Real-world evaluation of compliance and preference in Alzheimer's disease treatment: an observational study in Taiwan.

PURPOSE: Among the medications approved for Alzheimer's disease (AD), rivastigmine is the only one available as transdermal patch. The aim of this study was to evaluate compliance and caregivers' preference with oral and transdermal (rivastigmine) monotherapy in patients with mild-to-moderate AD from Taiwan. METHODS: Real-world Evaluation of Compliance And Preference in Alzheimer's disease treatment (RECAP) in Taiwan was a prospective, noninterventional, observational study with a 24-week (±8 weeks) observational period for each participant. Eligible patients were grouped into one of the two treatment cohorts based on the baseline AD therapy: oral (donepezil, galantamine, rivastigmine, or memantine) or transdermal (rivastigmine patch). The primary end points were caregiver preference and caregiver assessment of patients' compliance to the current medication (oral or transdermal medication) at Week 24 (end of the study). Safety was assessed by recording any adverse events. RESULTS: A total of 301 patients (age: 77.6±7.19 years) were enrolled from nine centers in Taiwan, of whom 138 (45.8%) patients were in the transdermal monotherapy cohort. Caregivers of patients who were exposed to both forms of therapies demonstrated a higher preference for transdermal rivastigmine monotherapy than the oral monotherapy (82.4% [n=61] versus 17.6% [n=13], P<0.0001); for patients treated with only one therapy, the caregivers' preference was significantly in favor of the treatment to which the patient was exposed (both P<0.0001). In both cohorts, patients showed good compliance, with an overall score of 8.65±1.38 on an 11-point scale. Of 301 enrolled patients, 102 (33.9%) reported at least one adverse event during the study (51 patients each in the two cohorts). CONCLUSION: With the higher caregiver preference and a good patient compliance, the trans-dermal rivastigmine patch is a suitable treatment choice for patients with mild-to-moderate AD, especially for patients intolerant to oral therapies.

Seasonality, clinical types and prognostic factors of Vibrio vulnificus infection.

INTRODUCTION: Vibrio vulnificus infection, an uncommon but life-threatening illness, manifests as two main types, primary septicemia and primary wound infections.  Little information regarding the seasonality of V. vulnificus infections in tropical areas and prognostic factors of primary V. vulnificus wound infections is available. METHODOLOGY: This retrospective study was conducted to include 159 V. vulnificus-infected admissions at our institution in southern Taiwan, 63 with primary septicemia (Group 1) and 96 with primary wound infections (Group 2), from 1999 to 2008, for analysis. RESULTS: The case-fatality rate was 24%. Eighty-eight percent of these cases occurred during April to November. During December to March, patients in Group 2 were less likely to have acquired the infection compared with those in Group 1. Group 1 was more likely to have comorbidities and a higher case-fatality rate compared to Group 2. In multivariate analysis, hemorrhagic bullous skin lesions/necrotizing fasciitis (P=0.024), lesions involving two or more limbs (P=0.043), and shock on admission (P=0.015) were related to an increased mortality risk, while surgery < 24 hours after admission (P=0.001) was related to a decreased mortality risk in Group 1; however, hemorrhagic bullous skin lesions/necrotizing fasciitis (P=0.045) was the only prognostic factor in Group 2. CONCLUSION: The presence of hemorrhagic bullous lesion/necrotizing fasciitis is the main prognostic factor for primary septicemia or primary wound infections caused by V. vulnificus. Persons with an underlying immunocompromised status should avoid consuming raw/undercooked seafood or exposing wounds to seawater and should wear clothing during handling of seafood/fishing, especially in warmer months.

Rapid Emergency Medicine Score as a main predictor of mortality in Vibrio vulnificus-related patients.

