[SOMETHING ABOUT DEFINITION AND EPIDEMIOLOGY OF SEPSIS].

The prevalence of sepsis continues to increase, although, thanks to the efforts of the campaigns and the development of guidelines for sepsis treatment, the fatality rates have diminished, however, the sepsis total mortality is growing due to increased morbidity. Sepsis should be considered as an emergency almost similar to acute myocardial infarction. With regard to the high prevalence and high mortality rate, it is important to improve the definition of sepsis. This definition is also important in different researches, as well as in the application of the results in daily practice. In January 2014, at the 43rd Annual Congress of Society of Critical Care Medicine in San Francisco, the work on establishing a new definition of sepsis was started. New definition of sepsis probably would represent what is known today as severe sepsis. The new definition could probably be accomplished during 2015.

[DEVICE-ASSOCIATED HEALTHCARE INFECTION AND SEPSIS IN INTENSIVE CARE UNIT].

The incidence of healthcare-associated infections and sepsis (HAIs) is 5-10 times higher in patients in intensive care units (ICUs) than in those at other hospital departments. Predisposition for these lies in many intrinsic (disease severity, loss of immunity) and extrinsic factors (frequent use of broad-spectrum antibiotics with consequent presence of antibiotic-resistant pathogens). The majority of HAIs in ICUs are associated with the use of invasive devices (DA-HAIs; device-associated healthcare-associated infections) (19%). Their incidence differs among specific types of ICUs (2%-49%). The most frequent DA-HAI are central line-associated bloodstream infections (CLA-BSI), ventilator-associated pneumonia (VAP), catheter-associated urinary tract infection (CAUTI) and surgical site infections (SSI). SSI is most often described as a distinct and separate entity of HAIs in ICUs. Recently, gram-negative bacilli (Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter spp.) are more frequently isolated in DA-HAIs than gram-positive ones (Staphylococcus aureus, Enterococcus spp.), often present as resistant strains. On the other hand, urinary or/and systemic infections tend to increase. DA-HAIs endanger and slow down patient recovery, prolong hospital stay, and generally increase the mortality rate. DA-HAIs are of special interest of the Hospital Committee Center for Infective Disease in order to improve patient safety and reduce total cost allocated for prevention of DA-HAIs. DA-HAI rate is the most useful intra- and inter-hospital measure to compare surveillance and effectiveness of preventive procedures among different ICU types.

[MANAGEMENT OF ADULT SEPTIC PATIENT IN EMERGENCY UNIT].

Early identification of sepsis is crucial to improve patient outcomes. Yet, sepsis can be difficult to differentiate in Emergency Unit. Sepsis treatment includes fluid resuscitation as soon as possible, starting with >1000 mL of crystalloids or 500 mL of colloids for 30 min. Acute kidney injury is a serious complication of sepsis, associated with increased mortality, prolonged hospital stay and increased cost of care. In patients with sepsis, it would be useful to have some biomarkers of early organ damage, to improve the capacity for early recognition and diagnosis of acute kidney injury.

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.

Anxiolytic effect of BPC-157, a gastric pentadecapeptide: shock probe/burying test and light/dark test.

AIM: To study anxiolytic effect of a gastric pentadecapeptide, BPC-157. METHODS: In shock probe/burying test, pentadecapeptide BPC-157 (10 microg/kg, 10 ng/kg, ip), diazepam (0.075, 0.0375 mg/kg, ip), and an equivolume of saline (5 mL/kg, ip) were given at 30 min prior test. In light/dark test, the same dosage of diazepam, BPC-157, and saline were given at 45 min prior procedure. RESULTS: Shock probe/burying test: rats treated with either diazepam or pentadecapeptide BPC-157 were much less afraid after the shock: almost not burying and the total time spent in burying was clearly less than in controls. However, while in the diazepam treated rats the number of shocks received increased over control values, in pentadecapeptide BPC-157 treated groups the number of shocks remained not modified compared with the control values. Light/dark test: after exposure to the intense light, diazepam treated mice had longer latencies of crossing to the dark compartment, a greater number of crossing and a greater number of exploratory rearing, and spent longer time in the light compartment, as compared to the control mice, while BPC-157 mice had a similar behavior to that of the control mice. In contrast with the effect in light area, in dark zone diazepam produced no change with respect to controls, while BPC-157 (10 microg/kg) mice had a greater number of crossing and a greater number of exploratory rearing. CONCLUSION: Both diazepam and BPC-157 displayed a bidirectional effect, but the activity of pentadecapeptide BPC-157 was particular, and different from diazepam.

