An efficient perovskite solar cell with symmetrical Zn(ii) phthalocyanine infiltrated buffering porous Al2O3 as the hybrid interfacial hole-transporting layer.

A new Zn(ii) phthalocyanine (Pc) based low bandgap HTM is introduced for perovskite solar cells. Steady state and time-resolved photoluminescence (PL) measurements indicated an evenly matched hole extraction efficiency between sym-HTPcH and spiro-OMeTAD. On account of the low film quality and resulting high recombination, Zn(ii) Pc normally cannot work as an effective HTM. We adopted insulating Al2O3 for the infiltration of sym-HTPcH to form a hybrid interfacial buffer layer, affording perovskite solar cells (PSCs) with an average PCE value of up to 12.3%, which is a significant improvement with respect to the control cell without the meso-Al2O3 layer (4.21%) and is the highest value ever reported for Zn(ii) phthalocyanine based devices under AM1.5G standard conditions. A hysteresis test revealed that our device structure with the new HTM exhibited a balanced charge extraction behaviour.

Complexity of the HVR-1 quasispecies and disease activity in patients with hepatitis C.

BACKGROUND: Hepatitis C virus (HCV) easily undergoes genomic changes, especially in the hypervariable region (HVR) in the N-terminus of the E2/NS1 region. The quasispecies nature of HCV may have important biological implications in relation to viral persistence; however, the relationship between disease activity of chronic HCV infection and development of the genomic complexity have yielded conflicting results. We explored the changes in the complexity of the HVR-1 in the natural course of chronic HCV infection with and without elevation of serum alanine transaminase (ALT) levels. MATERIALS AND METHODS: Ten patients with chronic hepatitis C proven by liver biopsy, who showed persistent elevation of the serum ALT levels, and 15 patients with chronic HCV infection and persistently normal serum ALT levels (PNAL) were enrolled in this study. The number of the HCV quasispecies was determined twice for each patient at an interval of mean 2.5 years by fluorescence single-strand conformation polymorphism and sequence analysis. RESULTS: There was no significant difference in the changes in the number of quasispecies during the follow-up period between chronic hepatitis C and PNAL. There was also no significant difference in the change in the number of variable nucleotides sites between the two groups. In these patients, the number of quasispecies and the diversity of HVR-1 were correlated with platelet counts and serum hyaluronic acid levels previously shown to be associated with disease progression. CONCLUSION: Our results suggested that the disease activity is not always related to the generation of the HVR-1 quasispecies complexity.

Interaction of VEGF to gastric low grade MALT lymphoma by Helicobacter heilmannii infection in C57/BL/6 mice.

UNLABELLED: Helicobacter heilmannii (Hh) has been clinically reported to have some relation to gastric low grade MALT lymphoma. Recently, we have formed the gastric MALT lymphoma in C57BL/6 mice. MATERIALS AND METHODS: C57BL/6 mice infected with Hh from cynomolgus monkey for more than 6 months were used. The macroscopic, immunohistochemical and electron microscopic observation was performed RESULTS: MALT lymphoma was formed in almost 100% of the infected mice. Increased VEGF-A and Flt-3 immunoreactivity was recognized. CONCLUSION: Hh was shown to be related to the formation of MALT lymphoma and VEGF is suggested to play a role in this lymphoma.

Expression of leptin in two-layered culture of gastric mucous cells and fibroblasts: effect of Helicobacter pylori attachment.

BACKGROUND: Our recent histochemical studies have revealed an increase in myofibroblasts and in leptin and its receptor in endothelial cells, and myofibroblasts in Helicobacter pylori-infected human and Mongolian gerbil fundic mucosa. AIM: The present study was undertaken to clarify the H. pylori-induced interaction between leptin in cultured gastric surface mucous cells and fibroblasts. METHODS: GSM06 cells were incubated with an air- liquid interface on a collagen gel layer containing mouse fibroblast cell line L929. Medium containing H. pylori bacilli (ATCC43504) at 10-100 times higher concentration than the GSM06 cells was added from the luminal side and the localization of leptin was observed by immunohistochemistry. The transformation of L929 cells to myofibroblasts was detected by electron microscopy and PR 2D3 immunoreactivity. RESULTS: L929 cells in the control group showed a spindle shape with scarce cytoplasm. In the H. pylori-treated group, L929 cells showed features characteristic of myofibroblasts, and most GSM06 and L929 cells showed leptin immunoreactivity. In contrast, L929 cells incubated with H. pylori alone did not undergo this differentiation. CONCLUSIONS: Attachment of H. pylori to surface epithelial cells caused conversion of fibroblasts to myofibroblasts. We suggest that leptin plays a role in this transformation.