OBJECTIVES: Vibrio vulnificus causes potentially life-threatening and rapidly progressing infections. Therefore, the severity-of-illness assessment appears to be important for V vulnificus-infected patients at the time of admission. The aim of our study was to evaluate the performance of the severity-of-illness scoring model on admission in V vulnificus-infected patients. METHODS: One hundred seventy-one consecutive patients (mean age: 63.1 ± 12.3 years) with V vulnificus infection who were admitted to a teaching hospital between January 1999 and June 2010 were included in the study. Demographic and clinical characteristics, illness severity on admission, treatment, and outcomes were collected for each patient and extracted for analysis. Logistic regression and receiver operating characteristic curve analyses were performed. RESULTS: The mean Rapid Emergency Medicine Score (REMS) on admission was 6.5 ± 3.0 points. During hospitalization, 68 patients (40%) required intensive care. The overall case-fatality rate was 25%. In multivariate analysis, the presence of underlying liver disease (P = .002), hemorrhagic bullous lesions/necrotizing fasciitis (P = .012), and higher REMS values on admission (P < .0001) were associated with increased mortality risk; a time span <24 hours between arrival and surgical treatment was associated with a decreased mortality risk (P = .007). Additionally, the area under the receiver operating characteristic (ROC) curve for the REMS in predicting mortality risk was 0.895 (P < .0001). An optimal cut-off REMS ≥8 had a sensitivity of 81% and a specificity of 85%, with a 26.6-fold mortality risk (P < .0001) and a 12.5-fold intensive care unit admission risk (P < .0001). CONCLUSION: The REMS could provide clinicians with an effective adjunct risk stratification tool for V vulnificus-infected patients.

Complicated acute motor axonal neuropathy with delayed acute respiratory distress syndrome and rapidly progressive glomerulonephritis: a case report.

PURPOSE: Acute motor axonal neuropathy (AMAN), a variant of Guillain Barre syndrome (GBS), is frequently induced by the antecedent infection of some atypical pathogen, such as Campylobacter jejuni, Mycoplasma pneumonia and some virus. It is generally accepted that corticosteroids and immunosuppressants are not recommended in patients with GBS including AMAN. However, if systemic autoimmune reaction developed, the principle of management might be changed. CASE REPORT: We report a young man who rapidly developed acute motor axonal neuropathy. Although plasma exchange had been given, the violent immunological reaction was unable to be controlled, prolonged leukemoid reaction and high level of autoimmunological titers, including C-reactive protein (CRP), rheumatoid factor (Rf), and antineutrophil cytoplasmic autoantibody (ANCA) persisted. Consequently, two months later, this patient developed acute respiratory distress syndrome (ARDS) and type 3 of rapidly progressive glomerulonephritis (RPGN) with rapid decline of renal function until immunosuppressants were given. CONCLUSION: AMAN combined with the violent systemic autoimmune reaction strongly indicated an uneven disease course and implied that only standard plasmapheresis is not sufficient and corticosteroids with immunosuppressant should be added in early stage.

Reversible oro-lingual dyskinesia related to lithium intoxication.

PURPOSE: To report the first case of Taiwanese with lithium intoxication presenting as oro-lingual dyskinesia. CASE REPORT: A 68-year-old man had bipolar disorder with chronic lithium treatment. He had acute conscious disturbance, atrial flutter, myoclunus of limbs, and oro-lingual dyskinesia. Biochemistry study revealed elevated blood urea nitrogen, creatinine, and lithium level (3.43 Eq/L). The lithium is discontinued and he received conservational treatment. Along with reduction of serum lithium level, his involuntary movement subsided following by clear consciousness. He had no residual neurological deficit in 3 years of follow up. CONCLUSION: Oro-lingual dyskinesia is a rare presentation of lithium intoxication. This case reminds us such diagnostic possibilities especially in elder patients who receive a chronic lithium therapy.

The Laboratory Risk Indicator for Necrotizing Fasciitis score for discernment of necrotizing fasciitis originated from Vibrio vulnificus infections.

