ABSTRACT
BACKGROUND: Several experimental studies have suggested beneficial effects of Ceriporia lacerata on glucose metabolism. However, there has been no human study assessing the effects of C. lacerata on glucose metabolism. Therefore, we investigated whether C. lacerata improves glucose control and insulin resistance in type 2 diabetes patients. METHODS: Ninety patients diagnosed with type 2 diabetes (T2DM) for more than 6 months were enrolled. Subjects were randomly divided into placebo (n = 45) or C. lacerata (n = 45) groups and then assigned to take placebo or C. lacerata capsules (500 mg/capsule) for a 12-week intervention period. Biochemical markers, including fasting glucose, 2-hour postprandial plasma glucose, and lipid profile levels, as well as insulin, c-peptide, and Hba1c, were measured. Furthermore, insulin sensitivity indices, such as HOMA-IR, HOMA-beta, and QUICKI, were assessed before and after the 12-week administration. RESULTS: Eighty-four patients completed the study. There were no significant differences in fasting, postprandial glucose, HbA1c, or lipid parameters. HOMA-IR and QUICKI indices were improved at week 12 in the C. lacerata group, especially in subjects with HOMA-IR of 1.8 or more (p < 0.05). Fasting, postprandial c-peptide, and insulin levels decreased at week 12 in the C. lacerata group (p < 0.05). These significant differences were not observed in the placebo group. CONCLUSION: Twelve-week administration of C. lacerata in T2DM patients resulted in significant improvement in insulin resistance, especially in those with lower insulin sensitivity. A larger population study with a longer follow-up period and an effort to elucidate the mechanism is warranted to further assess the effects of C. lacerata on T2DM patients.
Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Insulin Resistance/physiology , Plant Extracts/pharmacology , Polyporales/metabolism , Adult , Blood Glucose/metabolism , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/physiopathology , Female , Glycated Hemoglobin/metabolism , Humans , Insulin/blood , Male , Middle Aged , Plant Extracts/metabolism , Plant Extracts/therapeutic useABSTRACT
INTRODUCTION: The German rectal study published in 2004 established neoadjuvant chemoradiation as a standard of care for locally advanced rectal cancer and current National Comprehensive Cancer Network guidelines endorse several preoperative regimens. Upfront surgery, however, is considered substandard care. In the era of evolving treatment paradigms for locally advanced rectal cancer, we sought to assess trends and predictors of receipt of upfront surgery for stage II to III rectal cancer. METHODS: The National Cancer Database was used to identify patients diagnosed with clinical stage II to III rectal adenocarcinoma between 2006 and 2016. Multivariable logistic regression defined adjusted odds ratios and associated 95% confidence intervals of receipt of upfront definitive surgery. The timing of upfront surgery relative to day of diagnosis and rate of receipt of adjuvant therapy were also estimated. RESULTS: Among 51,562 patients, 6411 (12.4%) were treated with upfront surgery, which decreased from 16.7% in 2006 to 7.1% in 2016 (P<0.001). The majority of patients (5737 [89.5%]) had definitive surgery after initial diagnostic biopsy. Variables associated with receipt of upfront surgery included female sex, older age, higher comorbidity score, and treatment at a community cancer center (P<0.001). Among those receiving upfront surgery, 2904 (45.3%) received adjuvant radiation therapy, 3218 (50.2%) received adjuvant chemotherapy, and 2559 (39.9%) received no further treatment. CONCLUSIONS: The proportion of patients with clinical stage II to III rectal cancer treated with upfront surgery has steadily declined since 2006, however, certain subgroups appear to remain at greater risk. Further research is needed to better elucidate patient and systems-level factors contributing to these disparities in care.
