All-trans retinoic acid suppresses liver injury induced by Propionibacterium acnes and lipopolysaccharide in rats

All-trans retinoic acid (ATRA) has been reported to exert major effects on the immune system, including monocytes/macrophages. The present study was designed to determine whether ATRA would modulate macrophage-associated liver injury induced by Propionibacterium acnes and lipopolysaccharide (LPS) in rats. All-trans retinoic acid administration alleviated the liver injury and reduced the incidence of death following hepatic failure. Serum alanine aminotransferase (ALT) levels 5 h after, and survival rates within 12 h after the administration of LPS were significantly lower in the ATRA-treated group (134 ± 119 IU/L and 72.7%) compared with the control group (713 ± 411 IU/L and 18.2%; P < 0.05). Histological findings supported these results. These effects may be due to suppression of tumour necrosis factor-α (TNF-α) and superoxide anions produced by activated macrophages. Serum levels of TNF-α 1 h after LPS administration were significantly lower in the ATRA-treated group (60.5 ± 7.0 ng/mL) as compared with the control group (105.2 ± 39.3 ng/mL; P < 0.05). Formazan deposition that was generated by the perfusion of the liver with nitroblue tetrazolium, also suggested suppression of the release of superoxide anions from hepatic macrophages. These results suggest that ATRA acts as an immunomodulator in liver injury by suppressing the activation of liver macrophages.     

Vitamin D-dependent rickets type I and type II

Two distinct hereditary defects, vitamin D-dependent rickets type I (VDDR I) and type II (VDDR II), have been recognized in vitamin D metabolism. VDDR I is suggested to be a deficiency of the renal 25-hydroxyvitamin D (25(OH)D)-1α-hydroxylase. Muscle weakness and rickets are the prominent clinical findings. A normal physiologic dose of 1α-hydroxyvitamin D₃ and 1,25-dihydroxyvitamin D₃ is sufficient to maintain remission of rickets in this disorder. VDDR II consists of a spectrum of intracellular vitamin D receptor (VDR) defects and is characterized by the early onset of severe rickets and associated alopecia. This can be attributed to mutations in the VDR gene. Massive doses of vitamin D analogs and calcium supplementation is usually required for the treatment; however, the response to therapy is sometimes variable.     

Atrial Electrograms and Activation Sequences in the Transition Between Atrial Fibrillation and Atrial Flutter

Transition Between Atrial Fibrillation and Flutter. Introduction: The eletrophysiologic mechanism of atrial fibrillation (AF) has a wide spectrum, and it seems that some atrial regions are essential for the occurrence of a particular type of AF. We focused on one type of AF: AF associated with typical atrial flutter (AFI), which was right atrial (RA) arrhythmia, and sought to investigate intra-atrial electrograms and activation sequences in the transition between AF and AFL.
Methods and Results: Intra-atrial electrograms and activation sequences in the R.A free wall and the septum were evaluated in the transition between AF and AFL in seven patients without organic heart disease (all men; mean age 57 ± 11 years). In five episodes of the conversion of AFL into AF, the AFL cycle length was shortened (from 211 ± 6 msec in stable AFL to 190 ± 15 msec before the conversion, P, 0.001). Interruption of the AFL wavefront and an abrupt activation sequential change induced by a premature atrial impulse resulted in fractionation and disorganization of the septal electrograms. During sustained AF, septal electrograms were persistently fractionated with disorganized activation sequences. However, the RA free-wall electrograms were organized, and the activation sequence was predominantly craniocaudal rather than caudocranial throughout AF. In 12 episodes of the conversion of AF into AFL, the AF cycle length measured in the RA free wall increased (from 165 ± 26 msec at the onset of AF to 180 ± 24 msec before the conversion, P, 0.001). AFL resumed when fractionated septal electrograms were separated and organized to the caudocranial direction, despite the RA free-wall electrograms remaining discrete and sharp with an isoelectric line.
Conclusion: Changes of the electrogram and activation sequence in the atrial septum played an important role in the transition between AF and AFL.     

Bile acids influence hepatic chemiluminescence in normal and oxidative-stressed rats†

The aim of the present study was to clarify whether bile acids influence chemiluminescence (CL) in the liver in vivo. Hepatic CL was determined on the surface of the liver of anaesthetized rats by using a photon counter. In normal rats, hepatic CL was significantly decreased 30 min after enteral administration of chenodeoxycholic acid (CDCA) or deoxycholic acid (DCA), but returned to its initial level 3 h later, after part of the CDCA administered was metabolized. Ursodeoxycholic acid (UDCA) and cholic acid had no effect on CL. In contrast, hepatic CL was markedly increased 30 min after CDCA or DCA administration in rats given either buthionine sulphoximine (BSO), an inhibitor of γ-glutamylcysteine synthetase, or diethyldithiocarbamate (DDC), an inhibitor of both superoxide dismutase and glutathione peroxidase. Chenodeoxycholic acid further increased the CL of BSO- or DDC-treated rats during inhalation of oxygen via a tracheal cannula. Coadministration of UDCA eliminated the effects of CDCA on the hepatic CL of normal and BSO- or DDC-treated rats with or without oxygen inhalation. We conclude that cytotoxic bile acids, such as CDCA, increase CL in the antioxidants-depleted or oxidative-stressed liver in vivc, but that UDCA prevents CDCA from developing CL.     

