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.

The history of Croatian Trauma Society - a brief overview.

Croatian Trauma Society (CTS) has a 51 year of history and tradition. This article represents a brief overview from the times when it was founded, June 30, 1961, until the present time. It tells us about the idea how, where and when the "Section for Traumatology" was founded, its activities and influence not only to promote patient trauma care but initiation of other societies dealing with traumatized patients as well, including the evolution of the CTS itself. The authors thank to all the contributors that made this article possible.

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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.

Febrile ulceronecrotic pityriasis lichenoides et varioliformis acuta with fatal outcome.

Ulceronecrotic Mucha-Habermann disease is a severe, febrile form of pityriasis lichenoides et varioliformis acuta. The condition may sometimes have a fatal outcome, especially in elderly patients. In this paper, we are reporting on a 60-year-old male patient who suffered from the eruption of erythematous, haemorrhagic, ulceronecrotic papules accompanied by high temperature. Erosions and ulceronecrotic papules covered over 80% of his body. Three weeks after his admittance to our hospital, clinical signs resembling ileus together with the leucocytosis occurred. The patient was transferred to the department of internal medicine and later to the surgery department. The fulminant course of the disease could not be stopped, and the patient died of severe intestinal and colon gangrene caused by the massive thrombosis of superior mesenteric artery. Up to date, only 23 cases of this severe form of the disease have been reported, and even with the early recognition, fulminant course may lead to death.

Non-aromatic naphthalane preparation; preliminary clinical study in the treatment of psoriasis vulgaris.

This study aimed to prove the similarity of the composition of non-aromatic Croatian naphthalane (NAN) with brown naphthalane (BN), which is used in the treatment of psoriasis vulgaris. The comparison of the compositions was performed by obtaining GC fingerprints, which were supported by GC-MS data. In spite of remarkable differences in general profiles of the GC chromatograms, lower and medium molecular weight components of NAN were found to be qualitatively the same as the saturated constituents of BN. Quantitatively, lower molecular weight components as well as all n-alkanes were comparatively lower in NAN. NAN, additionally, contained higher molecular weight components, among which there were saturated oligocyclic hydrocarbons (up to pentakishomohopanes), described as responsible for the curing effect of naphthalane. The composition characteristics of NAN including its non-aromatic character made it suitable for a clinical study. In the treatment, the efficacy was determined by means of comparison of Psoriasis Area Severity Indices, PASI, at the beginning and at the end of the therapy. Adult volunteer-patients, nine males and six females, applied NAN over the whole body, except the scalp, at the room temperature for 20 min and this was followed by the selective UVB radiation. After the 3-week therapy, all essential clinical manifestations as erythema, desquamation and infiltration were significantly reduced in 14 patients; in nine cases the improvement was 50-93%, while the state of five patients improved between 25 and 50%. In one case, there was no obvious change. No exacerbation occurred during the therapy period. No adverse effect on hematological or biochemical parameters was noticed.

Detection and genotyping of Borrelia burgdorferi sensu lato by polymerase chain reaction.

AIM: To isolate and genotype Borrelia burgdorferi genospecies in serum samples of Croatian patients with erythema migrans. METHODS: DNA isolates from sera of patients with erythema migrans were analyzed by nested polymerase chain reaction (PCR), amplifying a segment of flagellin gene with primers encompassing the conserved region of the gene. To screen PCR products for heterogeneity, we performed single-stranded conformation polymorphism (SSCP) analysis. The samples showing differences in SSCP patterns were sequenced, and the sequence compared in the GeneBank for sequence homology with known Borrelia burgdorferi genospecies. We also constructed phylogenetic tree of all known borrelial sequences. RESULTS: The nested PCR method using specially designed flagellin gene primers, achieved the sensitivity of 10 genome copies (0.01 pg of purified Borrelia burgdorferi DNA from culture) by dilution analysis. The assay specificity was confirmed by amplification of a part of the flagellin gene from different bacterial species. The primer pairs successfully amplified only Borrelia burgdorferi flagellin gene. The genome of Borrelia burgdorferi sensu lato was detected in the sera of all 10 tested patients with erythema migrans. Sequence data and phylogenetic analysis confirmed that all amplified samples belonged to Borrelia afzelii genospecies. CONCLUSION: Phylogenetic tree analysis placed the borrelial isolates together with Borrelia afzelii sequences into a single group. This finding was additionally supported by sequence homology analysis, which produced a homology score of 99%. In patients with erythema migrans who come from the northwest Croatia, an endemic area for Lyme borreliosis, Borrelia afzelii was the cause of skin manifestations of Lyme borreliosis.

The possible role of skin surface lipid in rosacea with epitheloid granulomas.

