Antibody-mediated rejection of renal allografts: diagnostic pitfalls and challenges.

Antibody-mediated rejection (ABMR) is a major obstacle to the long-term success in kidney transplantation. Diagnosis of ABMR is determined according to the internationally recognized Banff criteria. However, a significant proportion of patients does not meet all the defined criteria, and the outcome of such cases remains poorly understood. The histology of ABMR frequently lacks sensitivity and specificity. More importantly, mixed forms of ABMR and T cell-mediated rejection as well as findings of nonspecific injury are common in clinical settings. Donor-specific anti-HLA antibodies (DSA) are detectable only in half of the ABMR cases by histology. Prognostic role of non-HLA antibodies against various endothelial proteins has been discussed. Antibody independent NK cell activation reflecting killer-cells' inhibitory receptor incompatibility is suggested in microvascular inflammation in DSA negative patients. Molecular assessment of ABMR has been prioritized to overcome high interobserver variability and improve diagnostics in mixed forms of rejections and in DSA negative cases. Finally, donor-derived cell-free DNA detected in a recipient's peripheral blood sample has been proposed as a noninvasive marker for diagnosis of graft rejection, and thus might serve as a liquid biopsy in the near future. Despite all achievements, diagnosing ABMR in kidney allografts remains to be a challenge in a significant number of cases.

Confocal laser endomicroscopy in the diagnostics of gastrointestinal lesions literary review and personal experience.

INTRODUCTION: Confocal laser endomicroscopy (CLE) is a new method enabling real-time histopathological diagnosis. Two platforms of CLE are used standardly: the so called probe-based CLE in which an endomicroscopic probe is inserted through an endoscope, and so-called needle-based CLE inserted through a needle. METHODS: CLE enables evaluation of epithelial and subepithelial structures with 1000x magnification in any part of the gastrointestinal system. The main advantage over conventional biopsies can be immediate diagnosis and larger area evaluated. CLE might play a promising role in indeterminate biliary lesions where biopsies are often not sufficient and fail to allow for accurate diagnosis. CLE can also have a promising potential in pancreatic lesions where it is used along with the needle designed for tissue aspiration during endosonography. It is also possible to use CLE in other organ systems and medical specialties, e.g. in pneumology, neurosurgery, ENT and others. CONCLUSION: CLE is a promising diagnostic method; however, it is unlikely to replace standard biopsies currently since these are still considered a gold standard of histopathological diagnosis. High purchase price is a main disadvantage of the method, hampering its expansion in medicine. Key words: confocal laser endomicroscopy CLE biliary strictures pancreatic lesions esophageal carcinoma Rozhl Chir 2018;97:531-538.

The early effect of dextran sodium sulfate administration on carbachol-induced short-circuit current in distal and proximal colon during colitis development.

Increased colonic Cl(-) secretion was supposed to be a causative factor of diarrhea in inflammatory bowel diseases. Surprisingly, hyporesponsiveness to Cl(-) secretagogues was later described in inflamed colon. Our aim was to evaluate changes in secretory responses to cholinergic agonist carbachol in distal and proximal colon during colitis development, regarding secretory activity of enteric nervous system (ENS) and prostaglandins. Increased responsiveness to carbachol was observed in both distal and proximal colon after 3 days of 2 % dextran sodium sulfate (DSS) administration. It was measured in the presence of mucosal Ba(2+) to emphasize Cl(-) secretion. The described increase was abolished by combined inhibitory effect of tetrodotoxin (TTX) and indomethacin. Indomethacin also significantly reduced TTX-sensitive current. On the 7th day of colitis development responsiveness to carbachol decreased in distal colon (compared to untreated mice), but did not change in proximal colon. TTX-sensitive current did not change during colitis development, but indomethacin-sensitive current was significantly increased the 7th day. Decreased and deformed current responses to serosal Ba(2+) were observed during colitis induction, but only in proximal colon. We conclude that besides inhibitory effect of DSS on distal colon responsiveness, there is an early stimulatory effect that manifests in both distal and proximal colon.

Glucocorticoid availability in colonic inflammation of rat.

Recent in vitro studies have shown the involvement of pro-inflammatory cytokines in the regulation of the local metabolism of glucocorticoids via 11beta-hydroxysteroid dehydrogenase type 1 and type 2 (11HSD1 and 11HSD2). However, direct in vivo evidence for a relationship among the local metabolism of glucocorticoids, inflammation and steroid enzymes is still lacking. We have therefore examined the changes in the local metabolism of glucocorticoids during colonic inflammation induced by TNBS and the consequences of corticosterone metabolism inhibition by carbenoxolone on 11HSD1, 11HSD2, cyclooxygenase 2 (COX-2), mucin 2 (MUC-2), tumor necrosis factor alpha (TNF-alpha), and interleukin 1beta (IL-1beta). The metabolism of glucocorticoids was measured in tissue slices in vitro and their 11HSD1, 11HSD2, COX-2, MUC-2, TNF-alpha, and IL-1beta mRNA abundances by quantitative reverse transcription-polymerase chain reaction. Colitis produced an up-regulation of colonic 11HSD1 and down-regulation of 11HSD2 in a dose-dependent manner, and these changes resulted in a decreased capacity of the inflamed tissue to inactivate tissue corticosterone. Similarly, 11HSD1 transcript was increased in colonic intraepithelial lymphocytes of TNBS-treated rats. Topical intracolonic application of carbenoxolone stimulated 11HSD1 mRNA and partially inhibited 11HSD2 mRNA and tissue corticosterone inactivation and these changes were blocked by RU-486. The administration of budesonide mimicked the effect of carbenoxolone. In contrast to the local metabolism of glucocorticoids, carbenoxolone neither potentiates nor diminishes gene expression for COX-2, TNF-alpha, and IL-1beta, despite the fact that budesonide down-regulated all of them. These data indicate that inflammation is associated with the down-regulation of tissue glucocorticoid catabolism. However, these changes in the local metabolism of glucocorticoids do not modulate the expression of COX-2, TNF-alpha, and IL-1beta in inflamed tissue.