Subject(s)
Adenocarcinoma/surgery , Digestive System Surgical Procedures/mortality , Rectal Neoplasms/surgery , Time-to-Treatment/statistics & numerical data , Time-to-Treatment/trends , Adenocarcinoma/pathology , Adult , Aged , Aged, 80 and over , Cohort Studies , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Staging , Rectal Neoplasms/pathology , Survival RateABSTRACT
BACKGROUND AND AIMS: Coffee is known to have a beneficial effect on various liver diseases. The aim of this retrospective longitudinal study was to investigate an association between the amount of coffee consumption and the incidence of fatty liver disease in Korean adults. METHODS AND RESULTS: Data from a total of 91,436 male and female subjects with the mean follow-up period of 2.8 years were analyzed. The incidence of fatty liver was not associated with the amount of coffee consumption at baseline, but it was associated with the change in the amount of coffee consumption at the follow-up period. Multiple linear regression analyses showed that hazard ratios for incidence of fatty liver disease were significantly low in "increase" group comparing with "no change" group in fully adjusted model. When a subgroup analysis by gender was conducted, similar significant results were observed in male subjects, but not in females. CONCLUSIONS: The increment in the amount of coffee consumption is associated with the lower incidence of fatty liver in Korean men and suggests that increasing the coffee consumption may have a protective effect on fatty liver.
Subject(s)
Coffee , Fatty Liver/prevention & control , Adult , Fatty Liver/diagnosis , Fatty Liver/epidemiology , Female , Humans , Incidence , Longitudinal Studies , Male , Middle Aged , Protective Factors , Retrospective Studies , Risk Factors , Seoul/epidemiology , Sex FactorsABSTRACT
BACKGROUND: The elderly population is growing rapidly worldwide and sarcopenia, which is considered as a new geriatric syndrome has become an important issue. In particular, diabetes is known to be an important risk factor for sarcopenia. In this study, we investigated the effects of Korean Red Ginseng (KRG) on biomarkers of sarcopenia in middle and old age diabetes patients. PATIENTS AND METHODS: This study was a randomized, double-blind, placebo-controlled trial. Participants were randomly allocated to either the placebo or KRG group and took corresponding tablets for 24 weeks. The primary outcomes were changes in sarcopenia biomarkers at week 24. Secondary outcomes were changes in inflammatory and antioxidant markers and lean body mass at week 24. RESULTS: Fifty-nine patients completed the study. Follistatin and sex hormone binding globulin (SHBG) were significantly improved in KRG group. In the subgroup analysis, female postmenopausal patients over the age of 55 showed a significant improvement in serum SHBG, follistatin, and growth differentiation factor 15 (GDF-15) and an attenuated reduction in Troponin T (TNT) after the administration of KRG. CONCLUSION: Twenty-four week administration of KRG in diabetes patients resulted in a significant improvement in follistatin and SHBG levels, especially in old postmenopausal women. A further, larger population study with a longer follow-up period is warranted to verify and understand the effects of KRG on sarcopenia.
Subject(s)
Diabetes Mellitus, Type 2 , Panax , Sarcopenia , Aged , Biomarkers , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Female , Humans , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Sarcopenia/drug therapyABSTRACT
BACKGROUND: Many Type 2 diabetes (T2DM) patients in Korea take Korean Red Ginseng (KRG) for various reasons. In this study, we investigated the effects of KRG administration on diabetic peripheral neuropathy in T2DM patients. METHODS: This study was a randomized, double-blind, placebo-controlled trial. Participants were randomly allocated to either the placebo or KRG group and took corresponding tablets for 24 weeks. The primary outcomes were changes in current perception threshold (CPT) at week 24. Secondary outcomes were altered fasting plasma glucose, HbA1c, and various metabolic and inflammatory markers at week 24. RESULTS: Sixty-one patients completed the study. The CPT of the lower extremities at various frequencies exhibited significant improvements at week 24 in the KRG group. Other metabolic parameters were not altered after 24 weeks in both groups. In the subgroup analysis, CPT levels were improved in those with a longer diabetes duration or who already had neuropathy at the beginning of the study, and insulin resistance was improved in patients with a shorter diabetes duration. CONCLUSION: Twenty-four week administration of KRG in T2DM patients resulted in a significant improvement in neuropathy, especially in those with a longer diabetes duration. A further, larger population study with a longer follow-up period is warranted to verify the effects of KRG on diabetic neuropathy.
Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Diabetic Neuropathies/drug therapy , Medicine, Korean Traditional , Panax , Plant Extracts/therapeutic use , Sensory Thresholds/physiology , Touch Perception/physiology , Aged , Blood Glucose , Diabetes Mellitus, Type 2/physiopathology , Diabetic Neuropathies/physiopathology , Double-Blind Method , Female , Humans , Insulin Resistance/physiology , Male , Middle Aged , Treatment OutcomeABSTRACT
BACKGROUND: Metformin can cause serum vitamin B12 deficiency, but studies on the influence of its duration and dose are lacking. We investigated vitamin B12 deficiency in patients with type 2 diabetes using metformin, in conjunction with other related factors. METHOD: This cross-sectional study included 1111 patients with type 2 diabetes who took metformin for at least 6 months. Serum vitamin B12 levels were quantified using a competitive-binding immunoenzymatic assay, and vitamin B12 deficiency was defined as serum B12 <300âpg/mL. Information on metformin use and confounding variables were collected from records or questionnaires and interviews. RESULT: Serum vitamin B12 deficiency occurred in 22.2% of patients (nâ=â247). After adjusting for confounders, a 1âmg increase in daily metformin dose was associated with a 0.142âpg/mL decrease in vitamin B12 (Pâ<â.001). Compared with a daily dose of <1000âmg, the adjusted odds ratios for 1000 to 1500, 1500 to 2000, and ≥2000âmg metformin were 1.72 (Pâ=â.080), 3.34 (Pâ<â.001), and 8.67 (Pâ<â.001), respectively. Vitamin B12 deficiency occurred less often in patients taking multivitamins (odds ratio 0.23; Pâ<â.001). After adjusting for confounding factors, there was no correlation between B12 deficiency and duration of metformin use. Serum homocysteine levels showed significant negative correlation with vitamin B12. CONCLUSION: Metformin at ≥1500âmg/d could be a major factor related to vitamin B12 deficiency, whereas concurrent supplementation of multivitamins may potentially protect against the deficiency. Serum homocysteine levels were negatively correlated with vitamin B12 levels, suggesting that B12 deficiency due to metformin use may occur at the tissue level. However, this hypothesis will require further study.
Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/therapeutic use , Metformin/therapeutic use , Vitamin B 12 Deficiency/chemically induced , Age Factors , Aged , Alcohol Drinking/epidemiology , Anemia/epidemiology , Cross-Sectional Studies , Diabetes Mellitus, Type 2/epidemiology , Dose-Response Relationship, Drug , Female , Folic Acid/blood , Homocysteine/blood , Humans , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/adverse effects , Male , Metformin/administration & dosage , Metformin/adverse effects , Middle Aged , Odds Ratio , Republic of Korea , Time Factors , Vitamin B 12/blood , VitaminsSubject(s)
Cancer Survivors/psychology , Cancer Survivors/statistics & numerical data , Complementary Therapies/psychology , Complementary Therapies/statistics & numerical data , Disclosure , Neoplasms/psychology , Neoplasms/therapy , Physician-Patient Relations , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Patient Compliance , United States , Young AdultABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Korean red ginseng (KRG) has been traditionally used to treat diabetes. Ginsenosides are considered as the major bioactive components mediating anti-diabetic effects of KRG. However, considering that ginsenosides account for only about 3-4% of ginsengs, other fractions of KRG may also carry potential anti-diabetic effects. There is no study reporting the differentiated effects of ginsenosides (Spn) and non-saponin fractions (NSpn) of KRG on glycemic control. AIM OF THE STUDY: We investigated the effects of KRG, Spn, and NSpn on the indications of glycemic control and sought to elucidate physiological factors contributing their effects. MATERIALS AND METHODS: Human T2DM mimicking Nagoya-Shibata-Yasuda (NSY/hos) mice were given KRG, Spn, or NSpn admixed in rodent diet at 200â¯mg/kg/day for 24 weeks. Glycemic and obesity indications, blood lipid profile, systematic and local oxidative stress markers in metabolically important organs, and systematic inflammatory markers were assessed. Molecular assessments associated with glycemic control in liver and skeletal muscle were further performed. RESULTS: KRG attenuated deterioration in glucose homeostasis as evidenced by significantly lower fasting blood glucose from 22nd week and AUC during GTT at the end of the experiment compare to control. Spn enhanced insulin secretion in response to glucose stimulation and reduced protein level of glycogen phosphorylase in liver. On the other hand, NSpn ameliorated oxidative stress and inflammation. Some beneficial effects of Spn and NSpn were reflected in KRG treated mice. KRG also attenuated the accumulation of malondialdehyde in skeletal muscle and, accordingly, enhanced insulin responsiveness compare to control. CONCLUSION: Anti-diabetic properties of KRG are not solely determined by the contents of ginsenosides but the harmonic functions of its different fractions.
Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/pharmacology , Panax/chemistry , Plant Extracts/pharmacology , Animals , Blood Glucose/drug effects , Diabetes Mellitus, Type 2/blood , Disease Models, Animal , Drug Evaluation, Preclinical , Ginsenosides/isolation & purification , Ginsenosides/pharmacology , Humans , Hypoglycemic Agents/isolation & purification , Hypoglycemic Agents/therapeutic use , Male , Medicine, Chinese Traditional/methods , Mice , Mice, Inbred Strains , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Plant Extracts/therapeutic use , Treatment OutcomeABSTRACT
Both sorafenib and mammalian target of rapamycin inhibitor (mTORi) have antitumor effects. This study aimed to evaluate their antitumor effects in liver transplantation (LT) recipients with hepatocellular carcinoma (HCC) recurrence. We performed a laboratory study using sorafenib and mTORi and subsequently validated their survival benefit in a clinical LT setting. In the laboratory study, the HepG2.2.15 liver tumor cell line and 5 patient-derived graft HCC cell lines were used for in vitro cytotoxic studies. After treatment with everolimus and sorafenib, cell viability and apoptosis assays revealed noticeable cytotoxic effects with individual agents and augmented effects by combination therapy. An in vivo mouse study also demonstrated similar cytotoxic outcomes. In the clinical study including 232 LT recipients with HCC recurrence, the 3-month medication drop-out rate was 35.6% for sorafenib administration and 23.5% for mTORi administration. Postrecurrence survival rates were not different according to sorafenib administration (P = 0.17) but were significantly improved following mTORi administration (P < 0.001). In mTORi subgroups with and without sorafenib, there was no difference in the overall postrecurrence patient survival period (P = 0.26), indicating an absence of synergistic or additional antitumor effect from sorafenib. The median progression-free and overall survival period was 6.4 and 11.8 months, respectively, after sorafenib administration. Time of tumor recurrence and use of mTORi were independent risk factors. In conclusion, our laboratory study demonstrated synergistic antitumor effects of sorafenib and mTORi, but this was not reproduced in our clinical LT study. Our clinical result of mTORi administration showed improved postrecurrence survival, thus administering mTORi in LT recipients with HCC recurrence appears worthwhile. However, the antitumor effect of sorafenib on posttransplant recurrence was not determined in this retrospective study, thus requiring further studies with early start of sorafenib administration. Liver Transplantation 24 932-945 2018. © 2018 AASLD.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Hepatocellular/drug therapy , Liver Neoplasms/drug therapy , Liver Transplantation , Neoplasm Recurrence, Local/drug therapy , Sorafenib/therapeutic use , TOR Serine-Threonine Kinases/antagonists & inhibitors , Animals , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/surgery , Cell Survival/drug effects , Female , Hep G2 Cells , Humans , Liver Neoplasms/mortality , Liver Neoplasms/surgery , Male , Mice, Inbred NOD , Mice, Nude , Mice, SCID , Middle Aged , Neoplasm Recurrence, Local/mortality , Postoperative Period , Progression-Free Survival , Retrospective Studies , Survival Analysis , Time Factors , Xenograft Model Antitumor AssaysABSTRACT
