Interferon alfa-2a treatment for chronic hepatitis C without cirrhosis and its effects on the incidence of hepatocellular carcinoma

The aim of interferon treatment for chronic hepatitis C is eradication of the hepatitis C virus during the early stages of the disease to prevent progression to liver cirrhosis or hepatocellular carcinoma. However, the effects of interferon on preventing the development of hepatocellular carcinoma for chronic hepatitis C without cirrhosis remain obscure. We wished to study these effects. In this retrospective study, we followed up 66 patients with chronic hepatitis C who were treated with interferon alfa-2a (total dose 324 to 792 MIU) for an average period of 3 years after treatment. Of these 66 patients, 3 patients developed hepatocellular carcinoma during the follow-up period (range, 0.3 to 2.8 years; yearly incidence 1.5%). All 3 patients were among 27 patients who did not respond to interferon treatment. Of these 3 patients, 1 patient developed liver cirrhosis after interferon treatment, and the histologic staging of the remaining 2 patients before interferon treatment was F3, according to the new Inuyama classification. None of the 18 patients who were complete responders to interferon treatment or the 21 patients with incomplete responses developed hepatocellular carcinoma. Our results suggest that patients with chronic hepatitis C who have no response to interferon treatment and histologically advanced disease should be closely followed up after interferon treatment, although the mechanism of malignant transformation to hepatocellular carcinoma in patients with chronic hepatitis C virus infection is still obscure.     

Sustained release of basic fibroblast growth factor using gelatin hydrogel improved left ventricular function through the alteration of collagen subtype in a rat chronic myocardial infarction model

Objective

Chronic myocardial infarction (CMI) tends to be resistant to treatments possibly due to extensive solid fibrotic scar, hypoxia mediated by poorly vascularized environment, and/or inflammation and apoptosis. Here we aimed to testify the therapeutic effects of sustained release of basic fibroblast growth factor (bFGF) using gelatin hydrogel (GH) in a rat chronic MI model and to elucidate the therapeutic mechanism including the alteration of extracellular matrix component.

Methods

CMI model rats are prepared by the permanent ligation of proximal left anterior descending coronary artery. After 4 weeks, GH sheets (GHSs) with bFGF (100 µg) (bFGF group) or with phosphate-buffered saline (Vehicle group) were implanted to the CMI models to evaluate the effect of bFGF–GHS on chronic scar tissue. Sham operation group was also prepared (n?=?5 for each).

Results

4 weeks after implantation, bFGF–GHS significantly improved cardiac contractile function (fractional shortening: 21.8?±?1.1 vs 21.5?±?1.3 vs 29.7?±?1.8%; P?<?0.001/fractional area change: 33.0?±?1.4 vs 34.1?±?2.3 vs 40.6?±?1.8%; P?<?0.001) (Sham vs Vehicle vs bFGF) accompanied with neovascularization. Immunohistochemical studies revealed that bFGF–GHS increased collagen III/I ratio indicating the alteration of solid scar tissue. Quantitative RT-PCR results showed a decrease of collagen I mRNA expression within border MI zone.

Conclusions

The implantation of bFGF–GHS altered the collagen subtype of the fibrotic scar more suitable for tissue repair. The treatment of sustained-release bFGF may be promising for ischemic heart disease through chronic pathology.

     

Physical fitness in persons with hemiparetic stroke: its structure and longitudinal changes during an inpatient rehabilitation programme

