bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vardenafil protects isolated rat hearts at reperfusion dependent on GC and PKG
Authors: Maas O , Donat U , Frenzel M , Rütz T , Kroemer H K , Felix S B , Krieg T 
Published: March 2008

Background and purpose: The type‐5 PDE inhibitor vardenafil reduces myocardial infarct size in situ, following ischemia/reperfusion, when applied at reperfusion in animal models. Little is known about the underlying protective signaling. Here, we test whether vardenafil is protective in rat isolated hearts and in a cell model of calcium stress.Experimental approach: Infarct size in rat isolated hearts was measured after a 30 min regional ischemia and 120 min reperfusion. Vardenafil (1 nM–1 μM) was infused during reperfusion. HL‐1 cardiomyocytes were loaded with tetramethylrhodamine ethyl ester (TMRE), a fluorescent marker of mitochondrial membrane potential (ψm).Key results: Vardenafil at reperfusion reduced infarct size as percentage of the ischemic zone from 45.8±2.0% in control hearts to 26.2±2.7% (P<0.001) only at 10 nM, whereas higher or lower dosages failed to protect. This protective effect was blocked by co‐administration of either the GC inhibitor, 1H‐(1,2,4)oxadiazolo(4,3‐a)quinoxalin‐1‐one (ODQ), or the PKG inhibitor, KT‐5823. HL‐1 cardiomyocytes, loaded with TMRE, were treated for 80 min with the calcium ionophore, calcimycin, to induce calcium stress. This reduced the mean cell fluorescence to 63.3±3.8% of baseline values and vardenafil protected against this fall (78.6±3.6%, P<0.01). The vardenafil‐induced protection of HL‐1 cells was blocked by ODQ, KT‐5823 or the PKG‐inhibiting peptides DT‐2 and DT‐3, confirming a role for GC and PKG.Conclusions and implications: These results further support the hypothesis that PDE‐5 inhibitors are protective in ischemic hearts, in addition to their known clinical effects in the treatment of erectile dysfunction in men.
Endothelium removal augments endothelium‐independent vasodilatation in rat mesenteric vascular bed
Authors: Iwatani Y , Kosugi K , Isobe‐Oku S , Atagi S , Kitamura Y , Kawasaki H 
Published: March 2008

Background and purpose: The vascular endothelium regulates vascular tone by releasing various endothelium‐derived vasoactive substances to counteract excess vascular response. We investigated whether the vascular endothelium regulates vasodilatation via released endothelium‐derived contracting factors (EDCFs), by examining the effect of endothelium removal on responses to periarterial nerve stimulation (PNS) and various vasodilator agents.Experimental approach: The rat mesenteric vascular bed was perfused with Krebs solution. Vasodilator responses to PNS and 5 min perfusion of vasodilator agents in preparations with endothelium were compared with those in the same preparations without endothelium. The endothelium was removed by 30 s perfusion with sodium deoxycholate.Key results: Endothelium removal significantly augmented vasodilator responses to PNS and calcitonin gene‐related peptide (CGRP), isoprenaline (β‐adrenoceptor agonist), SNP and 8‐bromo‐cGMP (8‐Br‐cGMP; cGMP analogue) but not BAY41‐2272 (soluble guanylate cyclase activator). The augmentation of SNP‐induced vasodilatation after denudation was much greater than that of CGRP‐ or isoprenaline‐induced vasodilatation. In the preparations with an intact endothelium, L‐NAME (nitric oxide synthase inhibitor) significantly augmented vasodilator responses to PNS and CGRP, isoprenaline, SNP and 8‐Br‐cGMP, but not BAY41‐2272. Indomethacin (cyclooxygenase inhibitor) and seratrodast (thromboxane A2 receptor antagonist), but not phosphoramidon (endothelin‐1‐converting enzyme inhibitor) or BQ‐123 (selective endothelin type A receptor antagonists), significantly augmented vasodilator responses to PNS and CGRP, isoprenaline, SNP and BAY41‐2272.Conclusion and implication: These results suggest that the endothelium in rat mesenteric arteries regulates and maintains vascular tone via counteracting not only vasoconstriction through releasing endothelium‐derived relaxing factors, but also vasodilatation, in part by releasing an EDCF, thromboxane A2.
Serotonin decreases HIV‐1 replication in primary cultures of human macrophages through 5‐HT1A receptors
Authors: Manéglier B , Guillemin G J , Clayette P , Rogez‐Kreuz C , Brew B J , Dormont D , Advenier C , Therond P , Spreux‐Varoquaux O 
Published: March 2008

