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Journal of Diabetes Research 2016Recent studies have shown the positive association between increased circulating BCAAs (valine, leucine, and isoleucine) and insulin resistance (IR) in obese or diabetic... (Review)
Review
Recent studies have shown the positive association between increased circulating BCAAs (valine, leucine, and isoleucine) and insulin resistance (IR) in obese or diabetic patients. However, results seem to be controversial in different races, diets, and distinct tissues. Our aims were to evaluate the relationship between BCAA and IR as well as later diabetes risk and explore the phenotypic and genetic factors influencing BCAA level based on available studies. We performed systematic review, searching MEDLINE, EMASE, ClinicalTrials.gov, the Cochrane Library, and Web of Science from inception to March 2016. After selection, 23 studies including 20,091 participants were included. Based on current evidence, we found that BCAA is a useful biomarker for early detection of IR and later diabetic risk. Factors influencing BCAA level can be divided into four parts: race, gender, dietary patterns, and gene variants. These factors might not only contribute to the elevated BCAA level but also show obvious associations with insulin resistance. Genes related to BCAA catabolism might serve as potential targets for the treatment of IR associated metabolic disorders. Moreover, these factors should be controlled properly during study design and data analysis. In the future, more large-scale studies with elaborate design addressing BCAA and IR are required.
Topics: 3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); Adaptor Proteins, Signal Transducing; Amino Acids, Branched-Chain; Diabetes Mellitus; Diet; Genotype; Humans; Insulin Resistance; Metabolome; Minor Histocompatibility Antigens; Obesity; Phenotype; Pregnancy Proteins; Protein Phosphatase 2C; Racial Groups; Sex Factors; Transaminases; Weight Loss
PubMed: 27642608
DOI: 10.1155/2016/2794591 -
The Turkish Journal of Gastroenterology... Jul 2016The natural history of primary biliary cirrhosis (PBC) is extremely variable. The extraction and analysis of available information from placebo-treated patients in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND/AIMS
The natural history of primary biliary cirrhosis (PBC) is extremely variable. The extraction and analysis of available information from placebo-treated patients in randomized controlled trials of PBC treatment would facilitate the study of the natural history of PBC. The aim of the present study was to determine important clinical information regarding the natural history of PBC patients without effective treatment.
MATERIALS AND METHODS
A search of the PubMed, EMBASE and Cochrane Library databases was performed by two authors. Twelve randomized placebo-controlled clinical trials for PBC patients without decompensated cirrhosis were retrieved for further review. Pooled estimates of biochemical measurements, histological scores and clinical outcomes associated with PBC were calculated in the placebo group.
RESULTS
Placebo-treated PBC patients displayed a significant decrease in serum alkaline phosphatase and very slight fluctuations in the other biochemical parameters during the 2-year follow-up. Meanwhile, histological progression was observed in 39.4% of the placebo-treated patients, and a moderate deterioration in histological scores was noted after 2 years. The pooled 2-year rates of death, transplantation and development of varices were 11.4%, 8.7% and 10.6%, respectively, in placebo-treated PBC patients.
CONCLUSION
This review provides a foundation for further epidemiologic investigations in untreated patients and ursodeoxycholic acid-resistant patients with PBC. Biochemical responses after 2 years may provide some information on disease progression and therapeutic response in PBC.
