Duodenocolic fistula healing by pentadecapeptide BPC 157 in rats. A cytoprotection viewpoint.

Using duodenocolic fistula in rats, this study attempts to highlight the particular cytoprotection aspects of the healing of fistulas and therapy potential of the stable gastric pentadecapeptide BPC 157, a cytoprotection mediator (i.e. upgrading minor vessels to induce healing at both fistula's sides). Upon duodenocolic fistula creation (two 'perforated' lesions put together) (assessed at 3, 6, 9, 12, and 15 min), BPC 157, given locally at the fistula, or intragastrically (10 µg/kg, 10 ng/kg), rapidly induces vessel 'recruitment', 'running' toward the defect, simultaneously at duodenum and colon, providing numerous collaterals and branching. The mRNA expression studies done at that time provided strongly elevated (nitric oxide synthase 2) and decreased (cyclooxygenase-2, vascular endothelial growth factor A, nitric oxide synthase (NOS)-1, NOS-3, nuclear factor-kappa-B-activating protein) gene expression. As therapy, rats with duodenocolic fistulas, received BPC 157 10 µg/kg, 10 ng/kg, per-orally, in drinking water till sacrifice, or alternatively, intraperitoneally, first application at 30 min after surgery, last at 24 h before sacrifice, at day 1, 3, 7, 14, 21, and 28. Controls exhibited both defects persisting, continuous fistula leakage, diarrhea, continuous weight loss, advanced adhesion formation and intestinal obstruction. Contrary, all BPC 157-treated rats have closed both defects, duodenal and colonic, no fistula leakage (finally, maximal instilled volume corresponds to healthy rats), no cachexia, the same weight as before surgery, no diarrhea, markedly less adhesion formation and intestinal passage obstruction. Thus, BPC 157 regimens resolve the duodenal/colon lesions and duodenocolic fistulas in rats, and rapid vessels recovery appears as the essential point in the implementation of the cytoprotection concept in the fistula therapy.

Novel insight into Robert's cytoprotection: complex therapeutic effect of cytoprotective pentadecapeptide pentadecapeptide BPC 157 in rats with perforated stomach throughout modulation of nitric oxide-system. Comparison with L-arginine, ranitidine and pantoprazole therapy and L-NG-nitro-L-arginine methyl ester worsening.

Surgically perforated stomach (since direct injury in rats until persisting defect and huge adhesions (day 1, day 7)) fairly represent an unresolved cytoprotection issue, and thereby, we focused resolving of the immediate triad, particular vascular failure (vessels 'disappear'/empty), prolonged bleeding, debilitated defect large widening. Agents (mg/kg) or saline (controls) were given at 1 min post-injury as an abdominal bath (10 ml/rat throughout 2 min). Within 1 - 15 min post-injury period, with cytoprotective BPC 157 (0.01 µg), the rapidly restored vessels 'run' (vessels filled/reappeared) toward the perforated defect, and there is less bleeding, and defect contraction; advanced perforated lesion healing (day 1) to complete healing (day 7), and less adhesions. With pantoprazole (10 mg), early (vessels (worsening), bleeding (prolongation), defect (attenuated widening)) effect means eventual lesions and adhesions severity as in controls. Ranitidine (10 mg) early effect (vessels (improvement), bleeding (less bleeding), defect (eliminated widening, defect not changed)) means final lesions attenuation, but not complete healing, less adhesions. L-NAME (5 mg) early (vessels worsening, less bleeding, attenuated defect widening) and final (lesions aggravation, more adhesions) effect, versus L-arginine (100 mg) early (vessels improvement, more bleeding, attenuated defect widening) and final (lesions attenuation, less adhesions) effect, combined few simultaneously occurring nitric oxide (NO)-system distinct processes. Finally, in the stomach tissue surrounding defect, increased malondialdehyde (MDA)- and decreased NO-values, BPC 157 reversed to the normal healthy values, and mRNA expression studies (Cox2, VEGFa, Nos1, Nos 2, Nos3, Nkap (NF-kappa-B-activating protein gene)), done at that very early post-perforation-time, indicate a way how BPC 157 may act beneficially in the perforated stomach lesion throughout NO- and prostaglandinds-system.