Background and purpose: 5‐HT (serotonin) is known to be involved in neuroinflammation and immunoregulation. The human immunodeficiency virus (HIV) targets cells such as monocytes/macrophages, which colocalize with 5‐HT‐releasing cell types, mostly platelets. In this study, we investigated the effects of 5‐HT on HIV‐1‐infected macrophages in vitro.Experimental approach: Human macrophages cultured in serum‐free medium were treated over 7 days with 5‐HT at three concentrations (0.01, 1 and 100 μM) with or without agonists and antagonists of 5‐HT1A and 5‐HT2 receptors. After 7 days of treatment, macrophages were infected with HIV‐1/Ba‐L and virus replication was monitored over 16 days and expression of proviral HIV DNA was investigated by PCR after 24 h of infection. Cell surface expression of HIV‐1/Ba‐L receptor (CD4) and coreceptor (CCR5) was investigated by flow cytometry. The CCR5 ligand, macrophage inflammatory protein‐1α (MIP‐1α), was quantified by ELISA in cell culture supernatants and MIP‐1α mRNA expression was assessed by reverse transcriptase‐PCR.Key results: In vitro, 5‐HT downregulated the membranous expression of CCR5 and led to a decrease of HIV‐1 infection, probably through its action on 5‐HT1A receptors. 5‐HT (100 μM) was also able to induce overexpression of MIP‐1α mRNA leading to an increase of MIP‐1α secretion by human macrophages.Conclusions and implications: The effects of 5‐HT on HIV infection could be a consequence of the increase in MIP‐1α concentrations and/or CCR5 receptor downregulation. These results suggest that 5‐HT can inhibit the replication of HIV‐1 in primary culture of human macrophages through its action on 5‐HT1A receptors.
Na+/Ca2+exchanger inhibition exerts a positive inotropic effect in the rat heart, but fails to influence the contractility of the rabbit heart
Authors: Farkas A S , Acsai K , Nagy N , Tóth A , Fülöp F , Seprényi G , Birinyi P , Nánási P P , Forster T , Csanády M , Papp J G , Varró A , Farkas A 
Published: March 2008

Background and purpose:The Na+/Ca2+exchanger (NCX) may play a key role in myocardial contractility. The operation of the NCX is affected by the action potential (AP) configuration and the intracellular Na+concentration. This study examined the effect of selective NCX inhibition by 0.1, 0.3 and 1.0 μMSEA0400 on the myocardial contractility in the setting of different AP configurations and different intracellular Na+concentrations in rabbit and rat hearts.Experimental approach:The concentration‐dependent effects of SEA0400 onINa/Cawere studied in rat and rabbit ventricular cardiomyocytes using a patch clamp technique. Starling curves were constructed for isolated, Langendorff‐perfused rat and rabbit hearts. The cardiac sarcolemmal NCX protein densities of both species were compared by immunohistochemistry.Key results:SEA0400 inhibited INa/Cawith similar efficacy in the two species; there was no difference between the inhibitions of the forward or reverse mode of the NCX in either species. SEA0400 increased the systolic and the developed pressure in the rat heart in a concentration‐dependent manner, for example, 1.0 μMSEA0400 increased the maximum systolic pressures by 12% relative to the control, whereas it failed to alter the contractility in the rabbit heart. No interspecies difference was found in the cardiac sarcolemmal NCX protein densities.Conclusions and implications:NCX inhibition exerted a positive inotropic effect in the rat heart, but it did not influence the contractility of the rabbit heart. This implies that the AP configuration and the intracellular Na+concentration may play an important role in the contractility response to NCX inhibition.
Carbamazepine hepatitis: the clinicopathological spectrum
Authors: WILLIAMS S. J. , RUPPIN D. C. , GRIERSON J. M. , FARRELL G. C. 
Published: March 2008