Pentadecapeptide BPC 157 cream improves burn-wound healing and attenuates burn-gastric lesions in mice.

The effects of the gastric pentadecapeptide BPC 157 were investigated when administered topically or systemically in burned mice. This agent is known to have a beneficial effect in a variety of models of gastrointestinal lesions, as well as on wound or fracture healing. Deep partial skin thickness burns (1.5x1.5 cm) covering 20% of total body area, were induced under anesthesia on the back of mice by controlled burning and gastric lesions were assessed 1, 2, 3, 7, 14 and 21 days following injury. The first application of BPC 157 was immediately following burning, and thereafter, once daily, until 24 h before sacrifice. In the initial experiments, exposure to direct flame for 5 s, the BPC 157 was applied at 10 microg or 10 ng/kg b.w. intraperitoneally (i.p.) by injection or alternatively, topically, at the burn, as a thin layer of cream (50 microg of BPC 157 dissolved in 2 ml of distilled water was mixed with 50 g of commercial neutral cream (also used as local vehicle-control)), while silver sulfadiazine 1% cream was a standard agent acting locally. Others received no local medication: they were treated i.p. by injection of distilled water (distilled water-control) or left without any medication (control). In subsequent experiments involving deeper burns (direct flame for 7 s), BPC 157 creams (50 microg, 5 microg, 500 ng, 50 ng or 5 ng of BPC 157 dissolved in 2 ml of distilled water was mixed with 50 g of commercial neutral cream), or vehicle as a thin layer of cream, were applied topically, at the burn. Compared with untreated controls, in both experiments, in the BPC 157 cream-treated mice all parameters of burn healing were improved throughout the experiment: less edema was observed and inflammatory cell numbers decreased. Less necrosis was seen with an increased number of capillaries along with an advanced formation of dermal reticulin and collagen fibers. An increased number of preserved follicles were observed. Two weeks after injury, BPC 157 cream-treated mice completely reversed the otherwise poor re-epithelization ratio noted in the untreated control or mice treated with vehicle only. Tensiometry investigation showed an increased breaking strength and relative elongation of burned skin, while water content in burned skin decreased. This was, however, not the case with the vehicle or silver sulfadiazine. Relative to the control values, in silver sulfadiazine cream-treated mice, only collagen fiber formation was increased, in addition to a decreased inflammatory cell number. Relative to control values, BPC 157 given i.p. decreased the number of inflammatory cells, lowered water content in burned skin, and raised breaking strength and relative elongation of burned skin during tensiometry. Through the experimental period, gastric lesions were continuously noted in all thermally injured mice left without local medication and they were consistently attenuated only by BPC 157 treatments: either given i.p. (at either dose), or given locally (at either concentration). Other treatments (i.e. local treatment with silver sulfadiazine cream or neutral cream in mice subjected for 5 s to direct flame), led to only poor, if any attenuation. This stable gastric pentadecapeptide appears to be active and gives a stimulation to burn healing at the defect site. The agent may act by causing an upregulation of the growth factors, as well as influencing other local factors.

Ethanol gastric lesion aggravated by lung injury in rat. Therapy effect of antiulcer agents.

