The ulcerogenic potential of dopamine antagonists and L-NAME in rats provides unresolved issues of anti-emetic neuroleptic application in both patients and experimental studies. Therefore, in a 1-week study, we examined the pressures within the lower oesophageal and the pyloric sphincters in rats [assessed manometrically (cm HO)] after dopamine neuroleptics/prokinetics, L-NAME, L-arginine and stable gastric pentadecapeptide BPC 157 were administered alone and/or in combination. Medication (/kg) was given once daily intraperitoneally throughout the 7 days, with the last dose at 24 h before pressure assessment. Given as individual agents to healthy rats, all dopamine antagonists (central [haloperidol (6.25 mg, 16 mg, 25 mg), fluphenazine (5 mg), levomepromazine (50 mg), chlorpromazine (10 mg), quetiapine (10 mg), olanzapine (5 mg), clozapine (100 mg), sulpiride (160 mg), metoclopramide (25 mg)) and peripheral(domperidone (10 mg)], L-NAME (5 mg) and L-arginine (100 mg) decreased the pressure within both sphincters. As a common effect, this decreased pressure was rescued, dose-dependently, by BPC 157 (10 µg, 10 ng) (also note that L-arginine and L-NAME given together antagonized each other's responses). With haloperidol, L-NAME worsened both the lower oesophageal and the pyloric sphincter pressure, while L-arginine ameliorated lower oesophageal sphincter but not pyloric sphincter pressure, and antagonized L-NAME effect. With domperidone, L-arginine originally had no effect, while L-NAME worsened pyloric sphincter pressure. This effect was opposed by L-arginine. All these effects were further reversed towards a stronger beneficial effect, close to normal pressure values, by the addition of BPC 157. In addition, NO level was determined in plasma, sphincters and brain tissue. Thiobarbituric acid reactive substances (TBARS) were also assessed. Haloperidol increased NO levels (in both sphincters, the plasma and brain), consistently producing increased TBARS levels in the plasma, sphincters and brain tissues. These effects were all counteracted by BPC 157 administration. In conclusion, we revealed that BPC 157 counteracts the anti-emetic neuroleptic class side effect of decreased pressure in sphincters and the dopamine/NO-system/BPC 157 relationship.

No abstract

No abstract

We revealed a new point with cyclophosphamide (150 mg/kg/day intraperitoneally for 7 days): we counteracted both rat stomach and duodenal ulcers and increased NO- and MDA-levels in these tissues. As a NO-system effect, BPC 157 therapy (10 µg/kg, 10 ng/kg, intraperitoneally once a day or in drinking water, till the sacrifice) attenuated the increased NO- and MDA-levels and nullified, in rats, severe cyclophosphamide-ulcers and even stronger stomach and duodenal lesions after cyclophosphamide + L-NAME (5 mg/kg intraperitoneally once a day). L-arginine (100 mg/kg intraperitoneally once a day not effective alone) led L-NAME-values only to the control values (cyclophosphamide + L-NAME + L-arginine-rats). Briefly, rats were sacrificed at 24 h after last administration on days 1, 2, 3, or 7, and assessment included sum of longest lesions diameters (mm) in the stomach and duodenum, oxidative stress by quantifying thiobarbituric acid reactivity as malondialdehyde equivalents (MDA), NO in stomach and duodenal tissue samples using the Griess reaction. All these parameters were highly exaggerated in rats who underwent cyclophosphamide treatment. We identified high MDA-tissue values, high NO-tissue values, ulcerogenic and beneficial potential in cyclophosphamide-L-NAME-L-arginine-BPC 157 relationships. This suggests that in cyclophosphamide damaged rats, NO excessive release generated by the inducible isozyme, damages the vascular wall and other tissue cells, especially in combination with reactive oxygen intermediates, while failing endothelial production and resulting in further aggravation by L-NAME which was inhibited by L-arginine. Finally, BPC 157, due to its special relations with NO-system, may both lessen increased MDA- and NO-tissues values and counteract effects of both cyclophosphamide and L-NAME on stomach and duodenal lesions.

No abstract

SUMMARY -We report a case of biliary cyst type II which, independently of its a priori benign nature, caused numerous complications such as recurrent cholangitis and pancreatitis, as well as subsequent hepatic fi brosis and the potential danger of choledochocele perforation. Although they are benign, biliary/choledochal cysts can cause numerous disorders such as cholestasis, leading to cholangitis and pancreatitis and biliary sepsis, and due to chronic infl ammation of the biliary system even cholangiocarcinogenesis. Our fi ndings showed that sometimes this type of biliary cyst (according to the available literature the rarest and most benign type), as well as type I cyst, should undergo timely radical excision. In our patient, timely choledochocele resection would have certainly contributed to the reduction of subsequent complications, as well as to obviating repeated invasive diagnostic and surgical procedures.

No abstract

The management of patients with acute severe ulcerative colitis and SARS-CoV-2 presents a clinical challenge. We report on the first case of a patient with acute severe ulcerative colitis and mild coronavirus disease 2019 (COVID-19) who received rescue infliximab therapy, followed by a relapse caused by enterohemorrhagic Escherichia coli 0157:H7. The treatment challenges we faced were biologic therapy administration during active COVID-19, about which little was known at the time, and how to treat EHEC due to the risk of hemolytic uremic syndrome. Acute severe ulcerative colitis was treated with rescue infliximab therapy, and enteric infection with an antibiotic, both with satisfactory clinical response. The decision to induce biologic therapy for inflammatory bowel disease relapse in SARS-CoV-2-positive patients should be made on a case-to-case basis and should be driven by the dominant disease. Our patient tested positive for SARS-CoV-2, but actually had mild disease. At the same time, she had acute severe ulcerative colitis, so we started anti-tumor necrosis factor therapy despite serological tests and the recommendation to delay biological therapy administration for two-weeks. Second, due to severity of the first flare, COVID-19, and the patient's general condition, we opted for an antibiotic treatment of Escherichia coli 0157:H7 while monitoring the parameters of potential hemolytic uremic syndrome development.