PURPOSE: The purpose of this study was to examine the efficacy and safety of adding ω-3 fatty acids to rosuvastatin in patients with residual hypertriglyceridemia despite statin treatment. METHODS: This study was a multicenter, randomized, double-blind, placebo-controlled study. After a 4-week run-in period of rosuvastatin treatment, the patients who had residual hypertriglyceridemia were randomized to receive rosuvastatin 20 mg/d plus ω-3 fatty acids 4 g/d (ROSUMEGA group) or rosuvastatin 20 mg/d (rosuvastatin group) with a 1:1 ratio and were prescribed each medication for 8 weeks. FINDINGS: A total of 201 patients were analyzed (mean [SD] age, 58.1 [10.7] years; 62.7% male). After 8 weeks of treatment, the percentage change from baseline in triglycerides (TGs) and non-HDL-C was significantly greater in the ROSUMEGA group than in the rosuvastatin group (TGs: -26.3% vs -11.4%, P < 0.001; non-HDL-C: -10.7% vs -2.2%, P = 0.001). In the linear regression analysis, the lipid-lowering effect of ω-3 fatty acids was greater when baseline TG or non-HDL-C levels were high and body mass index was low. The incidence of adverse events was not significantly different between the 2 groups. IMPLICATIONS: In patients with residual hypertriglyceridemia despite statin treatment, a combination of ω-3 fatty acids and rosuvastatin produced a greater reduction of TGs and non-HDL-C than rosuvastatin alone. Further study is needed to determine whether the advantages of this lipid profile of ω-3 fatty acids actually leads to the prevention of cardiovascular event. ClinicalTrials.gov identifier: NCT03026933.
Subject(s)
Docosahexaenoic Acids/therapeutic use , Eicosapentaenoic Acid/therapeutic use , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Hypertriglyceridemia/drug therapy , Rosuvastatin Calcium/therapeutic use , Aged , Docosahexaenoic Acids/adverse effects , Double-Blind Method , Drug Combinations , Drug Therapy, Combination , Eicosapentaenoic Acid/adverse effects , Female , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Male , Middle Aged , Rosuvastatin Calcium/adverse effects , Treatment OutcomeABSTRACT
We investigated the anti-lipogenic effect of betaine in rats fed methionine and choline-deficient diet (MCD). Intake of MCD for 3 wk resulted in a significant accumulation of hepatic lipids, which was prevented by betaine supplementation in drinking water (1%). Phosphorylation of AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC), sterol regulatory element-binding protein-1c (SREBP-1c), and liver kinase B1 (LKB1) was inhibited by MCD intake, and these changes were all inhibited by betaine feeding. Meanwhile, betaine supplementation reversed the reduction of methionine and S-adenosylmethionine (SAM), and the elevation of homocysteine levels in the liver, which could be attributable to the induction of betaine-homocysteine methyltransferase (BHMT) and methionine adenosyltransferase (MAT). Different cell lines were used to clarify the role of homocysteine on activation of the AMPK pathway. Homocysteine treatment decreased pAMPK, pACC, pSREBP-1c and pLKB1 in HepG2 cells. Metformin-induced activation of AMPK was also inhibited by homocysteine. Treatment with hydroxylamine, a cystathionine ß-synthase inhibitor, resulted in a reduction of pAMPK, pACC and pSREBP-1c, accompanied by an elevation of intracellular homocysteine. Betaine treatment prevented the homocysteine-induced reduction of pAMPK, pACC, pSREBP-1c and pLKB1 in H4IIE cells, but not in HepG2 cells. Also the elevation of cellular homocysteine and inhibition of protein expression of BHMT were prevented by betaine only in H4IIE cells which express BHMT. The results suggest that the beneficial effect of betaine against hepatic lipid accumulation may be attributed, at least in part, to the depletion of homocysteine via up-regulation of BHMT in hepatocytes.