BACKGROUND: The Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score has been verified as a useful diagnostic tool for detecting necrotizing fasciitis (NF). Its application, however, is mainly for NF types I and II. The practical relevance of the LRINEC score for Vibro vulnificus-related skin and soft tissue infection (SSTI) was hardly ever investigated. The aim of this study was to assess the applicability of the LRINEC scoring system and to identify NF-predicting factors in patients with V. vulnificus-caused SSTI. METHODS: A retrospective study was conducted, enrolling 125 consecutive patients diagnosed with V. vulnificus-related SSTI who were admitted to a teaching hospital between January 2003 and December 2011. Demographics, laboratory data, comorbidities, treatment, and outcomes were collected for each patient and extracted for analysis. Logistic regression and receiver operating characteristic curve analyses were performed. RESULTS: The mean (SD) age of the 125 patients was 63.0 (10.9) years; 58% of the patients were male. The mean (SD) LRINEC score at admission was 2.4 (1.9) points. Of the 125 patents, 72 (58%) had NF. Multivariate analysis revealed that the presence of hemorrhagic bullous lesions (p = 0.002) and higher LRINEC scores at admission (p < 0.0001) were significantly associated with the presence of NF. In addition, the area under the receiver operating characteristic curve for the LRINEC scoring model for detecting NF was 0.783 (p < 0.0001). An optimal cutoff LRINEC score of 2 or greater had a sensitivity of 71%, a specificity of 83%, and a positive predictive value of 85%, with an 11.9-fold increased risk for the presence of NF (p < 0.0001). CONCLUSION: We have demonstrated that the LRINEC score and hemorrhagic bullous/blistering lesions are significant predictors of NF in patients with V. vulnificus-related SSTI. V. vulnificus-infected patients having hemorrhagic bullous/blistering lesions or with an LRINEC score of 2 or greater should be thoughtfully evaluated for the presence of NF. LEVEL OF EVIDENCE: Diagnostic test study, level II.

Post-infectious opsoclonus and reversible magnetic resonance imaging changes: a case report and review of the literatures.

PURPOSE: Opsoclonus is a rare neurological disorder in adult. The etiology of opsoclonus includes parainfectious, paraneoplastic, toxic, and metabolic disorders. We reported an old female with post-infectious opsoclonus who had a benign clinical course and reversible brain MRI lesions, and its review of the literature. CASE REPORT: A 67-year-old woman presented with opsoclonus and truncal ataxia for two weeks. The magnetic resonance imaging (MRI) showed the hyperintensity lesions in bilateral medial thalamus, hypothalamus, and tegmentum of pons on Fluid-attenuated inversion recovery (FLAIR) imaging. Investigations of neoplasm and autoimmune disorders showed negative findings. Clinical symptoms subsided in two-week duration and MRI abnormalities also disappeared one month later. CONCLUSION: A benign clinical course and reversible MRI lesions could be found in the patients with postinfectious opsoclonus such as our case. However, detailed investigations and long-term follow-up are needed to exclude paraneoplastic or other systemic and immunological disorders.

Anti-glycative and anti-inflammatory effects of protocatechuic acid in brain of mice treated by D-galactose.

Protocatechuic acid (PCA) at 0.5%, 1% or 2% was supplied to D-galactose (DG) treated mice for 8 week. PCA intake at 2% increased its deposit in brain. DG treatment increased brain level of reactive oxygen species, protein carbonyl, carboxymethyllysine, pentosidine, sorbitol, fructose and methylglyoxal (P<0.05). PCA intake, at 1% and 2%, lowered brain level of these parameters (P<0.05). DG treatments enhanced activity and protein expression of aldose reductase (AR) and sorbitol dehydrogenase, as well as declined glyoxalase I (GLI) activity and protein expression (P<0.05). PCA intake at 1% and 2% reduced activity and protein expression of AR (P<0.05), and at 2% restored GLI activity and expression (P<0.05). DG injection also elevated cyclooxygenase (COX)-2 activity and expression, and increased the release of interleukin (IL)-1beta, IL-6, tumor necrosis factor-alpha and prostaglandin E(2) in brain (P<0.05). PCA intake decreased these cytokines (P<0.05), and at 1% and 2% suppressed COX-2 activity and expression (P<0.05). PCA intake at 1% and 2% also lowered DG-induced elevation in activity, mRNA expression and protein production of nuclear factor kappa B p65 (P<0.05). These findings suggest that the supplement of protocatechuic acid might be helpful for the prevention or alleviation of aging.

Anti-oxidative, anti-glycative and anti-apoptotic effects of oleanolic acid in brain of mice treated by D-galactose.