Polymorphisms of NS5B protein relates to early clearance of hepatitis C virus by interferon plus ribavirin: a pilot study.

Although randomized trials have shown enhancement of efficacy for combination therapy with interferon (IFN) alpha-2b and ribavirin compared with IFN monotherapy as first-line treatment for chronic hepatitis C, infection with genotype 1b and high viremia are still associated with significantly low response rates compared with non-1 genotypes and low viremia. We analysed amino acid sequences of the viral RNA-dependent RNA polymerase (RdRP) or nonstructural protein 5B (NS5B), responsible for ribavirin misincorporation into RNA products in patients with genotype 1b-related chronic hepatitis C and high viremia, and examined the relationship between such RdRp polymorphisms, and the initial decline in viral load induced by combination therapy with IFN-alpha and ribavirin. Substitution of glutamic acid to lysine at the 124th position (E124K) and of isoleucine to valine at the 85th position (I85V) were found to be closely associated with a potent decline of viral load and viral clearance at 8 weeks of treatment (five of five patients, coincidence rate 100%). In conclusion, our results suggest that the polymorphisms of E124K and I85V identified in NS5B protein are crucial for early viral clearance in patients with genotype 1b and high viremia by combination therapy with IFN and ribavirin, and that detection of amino acid sequence motifs might enable prediction of clinical efficacy.

Rebamipide binds to iNOS-positive cells in acetic acid-treated but not in ethanol-treated rat gastric mucosa.

BACKGROUND: Rebamipide is a gastroprotective agent to stimulate prostaglandin generation in gastric mucosa and attenuate the activity of neutrophils, but direct evidence for the effector sites of this agent has remained to be clarified. AIM: The present study was undertaken to show the effector sites of rebamipide in control and ulcer-provoked rats. METHODS: The rats were divided into control, acetic acid- and ethanol-treated rats. In the acetic acid-treated group, 100% acetic acid was attached to the serosal surface of the stomach for 30 s, 7 days before the experiments. In the ethanol-treated group, a dose of 0.5 mL/100 g body weight of 50% ethanol was administered through orogastric intubation 2 h before the experiments. Using the unfixed cryostat sections, aqueous solution of 3H-rebamipide was applied and the localization of the binding sites of rebamipide was investigated by autoradiography. RESULTS: In the control rats, rebamipide was found to bind to the surface epithelial cells. In the ethanol-treated group, few binding sites were observed in the damaged gastric mucosa. In the acetic acid-treated group, the marked accumulation of the binding sites of 3H-rebamipide was observed in the mesenchymal cells in the lamina propria mucosae between the regenerated gastric epithelial cells. Combination of autoradiography and immunohistochemistry has revealed that iNOS-immunoreactive cells had the strong binding of rebamipide in the acetic acid-treated group. Some of these cells were CD68-positive macrophages, while others were CD68-negative, corresponding to polymorphonuclear leucocytes. In the ethanol-treated acute gastric mucosal injury group, few binding sites were observed in the damaged gastric mucosa. CONCLUSIONS: Autoradiography has made it clear that rebamipide binds to iNOS-positive cells in the gastric mucosa 7 days after acetic acid-treatment.

Interaction of leptin with gastric myofibroblast transdifferentiation in Helicobacter pylori-infected Mongolian gerbils: the effect of rebamipide.

BACKGROUND: Our recent histochemical studies have revealed the marked increase of myofibroblasts in the Helicobacter pylori-infected Mongolian gerbil fundic mucosa, while the mediators, which facilitate the conversion of fibroblasts to the myofibroblasts have remained unknown. AIM: The present study was undertaken to clarify the alteration of leptin in the control and H. pylori-infected Mongolian gerbil stomach. The effector sites of rebamipide were also investigated in relation to leptin. METHODS: The localization of leptin was investigated by the indirect immunofluorescence. Plasma leptin levels were determined by ELISA method. The localization of 3H-rebamipide binding sites was investigated by autoradiography. RESULTS: Serum leptin content in H. pylori-infected Mongolian gerbils was significantly increased. The presence of leptin immunoreactivity was recognized in the endothelial cells of the microcirculatory network and very weakly in the glandular cells in the control group, while in the H. pylori-infected group leptin was markedly recognized in the mesenchymal cells. Rebamipide bound to the fibroblasts and surface mucous cells and decreased the leptin immunoreactivity in the gastric mucosa. CONCLUSIONS: Leptin was mostly found in the mesenchymal cells. Rebamipide administration brought about the decrease of leptin in the gastric mucosaof the H. pylori-infected gerbils.