Hemorrhagic mucosal lesions in the stomach in the rat induced by an intragastrical application of 1 ml of 50 or 75% ethanol were aggravated by preceding lung damage provoked by an intratracheal instillation of pyrogen-free saline or HCl (pH 1.75) or 50-h exposure to 100% oxygen. Due to the particular preceding aggravating circumstances, these lesions were taken to be of a special kind, rather than ordinary. So far, it is not known whether and how antiulcer agents may influence these lesions. Rats received an intratracheal (i.t.) HCl instillation [1.5 ml/kg HCl (pH 1.75)] (lung-lesion), and an intragastric instillation of 96% ethanol (gastric lesion; 1 ml/rat, 24 h after i.t. HCl instillation), and were sacrificed 1 h after ethanol. Basically, in lung injured rats, the subsequent ethanol-gastric lesion was markedly aggravated. This aggravation, however, in turn, did not affect the severity of the lung lesions in the further period, at least for a 1-h observation. Taking intratracheal HCl-instillation as time 0, a gastric pentadecapeptide, GEPPPGKPADDAGLV, M.W.1419, coded BPC 157 (PL-10, PLD-116; 10 microg, 10 ng, 10 pg), ranitidine (10 mg), atropine (10 mg), omeprazole (10 mg), were given [/kg, intraperitoneally (i.p.)] (1) once, only prophylactically [as a pre-treatment (at -1 h), or as a co-treatment (at 0)], or only therapeutically (at +18 h or +24 h); (2) repeatedly, combining prophylactic/therapeutic regimens [(-1 h)+(+24 h) or (0)+(+24 h)], or therapeutic/therapeutic regimens [(+18 h)+(+24 h)]. In general, the antiulcer agents did protect against ethanol gastric lesions regardless of the presence of the severe lung injury, in all of the used regimens. Of note, combining their prophylactic and salutary regimens (at -1 h/+24 h, or at 0/+24 h) may increase the antiulcer potential, and the effect that had been not seen already with single application, became prominent after repeated treatment.

Cysteamine-colon and cysteamine-duodenum lesions in rats. Attenuation by gastric pentadecapeptide BPC 157, cimetidine, ranitidine, atropine, omeprazole, sulphasalazine and methylprednisolone.

Recently, we showed cysteamine-duodenal lesions without gastric acid, since they were induced also in gastrectomized rats, as in naive rats, and they were inhibited by the novel stomach pentadecapeptide BPC 157 as well as standard antiulcer drugs (i.e. cimetidine, ranitidine, omeprazole, bromocriptine, atropine). Therefore, as an advantage of considering cysteamine as a directly acting cytotoxic agent and mentioned agents as direct cytoprotective agents, the present focus was on the ulcerogenic effect of cysteamine and protective effect of gastroduodenal antiulcer agents outside upper gastrointestinal tract (i.e. in colon). Intrarectal administration of the cysteamine (200 or 400 mg/kg b.w) produced severe colon lesions (i.e. transmural inflammation with serosal involvement) in rats (30 min-72 h-experimental period), apparently distinctive from smaller lesions after non-specific irritant enema [diluted HCl solution, pH 3.8 (adjusted to pH of cysteamine solution (pH 3.8)]. All of the tested antiulcer agents were applied simultaneously with cysteamine enema (8 cm from the anus, in a volume of the 1.0 ml/rat) intraperitoneally (i.p.), intragastrically (i.g.) or intrarectally (i.r.). Pentadecapeptide BPC 157 (10 microg or 10 ng/kg b.w.), given in either regimen, previously shown to have, besides others, a particular beneficial activity just in the intestinal mucosa, inhibited these cysteamine colon lesions (assessed after 30 min, 60 min, 180 min, 24 h, 48 h, 72 h following cysteamine in a dose of either 200 or 400 mg/kg i.r.). Cysteamine-colon lesions were also attenuated by standard antiulcer agents (mg/kg b.w.), given i.p., i.g., or i.r., such as ranitidine (10), cimetidine (50), omeprazole (10), atropine (10), together with methylprednisolone (1), and sulphasalazine (50, i.r.), assessed 30 min following application of 200 mg of cysteamine. Finally, standard cysteamine duodenal lesions (assessed 24 h after a subcutaneous application of 400 mg/kg of cysteamine) were also attenuated by these agents application (given in the same doses, i.p., 1 h before cysteamine), with only exception to sulphasalazine. Thus, the extended cysteamine specific ulcerogenic effect, cysteamine colon/duodenum lesion-link and an extenuation of agents protection from upper to lower part of gastrointestinal tract (i.e. stomach pentadecapeptide BPC 157, standard antiulcer agents, cimetidine, ranitidine, atropine, omeprazole) and vice versa (remedies for inflammatory bowel disease) evidenced in the present study may be potentially important for both further experimental and clinical research.