Panel Reactive Antibody Responses Against Influenza Vaccination in Kidney Transplant Recipients.

INTRODUCTION: Seasonal influenza is an important cause of morbidity and mortality in the post-transplant period; therefore, the influenza vaccination has been recommended for all kidney transplant recipients before the influenza season. However, at least theoretically, the introduction of antigens via vaccines may trigger rejection attacks by causing an antibody response. In this study, we examined the development of de novo panel reactive antibody (PRA) development against the influenza vaccine in kidney transplant recipients. MATERIALS AND METHODS: Overall, 41 kidney transplant recipients who received the influenza vaccination and 50 kidney transplant recipients (study group) who refused to receive the influenza vaccination (control group) were enrolled in the study. Following basal biochemistry examination, the inactivated trivalent influenza vaccine was administered intramuscularly. Panel reactive antibodies were screened in all patients before and after vaccination on days 30 and 180. The primary outcome variable was development of de novo panel reactive antibodies. RESULTS: One patient in the study group developed de novo class I and II PRA at 6 months after vaccination (P > .05), while no antibody development was noted in the control group. Graft dysfunction or biopsy-confirmed rejection was not observed during the follow-up period in both groups. CONCLUSION: The influenza vaccination is generally effective and safe in solid organ transplant recipients. The vaccination procedure has the potential to trigger antibody development and occurrence of rejection. Therefore, vaccinated kidney transplant recipients should be monitored more carefully with regard to PRA; if the graft deteriorates, a rapid transplant biopsy should be performed.

Relevance of Flow Cytometric Auto-Crossmatch to the Post-transplant Course of Kidney Transplant Recipients.

INTRODUCTION: The crossmatch test is essential prior to kidney transplantation (tx) to confirm compatibility between the donor and the recipient. However, its results can be misleading due to "undetectable antibodies" in the recipient's serum. To establish if undetectable autoantibodies are responsible for a positive result, an auto-crossmatch test can be performed. In this study, we aim to determine the long-term prognostic value of auto-flow cytometric auto-crossmatch (FCXM) test on kidney survival in kidney tx recipients. MATERIALS AND METHODS: The primary outcome variable was reduced renal function. Secondary endpoints were incidence of biopsy-confirmed chronic antibody-mediated rejection (CAMR) and recurrent glomerulonephritis (GN). RESULTS: There were no differences regarding initial serum creatinine levels between the study and control groups (P = .441). Patients who had positive auto-B FCXM had a significantly reduced renal function compared with the control group (P = .016). Four patients developed biopsy-confirmed CAMR in the study group and 1 patient in the control group (P = .047). Five patients had biopsy-confirmed recurrent GN in the GN study group, and only 1 patient had recurrent GN in the GN control group (P = .026). DISCUSSION: Kidney transplant recipients with positive auto-FCXM test had significantly reduced renal function and a higher incidence of recurrent GN and CAMR compared with the control group. The findings of this study suggest a potential role of auto-antibody causing positive auto-FCXM test result, meanwhile increasing the risk of CAMR, recurrent GN, and new-onset diabetes after tx.

A Novel Biomarker for Post-Transplant Recurrent IgA Nephropathy.