The examination was carried out in 50 rosacea patients (30 females and 20 males) in order to establish the connexion between skin surface lipids, infestation with Demodex folliculorum and previous local corticosteroid treatment with the appearance of epitheloid granulomas. Our analysis showed three types of histological conditions: 1) chronic dermatitis of the rosacea type was noted in 15 patients (30%); 2) granulomas composed of epitheloid cells was found in 16 patients (32%). In three female patients of this group presence of caseous necrosis associated with epitheloid granuloma was noted, too; 3) prevalence of perifollicular absceses was found in 19 patients (38%). Demodex folliculorum was detected in 43 rosacea patients (86%), considerably more then in the control group. The normal value of the skin surface lipids was found in 9 female rosacea patients (30%) and in 9 female controls (43%), in 8 male rosacea patients (40%) and in 5 males controls (33%). Lower amounts of skin surface lipids were found in 19 female rosacea patients (63%) and in 9 female controls (43%), in 4 male rosacea patients (20%) and in 1 male control (7%). Higher amounts of skin surface lipids were found in 2 female rosacea patients (7%) and in 3 female controls (14%), in 8 male rosacea patients (40%) and in 9 male controls (60%). Lower quantities of lipids determined a higher incidence of Demodex folliculorum in rosacea patients. Demodex folliculorum were also more frequently detected in patients who had previously been treated with topical corticosteroids (even in 91.9%), what was often followed by epitheloid granulomas. The treatment with tetracycline yielded good or excellent results in 90% of all the patients.

[Evaluation of the effect of local corticosteroids in the phototherapy of psoriasis]. / Evaluacija djelovanja lokalnih kortikosteroida u fototerapiji psorijaze.

An open clinical trial was carried out in order to establish to what extent the application of topical corticosteroids with the UVB therapy influences the complete dosage of the UVB radiation required for the clearing of psoriasis and the duration of remission. Out of 30 patients who were administered the suberythemogenic UVB dosage, 15 received a topical corticosteroid and 15 an indifferent ointment (u. emolliens). Although the therapeutic response was initially somewhat more immediate in the corticosteroid--UVB group, there is no statistically significant difference between these two groups in the total UVB dosage required for the remission of the disease. The patients in the topical corticosteroid--UVB group remained in remission longer than the patients in the control group receiving no local corticosteroid.

[Hypersensitivity vasculitis caused by ethyl biscoumacetate]. / Hipersenzitivni vaskulitis izazvan etilbiskumacetatom.

A case report of a 61-year-old patient with hypersensitive vasculitis caused by ethylbiscumacetate is presented. After the implantation of the artificial aortic valve the patient was treated with medigoxine, furosemide, dipiridamole, disopiramide, potassium chloride and ethylbiscumacetate. Among these drugs furosemide and ethylbiscumacetate are reported to cause hypersensitive vasculitis. On the basis of the past medical history, clinical and histological findings furosemide was ruled out as a causative agent. The diagnosis was confirmed by the skin biopsy and finding of a normal biologic activity of protein C. The discontinuance of all previous drugs and administration of methylprednisolone led to improvement in the skin lesions of the patient. The need for continuous anticoagulant therapy was the reason for fepromarone to be given, achieving good anticoagulant effect, without any side effects. According to the criteria of Karch and Lasagna the degree of connection between drug use and side effects in this case belongs to the category "probable".

Combination of cyclosporin and methotrexate for prophylaxis of acute graft-versus-host disease after allogeneic bone marrow transplantation for leukemia.

From May 1985 to July 1989, 76 patients with leukemia (30 acute myelogenous leukemia, 24 acute lymphoblastic leukemia and 22 chronic myeloid leukemia) were randomized to receive either cyclosporin (CSP) alone (n = 39) or CSP combined with methotrexate (CSP + MTX, n = 37) for graft-versus-host disease (GVHD) prophylaxis. Patients were conditioned with total body radiation and cyclophosphamide followed by bone marrow infusion from an HLA-identical sibling. Engraftment of the transplanted bone marrow was similar in both groups. The incidence of moderate to severe acute GVHD was significantly higher in the CSP group compared with the CSP + MTX group (20 (51%) versus 9 (25%), chi 2 = 4.76, p less than 0.02). There was no significant difference in the incidence of chronic GVHD. Survival was significantly better for the CSP + MTX group (63 +/- 16%) compared to CSP alone (42 +/- 18%). Leukemia-free survival tended to be better for the CSP + MTX group (55 +/- 17% versus 32 +/- 16%).

Occurrence of hereditary bullous epidermolyses in Croatia.

To determine the occurrence of hereditary bullous epidermolyses (EB) in Croatia, Yugoslavia, from 1960 to 1987, cases were gathered from the hospital files of dermatologic and pediatric clinics and departments throughout the area. The diagnosis of EB type was made on the basis of clinical features, patients' histories, and light microscopy and electron microscopy findings. Fifty families with 58 patients were registered; 44 patients were examined personally by one of the authors. The most frequent type of EB in Croatia was recessive dystrophic EB Hallopeau-Siemens, occurring in 35 of the 58 individuals. Regional accumulation of cases within the Varazdin area was noted (13 patients). Prevalence of EB in Croatia is 0.956 cases per 100,000 inhabitants. One case of recessive dystrophic EB Hallopeau-Siemens occurred in about every 52,000 live births.