Lung lesions and anti-ulcer agents beneficial effect: anti-ulcer agents pentadecapeptide BPC 157, ranitidine, omeprazole and atropine ameliorate lung lesion in rats.

Anti-ulcer agents may likely attenuate lesions outside the gastrointestinal tract, since they had protected gastrectomized rats (a "direct cytoprotective effect"). Therefore, their therapeutic potential in lung/stomach lesions were shown. Rats received an intratracheal (i.t.) HCl instillation [1.5 ml/kg HCl (pH 1.75)] (lung lesion), and an intragastric (i.g.) instillation of 96% ethanol (gastric lesion; 1 ml/rat, 24 h after i.t. HCl instillation), then sacrificed 1 h after ethanol. Basically, in lung-injured rats, the subsequent ethanol-gastric lesion was markedly aggravated. This aggravation, however, in turn, did not affect the severity of the lung lesions in the further period, at least for 1 h of observation. Taking intratracheal HCl-instillation as time 0, a gastric pentadecapeptide, GEPPPGKPADDAGLV, M.W.1419, coded BPC 157 (10 microg, 10 ng, 10 pg), ranitidine (10 mg), atropine (10 mg), omeprazole (10 mg), were given [/kg, intraperitoneally (i.p.)] (i) once, only prophylactically [as a pre-treatment (at -1h)], or as a co-treatment [at 0)], or only therapeutically (at +18h or +24 h); (ii) repeatedly, combining prophylactic/therapeutic regimens [(-1 h)+(+24 h)] or [(0)+(+24 h)], or therapeutic/therapeutic regimens [(+18 h)+(+24 h)]. For all agents, combining their prophylactic and salutary regimens (at -1 h/+24 h, or at 0/+24 h) attenuated lung lesions; even if effect had been not seen already with a single application, it became prominent after repeated treatment. In single application studies, relative to controls, a co-treatment (except to omeprazole), a pre-treatment (at -1 h) (pentadecapeptide BPC 157 and atropine, but not ranitidine and omeprazole) regularly attenuated, while therapeutically, atropine (at +18 h), pentadecapeptide BPC 157 highest dose and omeprazole (at +24 h), reversed the otherwise more severe lung lesions.

Portal hypertension and liver lesions in chronically alcohol drinking rats prevented and reversed by stable gastric pentadecapeptide BPC 157 (PL-10, PLD-116), and propranolol, but not ranitidine.

Liver lesions and portal hypertension in rats, following chronic alcohol administration, are a particular target for therapy. Portal hypertension (mm Hg) assessed directly into the portal vein, and liver lesions induced by 7.28 g/kg b.w. of alcohol given in drinking water for 3 months, were counteracted by a stable gastric pentadecapeptide BPC 157, GEPPPGKPADDAGLV, M.W. 1419, known to have a beneficial effect in a variety of models of gastrointestinal or liver lesions (10 microg or 10 ng/kg b.w. i.p. or i.g.) and propranolol (10 mg/kg b.w. i.g.), but not ranitidine (10 mg/kg b.w. i.g.) or saline (5 ml/kg b.w. i.p./i.g.; control). The medication (once daily) was throughout either the whole 3 months period (1) or the last month only (2) (last application 24 h before sacrifice). In the background of 7.28 g/kg/daily alcohol regimen similar lesions values were assessed in control rats following alcohol consumption, after 2 or 3 months of drinking. Both prophylactic and therapeutic effects were shown. After a period of 2 or 3 months, in all control saline [intragastrically (i.g.) or intraperitoneally (i.p.)] treated rats, the applied alcohol regimen consistently induced a significant rise of portal blood pressure values over values noted in healthy rats. In rats that received gastric pentadecapeptide BPC 157 or propranolol the otherwise raised portal pressure was reduced to the values noted in healthy rats. Besides, a raised surface area (microm(2)) and increased circumference (microm) of hepatocyte or hepatocyte nucleus [HE staining, measured using PC-compatible program ISSA (VAMS, Zagreb, Croatia)] and an advanced steatosis [scored (0-4), Oil Red staining] (on 100 randomly assigned hepatocytes per each liver), an increased liver weight, all together parallel a raised portal pressure in controls. Some of them were completely eliminated (not different from healthy rats, i.e. portal pressure, the circumference and area of hepatocytes, liver weight), while others were markedly attenuated (values less than in drinking controls, still higher than in healthy rats, i.e. circumference and area of hepatocytes nucleus). On the other hand, ranitidine application attenuated only steatosis development. In summary, despite continuous chronic alcohol drinking, pentadecapeptide BPC 157, and propranolol may prevent portal hypertension as well as reverse already established portal hypertension along with related liver disturbances.

