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Summarized text of Croatian Consensus Conference on Viral Hepatitis of 2009 comprises the following chapters: 1) Epidemiology, 2) Clinical Picture, 3) Diagnostic Procedure, 4) Aims of Treatment of Viral Hepatitis, 5) Terminology, 6) Medicaments (6.1. Interferon, 6.2. Analogues of Nucleozides and Nucleotides), 7) Hepatitis B (7.1. Serologic and Molecular HBV Diagnostics, 7.2. Terminology, 7.3. Whom to Treat? 7.4. Therapy), 8) Hepatitis C (8.1. Serologic and Molecular HCV Diagnostics, 8.2. Terminology, 8.3. Whom to Treat? 8.4. Therapy). Clinical, laboratory and histologic assessment of patients with chronic viral hepatitis (algorythm of pretherapeutic treatment ; histologic evaluation) and notions related to therapy of viral hepatitis (category of the patient and category of the response to treatment) are presented in related tables.

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Adaptive cytoprotection could be demonstrated in lesion attenuation within the whole gastrointestinal tract, in particular sequences, with onset and duration longer than the initial short-lasting period (i.e. one hour) defined by Robert in the stomach only. Adaptive cytoprotection possibly appeared and lesions were attenuated when the stomach, duodenum or colon, in various combinations and sequences, were challenged with initial (mild) and/or final (strong) irritants over a two-week period. Rats were challenged with the mild or strong irritants 25% or 96% ethanol intragastrically 1 ml/rat (stomach) and cysteamine 40 mg or 400 mg/kg subcutaneously (duodenum), or intrarectally (colon). To postulate the prostaglandin relationship known in Robert's cytoprotection and adaptive cytoprotection, indomethacin (1 mg/kg subcutaneously) was given simultaneously with the second challenge. Administering the mild and strong irritant protocols within the same part of the gastrointestinal tract, adaptive cytoprotection presents in the stomach (1 h to 14 days), duodenum (2 h to 14 days), but not in the colon. With these protocols applied to different parts of the gastrointestinal tract, adaptive cytoprotection cross-reaction was evident in the stomach-duodenum, duodenum-stomach (1 h-14 days and 2 h-14 days), stomach-colon, and duodenum-colon (both 2-24 hours), but not in the colon-stomach or colon-duodenum. This protection was fully antagonized with indomethacin. As observed for a day and even weeks, stomach-duodenum-colon adaptive cytoprotection is an important new defensive phenomenon.

This is first demonstration thad GERD is associated with osteopenia/osteoporosis presentation, and this should be relevant for further both clinical and experimental studies.

Primary antibiotic resistance of Helicobacter pylori strains isolated at University Hospital Split.

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Aim. We focus whether the critical period for threatening outcome in prolonged esophagitis and relation with prolonged failure of lower esophageal sphincter (LES) and pyloric sphincter (PS) could be modified with a stable gastric pentadecapeptide BPC 157 , promising in inflammatory bowel disease (PLD116, PL14736, Pliva). It attenuates esophago-jejunal anastomosis-esophagitis (J Phys, 1999) (1 month), and recovers and maintains esophageal mucosal integrity and sphincters pressure for 1 year (Gastroenterology, 2004) in rats that had grossly intact GI tract with the essential function failure mimicked by tubes into LES and PS. Methods. This procedure induces prominent esophagitis, LES- and PS-malfunction (one tube inserted into LES, and the other tube into PS, for 1 week, then both artlessly removed), gastroduodenal contents reflux. Now, considerably extending esophagitis period, BPC 157 effect was compared in these esophagitis rats with grossly intact GI-tract with essential function failure, after 12 and 20 months, with respect to normal-healthy rats and (i) sphincters pressure (LES, PS) and (ii) esophagitis attenuation. Assessed at 12 or 18 months of esophagitis: (i) LES-, PS- pressure (cm H2O). Water manometer connected with drainage port of Foley catheter was implanted into the stomach either through esophageal or duodenal incision before BPC 157 or saline (1 ml/rat ; 5ml/kg) were given directly into the stomach ; assessment was at 5 min thereafter. (ii) Reflux esophagitis. Macro- (scored 0 (normal) to 4 (the worst)) as well as micro-scopically (program SFORM, VAMSTECH-Software Company, Croatia) ; BPC 157 (10 µ ; g /kg) i.p. once daily or in drinking water. Results. (i) Sphincter pressure. Esophagitis-rats present a marked sphincter dysfunction, constantly lessened LES- and PS-pressure. For both LES and PS, BPC 157 (a) promptly increases the decreased values till the level in healthy, then, (b) maintains pressure preserved at the healthy level during 12-18 months period, while (c) in normal rats, it increases LES- , but decreases PS- pressure (Fig. 1). (ii) Esophagitis-attenuation. BPC 157 attenuates esophageal lesion at either region, and either interval. Thinner epithelium and superficial corneal layer in controls (12-18 months) than in naive healthy and BPC 157 treated animals. Controls (12 months) present a stratification derangement in contrast to healthy controls and BPC treated animals.