Abstract Despite 20 years of widespread use, carbamazepine has rarely been implicated as causing hepatic drug reactions. The observation of eight cases of carbamazepine hepatitis during a 3‐year period afforded an unusual opportunity to describe the clinicopathological spectrum of this reaction. The eight patients (four males, four females, aged 44–83 years) presented with fever, anorexia and malaise within 12 weeks of starting carbamazepine. Clinical features included swinging fever, jaundice (six cases) and right upper quadrant abdominal pain and tenderness which frequently led to a clinical diagnosis of cholangitis; rash and eosinophilia were not present. Serum transaminase and alkaline phosphatase values variably suggested cholestasis (three patients), predominantly hepatocellular injury (one patient) or were mixed (four patients). However, in all four patients subjected to liver biopsy, the histological picture was a granulomatous hepatitis.Cessation of carbamazepine resulted in rapid resolution of symptoms with normalization of biochemical abnormalities within 4 weeks. In two patients who were rechallenged with carbamazepine, symptoms and abnormal serum biochemistry recurred within 24 h. It is suggested that carbamazepine causes hepatic drug reactions more commonly than has been previously recognized. Although the clinical and laboratory picture may suggest cholangitis, the usual histological finding is a granulomatous hepatitis. Prompt resolution can be expected in the majority of cases upon withdrawal of the drug.
Chronic duodenal ulcer, marital status and personality pattern. A case‐control study
Authors: FUNG L. H. , GILLIGAN I. J. , TALLEY N. J. , PIPER D. W. 
Published: March 2008

Abstract The aim of the study was to assess the association of chronic duodenal ulcer (DU) with marital status and psychological factors. Sixty‐six consecutive patients with DU were compared with 66 randomly selected age, sex, and social‐grade matched community controls, with regard to marital status and personality profile. Personality was assessed at interview by the Spielberger State‐Trait Anxiety Questionnaire, Beck Depression Inventory, Costello‐Comrey Personality Questionnaire and the Eysenck Personality Inventory.It was found that patients with higher scores on the Beck Depression Inventory and patients who were unmarried were significantly more likely to have DU (odds ratio = 1.2 and 3.3, respectively). None of the other psychometric measures were statistically significant on a multivariate analysis. However, the absolute differences observed and the odds ratio for depression were small. The results suggest that the psychological factors studied were of only minor clinical importance in DU.
Clinical spectrum of chronic Budd‐Chiari syndrome and surgical relief for ‘coarctation’ of the inferior vena cava
Authors: MADANAGOPALAN N. , SOLOMON V. , JAYANTHI V. , RAGHURAM K. , BALAKUMAR M. , KANDASAMY I. , GAJARAJ A. , PANCHANADAM M. 
Published: March 2008