Anti-oxidative, anti-glycative and anti-apoptotic effects of oleanolic acid in brain from D-galactose treated mice were examined. Oleanolic acid at 0.05%, 0.1% and 0.2% was supplied to mice for 10 wk. D-Galactose treatment increased reactive oxygen species and protein carbonyl levels (P<0.05), and reduced activity and protein production of glutathione peroxide, superoxide dismutase and catalase in mice brain (P<0.05). Oleanolic acid intake dose-dependently lowered reactive oxygen species and protein carbonyl levels (P<0.05), and retained activity and expression of these enzymes (P<0.05). Brain levels of carboxymethyllysine, pentosidine and methylglyoxal were significantly increased in D-galactose treated mice (P<0.05). Oleanolic acid intake significantly decreased the level of these parameters (P<0.05). D-Galactose treatments enhanced brain activity and protein expression of aldose reducatse (AR); and declined glyoxalase I (GLI) activity and expression (P<0.05). Oleanolic acid intake dose-dependently diminished AR activity and expression (P<0.05), only at 0.2% retained GLI activity and expression (P<0.05). D-Galactose treatment up-regulated the activity, mRNA expression and protein production of nuclear factor-κB (NF-κB) p65, Bax and cleaved caspase-3 (P<0.05), as well as suppressed Bcl-2 production (P<0.05). Oleanolic acid intake at 0.1% and 0.2% suppressed NF-κB p65, Bax and cleaved caspase-3 production, and retained Bcl-2 expression (P<0.05). These findings support that oleanolic acid may be a potent neuro-protective agent against aging.

Anti-inflammatory and antifibrotic effects of naringenin in diabetic mice.

Renal protective effects of naringenin at 0.5, 1, and 2% of the diet in diabetic mice were examined. Naringenin supplemented at 1 and 2% increased its deposit in liver and kidney of diabetic mice. Compared with the diabetic control group, naringenin treatments at 1 and 2% lowered plasma levels of glucose and blood urea nitrogen, as well as increased insulin level and creatinine clearance (P < 0.05). Naringenin treatments dose-dependently reduced renal tumor necrosis factor-α level and expression (P < 0.05) but only at 1 and 2% significantly decreased production and expression of interleukin (IL)-1ß, IL-6, and monocyte chemoattractant protein-1 (P < 0.05). Naringenin intake at 2% decreased renal formation and expression of type IV collagen, fibronectin, and transforming growth factor-ß1 (P < 0.05). This compound at 1 and 2% lowered protein kinase C activity and suppressed nuclear factor κB (NF-κB) p65 activity, mRNA expression, and protein production in kidney. However, this agent only at 2% diminished NF-κB p50 activity, mRNA expression, and protein production (P < 0.05). These results indicate that naringenin could attenuate diabetic nephropathy via its anti-inflammatory and antifibrotic activities.

Trans fatty acids enhanced ß-amyloid induced oxidative stress in nerve growth factor differentiated PC12 cells.

The effects of trans fatty acids, elaidic acid (trans-9, C18:1) and linoelaidic acid (trans-9, trans-12 C18:2), at 20 or 40 µM in nerve growth factor differentiated PC12 cells with or without beta-amyloid peptide (Aß) were examined. Elaidic acid treatment alone did not affect cell viability and oxidative injury associated markers (P > 0.05). However, co-treatments of elaidic acid and Aß led to more reduction in mitochondrial membrane potential (MMP) and Na⁺-K⁺-ATPase activity, and more increase in DNA fragmentation and 8-hydroxydeoxyguanosine (8-OHdG) production than Aß treatment alone (P < 0.05). Linoelaidic acid alone exhibited apoptotic and oxidative effects in cells via decreasing MMP and Na⁺-K⁺-ATPase activity, increasing reactive oxygen species (ROS) level, lowering glutathione content and glutathione peroxidase (GPX) activity (P < 0.05). The co-treatments of linoelaidic acid with Aß further enhanced oxidative damage via enhancing the generation of ROS, nitrite oxide and 8-OHdG, elevating caspase-3, caspase-8 and nitric oxide synthase activities, as well as declining GPX, catalase and superoxide dismutase activities (P < 0.05). These results suggested that the interaction of linoelaidic acid and Aß promoted oxidative stress and impaired mitochondrial functions in neuronal cells.

