Mesoionic oxatriazoles (MOTA): NO-donating characteristics and pharmacology.

Biological role of nitric oxide (NO), functioning of isoforms of NO synthetases (NOS) and pharmacology of principle NO-donors were reviewed. NO donating characteristics and pharmacology of 23 mesoionic oxatriazoles (MOTA) were compared with those of 5-morpholinosydnonimine (SIN-1), S-nitroso-N-acetylpenicillamine (SNAP), sodium nitroprusside (NaNP) and glyceryl trinitrate (GTN). It is concluded that in vitro NO donating profile of MOTA hardly can be used as a predicting measure for their pharmacological activities either in vitro or in vivo. If anything, fast NO releasers seem to be stronger vasorelaxants than MOTA with slow NO releasing properties. Still, among representatives of this last category of MOTA one may find efficient antithrombotic and thrombolytic agents. For instance, MOTA 5-oxides were more potent thrombolytics than SIN-1, SNAP or NaNP. Also MOTA with potent anti-platelet action in vitro seem to be potent relaxants of tracheal strips. In summary, by manipulating the chemical structures of MOTA one may obtain relative selectivity towards vasorelaxant, anti-platelet, thrombolytic or tracheorelaxant properties. Thus different categories of MOTA might be designed with a hope of achieving hypotensive, antithrombotic, thrombolytic or anti-asthmatic drugs.

Value of magnetic resonance cholangiography (MRC) in primary sclerosing cholangitis (PSC).

BACKGROUND: Magnetic resonance cholangiography is a relatively new method, hence it has not gained a proper status yet in the diagnostic algorithm in patients with bile duct diseases. Many authors believe that MRC is an effective method for the visualisation of bile ducts. The aim of the study is to evaluate MRC usefulness in patients with PSC. MATERIAL AND METHODS: The study material consisted of 4 patients with PSC (3 men and 1 woman) aged 23-50 years. Patients were subjected to liver MRI in transverse plane, and T1 and T2-weighted images were obtained. Additionally, magnetic resonance cholangiography was performed with Gyroscan 0.5 T unit and Magnevist contrast medium. RESULTS: The patients manifested cholestasis and hepatitis of different duration (range: 2-14 years). The biochemical analyses revealed FA ranging from 563 to 1114 IU/l, GGTP 157-1270 IU/L, AlAT 56-295 IU/L, AspAT 80-190 IU/L. Three out of four patients displayed significant increase in the level of ANCA antibodies. Histopathological investigation of the liver, conducted in 3 out of 4 patients, showed cholangitis et pericholangitis. ERCP was attempted in all the patients. In one case, irregular, overlapping and narrowed bile ducts were found, while in two cases it was impossible to fill intrahepatic ducts. ERCP was not performed due to technical obstacles encountered in one patient. All the subjects underwent MRC. In three cases, the segmental irregular dilatation of intrahepatic ducts was observed, while in one case intrahepatic ducts were poorly marked. The defect in the filling of initial segment of common bile duct was diagnosed in one patient. Another patient had a lesion adjacent to common bile duct--low signal intensity in T1 and the intensification after the administration of contrast medium indicate the presence of expansive process. CONCLUSIONS: 1. MRC is an accurate examination enabling the visualisation of all bile ducts in their natural size. 2. Simultaneous MRI of the liver allows for the diagnosis of focal lesions. 3. MRC may be used in those cases, where ERCP cannot be performed for technical reasons or when it is objected by the patient.

Autoimmune reactions in HBV and HCV.