Therapy effect of antiulcer agents on new chronic cysteamine colon lesion in rat.

After demonstration that cysteamine induced duodenal lesions in gastrectomized rats, while a number of antiulcer drugs mitigated these lesions, it was shown that one single intrarectal (i.r.) cysteamine application produced severe colon lesions in acute studies in rats. Thus, the further focus was on the protracted effect of cysteamine challenge (400 mg/kg b.w. i.r.) and therapy influence in chronic experiments in female rats. Regularly, cysteamine colon lesions were markedly mitigated by ranitidine (10), omeprazole (10), atropine (10), methylprednisolone (1), sulphasalazine (50; mg/kg), pentadecapeptide BPC 157 (PL-10, PLD-116; 10 microg or 10 ng/kg). Specifically, after 1 or 3 months following initial challenge (cysteamine 400 mg/kg i.r.) in female rat, the therapy [BPC 157 (PL-10, PLD-116 (10.0 microg or 10.0 ng/kg; i.g., i.p., i.r.), ranitidine, omeprazole, atropine, methylprednisolone, sulphasalazine (i.p.)] reversed the protracted cysteamine colon injury: the 1 week-regimen (once daily application) started after 1 month post-cysteamine, as well as the 2 weeks-regimen (once daily application), which started after 3 months. The effect on recidive lesion was also tested. These cysteamine lesions may reappear after stopping therapy (after stopping therapy for 3 weeks at the end of 2-weeks regimen started in 3 months-cysteamine female rats) in sulphasalazine group, while this reappearance is markedly antagonized in pentadecapeptide BPC 157 (PL-10, PLD-116)-rats (cysteamine-colon lesion still substantially low).

Chronic cytoprotection: pentadecapeptide BPC 157, ranitidine and propranolol prevent, attenuate and reverse the gastric lesions appearance in chronic alcohol drinking rats.

Unlike severe gastric damage acutely induced by ethanol administration in rat, the ulcerogenic effect of chronic alcohol administration (3.03 g/kg b.w. or 7.28 g/kg b.w.) given in drinking water, producing liver lesions and portal hypertension, is far less investigated. Therefore, focus was on the antiulcer effect of the gastric pentadecapeptide BPC 157, GEPPPGKPADDAGLV, M.W. 1419, known to have a beneficial effect in variety of gastrointestinal lesions models (10 microg or 10 ng/kg b.w. i.p. or i.g.), ranitidine (10 mg/kg b.w. i.g.) and propranol (10 mg/kg b.w. i.g.) or saline (5 ml/kg b.w. i.p./i.g.; control). They were given once daily (1) throughout 10 days preceding alcohol consumption, (2) since beginning of alcohol drinking till the end of the study, (3) throughout the last month of alcohol consumption, 2 months after alcohol drinking had been initiated. Gastric lesions were assessed, at the end of 3 months drinking [(1), (2)] or with respect to therapeutic effect of medication before medication or at the end of therapy. Pentadecapeptide BPC 157, ranitidine and propranolol may prevent gastric lesion development if given prophylactically, before alcohol drinking. Likewise, they attenuate the lesion appearance given once daily throughout the drinking period. Importantly, when given therapeutically, they may antagonize otherwise pertinent lesion presence in stomach mucosa of the drinking rats. Thus, these results demonstrate that pentadecapeptide BPC 157, ranitidine and propranol may prevent, attenuate or reverse the gastric lesions appearance in chronically alcohol drinking rats, and may be used for further therapy, while the other studies showed that their effect (except to ranitidine) is parallel with their beneficial effect on liver lesion and portal hypertension.