Antibiotic therapy for necrotizing fasciitis caused by Vibrio vulnificus: retrospective analysis of an 8 year period.

OBJECTIVES: To compare the effectiveness of a third-generation cephalosporin alone, a third-generation cephalosporin plus minocycline, and a fluoroquinolone in patients with necrotizing fasciitis (NF) caused by Vibrio vulnificus. METHODS: A retrospective review of case notes was performed for 89 patients who presented with NF caused by V. vulnificus and underwent surgical intervention within 24 h of admission between 2003 and 2010. Data on comorbidities, clinical manifestations, laboratory studies, treatments and outcomes were extracted for analysis. These patients were grouped according to the antimicrobials prescribed: those who received only a third-generation cephalosporin (Group 1; n = 18); a third-generation cephalosporin plus minocycline (Group 2; n = 49); or a fluoroquinolone with/without minocycline (Group 3; n = 22). RESULTS: The mean age of the 89 patients included in the study was 64.0 ± 12.0 years (range 33-89 years); 55% of the patients were male. There were no differences in age, sex or clinical characteristics among the three groups except that patients in Group 3 had a higher frequency of underlying chronic renal insufficiency than those in Groups 1 and 2 (P = 0.009). Groups 2 and 3 each had a significantly lower case fatality rate than Group 1 (61% in Group 1 versus 14% in Group 2, P = 0.0003; 61% in Group 1 versus 14% in Group 3, P = 0.0027), while no difference in case fatality rate was noted between Groups 2 and 3. CONCLUSIONS: Our data suggested that, in addition to primary surgery, fluoroquinolones or third-generation cephalosporins plus minocycline are the best option for antibiotic treatment of NF caused by V. vulnificus.

Preventive and therapeutic effects of caffeic acid against inflammatory injury in striatum of MPTP-treated mice.

Preventive or therapeutic effects of caffeic acid in brain of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treated mice against inflammatory injury were examined. Caffeic acid at 0.5, 1 or 2% was supplied either pre-intake or post-intake for 4 weeks. Brain caffeic acid content was increased by caffeic acid pre-intake at 1 and 2%, and post-intake at 2% (P < 0.05). MPTP treatment enhanced the release of interleukin (IL)-1beta, IL-6, tumor necrosis factor (TNF)-alpha, IL-4 and IL-10 (P < 0.05). Pre-intake of caffeic acid decreased the production of test cytokines (P < 0.05); however, post-intake only at 2% reduced the level of IL-1beta, IL-6 and TNF-alpha (P < 0.05). MPTP treatment up-regulated mRNA expression of inducible nitric oxide synthase (iNOS), neuronal NOS, cyclooxygenase (COX)-2, glial fibrillary acidic protein (GFAP) and ionized calcium binding adaptor molecule 1, and increased production of nitric oxide (NO) and prostaglandin E2 (PGE2) (P < 0.05). Caffeic acid pre-intake at test doses and post-intake at 2% declined the expression of iNOS, COX-2 and GFAP; and lowered the production of NO and PGE2 (P < 0.05). MPTP treatment suppressed mRNA expression of brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor and tyrosine hydroxylase (TH), and lowered dopamine level (P < 0.05). Caffeic acid pre-intake retained the expression of these factors, maintained TH activity and protein production, and dopamine synthesis (P < 0.05). These results suggest that caffeic acid is a potent neuroprotective agent against the development of Parkinson's disease.

Clinical outcomes and prognostic factors of cancer patients with pyogenic liver abscess.