BACKGROUND: Hepatotropic viruses HBV and HCV are capable of triggering autoimmune reactions (AIH). The aim of the study was the assessment of clinical course of AIH in patients with HBV and HCV, and the revision of treatment methods employed in these cases. MATERIAL AND METHODS: Among 120 patients with AIH and those qualified for antiviral therapy, 21 (17.5%) subjects were selected, including 16 with HCV (7 men and 9 women) and 5 with HBV (including 2 men and 3 women). AIH diagnosis was based on international criteria taking into account biochemical tests, autoantibodies and morphological picture of the liver. HBV infection was confirmed with the determination of HBV markers and HCV--with the presence of antiHCV and HCV RNA. RESULTS: The duration of infection at AIH diagnosis was difficult to assess in patients with HCV. AIH was diagnosed when patients were qualified for antiviral treatment. Three patients displayed high anti-LKM1, 8--ANA and SMA, two pts--ANA, two pts--SMA, one pt--ANA + pANCA and one--SMA + pANCA. Nine patients did not show hyperproteinaemia, and hypergammaglobulinaemia was not observed in 2 patients. Six patients suffered from other immunity disorders--thrombocytopenia, vasculitis, arthritis, visceral lupus erythematosus. The diagnosis of chronic hepatitis was confirmed by morphological examinations in 15 patients. Ten subjects received adrenocortical hormones, 3 patients were treated with adrenocortical hormones and azathioprine, 4 received interferon and 3 received no treatment. All patients with HBV proved HBeAg(-). In these patients, AIH symptoms developed 5-18 years after the diagnosis of HBV infection. Liver biopsy confirmed the diagnosis in 4 patients. SMA was observed in 2 subjects, ANA and SMA--in the remaining patients. All the subjects manifested typical biochemical changes as well as high IgG values. Extrahepatic exponents of immune process were observed in 3 patients. Three subjects were treated with Encorton (Prednisone), while 2 patients received Encorton and Azathioprine. CONCLUSIONS: Patients with HBV and HCV infections may manifest the features of AIH in the course of the disease, which requires careful attention while selecting treatment.

Correlation between liver damage and degree of gastric mucose colonization by Helicobacter pylori in subjects with parenchymatous liver damage.

BACKGROUND: Helicobacter pylori (H. pylori) is an important factor responsible for chronic inflammatory conditions of the gastric mucosa. It has been demonstrated in numerous animal studies that some Helicobacter species may cause parenchymatous liver damage. The aim of the study was to investigate whether there is any correlation between the incidence of parenchymatous liver damage, and the incidence and degree of colonization of the gastric mucosa by H. pylori. MATERIAL AND METHODS: The study was carried out in the group of 30 patients (14 females, 16 males) whose mean age was 37 years, hospitalized because of parenchymatous liver damage without clinical symptoms of cirrhosis. All the patients had gastroscopy and urease tests performed, and mucosal biopsies were taken for immunomorphological investigations. The patients were divided into groups, group I comprising those with positive, and group II with negative urease test results. RESULTS: Positive urease tests were obtained in 26/30 patients (group I), 18/26 of whom demonstrated macroscopic changes of the gastric mucosa visible in gastroscopy. Group II with negative urease test results comprised 4/30 patients, 2/4 of whom had detectable changes in the gastric mucosa. The presence of H. pylori antigens was demonstrated by gastric mucosa immunomorphology in all 30 patients. The degree of invasion of H. pylori was visualized by immunofluorescence, which allowed to differentiate deep mucosal invasion of H. pylori (bacterial antigens present in lymph follicles and at the base of muciferous glands) observed in group I in 14/26 and in group II in 1/4 cases and superficial invasion (epithelium and mucosal surface) observed in group I in 12/26, in group II in 3/4. CONCLUSIONS: The obtained results may suggest more frequent H. pylori infections in subjects with parenchymatous liver damage than in the population without liver damage. Immunofluorescence seems to be a highly sensitive method allowing for detection of even small degrees of gastric mucosa colonization by H. pylori.

Nitric oxide donation and nitrite assays in the presence of thiols and albumin as determined by Griess' and Werringloer's methods.