Topics: Female; Humans; Male; Middle Aged; Alkaline Phosphatase; Cholagogues and Choleretics; Disease Progression; Liver Cirrhosis, Biliary; Randomized Controlled Trials as Topic; Treatment Outcome; Ursodeoxycholic Acid
PubMed: 27458850
DOI: 10.5152/tjg.2016.15535 -
Advances in Nutrition (Bethesda, Md.) Mar 2016Many studies have reported that olive oil-based lipid emulsion (LE) formulas of soybean oil, medium-chain triglycerides, olive oil, and fish oil (SMOF) may be a viable... (Comparative Study)
Comparative Study Meta-Analysis Review
Many studies have reported that olive oil-based lipid emulsion (LE) formulas of soybean oil, medium-chain triglycerides, olive oil, and fish oil (SMOF) may be a viable alternative for parenteral nutrition. However, some randomized controlled clinical trials (RCTs) have raised concerns regarding the nutritional benefits and safety of SMOFs. We searched principally the MEDLINE, Cumulative Index to Nursing and Allied Health Literature, Scopus, EMBASE, and Cochrane Central Register of Controlled Trials databases from inception to March 2014 for the relevant literature and conducted a meta-analysis of 15 selected RCTs that 1) compared either olive oil- or SMOF-based LEs with soybean oil-based LEs and 2) reported plasma concentrations of α-tocopherol, oleic acid, and ω-6 (n-6) and ω-3 (n-3) long-chain polyunsaturated fatty acids (PUFAs) and liver concentrations of total bilirubin and the enzymes alanine transaminase, aspartate transaminase, alkaline phosphatase, and γ-glutamyl transferase. The meta-analysis suggested that SMOF-based LEs were associated with higher plasma concentrations of plasma α-tocopherol, oleic acid, and the ω-3 PUFAs eicosapentaenoic and docosahexaenoic acid. Olive oil- and SMOF-based LEs correlated with lower plasma concentrations of long-chain ω-6 PUFAs and were similar to soybean oil-based LEs with regard to their effects on liver function indicators. In summary, olive oil- and SMOF-based LEs have nutritional advantages over soybean oil-based LEs and are similarly safe. However, their performance in clinical settings requires further investigation.
Topics: Deficiency Diseases; Evidence-Based Medicine; Fat Emulsions, Intravenous; Fatty Acids, Essential; Fish Oils; Humans; Olive Oil; Parenteral Nutrition; Randomized Controlled Trials as Topic; Soybean Oil
PubMed: 26980811
DOI: 10.3945/an.114.007427 -
Acta Pharmaceutica Sinica. B Nov 2015Cysteine proteases continue to provide validated targets for treatment of human diseases. In neurodegenerative disorders, multiple cysteine proteases provide targets for... (Review)
Review
Cysteine proteases continue to provide validated targets for treatment of human diseases. In neurodegenerative disorders, multiple cysteine proteases provide targets for enzyme inhibitors, notably caspases, calpains, and cathepsins. The reactive, active-site cysteine provides specificity for many inhibitor designs over other families of proteases, such as aspartate and serine; however, a) inhibitor strategies often use covalent enzyme modification, and b) obtaining selectivity within families of cysteine proteases and their isozymes is problematic. This review provides a general update on strategies for cysteine protease inhibitor design and a focus on cathepsin B and calpain 1 as drug targets for neurodegenerative disorders; the latter focus providing an interesting query for the contemporary assumptions that irreversible, covalent protein modification and low selectivity are anathema to therapeutic safety and efficacy.
PubMed: 26713267
DOI: 10.1016/j.apsb.2015.08.001 -
Drug Design, Development and Therapy 2015Ursodeoxycholic acid (UDCA) is the standard treatment for primary biliary cirrhosis (PBC), but not all cases respond well. Evidence has shown that combination therapy of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIM
Ursodeoxycholic acid (UDCA) is the standard treatment for primary biliary cirrhosis (PBC), but not all cases respond well. Evidence has shown that combination therapy of UDCA with bezafibrate significantly improved liver function. A meta-analysis was performed to assess the efficacy and safety of UDCA and bezafibrate combination therapy in the treatment of PBC.
RESULTS
Nine trials, with a total of 269 patients, were included in the analysis. The bias risk of these trials was high. Compared with UDCA alone, the combination with bezafibrate improved the Mayo risk score (mean difference [MD], 0.60; 95% confidence interval [CI], 0.25-0.95; P=0.0008) and liver biochemistry: alkaline phosphatase (MD, -238.21 IU/L; 95% CI, -280.83 to -195.60; P<0.00001); gamma-glutamyltransferase (MD, -38.23 IU/L; 95% CI, -50.16 to -25.85; P<0.00001); immunoglobulin M (MD, -128.63 IU/L; 95% CI, -151.55 to -105.71; P<0.00001); bilirubin (MD, -0.20 mg/dL; 95% CI, -0.33 to -0.07; P=0.002); triglycerides (MD, -26.84 mg/dL; 95% CI, -36.51 to -17.17; P<0.0001); total cholesterol (MD, -21.58 mg/dL; 95% CI, -30.81 to -12.34; P<0.0001), and serum alanine aminotransferase (MD, -10.24 IU/L; 95% CI, -12.65 to -78.5; P<0.00001). However, combination therapy showed no significant differences in the incidence of all-cause mortality or pruritus, and may have resulted in more adverse events (risk ratio [RR], 0.22; 95% CI, 0.07-0.67; P=0.008).