OBJECTIVE: To test the hypothesis that the structure of fitness in patients with hemiparetic stroke can be categorized into impairment/disability, cardiopulmonary, muscular and metabolic domains, and to study longitudinal changes in their fitness during an inpatient rehabilitation programme. DESIGN: Structure analysis of multiple fitness parameters with principal component analysis (PCA), and a before and after trial. SETTING: Tertiary rehabilitation centre in Japan. PATIENTS: One hundred and seven consecutive inpatients with hemiparetic stroke. INTERVENTION: A conventional stroke rehabilitation programme consisting of 80 minutes of physical therapy and occupational therapy sessions five days a week, and daily rehabilitation nursing for a median duration of 105.5 days. MAIN OUTCOME MEASURES: Principal component scores extracted from measurement of paresis/daily living (the Stroke Impairment Assessment Set (SIAS) and the Functional Independence Measure (FIM)); muscular (grip strength (GS), knee extensor torque, and cross-sectional areas of thigh muscles); metabolic (body mass index (BMI) and fat accumulation on CT); cardiopulmonary (heart rate oxygen coefficient (HR-O2-Coeff) obtained with a graded bridging activity and a 12-minute propulsion distance). RESULTS: PCA categorized the original 15 variables into four factors corresponding to paresis/activities of daily living, muscular, metabolic and cardiopulmonary domains, and explained 78.1% of the total variance at admission and 69.6% at discharge. Except the metabolic domain, PCA scores for the other three domains improved significantly at discharge (paired t-test, p < 0.05). CONCLUSION: The hypothetical structure of fitness was confirmed, and the PCA scores were useful in following longitudinal changes of fitness during inpatient rehabilitation.     

Expression of the P2Y2 receptor on the rat ocular surface during a 1-year rearing period

Purpose

P2Y₂ receptors are expressed on ocular surface tissues. Diquafosol ophthalmic solution (DIQUAS^® ophthalmic solution 3 %; Santen Pharmaceutical Co., Ltd.) acts on these receptors and promotes the secretion of water and mucin. It has been shown to be an efficient dry eye treatment. If P2Y₂ receptor expression on the ocular surface decreases with age, the effect of diquafosol may be reduced in elderly persons. In this study, we investigated the changes in P2Y₂ receptor expression on the rat ocular surface over an extended period of time.

Methods

P2Y₂ receptor expression in the conjunctiva, cornea, meibomian gland and lacrimal glands of male and female Sprague–Dawley rats was examined from 5 weeks until 53 weeks of age using immunostaining and quantitative-PCR.

Results

In the immunohistological examinations, P2Y₂ receptor expression was observed in the conjunctival epithelium containing goblet cells, corneal epithelium, meibomian gland ductal epithelium and lacrimal gland ductal epithelium. However, its expression was not significantly different between each age group or between sexes. Regarding P2Y₂ receptor mRNA expression, there was an age-related increase in the bulbar conjunctiva. In particular, a significant increase was observed in the 53-week-old age group as compared to the 5-week-old female age group. However, age-related changes in expression were not observed in the cornea or meibomian gland in males or females.

Conclusions

We observed no significant age-related decrease was observed for P2Y₂ receptor protein and mRNA expression on rat ocular surface tissues.     

Survey of the Effects of a Column for Adsorption of β2‐Microglobulin in Patients With Dialysis‐Related Amyloidosis in Japan

Dialysis‐related amyloidosis is a serious complication of long‐term hemodialysis. Its pathogenic mechanism involves accumulation of β2‐microglobulin in the blood, which then forms amyloid fibrils and is deposited in tissues, leading to inflammation and activation of osteoclasts. Lixelle, a direct hemoperfusion column for adsorption of β2‐microglobulin, has been available since 1996 to treat dialysis‐related amyloidosis in Japan. However, previous studies showing the therapeutic efficacy of Lixelle were conducted in small numbers of patients with specific dialysis methods. Here, we report the results of a nationwide questionnaire survey on the therapeutic effects of Lixelle. Questionnaires to patients and their attending physicians on changes in symptoms of dialysis‐related amyloidosis by Lixelle treatment were sent to 928 institutions that had used Lixelle, and fully completed questionnaires were returned from 345 patients at 138 institutions. The patients included 161 males and 184 females 62.9 ± 7.7 years age, who had undergone dialysis for 25.9 ± 6.2 years and Lixelle treatment for 3.5 ± 2.7 years. Based on self‐evaluation by patients, worsening of symptoms was inhibited in 84.9–96.5% of patients. Of the patients, 91.3% felt that worsening of their overall symptoms had been inhibited, while attending physicians evaluated the treatment as effective or partially effective for 72.8% of patients. Our survey showed that Lixelle treatment improved symptoms or prevented the progression of dialysis‐related amyloidosis in most patients.     