Role of adenosine in renal protection induced by a brief episode of ischemic preconditioning in rats.

The protective effect of a brief episode of ischemic preconditioning was examined at an early phase of ischemic-reperfusion injury in the rat kidney. Rats were subjected to 50 min of left renal artery occlusion followed by 120 min of reperfusion. Ischemic preconditioned rats were subjected to preconditioning with two cycles of 3-min ischemia and 5-min reperfusion (IPC). Ischemic-reperfusion injury led to a low recovery of the glomerular filtration rate (GFR). Overt morphological changes, consisting of blood trapping and tubular collapse, were seen. IPC improved the recovery of GFR and renal morphology. The IPC effect was not blocked by 8-(p-sulfophenyl)-theophylline (SPT), a non-selective adenosine receptor antagonist, by 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), a selective A1-receptor antagonist, or by 3,7-dimethyl-1-propargylxanthine (DMPX), a selective A2-receptor antagonist. Intravenous infusion of adenosine (30 microg/min per rat, for 5 min) prior to the 50-min occlusion improved the recovery of GFR, and this protection of GFR was blocked by SPT. Thus, both IPC and exogenous adenosine attenuated ischemic-reperfusion injury of the kidney. However, because three adenosine receptor antagonists failed to abolish the protective effect of IPC, there is no evidence to indicate that activation of adenosine receptors contributes to the IPC effect in the kidney.

Alcohol and the pancreas.

This article represents the proceedings of a workshop at the 2000 ISBRA Meeting in Yokohama, Japan. The presentations were (1) Phenotypic alteration of myofibroblast during ethanol-induced pancreatic injury: its relation to bFGF, by Masahiko Nakamura, Kanji Tsuchimoto, and Hiromasa Ishii; (2) Activation of pancreatic stellate cells in pancreatic fibrosis, by Paul S. Haber, Gregory W. Keogh, Minoti V. Apte, Corey S. Moran, Nancy L. Stewart, Darrell H.G. Crawford, Romano C. Pirola, Geoffrey W. McCaughan, Grant A. Ramm, and Jeremy S. Wilson; (3) Pancreatic blood flow and pancreatic enzyme secretion on acute ethanol infusion in anesthetized RAT, by H. Nishino, M. Kohno, R. Aizawa, and N. Tajima; (4) Genotype difference of alcohol-metabolizing enzymes in relation to chronic alcoholic pancreatitis between the alcoholic in the National Institute on Alcoholism and patients in other general hospitals in Japan, by K. Maruyama, H. Takahashi, S. Matsushita, K. Okuyama, A. Yokoyama, Y. Nakamura, K. Shirakura, and H. Ishii; and (5) Alcohol consumption and incidence of type 2 diabetes, by Katherine M. Conigrave, B. Frank Hu, Carlos A. Camargo Jr, Meir J. Stampfer, Walter C. Willett, and Eric B. Rimm.

Influence of the light schedule on the toxic interaction between propranolol and disopyramide in chick embryos.

The effect of the light schedule on toxic interactions between propranolol and disopyramide were studied in chick embryos. Fertilized eggs of White Leghorns were incubated under dark conditions and investigated, on two occasions, under light conditions or under dark conditions. Propranolol, with and without disopyramide, was injected into the air sac of fertilized eggs on the 16th day of incubation. Electrocardiograms (ECGs) were recorded 0 to 60 min after the injection. After the injection of propranolol with disopyramide, the heart rate was significantly decreased compared with the injection of propranolol alone under light conditions. In addition, this toxic interaction between propranolol and disopyramide was more severe under dark conditions than under light conditions. These findings indicate that manipulation of the light schedule has a marked influence on the toxic interaction between propranolol and disopyramide in chick embryos.

[A case of fatal acute sodium azide poisoning].

A case of fatal sodium azide poisoning induced by suicidal ingestion was reported. When the patient arrived, her vital signs such as consciousness and blood pressure, were normal. But 25 hours after ingestion, she died from metabolic acidosis, ARDS (acute respiratory distress syndrome) and acute cardiac failure. We detected the azide ion in patient's serum using GCMS method and measured the blood concentration of sodium azide using the GC/NPD method. The half-life period of sodium azide in blood was calculated as about 2.5 hours.