Occult gastrointestinal bleeding in rugby player.

BACKGROUND: Local ischemia and mechanical trauma to hollow abdominal organs are quoted as a cause of gastrointestinal (GI) bleeding during and after long distance running. There are no data on athletes from rugby and other contact sports where mechanical trauma of the abdomen is frequent. METHODS: Occult bleeding in the stool of Croatian national rugby team players has been investigated during and after qualification match with Italy for the World Cup 1999 on June 6th 1998 in Makarska, Croatia. One player with positive test was followed and examined in detail after the game. RESULTS: Among 11 Croatian players authors discovered one with a history of GI symptoms and one with conversion of negative to positive test for occult bleeding in stool after the match. The latter player had no GI symptoms or diseases, took no medications, played only 20 minutes in the match on forward position. Conversion has been found in the second stool sample after game (24 to 48 hours after game). The athlete was followed for 18 months. Persistent low values of hemoglobin, hematocrit and serum iron were revealed, as well as expressed hemorrhoids without signs of haemorrhage or inflammation. CONCLUSIONS: Lower incidence of GI bleeding among rugby players than among long distance runners minimize the importance of mechanical abdominal trauma in the etiology of GI bleeding during sports activity. Hemorrhoids are not quoted as a cause of GI bleeding after sport activity among athletes.

Angiotensin-converting enzyme gene polymorphism in patients with systemic lupus.

The renin-angiotensin-aldosterone system (RAAS) has been considered one of the probable pathophysiologic mechanisms involved in disease progression. Genetic polymorphism of the RAAS has been associated with the clinical course of renal disease. One of the genetic polymorphisms is a deletion or insertion of a 287 base pair fragment in intron 16 of the angiotensin-converting enzyme (ACE) gene. It is known that ACE gene polymorphism is present in humans and that it is associated with an increased risk of cardiovascular diseases, renal disease progression and sarcoidosis. In this study, the potential significance of ACE gene polymorphism in patients with systemic lupus erythematosus (SLE) was investigated. ACE gene polymorphism was determined in 18 patients with SLE and in 21 healthy volunteers as a control group. The mean age of patients was 38.5 years. All patients had a mean follow-up of 30.7 +/- 20.2 months (range 5-95 months). ACE genotypes were determined by the method of polymerase chain reaction. Proteinuria and creatinine were also followed. The frequency of DD, ID and II genotypes was 50%, 28% and 22% in SLE patients and 25%, 50% and 25% in healthy controls, respectively. DD genotype was more common in SLE patients than in the control group. The patients with II genotype had lower proteinuria and creatinine level than those with DD genotype (p < 0.05). The time to disease remission was shorter in patients with II genotype (p < 0.05). Study results indicated an increased frequency of D allele in SLE patients. The increased ACE activity in these patients pointed to the need of further studies of ACE gene polymorphism in SLE.

Pelvic neurilemmoma.

A case of a 37-year-old man admitted to our Department of Internal Medicine for medical evaluation of hypertension is reported. The patient had a 4-year history of oscillating hypertension prior to admission, however, with no major subjective complaints, except for pollakisuria. Clinical and biochemical assessment revealed no damage to target organs. Laboratory parameters showed normal values, except for hyperlipidemia. On routine ultrasonography of the pelvis confirmed a pelvic tumor of uncertain etiology, with no abdominal lymph node enlargement. No signs of metastasis were found. The patient was transferred to the Department of Surgery, where the tumor was removed in toto. Histopathologic analysis of the tumor, 11 x 8 x 8 cm in size, composed of cellular and mixoid areas with traces of collagenous connective tissue, necrosis, and tiny calcifications with scattered palisading nuclei and Verocay bodies, pointed to the diagnosis of a benign tumor, i.e. neurilemmoma. Postoperatively, the patient's subjective state was excellent, with normal blood pressure values, and without pollakisuria. A very large space-occupying lesion was responsible for compression of the neighboring organs, especially urinary bladder, resulting in pollakisuria. To our knowledge, pelvic localization of neurilemmoma, particularly a large one, is rare.