BACKGROUND: The serum levels of galactose-deficient immunoglobulin (Ig)A1 (Gd-IgA1) represent the most promising candidate biomarker for IgA nephropathy (IgAN). The aim of this study was to evaluate the serum levels of Gd-IgA1 as a novel noninvasive biomarker for post-transplant IgAN recurrence. METHODS: Serum Gd-IgA1 levels of 18 patients with recurrent IgAN were compared with control renal transplant recipients (n = 23) with non-recurrent IgAN and control non-transplant IgAN patients (n = 44) and healthy relatives (n = 11). Serum Gd-IgA1 levels of patients were measured with the use of KM55 enzyme-linked immunosorbent assay (ELISA). The effects of serum Gd-IgA1 concentrations on IgAN recurrence, post-transplant events, and graft survival were evaluated. RESULTS: All recurrent IgAN patients presented with renal dysfunction (mean serum creatinine, 1.62 ± 0.39 mg/dL) and detectable proteinuria at the time of diagnosis. Serum Gd-IgA1 levels of recurrent IgAN patients (8735 ± 10854 ng/mL [log10: 3.71 ± 0.45]) were significantly higher than those of non-recurrent IgAN patients (4790 ± 6089 ng/µL [log10: 3.31 ± 0.64]) (P = .027). Serum Gd-IgA1 levels of non-transplant IgAN patients were significantly higher (8791 ± 8700 ng/µL [log10: 3.79 ± 0.36]) than those of non-recurrent IgAN patients (4790 ± 6089 ng/µL [log10: 3.31 ± 0.64]) and healthy relatives (2615 ± 1611 ng/µL [log10: 3.34 ± 0.27]) (P < .001 and P = .021, respectively). Receiver-operating characteristic curve analysis revealed that the area under the curve for recurrence of IgAN was 0.69 (0.53-0.85) for serum Gd-IgA1 (P = .038). Biopsy-confirmed allograft rejection rates were similar in the recurrent IgAN group [3 (17%)] compared with the non-recurrent IgAN [6 (26%)] group (P = .47). Graft failure rate was not also significantly different in the recurrent IgAN group [4 (22.2%)] compared with the non-recurrent IgAN group [2 (8.7%)] (P = .224). CONCLUSIONS: This novel lectin-independent Gd-IgA1 ELISA that can detect serum Gd-IgA1 in patients with recurrent IgAN can be used as a biomarker for diagnosis and activity assessment of post-transplant recurrent IgAN.

Focused parathyroidectomy without intraoperative parathormone testing is safe after pre-operative localization with 18F-Fluorocholine PET/CT.

A focused surgical approach based on pre-operative localization replaced the classical four-gland exploration in patients with primary hyperparathyroidism (PHP). Sestamibi scanning and ultrasound are most often used localization modalities with reported sensitivity of 54-100% for identification of single gland disease. The aim of this study was to analyze the results of pre-operative localization with 18F-Fluorocholine PET/CT (FCh-PET) in patients with PHP. A retrospective review of 151 patients with PHP who underwent surgery after pre-operative localization with FCh-PET was performed. Only a focused parathyroidectomy without ioPTH testing had been done in patients with single adenoma on FCh-PET. Primary outcome was operative failure, defined as persistent PHP. According to pre-operative FCh-PET 126 (83,4%) patients had single adenoma, 22 (14,5%) multiglandular disease and the test was negative in only two patients. Intraoperative failure experienced 4/126 patients (3,3%) with single adenoma. Removed parathyroid glands were normal in three and hyperplastic in one patient with intraoperative failure. A limited bilateral neck exploration with ioPTH testing was used in 14/22 patients with double adenoma and a classical four-gland exploration without ioPTH testing was used in 8/22 patients with more than two pathological glands according to pre-operative FCh-PET. Intraoperative failure experienced 2/22 patients (9,1%). In two patients with negative FCh-PET a classical four-gland exploration without ioPTH testing was used and one experienced intraoperative failure. A preoperative localization with FCh-PET is a reliable test in patients with PHP. Patients with a single adenoma on FCh-PET can safely undergo a focused parathyroidectomy without ioPTH testing.

Duodenocutaneous fistula in rats as a model for "wound healing-therapy" in ulcer healing: the effect of pentadecapeptide BPC 157, L-nitro-arginine methyl ester and L-arginine.