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Influence of gender and age on colorectal carcinoma in southern Croatia.

Serious complications after carbamazepine poisoning, such as coma, seizures, respiratory failure, cardiac conduction abnormalities, and death are more likely with serum levels greater than 170 umol/l. We report a case of a single massive carbamazepine overdose in a 19-year-old male, following attempted suicide, without prior history of seizure disorder. On admission, three hours after ingestion, serum carbamazepine concentration was 179 umol/l and Glasgow Coma Scale scores 6. The patient was intubated and treated with multiple doses of activated charcoal for 48 hours. Twelve hours after ingestion, two repeated generalised myoclonic seizures were noted when serum carbamazepine levels peaked at 181 umol/l, and were successfully treated with diazepam. Carbamazepine serum level fell within the therapeutic range 63 hours after ingestion and the patient was discharged without any long-term sequelae. As there is noantidote for carbamaepine poisoning, supportive treatment remains the only, but usually potent option.

Despite an overall declining incidence, gastric adenocarcinoma remains the second most common cause of death from malignant disease worldwide. About 85 percent of stomach cancers are adenocarcinomas, with 15 percent due to lymphomas and gastrointestinal stromal tumors. High rates are observed in Japan, China, Finland, and Eastern Europe, and low incidence is observed in Western Europe and USA. The annual incidence of gastric cancer in Croatia in the last thirty years is in decline, though it is still rather high at approximately 30 cases per 100, 000 in the male population and 23 cases per 100, 000 in females.

Osnovni su ciljevi terapije virusnog hepatitisa eradikacija infekcije u ranoj fazi bolesti, prevencija progresije bolesti ka dekompenziranoj cirozi jetre te prevencija razvoja hepatocelularnog karcinoma. Kako te ciljeve u velikog broja bolesnika nije moguće postići sada dostupnom terapijom, zadovoljavamo se često surogatnim ciljevima poput indukcije remisije bolesti, pokušaja preveniranja relapsa bolesti te smanjenja broja hepatocelularnih karcinoma u kronično inficiranih bolesnika. Sekundarni je cilj smanjenje broja nosilaca virusa koji su rezervoar virusa u općoj populaciji.

Background. Patients with chronic renal failure (CRF) often suffer from dyspeptic symptoms and have an increased incidence of gastritis, peptic ulceration, and upper gastrointestinal hemorrhage. It has been suggested that the main underlying reasons for the dyspepsia are a high serum gastrin level, a high concentration of urea in the serum and gastrointestinal mucosa, and Helicobacter pylori (H. pylori) infection. This study was performed to determine the prevalence of H. pylori infection in CRF patients and to assess the relationship between H. pylori infection and the severity of dyspeptic symptoms in these patients. Methods. Interviews, clinical examinations, and gastroduodenoscopies were performed ; gastric biopsies were obtained for the rapid urease test, histology, and culture ; and serum H. pylori-specific IgG was measured. Results. One hundred sixty-nine patients were included in the study: 55 CRF patients on chronic hemodialysis (Dialysis Group), 51 CRF patients not on dialysis (10

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The results suggest that the gastric pentadecapeptide BPC-157 may decrease reflux episodes of reflux esophagitis by increasing basal lower esophageal sphincter pressure and by accelerating gastric emptying.