Haloperidol-stomach lesions attenuation by pentadecapeptide BPC 157, omeprazole, bromocriptine, but not atropine, lansoprazole, pantoprazole, ranitidine, cimetidine and misoprostol in mice.

The focus was on haloperidol (central dopamine antagonist)-stomach lesion, a longly described suitable counterpart of dopamine blocker cysteamine-duodenal lesion. In this, the contribution of blockade of central/peripheral dopamine receptors and prostaglandins synthesis, along with influence of antiulcer agents was evaluated in mice. Male NMRI Hannnover mice were sacrificed 24 h after haloperidol (25 mg/kg b.w. i.p., given alone or with saline (haloperidol+saline) (i) or in combination (ii,iii)). Supporting central dopamine predominance for haloperidol stomach lesion induction, co-administration of peripheral dopamine receptor antagonist domperidone (5 mg/kg i.p.) (haloperidol+ domperidone) (ii), or prostaglandin synthesis inhibitor indomethacin (10 mg/kg s.c.) (haloperidol+ indomethacin) (iii) did not aggravate this lesion. (i) In haloperidol+saline challenged mice the lesions were inhibited by co-administration (/kg i.p.) of a gastric pentadecapeptide BPC 157, GlyGluProProProGlyLysProAlaAspAspAlaGlyLeuVal, M.W. 1419 (10 microg, 10 ng, 10 pg, but not 1 pg, 100 fg, 10 fg), bromocriptine (10 mg), omeprazole (10 mg, 100 mg, but not 1 mg). Atropine (10, 100, 200 mg), pirenzepine (10, 100, 200 mg), misoprostol (10, 100, 200 microg), pantoprazole (1, 10, 100 mg), lansoprazole (0.1, 1, 10 mg), cimetidine (10, 100, 200 mg) and ranitidine (10, 100, 200 mg) were not effective. (ii) Dopamine peripheral blockade influence: in haloperidol+domperidone mice, previously effective bromocriptine, pentadecapeptide BPC 157 (10 microg) or omeprazole (10 mg) did not attenuate stomach lesions. (iii) Prostaglandins synthesis blockade effect: in haloperidol+indomethacin mice, previously effective agents, bromocriptine or omeprazole were not active, while BPC 157 effect was only lessened.

[Continuous renal replacement therapy]. / Kontinuirana bubrezna nadomjesna terapija.

Acute renal failure (ARF) is a common clinical condition with significant mortality. Although intermittent hemodialysis (IHD) represents a standard method of renal replacement therapy in ARF, novel methods of continuous renal replacement therapy (CRRT) are becoming more important. CRRT allows an excellent control of uremia, volume and acid-base status, avoiding at the same time rapid fluctuations in effective plasma volume, plasma osmolality, or blood pressure. Methods of CRRT differ with respect to the predominant way of solute removal, utilizing convective clearance (continuous ultrafiltration and hemofiltration), diffusive clearance (continuous hemodialysis), or a combination of the both (continuous hemodiafiltration). Based on their properties, CRRT represent method of choice in the treatment of hemodynamically unstable patients with ARF.

Cases of acute poisoning admitted to Clinical Hospital Merkur in Zagreb in 1999.

This paper describes 170 cases of acute poisoning in 60 men and 110 women admitted to emergency room from January through November 1999. Ninety-eight percent of acute poisonings were self-inflicted, and 90% occurred at home. Drugs were used in 134 (79%) suicide attempts. Eighty-one acute poisonings were caused by benzodiazepines (48%) and 19 by antidepressants (11%). Alcohol intoxication, alone or combined with the intake of psychoactive drug (28 cases, 16%) predominated in men. Cocaine was the most common narcotic drug, taken by 31 patients (16%). Other acute poisonings involved ecstasy (4 cases), CO (6 cases), and HCl inhalation (2 cases). Previous suicide attempts due to depression were found in 68 patients (40%). Fifty patients (29%) were comatose on admission, 24 were transferred to intensive care, and 3 died. Data such as these can be very useful for handling self-inflicted acute poisonings and for planning long-term health care activities.