CONCLUSION
Combination therapy improved liver biochemistry and the prognosis of PBC, but did not improve clinical symptoms or incidence of death. Attention should be paid to adverse events when using bezafibrate.
Topics: Bezafibrate; Biomarkers; Chi-Square Distribution; Drug Therapy, Combination; Humans; Liver; Liver Cirrhosis, Biliary; Odds Ratio; Risk Factors; Treatment Outcome; Ursodeoxycholic Acid
PubMed: 26491252
DOI: 10.2147/DDDT.S92041 -
Drug Design, Development and Therapy 2015Although the effectiveness of treatment with ursodeoxycholic acid (UDCA) and fenofibrate for primary biliary cirrhosis (PBC) has been suggested by small trials, a... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
Although the effectiveness of treatment with ursodeoxycholic acid (UDCA) and fenofibrate for primary biliary cirrhosis (PBC) has been suggested by small trials, a systematic review to summarize the evidence has not yet been carried out.
METHODS
A meta-analysis of all long-term randomized controlled trials comparing the combination of UDCA and fenofibrate with UDCA monotherapy was performed via electronic searches.
RESULTS
Six trials, which included 84 patients, were assessed. Combination therapy with UDCA and fenofibrate was more effective than UDCA monotherapy in improving alkaline phosphatase (mean difference [MD]: -90.44 IU/L; 95% confidence interval [CI]: -119.95 to -60.92; P<0.00001), gamma-glutamyl transferase (MD: -61.58 IU/L; 95% CI: -122.80 to -0.35; P=0.05), immunoglobulin M (MD: -38.45 mg/dL; 95% CI: -64.38 to -12.51; P=0.004), and triglycerides (MD: -0.41 mg/dL; 95% CI: -0.82 to -0.01; P=0.05). However, their effects on pruritus (odds ratio [OR]: 0.39; 95% CI: 0.09-1.78; P=0.23), total bilirubin (MD: -0.05 mg/dL; 95% CI: -0.21 to 0.12; P=0.58), and alanine aminotransferase (MD: -3.31 IU/L; 95% CI: -14.60 to 7.97; P=0.56) did not differ significantly. This meta-analysis revealed no significant differences in the incidence of adverse events (OR: 0.21; 95% CI: 0.03-1.25; P=0.09) between patients treated with combination therapy and those treated with monotherapy.
CONCLUSION
In this meta-analysis, combination therapy with UDCA and fenofibrate was more effective in reducing alkaline phosphatase than UDCA monotherapy, but it did not improve clinical symptoms. There did not appear to be an increase in adverse events with combination therapy.
Topics: Cholagogues and Choleretics; Drug Therapy, Combination; Fenofibrate; Humans; Hypolipidemic Agents; Liver Cirrhosis, Biliary; Middle Aged; Randomized Controlled Trials as Topic; Ursodeoxycholic Acid
PubMed: 26045661
DOI: 10.2147/DDDT.S79837 -
BMC Infectious Diseases May 2015Mycobacterium tuberculosis (TB) infection of the liver, known as hepatic TB, is an extrapulmonary manifestation of TB. Hepatic TB has become more prevalent, likely as a... (Review)
Review
BACKGROUND
Mycobacterium tuberculosis (TB) infection of the liver, known as hepatic TB, is an extrapulmonary manifestation of TB. Hepatic TB has become more prevalent, likely as a result of the human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) epidemic. We sought to review case series to characterize the epidemiology, pathophysiology, clinical features, diagnosis, and treatment of hepatic TB and to comment on the impact of HIV co-infection on these characteristics.
METHODS
We conducted a systematic literature search in PubMed and ScienceDirect for articles pertaining to hepatic TB with human subjects from 1960 to July 2013.