The amelioration of corticosteroid-imparment of healing by a atable gastropentadecapeptide BPC-157 ( GEPPPGKPADDAGLV, M(w)1419, currently in early clinical trials for inflammatory bowel disease) was studied in thermally injured mice.Its effects on corticosteroid impaired healing of deep partial skin thiuckness burns, and burn-gastric lesions were investigated.Male NMRI-Hannover mice( sacrificed at 1-3, 7, 14 and 21 days following burning 20% of total burn area at the back ( open flame for 7s) received intraperitoneally( per kg bw) 6alpha-methylprednisolone( Depomedrol, 1.0 or 10.0mg) or an equal volume of saline ( 5.0ml), once daily, first application 30 min after injury, last 24h before sacrifice.The injuryas subsequently treated by topical application of a thin layer of pentadecapeptide BPC-157 cream at three different levels a neutral cream of no treatment.Pentadecapeptide BPC-157 consistently improved given burn healing( both microscopical and tensionmetry assessment) and countreracted corticosteroid-impairment of burn healing.In burn-gastric lesion investigation of the effects of BPC showed an anti-ulcer effect of its own in burned non-corticosteroid-treated mice and potentiated the anti-ulcer effect observed in 6 alpha-methylprednisolone-treated mice.Pentadecapeptide BPc-157 inhibited corticosteroid immunosuppression.In vitro, in spleenic cells assessment, animals( sacrificed at day 21) treated with 6alpha-methylprednisolone 1mgshowed decreased reactivity to nitrogen in comparation with control, healthyy animals, while the addition of BPC-157 ( 1micro/ g cream) returned cell reactivity to values noted in control healthy animals.

Uputvstva liječnicima pri upućivanju bolesnika na specijalističku dijsgnostiku i specijalističko-konzilijarne preglede u Kliničku bolnicu Split

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Gastric pentadecapeptide BPC 157 and esophagitis producing osteoporosis in male rat.

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Kolorektalni karcinom u kliničkoj bolnici u Splitu 2001-2002.

Leaded by intention to improve early diagnosis of colorectal carcinoma, as a starting point for further researches, we analyzed 174 cases of histologicaly proven adenocarcinomas of the large bowel diagnosed in the Clinical Hospital Split during two years period (2001-2002).

The aim of this multicenter, prospective, randomized and controlled study was to evaluate the efficacy of different doses of i.v. pantoprazole with regard to endoscopic sclerotherapy by polidocanol in preventing rebleeding from gastroduodenal ulcers F IIa, b. Patients with signs of recent ulcer bleeding F IIa, b on endoscopic examination were included. According to the random numbers table, endoscopic sclerotherapy using polidocanol and i.v. pantoprazole after endoscopic examination were performed during 72 h in one group (A1) while another group (A2) was administered pantoprazole only during 72 h. Endoscopic hemostasis with application of the same pantoprazole dose was performed in case of rebleeding within 72 h. Control endoscopic check-up was conducted after 72 h and F III was considered a final successful outcome. Pantoprazole was administered i.v. in the following doses: a) 80 mg bolus, and 8 mg/h during 72 h, b) 40 mg bolus, and then 3 × 40 mg during 72 h, c) 2 × 40 mg during the first 24 h and then 40 mg daily during 48 h. Statistical analysis was performed using chi-square test. A total of 136 pts had signs of ulcer FIIa, b bleeding (70 gastric and 66 duodenal ulcers), i.e. 80 men, mean age 58.8 yrs, and 56 women, mean age 41.2 yrs. More F IIa duodenal ulcers were found in group A1, and FIIb in group A2 (p = 0.002). There was no difference in rebleeding within 72 h between the groups (p = 0.581) (rebleeding was registered in 4 pts in group A1 and 5 pts in group A2), as well as in ulcer appearance after 72 hours (p = 0.355) (F III was established in 119 ulcers, FIIa, b in 8 ulcers in group A1 and FIIa, b in 9 ulcers in A2). Need for transfusions was similar in both groups. All pts completed the study ; per-protocol. Although gastric pH was not determined in this pilot study, clinical and endoscopic results indicate that all i.v. pantoprazole doses prevent rebleeding from FIIa, b gastric and duodenal ulcer regardless of injection sclerotherapy. The results also suggest that rebleeding from ulcers with F IIa, b can be prevented by standard pantoprazole daily 40 mg dose during 72 h without sclerotherapy.