ABSTRACTThis report presents the clinical features of 78 cases of the chronic Budd‐Chiari syndrome encountered over a period of 13 years. The diagnosis of hepatic venous outflow obstruction was confirmed by venographic studies in all cases. In 20 patients there was hepatic vein occlusion without inferior vena caval (IVC) obstruction (Group A). In 17 patients there was constriction of the IVC above the drainage site of the right hepatic vein which was patent (Group B). In 13 patients there was short segmental obstruction of the hepatic segment of the IVC along with blockage of the hepatic venous orifices (Group C). In 28 patients there was hepatic venous obstruction with long segment involvement of the IVC extending to varying lengths of the infrahepatic segment (Group D). Of particular interest are the operative findings in 12 of 17 patients of Group B of hour glass constriction of the IVC, which can be labelled as ‘coarctation of the IVC'. Dorsal cavoatrial bypass using a polytetra fluoroethylene graft has proved useful in Group B. Interesting histopathological findings of the liver in some of the cases are also described. The possible aetiology of the Group B cases is discussed.
Effect of diisopropyl 1,3‐dithiol‐2‐ylidinemalonate on rat liver and AFP‐positive cells in 3′‐Me‐DAB hepatocarcinogenesis
Authors: TAKINO TATSURO , IWAI MASAKI , OKUNO TADAO , ISHII MASARU , KOMATSU MASAMI , SUGIMOTO TATSUYOSHI 
Published: March 2008

ABSTRACTThe simultaneous administration of diisopropyl, 1,3‐dithiol‐2‐ylidinemalonate (malotilate) suppressed the proliferation of AFP‐positive oval cells, the formation of hyperplastic nodules and the appearance of clusters of AFP‐positive cells in rat liver with hyperplastic nodules in 3′‐methyl‐4‐dimethylaminoazobenzene (3′‐Me‐DAB) hepatocarcinogenesis. The development of hepatocarcinoma, induced by 3′‐Me‐DAB, was delayed in rats treated with malotilate; therefore, the simultaneous administration of malotilate worked as an inhibitory effect on 3′‐Me‐DAB hepatocarcinogenesis.
Portal circulation before and after sclerotherapy for oesophageal varices studied by radionuclide angiography
Authors: SHIOMI SUSUMU , IKEOKA NAOKO , KUROKI TETSUO , HARIHARA SHIGEYOSHI , KAMATA TEISUKE , KOBAYASHI KENZO , YAMAMOTO SUKEO , MONNA TAKEYUKI , OCHI HIRONOBU 
Published: March 2008

ABSTRACTRadionuclide angiography was used to generate curves of first‐pass radioactivity vs. time for the right hepatic lobe and both kidneys following the rapid intravenous injection of 10 mCi of 99mTc‐phytate. By analysis of the right hepatic curve, the arterial and portal components of the liver circulation were calculated in 21 healthy subjects and 183 patients, 39 with chronic hepatitis and 144 with cirrhosis of the liver.ABSTRACTIn the healthy subjects, the portal component (PC) of liver blood supply ranged from 64% to 79% (mean 71.5%). In patients with hepatitis the mean PC was 61.3%, and in patients with cirrhosis it was 37.9%. The PC was lower in cirrhotic patients with oesophageal varices than in those without (P < 0.001).ABSTRACTThe PC was assessed in 23 of the patients with cirrhosis before and after sclerotherapy for oesophageal varices. A paired t‐test showed significant rises in this component immediately after the final treatment (P < 0.001). Two months after this treatment, the mean PC had dropped significantly, approaching the pre‐treatment value (P < 0.001). One year after treatment, the PC had not dropped further.ABSTRACTThese findings suggest that this non‐invasive method may be useful for the assessment of portal circulatory changes in cirrhosis, and of results of sclerotherapy for oesophageal varices.
Human pepsinogens: A review of clinical and genetic aspects
Authors: WESTERVELD B.D. , PALS G. , DEFIZE J. , ERIKSSON A. E. , MEUWISSEN S. G. M. 
Published: March 2008