While very rarely reported, duodenocutanenous fistula research might alter the duodenal ulcer disease background and therapy. Our research focused on rat duodenocutaneous fistulas, therapy, stable gastric pentadecapeptide BPC 157, an anti-ulcer peptide that healed other fistulas, nitric oxide synthase-substrate L-arginine, and nitric oxide synthase-inhibitor L-nitro-arginine methyl ester (L-NAME). The hypothesis was, duodenal ulcer-healing, like the skin ulcer, using the successful BPC 157, with nitric oxide-system involvement, the "wound healing-therapy", to heal the duodenal ulcer, the fistula-model that recently highlighted gastric and skin ulcer healing. Pressure in the lower esophageal and pyloric sphincters was simultaneously assessed. Duodenocutaneous fistula-rats received BPC 157 (10 µg/kg or 10 ng/kg, intraperitoneally or perorally (in drinking water)), L-NAME (5 mg/kg intraperitoneally), L-arginine (100 mg/kg intraperitoneally) alone and/or together, throughout 21 days. Duodenocutaneous fistula-rats maintained persistent defects, continuous fistula leakage, sphincter failure, mortality rate at 40% until the 4(th) day, all fully counteracted in all BPC 157-rats. The BPC 157-rats experienced rapidly improved complete presentation (maximal volume instilled already at 7(th) day). L-NAME further aggravated the duodenocutaneous fistula-course (mortality at 70% until the 4(th) day); L-arginine was beneficial (no mortality; however, maximal volume instilled not before 21(st) day). L-NAME-worsening was counteracted to the control level with the L-arginine effect, and vice versa, while BPC 157 annulled the L-NAME effects (L-NAME + L-arginine; L-NAME + BPC 157; L-NAME + L-arginine + BPC 157 brought below the level of the control). It is likely that duodenocutaneous fistulas, duodenal/skin defect simultaneous healing, reinstated sphincter function, are a new nitric oxide-system related phenomenon. In conclusion, resolving the duodenocutanenous fistulashealing, nitric oxide-system involvement, should illustrate further wound healing therapy to heal duodenal ulcers.

Renal transplantation in a patient with chronic granulomatous disease: case report.

Chronic granulomatous disease (CGD) is a genetic disease caused by structural mutations in the enzyme NADPH oxidase that results in severe immunodeficiency. End-stage renal disease occurs in this patient population and is attributed to various factors, including infections, amyloidosis, and nephrotoxic anti-infective agents. In this report, we present our experience in transplantation for a patient with CGD complicated by isolated hepatic tuberculosis abscess. The course of the case demonstrates the absolute requirements for a multidisciplinary and compulsive approach before, during, and after transplantation. This case report also highlights the unexpectedly benign effects of immunosuppressive therapy in this patient population.

Stable gastric pentadecapeptide BPC 157 heals cysteamine-colitis and colon-colon-anastomosis and counteracts cuprizone brain injuries and motor disability.

Stable gastric pentadecapeptide BPC 157 was suggested to link inflammatory bowel disease and multiple sclerosis, and thereby, shown to equally counteract the models of both of those diseases. For colitis, cysteamine (400 mg/kg intrarectally (1 ml/rat)) and colon-colon anastomosis (sacrifice at day 3, 5, 7, and 14) were used. BPC 157 (10 µg/kg, 10 ng/kg) was applied either intraperitoneally once time daily (first application immediately after surgery, last at 24 hours before sacrifice) or per-orally in drinking water (0.16 µg/ml/12 ml/day till the sacrifice) while controls simultaneously received an equivolume of saline (5 ml/kg) intraperitoneally or drinking water only (12 ml/day). A multiple sclerosis suited toxic rat model, cuprizone (compared with standard, a several times higher regimen, 2.5% of diet regimen + 1 g/kg intragastrically/day) was combined with BPC 157 (in drinking water 0.16 µg or 0.16 ng/ml/12 ml/day/rat + 10 µg or 10 ng/kg intragastrically/day) till the sacrifice at day 4. In general, the controls could not heal cysteamine colitis and colon-colon anastomosis. BPC 157 induced an efficient healing of both at the same time. Likewise, cuprizone-controls clearly exhibited an exaggerated and accelerated damaging process; nerve damage appeared in various brain areas, with most prominent damage in corpus callosum, laterodorsal thalamus, nucleus reunions, anterior horn motor neurons. BPC 157-cuprizone rats had consistently less nerve damage in all damaged areas, especially in those areas that otherwise were most affected. Consistently, BPC 157 counteracted cerebellar ataxia and impaired forelimb function. Thereby, this experimental evidence advocates BPC 157 in both inflammatory bowel disease and multiple sclerosis therapy.