Up-regulation of E-cadherin and I-catenin in human hepatocellular carcinoma cell lines by sodium butyrate and interferon-alpha.

Human E-cadherin is a homophilic cell adhesion molecule and its expression is well preserved in normal human hepatocytes; a decrease in its expression has been observed in poorly differentiated hepatocellular carcinoma cells. We examined the alteration of E-cadherin and catenin expressions caused by differentiation inducers in human hepatocellular carcinoma cells. Hepatocellular carcinoma cell lines, HCC-T and HCC-M, were cultured with all-trans retinoic acid (ATRA), dexamethasone (DEX), sodium butyrate, and interferon-alpha. E-cadherin expression was only up-regulated by butyrate and interferon-alpha (IFN-alpha) in both cell lines, studied by means of fluorescence immunostaining and flow cytometry. The localization of E-cadherin staining was shown at their cell membrane. According to the increase in E-cadherin expression, beta-catenin expression appeared at the cell membrane of both cell lines when treated with butyrate and IFN-alpha. Such an appearance was not observed when cells were treated with ATRA and DEX. Western blotting showed that alpha- and y-catenin expression was not changed, while only the expression of beta-catenin increased. Beta-catenin oncogenic activation as a result of amino acid substitutions or interstitial deletions within or including parts of exon 3, which has been demonstrated recently, was not detected in these cell lines by direct deoxyribonucleic acid sequencing. These results suggest that the expression and interaction between E-cadherin and wild-type beta-catenin are potentially modulated by butyrate and IFN-alpha, and that these two agents are potent inhibitors of hepatocellular carcinoma cell invasion and metastasis.

Autonomic nervous regeneration in acetic acid-induced ulcer from the viewpoint of synapse formation--effect of basic fibroblast growth factor and sofalcone in the rat.

BACKGROUND: Monoclonal antibodies against GAP43 and synaptophysin, markers of regenerated nerves, have recently become available. AIM: To investigate the regeneration of the autonomic nerves after acetic acid treatment, as well as the effect of recombinant basic fibroblast growth factor (bFGF-CS23) and sofalcone on reinnervation. METHODS: Ulcers were induced by the direct application of 100% acetic acid to the serosal surface of the rat fundic stomach. Some rats were treated with bFGF-CS23 or sofalcone every 12 h after the acetic acid treatment. The immunohistochemical location of GAP43 and synaptophysin was observed by confocal laser microscopy, and the uptake sites of 14C-sofalcone were observed by autoradiography. RESULTS: Both GAP43 and synaptophysin immunoreactivities surrounding microvessels were weak in the control group, whereas in the acetic acid-treated group, these immunoreactivities were increased. Treatment with bFGF-CS23 and sofalcone increased these immunoreactivities. The binding sites of sofalcone coincided with the location of regenerated nerves and surface mucous cells. The progenitors of the autonomic nerves were more abundant than expected. CONCLUSION: Both bFGF and sofalcone seem to stimulate nerve regeneration.

Immunological and virological predictors of outcome during interferon-alpha therapy of chronic hepatitis C.

Results from a multicentre, clinical trial of interferon-alpha2a (IFN-alpha2a) for the treatment of chronic hepatitis C are reported. Serum hepatitis C virus (HCV) RNA levels were monitored as follows: before, and 2 days after, the first administration of IFN-alpha2a; during and at the end of treatment; and 6 months after completion of therapy. Peripheral blood lymphocyte subpopulations were measured, by two-colour flow cytometry, before and 3 h after the first intramuscular (i.m.) administration of 9 mega units (MU) of IFN-alpha2a. Virological responders had a significantly lower pretreatment level of CD11+ CD8- lymphocytes. Biochemical responders had significantly lower pretreatment levels of CD11- CD8+, human leucocyte antigen (HLA) DR- CD4- and HLA DR- CD8+ populations, and a higher pretreatment HLA DR+ CD4- population. These pretreatment differences disappeared 3 h after the first i.m. administration of IFN-alpha2a. CD11- CD8+ and HLA DR+ CD8+ cell populations became significantly lower in virological responders 3 h after the first i. m. administration of IFN-alpha2a. HLA DR+ CD4+ cell populations were increased less in biochemical responders. Thus, T-lymphocyte subpopulations were different between responders and non-responders to IFN therapy and IFN-modulated host immunity. Multivariate analysis showed that the pretreatment CD11+ CD8- cell population was an independent predictive factor of response to therapy. On the other hand, patients whose serum HCV RNA cleared or decreased within the first 2 days of IFN-alpha2a therapy were more likely to achieve a virological response. This predictive factor, however, was not an independent factor by multivariate analysis. These results suggest that host immunity is an important factor in response to IFN therapy, and HCV clearance within the first 2 days is a good predictive factor of response.