The antidepressant effect of an antiulcer pentadecapeptide BPC 157 in Porsolt's test and chronic unpredictable stress in rats. A comparison with antidepressants.

Various antidepressants have antiulcer activity. Likewise, the models currently used in ulcers and depression disorders research have a considerable degree of similarity. Therefore, the possibility that depression disorders could be effectively influenced by a primary antiulcer agent with a cyto/organoprotective activity, such as the novel stomach pentadecapeptide BPC 157, was investigated in two rat depression assays. First, a forced swimming test (a Porsolt's procedure) was used. As a more severe procedure, chronic unpredictable stress (after 5 d of unpredictable stress protocol, once daily drug application during stress procedure, open field-immobility test assessment at fourth or sixth day of medication) was used. In a forced swimming test, a reduction of the immobility time in BPC 157 (10 microg, 10 ng x kg(-1) i.p.) treated rats corresponds to the activity of the 15 mg or 40 mg (i.p.) of conventional antidepressants, imipramine or nialamide, respectively, given according to the original Porsolt's protocol. In chronic unpredictable stress procedure, particular aggravation of experimental conditions markedly affected the conventional antidepressant activity, whereas BPC 157 effectiveness was continuously present. The effect of daily imipramine (30 mg) medication could be seen only after a more prolonged period, but not after a shorter period (i.e., 4-d protocol). In these conditions, no delay in the effectiveness was noted in BPC 157 medication and a reduction of the immobility of chronically stressed rats was noted after both 4 and 6 d of BPC 157 (10 microg, 10 ng) medication.

Gastric mucosal lesions induced by complete dopamine system failure in rats. The effects of dopamine agents, ranitidine, atropine, omeprazole and pentadecapeptide BPC 157.

Up to now, for gastric lesions potentiation or induction, as well as determination of endogenous dopamine significance, dopamine antagonist or dopamine vesicle depletor were given separately. Therefore, without combination studies, the evidence for dopamine significance remains split on either blockade of dopamine post-synaptic receptor or inhibition of dopamine storage, essentially contrasting with endogenous circumstances, where both functions could be simultaneously disturbed. For this purpose, a co-administration of reserpine and haloperidol, a dopamine granule depletor combined with a dopamine antagonist with pronounced ulcerogenic effect, was tested, and the rats were sacrificed 24 h after injurious agent(s) administration. Haloperidol (5 mg x kg(-1) b.w. i.p.), given alone, produced the lesions in all rats. Reserpine (5 mg x kg(-1) b.w. i.p.), given separately, also produced lesions. When these agents were given together, the lesions were apparently larger than in the groups injured with separate administration of either haloperidol or reserpine alone. Along with our previous results, when beneficial agents were co-administered, all dopaminomimetics (bromocriptine 10 mg, apomophine 1 mg, amphetamine 20 mg x kg(-1) i.p.) apparently attenuated the otherwise consistent haloperidol-gastric lesions. Likewise, an apparent inhibition of the reserpine-lesions was noted as well. However, if they were given in rats injured with combination of haloperidol and reserpine, their otherwise prominent beneficial effects were absent. Ranitidine (10 mg), omeprazole (10 mg), atropine (10 mg), pentadecapeptide BPC 157 (Gly-Glu-Pro-Pro-Pro-Gly-Lys-Pro-Ala-Asp-Asp-Ala-Gly-Leu-Val) (10 microg or 10 ng x kg(-1) i.p.) evidently prevented both haloperidol-gastric lesions and reserpine-gastric lesions. Confronted with potentiated lesions following a combination of haloperidol and reserpine, these agents maintained their beneficial effects, noted in the rats treated with either haloperidol or reserpine alone. The failure of dopaminomimetics could be most likely due to more extensive inhibition of endogenous dopamine system activity, and need for remained endogenous dopamine for their salutary effect, whereas the beneficial activities of ranitidine, omeprazole, atropine, pentadecapeptide BPC 157 following dopamine system inhibition by haloperidol+reserpine suggest their corresponding systems parallel those of dopamine system, and they may function despite extensive inhibition of endogenous dopamine system activity.