CD34+ stem cell therapy in nonischemic dilated cardiomyopathy patients.

Recent trends indicate that patients with nonischemic dilated cardiomyopathy represent the largest subpopulation of heart failure patients with a significant need for alternative treatment modalities. Similar to patients with ischemic cardiomyopathy, patients with nonischemic dilated cardiomyopathy have been found to have myocardial regions with flow abnormalities, which may represent targets for neoangiogenic therapies. CD34(+) stem cells might contribute to the formation of new blood vessels from existing vascular structures in ischemic tissues by the direct incorporation of injected cells into the newly developing vasculature or by the production and secretion of angiogenic cytokines. This review summarizes the long-term clinical effects and potential underlying mechanisms of CD34(+) cell therapy in patients with nonischemic dilated cardiomyopathy.

Kidney transplant recipients with functioning grafts for more than 15 years.

BACKGROUND: Renal transplantation is the best renal replacement therapy because it significantly improves patient survival. The developments in transplantation and increasing number of patients with end-stage renal disease (ESRD) have unmasked long-term complications secondary to immunosuppressive drugs and chronic renal failure. METHODS AND RESULTS: Eighty-six renal transplant recipients with grafts that have functioned more than 15 years were included in the study. This cross-sectional retrospective analysis of demographic, clinical, and laboratory findings was conducted in 3 Turkish transplantation centers. The mean age was 30.4 ± 10.2 years at the time of the transplantation. The mean time between the transplantation and the study was 19.1 ± 3.6 years. At the time of the study, mean creatinine level was 1.52 ± 0.60 mg/dL, 70.09% of the patients displayed glomerular filtration rates <60 mL/min/1.73 m(2). Urinary protein excretion was 0.57 ± 0.65 g/d. Hypertension and hyperlipidemia were the most common comorbid diseases. Twelve patients had diabetes and 9 cardiovascular disease. Seventeen patients had been diagnosed with skin and 5 with non-skin cancer. CONCLUSIONS: As the number of recipients with long-term functioning grafts increases, long-term complications become evident, particularly chronic renal failure. Survivors should be evaluated regularly and treated early for risk factors and complications to improve long-term graft and patient survival.

Focus on ulcerative colitis: stable gastric pentadecapeptide BPC 157.

Stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, M.W. 1419) may be the new drug stable in human gastric juice, effective both in the upper and lower GI tract, and free of side effects. BPC 157, in addition to an antiulcer effect efficient in therapy of inflammatory bowel disease (IBD) (PL 14736) so far only tested in clinical phase II, has a very safe profile, and exhibited a particular wound healing effect. It also has shown to interact with the NO-system, providing endothelium protection and angiogenic effect, even in severely impaired conditions (i.e., it stimulated expression of early growth response 1 gene responsible for cytokine and growth factor generation and early extracellular matrix (collagen) formation (but also its repressor nerve growth factor 1-A binding protein-2)), important to counteract severe complications of advanced and poorly controlled IBD. Hopefully, the lessons from animal studies, particularly advanced intestinal anastomosis healing, reversed short bowel syndrome and fistula healing indicate BPC 157's high significance in further IBD therapy. Also, this supportive evidence (i.e., no toxic effect, limit test negative, LD1 not achieved, no side effect in trials) may counteract the problems commonly exercised in the use of peptidergic agents, particularly those used on a long-term basis.