Nitric oxide (NO) or nitrite (NO2-) were assayed using the Werringloer's method or the Griess' method, respectively, in the presence or absence of various thiols, amino acids, or albumin. This has been done because both methods are used to determine the generation of endogenous NO from L-arginine or exogenous NO from drugs in vivo, paying little attention to biological constituents which may affect results of these assays. Albumin, reduced glutathione (GSH), cysteine and N-acetylcysteine, but not other amino acids lowered the amount of NO2- as detected by Griess' method no matter whether sodium nitrite or 3-morpholinosydnonimine (SIN-1) were used as a source of NO2-. This happened probably because at low pH of the reaction mixture the corresponding nitrosothiols were formed and thus NO2- was not accessible for detection. However, this phenomenon was not seen when instead of SIN-1 another NO donor--S-nitroso-N-acetylpenicillamine (SNAP) was used. SNAP is a nitrosothiol itself and physiological low molecular thiols (e.g. GSH or cysteine) displaced NO from SNAP. An increase in the amount of released NO was detectable by both Werringloer's and Griess' methods. Only the presence of 700 microns of albumin steadily suppressed the detection of NO or NO2- no matter what was the source of these species. It is concluded that low molecular thiols and albumin may differently influence the detection of both NO and NO2- which derive from various NO donors or sodium nitrite.

[Vaccination against hepatitis B]. / Szczepienia przeciwko wirusowemu zapaleniu watroby typu B.

Current epidemiological problems, world strategy for vaccination as outlined in the Expanded Programme on Immunization of the WHO, structure of the hepatitis B virus, and vaccine-escape mutants were summarized briefly in the first part of the review. Later, generation of plasma-derived and recombinant vaccines containing S antigen only, and subsequently, S together with preS1 + preS2 antigens were described. The results of vaccination of adults and children with high risk of infection at two symposia held in our country in 1991 and 1994, were analysed. The role in prevention of the spread of viral hepatitis of high hygienic standard in all health care units and education of staff in terms of anti-infectious control was pointed out. Finally, the problem of persistence of anti-HBs antibodies in the years following the immunization was outlined.

[Studies of the lymphatic system in mice infected with Trichinella pseudospiralis as well as infected and stimulated by Phytohaemagglutin (PHA-P)]. / Badania ukladu limfatycznego myszy zarazonych T. pseudospiralis oraz zarazonych i stymulowanych fitohemaglutynina (PHA-P).

Mice CFW were infected per os with Trichinella pseudospiralis (150 larvae/mice). The mice were divided in two groups: nonstimulated and stimulated intraperitoneally with PHA-P at dose 10 mg/kg body weight. The animals were killed 7, 14, 21, 28, 42, 56, 70 and 150 day post infection (d.p.i.). Spleen et mesenteric lymph nodes were examined histopathologically (Hematoxylin-Eosin) and histochemically (nonspecific esterase reaction) for differentiation of T lymphocytes. The obtained results reveal that T. pseudospiralis infection caused weak mobilisation of mouse lymphatic system lasting only to 70 day of experiment. In the lymphatic organs of infected mice small number of T lymphocytes were observed mostly between 28 and 56 d.p.i. The intraperitoneally stimulation with PHA-P give rise to caused only little mobilisation of lymphatic tissue and small increase of T lymphocytes number. The obtained results were compared with analogic earlier experiments with T. spiralis infection.

[Influence of nalcrom (sodium cromoglycate) on the course of the intestinal phase of trichinellosis in mice]. / Wplyw Nalcromu (sodium cromoglycate) na przebieg jelitowej fazy wlosnicy u myszy.

The influence of Nalcrom (sodium cromoglycate) on the course of the intestinal phase of trichinellosis in mice was investigated. The animals infected with 200 Trichinella spiralis larvae were treated with Nalcrom between 7-20 or 3-20 days after infection (d.a.i.). The drug was administered in two doses: 0.6 or 1.7 mg/mouse/day. In the all groups of animals received Nalcrom higher number of mast cells and eosinophils than in the control groups was observed. These results are the opposite of those obtained with Nalcrom in ulcerative colitis in man.

