The clinical significance of fungi in atopic dermatitis

Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases and is caused by multiple factors including genetic factors, skin barrier defects, host immune responses, allergen sensitivity, environmental effects, and infections. Commonly, bacterial and viral infections are present in the eczematous lesions of AD patients and clearly aggravate the symptoms. However, studies of fungal infections in AD are limited in spite of the fact that there are reports showing that Malassezia, Candida, and some dermatophytes can affect the symptoms of AD. Moreover, certain fungal infections are sometimes overlooked and need to be considered particularly in AD patients with treatment failure as clinical features of those fungal infections could mimic eczematous lesions in AD. Here, we review the epidemiology, pathogenesis, clinical manifestations, and overlooked features of fungal infections associated with the symptoms of AD including the diagnosis and effectiveness of fungal treatments in AD patients.     

Targeted UV-B phototherapy for plaque-type psoriasis

OBJECTIVE: To determine whether targeted UV-B phototherapy is efficacious and safe in the treatment of localized psoriasis and whether there is a dose-response relationship. DESIGN: Randomized, evaluator-blind, controlled study. SETTING: Dermatology clinic in a large university-based hospital in Bangkok, Thailand. PATIENTS: Fourteen patients with stable, localized, plaque-type psoriasis. INTERVENTIONS: Patients were randomized to receive different fluences of targeted UV-B phototherapy 3 times weekly based on predetermined minimal erythema doses (MEDs). Treatment fluences were constant throughout the study period of 4 weeks. Follow-up was carried out until lesions returned to original state. MAIN OUTCOME MEASURES: Modified psoriasis area and severity index. RESULTS: All fluences of UV-B produced some clinical improvement and were very well tolerated. Fluences ranging from 1 to 6 multiples of MEDs resulted in clearance of lesions in some patients with 6 MEDs producing clearance in 77% of patients. The number of treatments required to clear psoriatic lesions when 2 to 6 MEDs were used was 5.0 to 6.1 treatments. The only adverse events observed were erythema, which was asymptomatic in most subjects, and hyperpigmentation. CONCLUSIONS: Incoherent, targeted UV-B phototherapy is a safe and efficacious treatment modality for localized psoriasis. Its value in other UV-B responsive conditions should be further investigated.     

Gastric mucosal secretions and lesions by different doses of streptozotocin in rats.

The effects of various doses of streptozotocin (STZ) on gastric mucosal secretions and lesions were investigated in rats. STZ at a dose as low as 30 mg/kg significantly increased plasma glucose (P less than 0.05). The elevation of plasma glucose was dependent on the dose on STZ (30-65 mg/kg) administered. The levels of SGOT, SGPT, bilirubin and BUN also increased with the dose of STZ. The secretory rate of gastric H+ decreased whereas the degree of mucosal hyperemia increased with increasing levels of plasma glucose. Treatment with insulin improved all abnormal conditions except the gastric mucosal lesions. The lesions occurred with low H(+)-secretory rate and low gastric emptying rate. It is suggested that STZ might act directly on the gastric mucosa. Its action depended on the dose administered and was not primarily related to the insulin deficit.     

4-Hydroxyacetophenone-Induced Choleresis in Rats is Mediated by the Mrp2-Dependent Biliary Secretion of Its Glucuronide Conjugate

Purpose The present study examined the underlying mechanism by which 4-hydroxyacetophenone (4-HA), a bioactive compound found in several medicinal herbs, exerts its potent stimulatory effects on hepatic bile secretion.Methods Bile flow, and biliary excretion of 4-HA, its metabolites, and inorganic electrolytes was examined in both normal Wistar rats and in TR^- Wistar rats that have a congenital defect in the multidrug resistance-associated protein-2, Mrp2/Abcc2. The effects of 4-HA were also examined in animals treated with buthionine sulfoximine to decrease hepatic glutathione (GSH) levels.Results In normal rats, 4-HA dramatically increased bile flow rate, whereas it failed to exert a choleretic effect in TR^- rats. This choleresis was not explained by increased biliary output of Na⁺, K⁺, Cl⁻ or HCO₃ ⁻, or by increased biliary GSH excretion. Depletion of hepatic GSH with buthionine sulfoximine had no effect on the 4-HA-induced choleresis. HPLC analysis revealed that a single major compound was present in bile, namely.4-hydroxyacetophenone-4-O-β-glucuronide, and that the parent compound was not detected in bile. Biliary excretion of the glucuronide was directly correlated with the increases in bile flow. In contrast to normal rats, this 4-HA metabolite was not present in bile of TR⁻ rats.Conclusions These results demonstrate that the major biliary metabolite of 4-HA in rats is the 4-O-β-glucuronide, a compound that is secreted into bile at high concentrations, and may thus account in large part for the choleretic effects of 4-HA. Transport of this metabolite across the canalicular membrane into bile requires expression of the Mrp2 transport protein.     