BPC 157 therapy to detriment sphincters failure-esophagitis-pancreatitis in rat and acute pancreatitis patients low sphincters pressure.

Possibly, acute esophagitis and pancreatitis cause each other, and we focused on sphincteric failure as the common causative key able to induce either esophagitis and acute pancreatitis or both of them, and thereby investigate the presence of a common therapy nominator. This may be an anti-ulcer pentadecapeptide BPC 157 (tested for inflammatory bowel disease, wound treatment) affecting esophagitis, lower esophageal and pyloric sphincters failure and acute pancreatitis (10 µg/kg, 10 ng/kg intraperitoneally or in drinking water). The esophagitis-sphincter failure procedure (i.e., insertion of the tubes into the sphincters, lower esophageal and pyloric) and acute pancreatitis procedure (i.e., bile duct ligation) were combined in rats. Esophageal manometry was done in acute pancreatitis patients. In rats acute pancreatitis procedure produced also esophagitis and both sphincter failure, decreased pressure 24 h post-surgery. Furthermore, bile duct ligation alone immediately declines the pressure in both sphincters. Vice versa, the esophagitis-sphincter failure procedure alone produced acute pancreatitis. What's more, these lesions (esophagitis, sphincter failure, acute pancreatitis when combined) aggravate each other (tubes into sphincters and ligated bile duct). Counteraction occurred by BPC 157 therapies. In acute pancreatitis patients lower pressure at rest was in both esophageal sphincters in acute pancreatitis patients. We conclude that BPC 157 could cure esophagitis/sphincter/acute pancreatitis healing failure.

Long-term prognostic value of coronary flow velocity reserve in renal transplant recipients.

BACKGROUND: In this prospective study, we sought to investigate the long-term prognostic value of coronary flow reserve (CFR) and carotid intima media thickness (IMT) estimates in renal transplant recipients without known coronary artery disease. METHODS: The 20 renal transplant recipients included in this study underwent CFR recordings performed by trans-thoracic Doppler echocardiography (TTDE) and carotid IMT measured by carotid Doppler ultrasonography. RESULTS: During a 3-year follow-up only one patient experienced a cardiac event. The baseline CFR and carotid IMT values of the patients were 1.77 ± 0.47 and 0.67 ± 0.15 mm, respectively. After 3 years of follow-up, there were no significant differences compared with baseline measurements with regard to CFR and IMT values. CFR values at the third year of follow-up showed significant correlation with age as well as IMT at baseline and at the third year. Upon multivariate analysis, baseline carotid IMT (ß = -0.562; P = .05) was a significant independent predictor of CFR at the third year. CONCLUSION: Carotid IMT showed a greater predictive value for impaired CFR in renal transplant recipients. CFR was not an independent predictor for cardiovascular events among renal transplant recipients within the first 3 years of follow-up measurements.

Outcome of kidney transplantation following end-stage renal disease due to reflux nephropathy.

BACKGROUND: Reflux nephropathy (RN) has an important place among the etiologies of end-stage renal disease (ESRD). In this retrospective study we sought to analyze posttransplantation complications among renal transplant recipients whose primary disease was RN. METHODS: Seven hundred forty-five patients who underwent transplantation in our institution between 1983 and 2006 were included in the study. The outcomes of patients with RN (Group 1) were compared with a control group (Group 2) that consisted of age-matched, nondiabetic patients whose primary disease was chronic glomerulonephritis or unknown etiologies. RESULTS: Group 1 consisted of 52 patients, including 20 males with a mean overall age of 25 years. Group 2 included 47 patients, including 21 males with a mean age of 27 years. There was no significant difference with regard to age, gender, donor type, donor age, modality of hemodialysis, or HLA match between the 2 groups. Group 1 graft survival rates in the first and fifth years were 95% and 90%, respectively, and in Group 2 they were 86% and 70%, respectively (P = .302 and P = .072, respectively). There was no significant difference with respect to follow-up duration, hospital stay, or incidence of biopsy-proven or clinically suspected acute rejection episodes between the groups. During the 6-year follow-up, the incidence of biopsy-proven chronic allograft nephropathy was the same in both groups. One patient in Group 1 and 2 in Group 2 died of cardiovascular issues; 1 Group 2 patient died of infection. The frequency of urinary tract infection in Group 1 was greater than that of Group 2 (40% vs, 23%; P = NS). CONCLUSION: Despite the higher incidence of urinary tract infections, there was no significant difference in posttransplantation complications or patient and graft survival rates between RN patients compared with the control group.

