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.

[HISTOPATHOLOGIC CHANGES IN SEPSIS].

Severe sepsis and septic shock are the major healthcare problem with high mortality and increasing incidence. Most cases of septic shock are caused by gram-negative bacilli or gram-positive cocci. In diagnostic algorithm, microbial culture and molecular analysis of tissue and body liquid should be obtained in patients with documented history of infection. Morphological analysis of tissue should be performed for diagnostic purpose in cases where the results of diagnostic tests are negative or when the patient clinically deteriorates despite standard therapeutic management of severe sepsis and septic shock. Morphological changes that can be found in a patient with sepsis include reversible and irreversible cell injury, cell necrosis, inflammatory and other pathological changes that can cause functional organ failure. Analysis of infectious agents can be performed using special methods, histochemical, immunohistochemical and immunofluorescence staining. Morphological analysis of pathological processes can be performed in cases of patient death. Autopsy is one of the most reliable methods to validate clinical diagnosis. In a patient with severe sepsis and septic shock, morphological analysis of tissue and organs, which can be performed during diagnostic algorithm, as well as on autopsy, presents diagnostic and final validation of clinical diagnosis and contributes to appropriate patient care, therapy and improved health quality.

Malignant melanoma ovarian metastasis mimicking acute tuboovarian abscess.

BACKGROUND: Metastases of malignant melanoma to the reproductive organs are occasionally encountered. They always represent a diagnostic challenge and they mimic various ovarian entities from primary ovarian malignancy to benign tumors. CASE: A 35-year-old woman presented with bilateral ovarian metastases which had clinical features of an acute state mimicking a tuboovarian abscess. The diagnosis was established postoperatively. CONCLUSION: Sophisticated imaging methods may be necessary in cases of ovarian tumors in patients with a previous history of melanoma with possible metastatic dissemination. Urgent admittance and treatment of these patients with a range of clinical symptoms can be critical and may lead to a wrong diagnosis. Attentive monitoring of ovarian morphology in women with treated malignant melanoma is mandatory to detect rare but possible metastatic sites. Regardless of surgical and adjuvant therapy dissemination of malignant melanoma to the ovary has unfortunately a poor prognosis.