PURPOSE: Pyogenic liver abscess (PLA) of cancer patients often has a poor prognosis, but corresponding prognostic factors are less investigated. This study aimed to identify predictors of mortality in cancer patients with PLA. PATIENTS AND METHODS: Medical records of 85 consecutive cancer patients (46 with hepatobiliary pancreatic cancer, 14 with gastrointestinal cancer, and 25 with non-digestive system cancer) having PLA who were admitted to two university hospitals were retrospectively reviewed. The predictors of mortality were determined using Cox regression model. RESULTS: The overall case fatality rate was 33%. In multivariate analysis, the greater Acute Physiology and Chronic Health Evaluation II score (P = 0.028), multiloculated abscess (P = 0.025), and polymicrobial infection (P = 0.003) were associated with mortality. In subgroup analysis of the 25 patients with multiloculated abscess undergoing percutaneous catheter drainage as primary treatment, the case fatality rates of patients with a solitary smaller abscess (size < 5 cm), those with a solitary larger abscess (size > 5 cm), and those with larger multiple abscesses were 0%, 36%, and 85%, respectively (P = 0.002; using χ (2) for trend). CONCLUSIONS: The advanced disease stage, multiloculated abscess, and polymicrobial infection posed a greater mortality risk in cancer patients with PLA. Moreover, an early surgical approach should be considered for cancer patients having large, multiloculated complex PLAs.

s-Allyl cysteine, s-ethyl cysteine, and s-propyl cysteine alleviate ß-amyloid, glycative, and oxidative injury in brain of mice treated by D-galactose.

The neuroprotective effects of s-allyl cysteine, s-ethyl cysteine, and s-propyl cysteine in D-galactose (DG)-treated mice were examined. DG treatment increased the formation of Aß(1-40) and Aß(1-42), enhanced mRNA expression of ß-amyloid precursor protein (APP) and ß-site APP cleavage enzyme 1 (BACE1), and reduced neprilysin expression in brain (P < 0.05); however, the intake of three test compounds significantly decreased the production of Aß(1-40) and Aß(1-42) and suppressed the expression of APP and BACE1 (P < 0.05). DG treatments declined brain protein kinase C (PKC) activity and mRNA expression (P < 0.05). Intake of test compounds significantly retained PKC activity, and the expression of PKC-α and PKC-γ (P < 0.05). DG treatments elevated brain activity and mRNA expression of aldose reductase (AR) and sorbitol dehydrogenase as well as increased brain levels of carboxymethyllysine (CML), pentosidine, sorbitol, and fructose (P < 0.05). Test compounds significantly lowered AR activity, AR expression, and CML and pentosidine levels (P < 0.05). DG treatments also significantly increased the formation of reactive oxygen species (ROS) and protein carbonyl and decreased the activity of glutathione peroxidase (GPX), superoxide dismutase (SOD), and catalase (P < 0.05); however, the intake of test compounds in DG-treated mice significantly decreased ROS and protein carbonyl levels and restored brain GPX, SOD, and catalase activities (P < 0.05). These findings support that these compounds via their anti-Aß, antiglycative, and antioxidative effects were potent agents against the progression of neurodegenerative disorders such as Alzheimer's disease.

Antiglycative effects of protocatechuic acid in the kidneys of diabetic mice.

Protocatechuic acid (PCA) at 2 or 4% was supplied to diabetic mice for 12 weeks. PCA treatments increased its deposit in organs and significantly reduced the plasma HbA1c level, the urinary glycative albumin level, and renal production of carboxymethyllysine (CML), pentosidine, sorbitol, and fructose (p < 0.05). However, PCA treatments only at 4% significantly decreased brain content of CML, pentosidine, fructose, and sorbitol (p < 0.05). PCA treatments at 2 and 4% significantly lowered renal activity and mRNA expression of aldose reductase and sorbitol dehydrogenase (p < 0.05), and PCA treatments only at 4% significantly enhanced renal glyoxalase I mRNA expression (p < 0.05). PCA treatments also dose-dependently decreased the renal level of type-IV collagen, fibronectin, and transforming growth factor-ß1 (p < 0.05), as well as dose-dependently diminished renal protein kinase C (PKC) activity (p < 0.05); however, PCA treatments only at 4% suppressed renal mRNA expression of PKC-α and PKC-beta (p < 0.05). PCA treatments at 4% significantly restored renal mRNA expression of peroxisome proliferator-activated receptor (PPAR)-α and PPAR-γ, as well as suppressed expression of the advanced glycation end-product receptor (p < 0.05). These findings suggest that the supplement of PCA might be helpful for the prevention or alleviation of glycation-associated diabetic complications.

Antioxidative and anti-inflammatory protection from carnosine in the striatum of MPTP-treated mice.

Mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were used to examine the neuroprotective effects of carnosine. Carnosine at 0.5, 1, and 2 g/L was directly added to the drinking water for 4 weeks. MPTP treatment significantly depleted striatal glutathione content, reduced the activity of glutathione peroxidase (GPX), superoxide dismutase (SOD), and catalase, increased malondialdehyde and reactive oxygen species levels, and elevated interleukin-6, nitrite, and tumor necrosis factor-α production as well as enhanced inducible nitric oxide synthase (iNOS) activity in the striatum (P < 0.05). The preintake of carnosine significantly attenuated MPTP-induced glutathione loss, retained the activity of GPX and SOD, diminished oxidative stress, and lowered inflammatory cytokines and nitrite levels as well as suppressed iNOS activity (P < 0.05). MPTP treatment significantly suppressed GPX mRNA expression and enhanced iNOS mRNA expression (P < 0.05). Carnosine preintake significantly elevated GPX mRNA expression and declined iNOS mRNA expression (P < 0.05). Preintake of carnosine also significantly improved MPTP-induced dopamine depletion and maintained 3,4-dihydroxyphenylacetic acid and homovanillic acid levels (P < 0.05). These results suggest that carnosine could provide antioxidative and anti-inflammatory protection for the striatum against the development of Parkinson's disease.

s-Ethyl cysteine and s-propyl cysteine alleviate beta-amyloid induced cytotoxicity in nerve growth factor differentiated PC12 cells.

Beta-amyloid peptide (Abeta) was used to induce cytotoxicity in nerve growth factor differentiated PC12 cells, and the effects of s-ethyl cysteine (SEC) and s-propyl cysteine (SPC) on anti-inflammatory protection, DNA fragmentation, mitochondrial membrane potential (MMP), and activity of Na(+)-K(+)-ATPase and caspases were examined. Abeta treatment significantly decreased cell viability and MMP, and increased lactate dehydrogenase (LDH) activity and DNA fragmentation (P < 0.05). The pretreatments from SEC or SPC at 2.5, 5, and 10 microM significantly enhanced cell viability and MMP, and lowered LDH activity and DNA fragmentation (P < 0.05). Abeta treatment also significantly decreased Na(+)-K(+)-ATPase activity and enhanced the activity of caspase-3 and caspase-8 (P < 0.05); however, the pretreatments from SEC or SPC significantly attenuated Abeta-induced reduction in Na(+)-K(+)-ATPase activity and elevation in caspase-3 and caspase-8 activities (P < 0.05). Abeta treatment increased the protein production and mRNA expression of interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha (P < 0.05). The pretreatments from SEC at 10 microM or SPC at 2.5, 5, and 10 microM significantly suppressed mRNA expression and decreased the protein production of these cytokines. These results suggested that SEC and SPC were potent neuroprotective agents against Alzheimer's disease.

Severity of disease as main predictor for mortality in patients with pyogenic liver abscess.

BACKGROUND: The purpose of this study was to explore the relationship between severity of illness at admission and mortality of patients with pyogenic liver abscess (PLA). METHODS: Medical records from 298 PLA patients > or =18 years old were reviewed. Severity of illness at admission was evaluated with the Acute Physiology and Chronic Health Evaluation (APACHE) II and the simplified acute physiology score (SAPS) II scoring systems. Stepwise logistic regression and receiver-operating-characteristic curve analyses were performed. RESULTS: The case-fatality rate was 10%. Multivariate analysis showed that APACHE II (P = .0004), SAPS II (P = .0008), the presence of gas-forming abscess (P <.0001), and the presence of anaerobic infection (P <.0001) all were associated with mortality. The area under the receiver-operating-characteristic curve was .884 (95% confidence interval .842 to .918) for APACHE II and .857 (95% confidence interval .812 to .895) for SAPS II, which were not significantly different (P = .490). The optimal cutoff APACHE II value of > or =15 had a sensitivity of 77% and a specificity of 92%, with a 20.3-fold risk of mortality (P <.0001). The SAPS II cutoff value of > or =28 had a sensitivity of 74% and a specificity of 82%, with a 7.2-fold risk of mortality (P = .008). CONCLUSIONS: Both the APACHE II and the SAPS II scoring methods are appropriate for assessing mortality of PLA patients.