When the earth trembles in the Americas: the experience of Haiti and Chile 2010.

The response of the nephrological community to the Haiti and Chile earthquakes which occurred in the first months of 2010 is described. In Haiti, renal support was organized by the Renal Disaster Relief Task Force (RDRTF) of the International Society of Nephrology (ISN) in close collaboration with Médecins Sans Frontières (MSF), and covered both patients with acute kidney injury (AKI) and patients with chronic kidney disease (CKD). The majority of AKI patients (19/27) suffered from crush syndrome and recovered their kidney function. The remaining 8 patients with AKI showed acute-to-chronic renal failure with very low recovery rates. The intervention of the RDRTF-ISN involved 25 volunteers of 9 nationalities, lasted exactly 2 months, and was characterized by major organizational difficulties and problems to create awareness among other rescue teams regarding the availability of dialysis possibilities. Part of the Haitian patients with AKI reached the Dominican Republic (DR) and received their therapy there. The nephrological community in the DR was able to cope with this extra patient load. In both Haiti and the DR, dialysis treatment was able to be prevented in at least 40 patients by screening and adequate fluid administration. Since laboratory facilities were destroyed in Port-au-Prince and were thus lacking during the first weeks of the intervention, the use from the very beginning on of a point-of-care device (i-STAT®) was very efficient for the detection of aberrant kidney function and electrolyte parameters. In Chile, nephrological problems were essentially related to difficulties delivering dialysis treatment to CKD patients, due to the damage to several units. This necessitated the reallocation of patients and the adaptation of their schedules. The problems could be handled by the local nephrologists. These observations illustrate that local and international preparedness might be life-saving if renal problems occur in earthquake circumstances.

High hepatotoxic dose of paracetamol produces generalized convulsions and brain damage in rats. A counteraction with the stable gastric pentadecapeptide BPC 157 (PL 14736).

We focused on stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, MW 1419, an anti-ulcer peptide efficient in inflammatory bowel disease trials (PL 14736), no toxicity reported) because of its hepatoprotective effects. We investigate a particular aspect of the sudden onset of encephalopathy with extreme paracetamol overdose (5 g/kg intraperitoneally) so far not reported: rapidly induced progressive hepatic encephalopathy with generalized convulsions in rats. BPC 157 therapy (10 microg, 10 ng, 10 pg/kg, intraperitoneally or intragastrically) was effective (microg-ng range) against paracetamol toxicity, given in early (BPC 157 immediately after paracetamol, prophylactically) or advanced stage (BPC 157 at 3 hours after paracetamol, therapeutically). At 25 min post-paracetamol increased ALT, AST and ammonium serum values precede liver lesion while in several brain areas, significant damage became apparent, accompanied by generalized convulsions. Through the next 5 hour seizure period and thereafter, the brain damage, liver damage enzyme values and hyperammonemia increased, particularly throughout the 3-24 h post-paracetamol period. BPC 157 demonstrated clinical (no convulsions (prophylactic application) or convulsions rapidly disappeared (therapeutic effect within 25 min)), microscopical (markedly less liver and brain lesions) and biochemical (enzyme and ammonium serum levels decreased) counteraction. Both, the prophylactic and therapeutic benefits (intraperitoneally and intragastrically) clearly imply BPC 157 (microg-ng range) as a highly effective paracetamol antidote even against highly advanced damaging processes induced by an extreme paracetamol over-dose.