Effects of cortisol pretreatment on the acute hepatotoxicity of aflatoxin B1

Effects of cortisol pretreatment on acute hepatotoxicity induced by aflatoxin B1 (AFB1) were investigated in female rats. Pretreatment of cortisol (1.0-10.0 mg/kg body weight) for 7 consecutive days markedly increased mortality rate, activity of plasma glutamic pyruvic transaminase (PGPT), plasma glutamic oxaloacetic transaminase (PGOT) and liver triglycerides induced by AFB1 (3.0 mg/kg body weight). The potentiating action of cortisol on hepatic necrosis of AFB1 showed a dose-dependent pattern. The possible mechanism of its action may be related to an increase in the activity of aniline hydroxylase and formation of AFB1-2,3-epoxide which in turn caused a marked increase in AFB1 binding to hepatic DNA and proteins, and lipid peroxide formation. Therefore, the potentiating action of cortisol on AFB1 hepatotoxicity may possibly increase the damage to DNA and membranes of various organelles.     

Effect of chronic K+ deficiency on contractile properties of soleus muscle in rats: evidence of sex differences

1. Alterations in skeletal muscle function of chronically K(+)-depleted male and female rats were investigated in isolated soleus muscles. 2. By 16 weeks K+ deficiency, plasma K+ concentrations in both male and female rats were reduced to approximately 2 mEq/L, which was accompanied by an approximate 50% reduction in muscle K+ content and a marked increase in muscle Na+ content. These changes were similar in both males and females. 3. Plasma creatine phosphokinase activity progressively increased with time in K(+)-depleted male rats, whereas only a slight increase was observed in female rats. 4. Maximum isometric twitch tension (Pt) and tetanic tension (Po) of K(+)-depleted soleus muscles from male rats was markedly suppressed; this was not seen for soleus muscles obtained from female rats. 5. After exposure to insulin in low-K+ solution, the contractile tension of soleus from the K(+)-depleted male rats was suppressed to a greater extent. 6. All alterations in muscle function during chronic K+ depletion were restored to normal after 2 weeks K+ repletion. 7. The results suggest that there is a preponderance for male over female rats in developing alterations in skeletal muscle function during chronic K+ deficiency. The changes may be associated with abnormalities of muscle membrane permeability and cellular function.     

l-[METHYL-(11)C] methionine positron emission tomography for target delineation in malignant gliomas: impact on results of carbon ion radiotherapy

PURPOSE: To assess the importance of (11)C-methionine (MET)-positron emission tomography (PET) for clinical target volume (CTV) delineation. METHODS AND MATERIALS: This retrospective study analyzed 16 patients with malignant glioma (4 patients, anaplastic astrocytoma; 12 patients, glioblastoma multiforme) treated with surgery and carbon ion radiotherapy from April 2002 to Nov 2005. The MET-PET target volume was compared with gross tumor volume and CTV, defined by using computed tomography/magnetic resonance imaging (MRI). Correlations with treatment results were evaluated between positive and negative extended volumes (EVs) of the MET-PET target for CTV. RESULTS: Mean volumes of the MET-PET targets, CTV1 (defined by means of high-intensity volume on T2-weighted MRI), and CTV2 (defined by means of contrast-enhancement volume on T1-weighted MRI) were 6.35, 264.7, and 117.7 cm(3), respectively. Mean EVs of MET-PET targets for CTV1 and CTV2 were 0.6 and 2.2 cm(3), respectively. The MET-PET target volumes were included in CTV1 and CTV2 in 13 (81.3%) and 11 patients (68.8%), respectively. Patients with a negative EV for CTV1 had significantly greater survival rate (p = 0.0069), regional control (p = 0.0047), and distant control time (p = 0.0267) than those with a positive EV. Distant control time also was better in patients with a negative EV for CTV2 than those with a positive EV (p = 0.0401). CONCLUSIONS: For patients with malignant gliomas, MET-PET has a possibility to be a predictor of outcome in carbon ion radiotherapy. Direct use of MET-PET fused to planning computed tomography will be useful and yield favorable results for the therapy.     

Protection of centrilobular necrosis by Curcuma comosa Roxb. in carbon tetrachloride-induced mice liver injury

Aim of the study

To investigate the protective effect and possible mechanism of Curcuma comosa hexane extract on CCl₄-induced liver injury in adult male mice.

Materials and methods

Hepatotoxicity was induced by an intraperitoneal injection of CCl₄ and was evaluated after 24 h from the elevations of plasma alanine transaminase (ALT) and aspartate transaminase (AST) activities, and histological analysis of liver injuries. Hexane extract of Curcuma comosa was given at different time points from 1 to 72 h, prior to CCl₄ administration and the protection from liver injury was assessed.

Results

CCl₄-induced damage to liver cells was resulted in elevations of plasma ALT and AST activities. Pretreatment with Curcuma comosa hexane extract 24 h at a dose of 100, 250, and 500 mg/kg BW resulted in a dose-dependent prevention of the increases in plasma ALT and AST activities as well as time dependent. The protective effect of the extract at a dose of 500 mg/kg BW was seen at 12–24 h. Pretreatment of the extract completely prevented elevation of plasma ALT and AST activities, and centrilobular necrosis. The protective effect of Curcuma comosa was associated with restoration of hepatic glutathione content, and CYP2E1 catalytic activity, and its mRNA and protein levels as well as increase in activity of glutathione-S-transferase (GST).

Conclusion

Curcuma comosa has a potent protective property against CCl₄-induced hepatic injuries via the activation of detoxifying mechanisms (GST) as well as reduction of the bioactive toxic metabolites. Therefore, Curcuma comosa may be beneficial for prevention of hepatotoxicity.