RESULTS
We obtained data on 618 hepatic TB patients from 14 case series. The most common reported signs and symptoms were hepatomegaly (median: 80%, range: 10-100%), fever (median: 67%, range: 30-100), respiratory symptoms (median: 66%, range: 32-78%), abdominal pain (median: 59.5%, range: 40-83%), and weight loss (median: 57.5%, range: 20-100%). Common laboratory abnormalities were elevated alkaline phosphatase and gamma-glutamyl transferase. Ultrasound and computerized tomography (CT) were sensitive but non-specific. On liver biopsy, smear microscopy for acid-fast bacilli had a median sensitivity of 25% (range: 0-59%), histology of caseating granulomas had a median sensitivity of 68% (range: 14-100%), and polymerase chain reaction for TB had a median sensitivity of 86% (range: 30-100%). Standard anti-tuberculous chemotherapy for 6 to 12 months achieved positive outcomes for nearly all patients with drug-susceptible TB.
CONCLUSIONS
Clinicians in TB-endemic regions should maintain a high index of suspicion for hepatic TB in patients presenting with hepatomegaly, fever, respiratory symptoms, and elevated liver enzymes. The most sensitive imaging modality is a CT scan, while the most specific diagnostic modality is a liver biopsy with nucleic acid testing of liver tissue samples. Upon diagnosis, 4-drug anti-TB therapy should promptly be initiated. HIV co-infected patients may have more complex cases and should be closely monitored for complications.
Topics: Acquired Immunodeficiency Syndrome; Coinfection; Global Health; Humans; Mycobacterium tuberculosis; Nucleic Acid Amplification Techniques; Prevalence; Tuberculosis, Hepatic
PubMed: 25943103
DOI: 10.1186/s12879-015-0944-6 -
Clinical Orthopaedics and Related... Dec 2014Identification of biomarkers associated with wear and tribocorrosion in joint arthroplasty would be helpful to enhance early detection of aseptic loosening and/or... (Review)
Review
BACKGROUND
Identification of biomarkers associated with wear and tribocorrosion in joint arthroplasty would be helpful to enhance early detection of aseptic loosening and/or osteolysis and to improve understanding of disease progression. There have been several new reports since the last systematic review (which covered research through mid-2008) justifying a new assessment.
QUESTIONS/PURPOSES
We sought to determine which biomarkers have the most promise for early diagnosis and monitoring of aseptic loosening and/or osteolysis related to wear or corrosion in total joint arthroplasty.
METHODS
We performed a systematic review using MEDLINE and EMBASE databases, covering the period through December 2013, and identified 1050 articles. We restricted the definition of biomarker to biomolecules and imaging parameters useful for diagnosis and monitoring of disease progression, only including articles in English. We chose 65 articles for full review, including 44 from the original search and 21 from subsequent hand searches. We used the 22 articles in which patients with total joint arthroplasty who had aseptic loosening and/or periimplant osteolysis unrelated to sepsis had been compared with patients with total joint arthroplasty with stable implants. There were 90 comparisons of these two patient populations involving 35 different biomarkers.
RESULTS
Diagnostic accuracy was assessed in nine of the 90 comparisons with the highest accuracy found for tartrate-resistant acid phosphatase 5b (0.96), although a separate comparison for this biomarker found a lower accuracy (0.76). Accuracy of > 0.80 was also found for crosslinked n-telopeptide of type I collagen, osteoprotegerin, and deoxypyridinoline. The most studied markers, tumor necrosis factor-α and interleukin-1β, were found to differ in the affected and control groups in < 30% of the comparisons. Thirty of the 35 biomarkers were studied in four or fewer separate comparisons with nearly half of the biomarkers (17) studied in only one comparison. Many of the comparisons were not able to eliminate a number of confounding variables, and there was only one prospective study.
CONCLUSIONS
Currently, there are no validated biomarkers for early diagnosis and monitoring of the biological sequelae of wear or tribocorrosion, although there are some promising leads, including markers of bone turnover.
Topics: Arthroplasty, Replacement; Biomarkers; Biomechanical Phenomena; Corrosion; Diagnostic Imaging; Humans; Joint Prosthesis; Joints; Osteolysis; Predictive Value of Tests; Prosthesis Design; Prosthesis Failure; Risk Factors; Stress, Mechanical; Treatment Outcome
PubMed: 24668073
DOI: 10.1007/s11999-014-3580-3