Long-term prognosis and prognostic factors of liver cirrhosis in the 1980s

Abstract The prognosis of 174 patients with cirrhosis during the 1980s (1981–89) was analysed. The estimated survival rates were 87.3% in 3 years and 68.5% in 5 years. During the follow-up period, 58 patients died: 20 of hepatocellular carcinoma (37.7%); 11 of hepatic failure (20.8%); eight of gastrointestinal bleeding (15.1%); and 14 of other causes (26.4%). Multivariate analysis revealed that serum albumin, indocyanine green retention rate at 15 min and white blood cell count were significantly associated with prognosis. The results were also compared to our previous study covering the 1970s (1971–80). The estimated survival rate was significantly improved compared to that during the 1970s (54.3% in 5 years, P < 0.001). In the 1980s, hepatic failure mortality significantly decreased ( P < 0.01), and non-liver-related mortality significantly increased ( P < 0.05). In summary, the prognosis of cirrhosis has improved in recent years, and changes of death cause and prognostic factors were observed. It was concluded that to evaluate the severity and prognosis of cirrhosis, new indices and appropriate classification were necessary.     

Effects of the timing of exercise on the night sleep

Abstract The effects of physical exercises taken at different times in the day upon subjective sleep feeling were examined in five healthy university students (aged 20–22 years); morning exercise, evening exercise, and late evening exercise. The late evening exercise with the strength of 50–60% VO₂max of 1 h has the effect of getting better subjective sleep feeling in the morning and the effect of the decreased daytime sleepiness.     

Effect of Intraatrial Reentry on Initiation of Atrioventricular Reentrant Tachycardia

We studied the effect of intratrial reentry (IAE) on initiation of orthodromic reentrant tachycardia (ORT) in 150 patients with Wolff-Parkinson-White syndrome using His-bundle recording and the atrial extrastimulus technique. IAR was initiated by premature atrial stimulation in 44 patients (29%), and it was followed by ORT in 16 patients (11%). In 8 patients (5%), IAR promoted the initiation of ORT, whereas in 5 patients (3%), IAR inhibited the initiation of ORT. These findings suggest that ORT is frequently induced following IAR. IAR, which was frequently observed during electrophysiological studies, seems to play an important role in the initiation of ORT.     

Case Report: Primary splenic non-Hodgkin's B cell lymphoma in a patient with chronic hepatitis C

A case of primary splenic lymphoma in a patient with chronic hepatitis C is reported. A 69-year-old man with chronic hepatitis C was admitted to Fukuoka City Hospital for evaluation of an enlarging splenic tumour. In the spleen, ultrasonographic examination revealed a hypoechoic tumour and computed tomography demonstrated a non-enhancing low density area measuring 7 cm in diameter; coeliac angiography revealed a hypovascular tumour. Gallium scintigraphy showed uptake of the radioisotope in the splenic tumour. A splenectomy was performed and the morphological and immunohistochemical findings of this tumour were compatible with those of non-Hodgin's B cell lymphoma. Recently, cases of malignant B cell lymphoma associated with hepatitis C virus infection have been reported. Lymphotropism of hepatitis C virus may play a pathological role in the development of non-Hodgkin's lymphoma. We emphasize the importance of considering lymphoma in the differential diagnosis of extrahepatic disorders during the course of chronic hepatitis C virus infections.     

Second‐Generation Everolimus‐Eluting Stents Compared to First‐Generation Drug‐Eluting Stents in Patients Treated for Multivessel Disease

Objective

This study aimed to compare the safety and efficacy of everolimus‐eluting stents (EES) to first‐generation drug‐eluting stents (DES) in multivessel disease (MVD).

Background

Second‐generation EES have demonstrated superiority over first‐generation DES for single‐vessel disease, although the merits of EES in MVD are less established.

Methods

A cohort of 1,285 patients (3,124 lesions) with ≥2 diseased vessels were treated with either first‐generation DES (n = 1,002) or EES (n = 283). The rates of death, myocardial infarction, target lesion revascularization, target vessel revascularization, definite stent thrombosis, and major adverse cardiac events (MACE), defined as the combined incidence of target vessel revascularization, death, and non‐fatal myocardial infarction, were compared at 1 year.

Results

Baseline characteristics were similar except for a lower left ventricular ejection fraction and a lower incidence of stable angina pectoris in the first‐generation DES group (P = 0.001 and 0.013, respectively). At 1 year, the MACE rate was lower in the EES group (9.5P% vs. 15.7%; P = 0.01). Multivariable analysis demonstrated that EES use predicted a higher chance of freedom from MACE at 1 year (hazard ratio 0.58 [0.38–0.87]; P = 0.009; 95% confidence interval).

Conclusions

The use of EES in patients with MVD is safe with signals for improved effectiveness compared to first‐generation DES. Randomized trials comparing new‐generation DES to coronary artery bypass grafting surgery are warranted.