Subject(s)
Betaine-Homocysteine S-Methyltransferase/metabolism , Betaine/metabolism , Dietary Fats/metabolism , Homocysteine/metabolism , Liver/metabolism , Up-Regulation , Animals , Humans , Male , Rats , Rats, Sprague-DawleyABSTRACT
INTRODUCTION: The aim of the study was to investigate predictors of mortality in patients hospitalized with hyperkalemia. MATERIAL AND METHODS: Data among hospitalized patients with hyperkalemia (serum potassium ≥ 5.1 mEq/l) were collected. Patients with end-stage renal disease on dialysis were excluded. RESULTS: Of 15,608 hospitalizations, 451 (2.9%) episodes of hyperkalemia occurred in 408 patients. In patients with hyperkalemia, chronic kidney disease, hypertension, diabetes, coronary artery disease and heart failure were common comorbidities. Acute kidney injury (AKI) and metabolic acidosis were common metabolic abnormalities, and 359 patients (88%) were on at least one drug associated with hyperkalemia. Mean duration to resolution of hyperkalemia was 12 ±9.9 h. Nonsteroidal anti-inflammatory drugs (HR = 1.59), highest potassium level (HR = 0.61), tissue necrosis (HR = 0.61), metabolic acidosis (HR = 0.77), and AKI (HR = 0.77) were significant independent determinants of duration prior to hyperkalemia resolution. Tissue necrosis (OR = 4.55), potassium supplementation (OR = 5.46), metabolic acidosis (OR = 4.84), use of calcium gluconate for treatment of hyperkalemia (OR = 4.62), AKI (OR = 3.89), and prolonged duration of hyperkalemia (OR = 1.06) were significant independent predictors of in-hospital mortality. CONCLUSIONS: Tissue necrosis, potassium supplementation, metabolic acidosis, calcium gluconate for treatment of hyperkalemia, AKI and prolonged duration of hyperkalemia are independent predictors of in-hospital mortality.
ABSTRACT
Black raspberry (Rubus occidentalis) has been known for its anti-inflammatory and anti-oxidant effects. However, short-term effects of black raspberry on lipid profiles and vascular endothelial function have not been investigated in patients with metabolic syndrome. Patients with metabolic syndrome (n = 77) were prospectively randomized into a group with black raspberry (n = 39, 750 mg/day) and a placebo group (n = 38) during a 12-week follow-up. Lipid profiles, brachial artery flow-mediated dilatation (baFMD), and inflammatory cytokines such as IL-6, TNF-α, C-reactive protein, adiponectin, sICAM-1, and sVCAM-1 were measured at the baseline and at the 12-week follow-up. Decreases from the baseline in the total cholesterol level (-22.8 ± 30.4 mg/dL vs. -1.9 ± 31.8 mg/dL, p < 0.05, respectively) and total cholesterol/HDL ratio (-0.31 ± 0.64 vs. 0.07 ± 0.58, p < 0.05, respectively) were significantly greater in the group with black raspberry than in the placebo group. Increases in baFMD at the 12-week follow-up were significantly greater in the group with black raspberry than in the placebo group (0.33 ± 0.44 mm vs. 0.10 ± 0.35 mm, p < 0.05, respectively). Decreases from the baseline in IL-6 (-0.4 ± 1.5 pg/mL vs. -0.1 ± 1.0 pg/mL, p < 0.05, respectively) and TNF-α (-2.9 ± 4.7 pg/mL vs. 0.1 ± 3.6 pg/mL, p < 0.05, respectively) were significantly greater in the group with black raspberry. The use of black raspberry significantly decreased serum total cholesterol level and inflammatory cytokines, thereby improving vascular endothelial function in patients with metabolic syndrome during the 12-week follow-up.