T1ρ is superior to T2 mapping for the evaluation of articular cartilage denaturalization with osteoarthritis: Radiological–pathological correlation after total knee arthroplasty

Purpose

We compared the diagnostic performance of T1ρ and T2 mappings in the evaluation of denatured articular cartilage with osteoarthritis of the knee.

Materials and methods

2D-Sagittal T1ρ and T2 mappings of the knee were obtained from 16 patients before total knee arthroplasty. After surgery, specimens of the femur and tibia were regionally segmented according to a 5-point scale of the severity of denaturalization. The T1ρ and T2 values in the full thickness of the articular cartilage in each region were measured by two observers. The two mappings were compared for their ability to differentiate between normal and denatured articular cartilage and also for their usefulness in grading the severity of the denaturalization using the area under receiver operating characteristic curves (Az). A p < 0.05 was considered significant for each analysis.

Results

The T1ρ mapping showed a significantly higher Az value than the T2 mapping for the differentiation between normal and denatured articular cartilage (p < 0.05). Regarding the assessment of the severity of denaturalization, T1ρ mapping could differentiate between normal and mild denaturalization (p < 0.05), but T2 mapping could not. However, there were no significant differences between the two mappings in the discrimination of mild versus moderate denaturalization or of moderate versus severe denaturalization. The two observers showed good agreement in the results (intraclass correlation coefficient = 0.81 for T1ρ and 0.92 for T2).

Conclusion

T1ρ mapping is superior to T2 mapping for the evaluation of denatured articular cartilage with osteoarthritis of the knee.     

Temperature effects on the disappearance and reappearance of corneal-endothelium primary cilia

Japanese Journal of Ophthalmology - To elucidate the specific functions of the primary cilia in corneal endothelial cells (CECs) by investigating the histological changes of corneal endothelium...     

Cytokine profiles of macular neovascularization in the elderly based on a classification from a pachychoroid/drusen perspective

Graefe's Archive for Clinical and Experimental Ophthalmology - To classify macular neovascularization (MNV) based on pachychoroid and drusen features and to examine the aqueous humor cytokine...     

Activation of two caspase cascades,caspase 8/3/6 and caspase 9/3/6, during photodynamic therapy using a novel photosensitizer,ATX-S10(Na), in normal human keratinocytes

Background/purpose Photodynamic therapy (PDT) is a potent treatment for skin tumors. Although the therapeutic effect of PDT is supposed to be due to cellular cytotoxicity, the precise mechanism is still unknown. ATX-S10(Na) [13,17-bis(1-carboxypropionyl)carbamoylethyl-8-ethenyl-2-hydroxy-3-hydroxyiminoethylidene-2,7,12,18-tetramethylporphyrin sodium salt], a novel hydrophilic chlorin photosensitizer, shows good accumulation in tumors and is suitable for use in PDT. In this study, we investigated the mechanism of PDT-induced cell death using ATX-S10(Na).Methods Following ATX-S10(Na) treatment for 12 h, normal human keratinocytes (NHK) were irradiated using a diode laser. PDT-induced cell death and the activity of various caspases were measured. Activation of Fas antigen was also determined by immunoprecipitation analysis. The expression of Bax, cytochrome c, and apoptosis-inducing factor (AIF) was determined by Western blotting.Results ATX-S10(Na)-PDT had induced apoptosis of NHK by 2 h and the maximal effect was observed at 6 h following irradiation. The effect was suppressed by pretreatment of NHK with inhibitors of caspases 3, 6, 8 and 9. A caspase activity assay revealed the sequential activation of caspases 8, 3 and 6, and caspases 9, 3 and 6, respectively. Immunoprecipitation analysis indicated multimerization of Fas antigen without Fas ligand binding in ATX-S10(Na)-PDT-treated NHK. Western blotting revealed cytosolic release of cytochrome c and AIF accompanied by decreased Bax expression in the cytosol.Conclusions ATX-S10(Na)-PDT induces apoptosis of NHK, and this was mediated by sequential activation of two caspase cascades, caspases 8, 3 and 6, and caspases 9, 3 and 6. This was accompanied by multimerization of Fas antigen and cytosolic release of cytochrome c and AIF.