg/kg per day; CB; n = 10), triple stenosing ligation of portal vein (TSLP) with saline solution (n = 10) and triple stenosing ligation of portal vein with budesonide (36 mg/kg per day; n = 10). In rats with prehepatic portal hypertension at 48 h of postoperative evolution, budesonide decreases the incidence of pancreatic edema, of peritoneal free exudate, of mesenteric adenopathies and prevents hypoproteinemia, hypoalbuminemia and hyper--globulinemia. Some of the macroscopic intra-abdominal alterations and some of the changes in the electrophoretic pattern found in portal hypertensive rats could have an inflammatory etiopathogeny because budesonide shows an effective prophylaxis.