Subject(s)
Endothelium, Vascular/drug effects , Lipids/blood , Metabolic Syndrome/blood , Rubus/chemistry , Ankle Brachial Index , Brachial Artery/drug effects , Carotid Intima-Media Thickness , Cytokines/blood , Dilatation , Double-Blind Method , Female , Humans , Inflammation/metabolism , Male , Metabolic Syndrome/drug therapy , Middle AgedABSTRACT
BACKGROUND: Studies support efficacy of ultraviolet (UV)A1 phototherapy, but little is known about recurrence after successful UVA1 treatment. OBJECTIVE: We sought to determine the frequency of recurrent activity after UVA1 phototherapy and variables associated with recurrence. METHODS: This was a case series and prospective cohort study of patients treated with UVA1 phototherapy with minimum 6 months of follow-up. Demographics, clinical features, and cumulative UVA1 dose were analyzed for association with recurrence. RESULTS: Of 37 patients, 46% (n = 17) had recurrence of active morphea lesions after successful UVA1 phototherapy. Two-year and 3-year (after the last UVA1 phototherapy treatment) recurrence rates were 44.5% (95% confidence interval 30.1%-62.2%) and 48.4% (95% confidence interval 33.2%-66.1%), respectively. The only variable associated with recurrence was duration of morphea before UVA1 (P value = .02, hazard ratio 1.15, 95% confidence interval 1.06-1.27). LIMITATIONS: The sample size limits conclusions. CONCLUSION: With the exception of increased duration of morphea, risk of recurrence is no different in adults and children, or between morphea subtypes, skin types, and medium- to high-dose regimens. This indicates treatment doses in the medium-high UVA1 range are adequate with respect to frequency of recurrence.
Subject(s)
Scleroderma, Localized/diagnosis , Scleroderma, Localized/radiotherapy , Ultraviolet Therapy/methods , Adolescent , Adult , Age Factors , Child , Cohort Studies , Confidence Intervals , Dose-Response Relationship, Radiation , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Phototherapy , Proportional Hazards Models , Prospective Studies , Recurrence , Risk Assessment , Severity of Illness Index , Sex Factors , Time Factors , Treatment Outcome , Young AdultABSTRACT
Previous studies suggested that the hepatoprotective activity of betaine is associated with its effects on sulfur amino acid metabolism. We examined the mechanism by which betaine prevents the progression of alcoholic liver injury and its therapeutic potential. Rats received a liquid ethanol diet for 6 wk. Ethanol consumption elevated serum triglyceride and TNFα levels, alanine aminotransferase and aspartate aminotransferase activities, and lipid accumulation in liver. The oxyradical scavenging capacity of liver was reduced, and expression of CD14, TNFα, COX-2, and iNOS mRNAs was induced markedly. These ethanol-induced changes were all inhibited effectively by betaine supplementation. Hepatic S-adenosylmethionine, cysteine, and glutathione levels, reduced in the ethanol-fed rats, were increased by betaine supplementation. Methionine adenosyltransferase and cystathionine γ-lyase were induced, but cysteine dioxygenase was down-regulated, which appeared to account for the increment in cysteine availability for glutathione synthesis in the rats supplemented with betaine. Betaine supplementation for the final 2 wk of ethanol intake resulted in a similar degree of hepatoprotection, revealing its potential therapeutic value in alcoholic liver. It is concluded that the protective effects of betaine against alcoholic liver injury may be attributed to the fortification of antioxidant defense via improvement of impaired sulfur amino acid metabolism.
Subject(s)
Amino Acids, Sulfur/metabolism , Antioxidants/metabolism , Betaine/pharmacology , Liver Diseases, Alcoholic/drug therapy , Animals , Body Weight/drug effects , Cyclooxygenase 2/genetics , Cysteine/metabolism , Cytosol/drug effects , Cytosol/metabolism , Dietary Supplements , Enzymes/metabolism , Gene Expression Regulation/drug effects , Glutathione/metabolism , Lipopolysaccharide Receptors/genetics , Liver/drug effects , Liver/metabolism , Liver/pathology , Liver Diseases, Alcoholic/genetics , Liver Diseases, Alcoholic/metabolism , Male , Nitric Oxide Synthase Type II/genetics , Organ Size/drug effects , Rats, Wistar , Tumor Necrosis Factor-alpha/geneticsABSTRACT
The metabolic disturbances that underlie systemic lupus erythematosus are currently unknown. A metabolomic study was executed, comparing the sera of 20 SLE patients against that of healthy controls, using LC/MS and GC/MS platforms. Validation of key differences was performed using an independent cohort of 38 SLE patients and orthogonal assays. SLE sera showed evidence of profoundly dampened glycolysis, Krebs cycle, fatty acid ß oxidation and amino acid metabolism, alluding to reduced energy biogenesis from all sources. Whereas long-chain fatty acids, including the n3 and n6 essential fatty acids, were significantly reduced, medium chain fatty acids and serum free fatty acids were elevated. The SLE metabolome exhibited profound lipid peroxidation, reflective of oxidative damage. Deficiencies were noted in the cellular anti-oxidant, glutathione, and all methyl group donors, including cysteine, methionine, and choline, as well as phosphocholines. The best discriminators of SLE included elevated lipid peroxidation products, MDA, gamma-glutamyl peptides, GGT, leukotriene B4 and 5-HETE. Importantly, similar elevations were not observed in another chronic inflammatory autoimmune disease, rheumatoid arthritis. To sum, comprehensive profiling of the SLE metabolome reveals evidence of heightened oxidative stress, inflammation, reduced energy generation, altered lipid profiles and a pro-thrombotic state. Resetting the SLE metabolome, either by targeting selected molecules or by supplementing the diet with essential fatty acids, vitamins and methyl group donors offers novel opportunities for disease modulation in this disabling systemic autoimmune ailment.