[Laparoscopic distal resection of the pancreas]. / Laparoskopická distální resekce pankreatu.

During the last two years, reports on laparoscopic procedures of the pancreas have been on increase. Laparoscopic resection of the pancreatic cauda is indicated, primarily, for benign cystic lesions of the cauda of the pancreas and for neuroendocrine tumors of the pancreas (mainly insulinomas). We have not recorded any report on the above procedure in the Czech literature. Therefore, in our case review, we have described laparoscopic distal resection of the pancreas with splenectomy for a pseudopapillary tumor of the pancreas.

Colitis up-regulates local glucocorticoid activation and down-regulates inactivation in colonic tissue.

BACKGROUND: Pro-inflammatory processes are counteracted by anti-inflammatory factors such as glucocorticoids. The response of target cells to glucocorticoids depends on several factors including prereceptor modulation of glucocorticoid signals via local glucocorticoid metabolism. This is determined by two isoforms of 11beta-hydroxysteroid dehydrogenase (11betaHSD); 11betaHSD1 operates in vivo as a reductase converting inactive 11-oxo glucocorticoids to active glucocorticoids cortisol or corticosterone, whereas 11betaHSD2 catalyses oxidation of active glucocorticoids to their inactive 11-oxo derivatives. The aim of this study was to investigate the changes in local metabolism of glucocorticoids and in the expression of 11betaHSD1 and 11betaHSD2 mRNA during colonic inflammation. METHODS: Acute colitis was induced by intracolonic administration of 2,4,6-trinitrobenzenesulphonic acid (TNBS) or by drinking a dextran sodium sulphate (DSS) solution. Metabolism of glucocorticoids was measured in tissue fragments in vitro and 11betaHSD1 and 11betaHSD2 mRNA abundance was quantified using real-time RT-PCR one week after administration of TNBS and 10 days after drinking the DSS solution. RESULTS: In both models of inflammatory bowel disease we observed down-regulation of corticosterone oxidation to 11-dehydrocorticosterone by 64% (TNBS) and 53% (DSS) and reciprocal stimulation of reduction of 11-dehydrocorticosterone to corticosterone by 83% and 54%, respectively. A similar pattern was observed at the level of mRNA; 11betaHSD1 mRNA was significantly higher (TNBS: increase by 660%; DSS: increase by 760%) and 11betaHSD2 mRNA lower (TNBS: decrease by 85%; DSS: decrease by 60%) during inflammation. CONCLUSIONS: Colitis induces local glucocorticoid activation from 11-oxo steroids and decreases glucocorticoid inactivation; i.e. inflammation increases local tissue ratio of active and inactive glucocorticoids. The results indicate that the changes in local metabolism of glucocorticoids could contribute to the control of an overshoot of inflammation processes in the colon.

[Report on the activity of the Central Commission on Ethics of the Ministry of Health 1990-1994]. / Zpráva o cinnosti Centrální etické komise Ministerstva zdravotnictví za funkcní období 1990 - 1994.

The authors summarize the most important activities of the Central ethical commission at home and abroad during four years of its existence. They mention documents elaborated for the needs of the broad public and local ethical commissions incl. the Statute of the central ethical commission. Experience with evaluation of ethical problems pertaining to relations between health professionals and the lay public indicate above all impaired mutual communication. The authors feel that wide publicity of ethical problems in the professional and lay press is essential and should be permanently stimulated.

[Ethics committees in the Czech Republic]. / Etické komise v Ceské republice.

The authors submit a report on the establishment and activities of new advisory organs which developed in hospitals and at medical faculties and bear the name of ethical commissions. Their task is to approve grants, advisory activities as well as organizing public discussions of ethical problems. The basis of the report are data obtained by means of questionnaires completed by 62 respondents. At present there are 20 ethical commissions in the Czech Republic, 19 local ones and one central one.

[Report on the activities of the Central Commission on Ethics of the Czech Ministry of Health 1990-1992]. / Zpráva o cinnosti centrální etické komise ministerstva zdravotnictví Ceské republiky v letech 1990-1992.

The central ethical commission (CEC) of the Czech Ministry of Health was founded in 1990. The authors submit a report on the activities of this advisory and expert in the sphere of medical ethics. They emphasize that a standpoint was elaborated regarding the problem of doping in the Czech Republic, a moral code of patients' rights and other important documents. The CEC takes into account also views of chairmen of local ethical commissions which were assembled by means of a questionnaire. The CEC foresee its future activity in particular in adequate presentation of its views to the professional and lay public.

[Adenoma of the ciliary body (author's transl)]. / Adenom des Ziliarkörpers.

An adenoma of the non-pigmented ciliary body was removed locally; 15 years later the eye was enucleated. The globe contained a small tumor with similar histological features but invasive growth.