ABSTRACTIn recent years clinical interest in the study of the proteolytic enzymes of the stomach has greatly increased. Human pepsinogens belong to the group of aspartic proteases and are categorized into two main groups: Pepsinogen A (PGA = PG I) and Pepsinogen C (PGC = PG II). Genetic models have been proposed to explain the inheritance of PGA, and a recent multigene model may be of value. PGA phenotypes in urine and gastric mucosa have been determined in healthy volunteers as well as in patients with different gastric disorders. An increased frequency of the ‘intense Pg5’ phenotype seems to be associated with gastric cancer and pre‐malignant conditions, such as atrophic gastritis. Reliable radio‐immunoassay and enzyme‐linked immunosorbent assay techniques have facilitated the study of serum levels of PGA and PGC in different patient groups; in particular, duodenal ulcer patients (high PGA levels) and patients with atrophic gastritis and/or gastric cancer (low PGA levels). The ratio serum PGA/PGC may be introduced for clinical application, being the most convenient non‐invasive marker for the detection of fundic atrophy. While the chromosome localization of pepsinogen has been established, further research is likely to concentrate on the structure and organization of the pepsinogen genes at the DNA‐level, as well as on the development of new isozyme specific monoclonal antibodies.
Delta‐agent infection in Taiwan
Authors: CHEN DING‐SHINN , SU IH‐JEN , LAI MING‐YANG , HSU HEY‐CHI , YANG PEI‐MING , SHEU JIN‐CHUAN , SUNG JUEI‐LOW 
Published: March 2008

Based on observations of a limited number of patients, delta (δ) infection has been reported to be infrequent in Taiwan. To further evaluate the role of δ‐infection in patients with hepatitis B virus (HBV) infection, serum samples of 493 subjects with acute and chronic HBV infections collected in 1976–85 were studied for anti‐δ by radioimmunoassay. Intrahepatic δ‐antigen was also studied by immunofluorescence in 12 anti‐δ‐positive patients. The overall prevalence of δ‐infection was 4.7%, consistent with previous studies. δ‐Infection had an even yearly distribution in the last decade. However, there were four groups with significantly higher frequencies: (i) 24% of 41 anti‐HBe‐positive patients with chronic active hepatitis (CAH); (ii) 21% of 14 HBsAg carriers with prominent lobular hepatitis; (iii) two of three HBsAg carriers with intravenous drug abuse; and (iv) two of seven with fulminant hepatitis. On the other hand, δ‐infection was uncommon in patients with chronic persistent hepatitis, cirrhosis, hepatocellular carcinoma, classical type B hepatitis, submassive necrosis and asymptomatic HBsAg carriers. δ‐Antigen was found in only two patients with CAH; one progressed to cirrhosis, and the other had disease regression on follow‐up. Overall, at least half of the δ‐superinfected HBsAg‐positive patients had a non‐progressive course on follow‐up.It was concluded that δ‐agent was introduced to Taiwan before 1976. Although it has played a role in some clinical settings of HBV infections, it is generally infrequent in Taiwan. The δ‐superinfection apparent in half the patients studied seems to have a non‐progressive course.
Immunogenicity study of low‐dose administration of hepatitis B virus vaccine in newborn infants: A cost reduction trial
Authors: CHUNG WHAN KOOK , CHOI KYU YONG , DON LEE CHANG , CHUNG JIN WU , SUN HEE SIK , CHUNG KYU WON , KIM BOO SUNG , CHUN CHUNG SIK , CHO KYOO HONG , KIM SEUNG JO 
Published: March 2008

Different doses of hepatitis B virus vaccine—prepared by Korea Green Cross Corporation, were given to healthy infants born to HBsAg‐negative mothers at birth, 1 and 6 months of age. A dose of 2 μg was administered intradermally in Group A and, in the three other groups, the vaccine was given intramuscularly (i.m.). An adequate follow‐up observation was possible for 9 months after birth in 22, 25, 23 and 21 infants in Groups A, B, C and D, respecvely.Group C (5 μg, i.m.) produced seroconversion most rapidly, showing the highest rate (96%) at 9 months of age. The lowest seroconversion rate (5%) was found at the age of 1 month in Group A subjects, but the rate increased to 91% after a booster dose was given at 6 months of age.While it can be concluded that a 5 μg i.m. dose of vaccine at 0, 1 and 6 months of age is optimum for the immunization of infants in efficacy and economy, a 2 μg intradermal dose can also be considered as an immunogenic and economical regimen, though the immune response is slower and a special technique is required for immunization.
Different effects of short‐ and long‐term dietary choline‐deficiency on hepatic microsomal phospholipids and drug oxidation
Authors: MURRAY MICHAEL , ZALUZNY LOUISE , CANTRILL ELIZABETH , FARRELL GEOFFREY C. 
Published: March 2008