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Besides a superior protection of the pentadecapeptide BPC 157 (an essential fragment of an organoprotective gastric juice peptide BPC) against different gastrointestinal and liver lesions, an acute anti-inflammatory and analgetic activity was also noted (1-8). For instance, pentadecapeptide BPC 157 administered either in ng or ug per kg range intraperitoneally, significantly reduced pain reaction in writhing (inflammatory and non-inflamatory, prostaglandin dependent and independent). consequently, its effect on chronic inflammation lesions, such as adjuvant arthritis, and non-steroidal anti-inflammatory agents (NSAIAs)-induced gastrointestinal lesion was simultaneously studied in rats. In gastrointestinal lesion (indomethacin 30mg/kg s.c.), aspirin (400 mg/kg i.g.) and diclofenac (125 mg/kg i.p.) studies, BPC 157 (10 ug or 10 ng/kg i.p.) was regularly given simultaneously and/or one hour prior to drug application (indomethacin). In the adjuvant arthritis (tail-application of 0, 2 ml of Freund's adjuvant) studies (14 days, 30 days, one year) BPC 157 (10 ug or 10 ng/kg i.p.) it was given as a single application (at 1 hour either before or following the application of Freund's adjuvant) or in a once daily regiment (0-14th day, 14-30th day, 14th day-one year). Given with the investigated NSAIAs, BPC 157 consistently reduced the otherwise prominent lesions in the stomach of the control rats, as well as the lesions in the small intestine in the indomethacin groups. In the adjuvant arthritis studies, the lesions development seems to be considerably reduced after single pentadecapeptide medication, and even more attenuated in rats daily treated with BP 157. As a therapy of already established adjuvant arthritis, its salutary effect consistently appeared already after two weeks of medication and it could be cleary seen also after one year of application. Taking togather all of these results, these data likely point to a special inflammatory and mucosa integrity protective effect.

A clear protection of G-I tract and an evident anti-inflammatory effect were shown for a novel stomach pentadecapeptide BPC(i.p./i.g.) in comparison with several reference standards in various ulcer models alog with a protection of endothelium. Thus, in the first experiments we evaluated whether this pentadecapeptide and other gastroprotective agents could affect the angiogenesis and healing process in vivo (using a slightly modified method of Szabo et al., AJM 9l, 1558, 1991). Number of new formed endothelial spacec inside new-formed granulation tissued in controls increased from 7, 94+/-1, 23 (day 3) to 14, 8+/-3, 12 (day 7) (P