Reduced in vitro immunoglobulin secretion from peripheral blood mononuclear cells in responders to high-dose interferon-alpha 2b treatment for chronic hepatitis C.

BACKGROUND/AIMS: Immunological status has been considered to correlate to the response to interferon therapy for chronic hepatitis C. The aim of this study was to evaluate the correlation between humoral immunity and long-term response to interferon treatment for chronic hepatitis C. METHODOLOGY: Seventy-one patients with chronic hepatitis C received 10 million units of interferon-alpha 2b three times a week for 24 weeks. Peripheral blood mononuclear cells were obtained before interferon-alpha 2b was administered and were cultured for 7 days. Immunoglobulin concentration in the culture supernatants was measured by enzyme-linked immunosorbent assay and correlation with the response to the therapy was evaluated. RESULTS: Serum ALT levels normalized in 51.4% and hepatitis C virus RNA disappeared in 35.7% six months after the end of therapy. Immunoglobulin production was significantly lower in the patients in whom serum ALT levels normalized than those in whom serum ALT levels remained elevated. The similar result was obtained when efficacy was evaluated on the basis of hepatitis C virus RNA disappearance. CONCLUSIONS: These results suggest that the less humoral immunity, the better response to interferon will be obtained in patients with chronic hepatitis C, meaning that the balance in T-helper function is one of key factors in the response to interferon treatment.

Induction of hepatic stellate cell proliferation by LPS-stimulated peripheral blood mononuclear cells from patients with liver cirrhosis.

We studied hepatic stellate cell proliferation in vitro. Peripheral blood mononuclear cells (PBMC) from patients with chronic active hepatitis C (CAH) and liver cirrhosis (LC) were cultured for 24h in the presence or absence of Escherichia coli lipopolysaccharides (LPS). Hepatic stellate cell proliferation induced by the culture supernatants was measured, and interleukin-1 (IL-1) and IL-6 levels in the culture supernatants were quantified. Culture supernatants of LPS-stimulated PBMC from LC patients induced rat hepatic stellate cell proliferation by almost 2.8-fold (stimulation index, 2.83 +/- 1.41) compared with when the cells were cultured without addition of PBMC culture supernatants. Production of IL-1beta was significantly higher in the culture supernatants of both CAH and LC patients than in those of ten healthy controls (P < 0.01 and P < 0.05, respectively). But there was no significant correlation between IL-1 production and the induction of hepatic stellate cell proliferation by the culture supernatants. Although there were no significant differences in IL-6 production by LPS-stimulated PBMC among healthy controls and CAH and LC patients, we observed a significant correlation between IL-6 production and the induction of hepatic stellate cell proliferation in the culture supernatants of LC patients. Rat hepatic stellate cells themselves produced IL-6, and treatment with IL-6 antisense oligodeoxynucleotides suppressed the cell proliferation, suggesting that IL-6 is an autocrine growth factor for hepatic stellate cells. The addition of human recombinant IL-6 (hrIL-6) augmented rat hepatic stellate cell proliferation, indicating that excessive IL-6 may further facilitate cell proliferation. These findings suggest that a cytokine cascade including IL-6 may participate in hepatic stellate cell proliferation in LC patients when they are exposed to endotoxin.

In vivo evaluation of the national cardiovascular center electrohydraulic total artificial heart.

We have been developing an electrohydraulic total artificial heart system. The system comprises an intrathoracic pumping unit composed of diaphragm type ellipsoidal blood pumps and an energy converter in addition to an electronics unit. The in vivo performance of the pumping unit was evaluated in a series of animal implantations with 3 calves weighing 62-85 kg. An interatrial shunt 4.5 mm in diameter was made in the atrial septum to compensate left-right imbalance. Two calves died early postoperatively, one of external controller power failure and the other of interatrial shunt stenosis due to thrombus formation. One calf, however, survived over 10 days under stable circulatory conditions. No abnormality was found in the oxygen metabolic condition or in major organ functions. The generation and dissipation of heat from the device was acceptable. This animal died of device malfunction caused by energy converter bearing breakdown. The device demonstrated a good anatomic fit without compromising the great vessels and adjacent tissues. It is concluded that the pumping unit has a sufficient in vivo basic performance although appropriate countermeasures are to be implemented against the detected problems concerning mechanical durability and interatrial shunt patency.