Prolonged administration of a choline‐deficient diet to male rats results in the development of hepatic cirrhosis and alterations in oxidative drug metabolism. The present study was designed to assess whether the changes in drug metabolism were related to the development of cirrhosis or merely to the effects of choline‐deficiency on hepatic microsomal lipid composition. Male rats were given a synthetic choline‐deficient diet for either 1 week (short‐term) or 30 weeks (long‐term), and results at each time were compared with age‐matched control rats given the same diet but with supplementary choline.After both 1 week and 30 weeks of the choline‐deficient dietary regimen, the proportion of microsomal phospholipid present as phosphatidylcholine was significantly decreased, and that present as phosphatidylethanolamine was significantly increased, compared with appropriate controls. However, microsomal cholesterol content (per mg of microsomal protein) was not significantly changed at either time. Cytochrome P‐450 levels and the turnover of ethylmorphine N‐demethylase (enzyme activity/nmol cytochrome P‐450) were significantly reduced in the cirrhotic (30 week) model whereas short‐term intake of the diet did not alter the levels of cither enzyme. These findings suggest that the effects of changes in phosphatidylcholine and phosphatidylethanolamine levels in choline‐deficiency cirrhosis have minimal importance with respect to changes in drug oxidation. Instead, altered regulation of specific cytochrome P‐450 isozymes appears to be the principal cause of impaired oxidation.
Serum pancreatic secretory trypsin inhibitor in pancreatic diseases
Authors: HAYAKAWA TETSUO , MURASE TOSHIYUKI , KONDO TAKAHARU , SHIBATA TOKIMUNE , SUGIMOTO YOSHIYUKI , KITAGAWA MOTOJI 
Published: March 2008

AbstractTo elucidate the diagnostic significance of serum pancreatic secretory trypsin inhibitor (PSTI) in pancreatic diseases, organ distribution of PSTI and abnormalities in serum PSTI were studied. The pancreas showed the highest content of PSTI, which was five times that of the stomach and almost 40 times that of the other organs. Serum PSTI and amylase were elevated in eight patients with acute pancreatitis, 27 and 11 patients of 47 with chronic pancreatitis, 31 and 13 of 36 with pancreatic cancer, and 67 and 62 of 109 with non‐pancreatic disease, respectively. PSTI levels were more sensitive to the presence of pancreatic disease than were amylase levels. The specificities in serum of healthy controls and patients with non‐pancreatic disease were similar for PSTI and amylase (69% vs 71%). In chronic pancreatitis and pancreatic cancer patients the efficiency of the PSTI assay was higher (P < 0.02) than the amylase assay (67% vs 63% for pancreatitis and 71% vs 66% for cancer). The sensitivity and efficiency of serum PSTI assay in chronic pancreatic diseases were superior to those of amylase.
Liver cell adenoma: A case report and a review of 30 cases reported in Japan
Authors: KOGURE KIMITAKA , NAGAMACHI YUKIO , SASAMOTO KIYOSHI , OGAWA TERUO 
Published: March 2008

AbstractA 38 year old man with a huge liver cell adenoma extending to the pelvis was treated by left lateral lobectomy. The tumour, which was well‐encapsulated by fibrous membrane, was 18 × 19 × 6 cm in size and weighed 1500g. Histopathologically, this tumour was composed of well‐differentiated liver cell trabeculae and a small number of pseudobiliary ducts, but no Glisson sheaths. For the past 4 years 8 months he has remained asymptomatic. Thirty cases of liver cell adenoma found in Japanese literature are reviewed here and possible pathogenic implications are discussed.