Since definition of cytoprotection as an important phenomenon independent from gastric acid by A. Robert in Gastroenterology 1979, a direct evidence about the definitive role of gastric acid is not provided. In the first experiments (Sikiric et al., Dig.Dis.Sci, 1997) along with a widely proclaimed independency between Robert's cytoprotection and gastric acid secretion, a total gastrectomy was performed to further define this pentadecapeptide cytoprotective capacity, as a "direct" cytoprotective effect. Both theoretically and practically, gastrectomy could be taken as a new experimental improvement to create an acid-free environmental logically needed for cytoprotective studies. In this, a clear evidence about suggested non-acid (cytoprotective) phenomenology was based on at least two convincing experimental demonstrations. Firstly, like in the intact rats, cysteamine-duodenal lesions could be induced also in gastrectomized rats, with esophagoduodenal terminoterminal anastomosis (as emphasised, cysteamine in otherwise used commonly as a duodenal ulcerogen duo to its supposed effect on gastric acid hypersecretion). Secondly, the pentadecapeptide BPC 157 would antagonize the duodenal cysteamine lesions also in gastrectomized animals, an effect shared with standar antiulcer drugs (cimetidine, ranitidine, omeprazole, bromcriptine, atropine). Thus, a "direct cytoprotection" was evidenced for pentadecapeptide BPC 157 and standard antiulcer agents in totally gastrectomized rats' duodenum challanged with cysteamin (shown to have a damaging effect essentially independent from gastric acid). In the second experiments (Sikiric et al., Gastroenterology 1997), considering gastrectomized acid free rats as an ideal model for long-term cytoprotective studies, and expending these findings, pentadecapeptide BPC 157 qwas shown to markedly attenuate terminolateral esophagojejunal anastomosis-reflux esophagitis also over a quite prolonged period (1, 2, 4 weeks), having an effect (medication, per kg b.w., given in drinking water since 24 hours after surgery till sacrifice) superior then other reference agents. Relative to the control values, less damaged mucosa was noted in the rats drinking (12, 5 ml/rat daily) ranitidine (125 mg), sucralfate (725 mg) (dose per kg b.w.) after one week esophagitis, but not further oserved in later invervals (microscopical assessment). Compared with these results, pentadecapeptide BPC 157 (125 ug or 125 ng) attenuation of esophagitis were apparently more pronounced, and clearly appeared in all tested intervals, assessed either macroscopically or microscopically. Thus, despite limitation, a generalization supporting a direct importance of a common cytoprotective approach, and particularly the importance of the pentadecapeptide BPC, could be clearly provided. A useful, long-lasting cytoprotective activity (apparently more prominent in BPC 157-rats, than in referece agents) could be likely exemplified as a suitable therapy in various, otherwise resistant conditions, such as reflux esophagitis as well.

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Fourty patients with alcoholic liver cirrhosis and refractory hyperbilirubinaemia were included in a prospective, double blind, comparative trial. Twenty of them were randomized to methylprednisolone (1 mg/kg/day i.m. over 3 days), and 20 to placebo (saline) of identical shape. In the active group a significant decrease in the bilirubin level (from 248 to 191 mumol/l, a drop by 23% ; p < 0.05) was observed, which was not the case in the control group (from 292 to 300 mumol/l, an increase by 2.7% ; p > 0.05). A decrease in the alkaline phosphatase activity was observed in both groups (by 11% in the active and by 20% in the control group: p < 0.05) while the encephalopathic indices did not improve in either. It is concluded that a short course of corticosteroid could speed-up the hospital stay and possibly slow down the progression of alcoholic cirrhosis.

Protection of gastrointestinal trackt and an evident anti-inflammatory effect have been shown by pentadecapeptide BPC 157, a fragment of organoprotective gastric juice peptide (BPC) (ip/ig) in comparison with several reference standards in various ulcer models. Since appearent effect on wound healing was also noted the BPC 157 effect on healing of colon-colon anasthomoses was further investigated. Methods male albino Wistar rats, 250 g b.w., were used for the experiments. Bursting pressure (mean + SEM, mm Hg) was mesured on postoperative days 2, 5 , 7, and 10 usin preaveusly described method. The rats were treated with BPC 157 (10 micrograms or 10 ng/kg) given either (a) immediately after colon restriction and colon-colon anasthomosis ig, ip or locally and sacrificed 2, 5, or ten days after, or (b) with an additional intragastric or intraperitoneal aplication 242 hr after first medication (sacrifized on postoperative day 2). Controls recieved an equivolume of saline (5 ml/kg). Results. After single administration of BPC 157, dose dependant increased inbursting presure and maximall bowel tension relative to control values (data shown togeather)was evident after two days. When aplied repeatedly, BPS resulted inarelative increased after two days at the lower BPS 157 dosage as well. Teken together this data indicate thet inacordince with its strong protective effect on gastrointestinal tracts BPS 157 beneficualy influences heacing of colon-colon anasthomoses and this was confirmed micorscopicaly and increasde bzrsting strenght particulary in the early postoperative period.