[Detection of asymptomatic HBV infection among pregnant women based on personal studies]. / Bezobjawowe zakazenie HBV w populacji kobiet ciezarnych na podstawie wlasnych badan.

The total seroprevalence of HBsAg among pregnant women in Gdansk region is 1.3%. Our examination was based on observation of 226 HBsAg chronic carrier pregnant women. The risk of infection on the way of inoculation in childhood took place in 68%, in 10.8% it was connected with occupation. The presence of HBsAg and HBeAg was revealed in 8.8%. During period of observation none of the women eliminated HBsAg. The clinical course of infection in our group was stable. Liver biopsy was performed in 47 cases. Hepatitis minimalis was found in 35 cases, fibrosis portalis in 2, hepatitis chronica persistens in 5 and normal histological liver structure in 2 cases. Asymptomatic carrier state didn't influence on the course of pregnancy and delivery.

[Changes in the aortic arch of calves with bacterial infections]. / Zmiany w luku aorty cielat w przebiegu infekcji bakteryjnych.

The autopsy and histopathological changes in the wall of aortic arch were presented in calves died of pulmonary and intestinal disorders. The bacteriological examinations of the internal organs demonstrated: E. coli, Pseudomonas aeruginosa Corynebacterium et al. Gelatinous edematous++ and hemorrhagic inflammatory centers of aortic arch adventitia were distinctly visible during thorax examination. In aortic arch the diagonal fissures of endothelium and deeper layers of the wall were found. In microscopical examination the heavy degenerative changes in the arch endothelium and deeper layers were observed. The fissures were from 0.5 to several millimeters in length and penetrated 1/3 to 1/2 thickness at the wall. The authors suggested that starting point of this changes are Gram-negative bacillary inflammatory centers in lungs. The bacterial endotoxins and vasoactive substances liberated by altered cells penetrated the aortic arch by the tissues continuity and in contact way.

An abnormality of arachidonic acid metabolism is not a generalized phenomenon in patients with aspirin-induced asthma.

Aspirin (ASA)-induced asthma is a distinct clinical syndrome in which bronchoconstrictive response to nonsteroidal anti-inflammatory drugs can be predicted on the basis of their in vitro activity as inhibitors of cyclooxygenase. In ten ASA-sensitive asthmatics and ten matched healthy controls we measured 12-hydroxy-eicosatetraenoic acid (12-HETE) production by platelets and 5-hydroxy-eicosatetraenoic acid (5-HETE) and leukotriene B4 (LTB4) production by polymorphonuclear leucocytes. The blood cells were obtained before administration of the threshold doses of ASA and during the ASA-induced reactions. Initial levels of eicosanoids determined did not differ between the two groups. In both groups, after ASA challenge, 12-HETE rose to similar levels while 5-HETE and LTB4 remained unchanged. These data do not support the concept that an abnormality in the regulation of arachidonic acid oxidative pathways in ASA-sensitive asthmatics is a generalized phenomenon which embraces the platelets and leucocytes; rather it is inhibition of cyclo-oxygenase within the tissues of the respiratory tract that triggers asthmatic attacks in the sensitive patients.

Salicylates and 12-lipoxygenase activity in human washed platelets.

In vitro salicylates /aspirin, salicylic acid, salicylamide and gentisic acid/ inhibited formation of 12-lipoxygenase products in intact human washed platelets which were stimulated with thrombin or arachidonic acid. Salicylates did not affect 12-lipoxygenase activity in platelet lysates. Ex vivo aspirin or salicylamide at a dose of 1 g given orally to healthy volunteers potentiated formation of 12-lipoxygenase products in washed platelets. It is concluded that the effect of salicylates on 12-lipoxygenase pathway is independent from their influence on cyclooxygenase activity in platelets and aspirin cannot be considered as a selective inhibitor of platelet cyclooxygenase.