Subject(s)
Lupus Erythematosus, Systemic/metabolism , Metabolome , Adolescent , Adult , Amino Acids/metabolism , Carbohydrate Metabolism , Cluster Analysis , Female , Humans , Lipid Metabolism , Lupus Erythematosus, Systemic/blood , Male , Metabolomics/methods , Sensitivity and Specificity , Young AdultABSTRACT
Many studies have documented that ginseng has antidiabetic and antiobesity effects, but the mechanism of the effects has not been elucidated. The aim of this study was to determine the effect of Korean red ginseng (KRG, Panax ginseng) and investigate the mechanism of antidiabetic and antiobesity effects in obese insulin resistant animal models. Sprague-Dawley (SD) rats were divided into three groups: a control group (group I) fed a normal diet, another group (group II) fed only high fat diet (HFD) and a third group (group III) fed HFD with KRG (200 mg/kg, oral) for 18 weeks. The body weight, food intake, adipose tissues, liver, kidney, pancreas, adiponectin, and leptin were measured. Blood glucose, insulin tolerance test, and hyperinsulinemic euglycemic clamp test were investigated. A significant weight reduction, especially fat mass reduction, was observed in the KRG treated group. Increased insulin sensitivity was found in the KRG treated group. We observed increased insulin signalling, increased phosphorylation of IR, IRS-1, Akt, and membranous GLUT4 in muscle by Western blotting assay. In conclusion, KRG may have antidiabetic and antiobesity effects due to partly increased insulin sensitivity by increased adipokine and partly enhanced insulin signalling.
Subject(s)
Adipose Tissue/drug effects , Anti-Obesity Agents/therapeutic use , Diet, High-Fat/adverse effects , Hypoglycemic Agents/therapeutic use , Insulin Resistance , Panax , Phytotherapy , Adipokines/metabolism , Adipose Tissue/metabolism , Animals , Anti-Obesity Agents/pharmacology , Blotting, Western , Dietary Fats/adverse effects , Disease Models, Animal , Glucose Transporter Type 4/metabolism , Hypoglycemic Agents/pharmacology , Insulin Receptor Substrate Proteins/metabolism , Male , Muscle, Skeletal/metabolism , Phosphorylation , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Rats , Rats, Sprague-Dawley , Receptor, Insulin/metabolism , Signal Transduction/drug effects , Weight Loss/drug effectsABSTRACT
BACKGROUND: Diet may play an important role in the management of patients with short bowel syndrome who have colon in continuity. However, macronutrient absorption has not been well characterized, and the most appropriate dietary constituents have not been well defined. OBJECTIVE: To define carbohydrate absorption characteristics in patients with short bowel syndrome and determine the potential role of pectin as a dietary substrate. METHODS: The authors studied the effect of a custom pectin-based supplement in 6 subjects (3 male/3 female) aged 29-67 years with jejunocolonic anastomosis, 4 of whom required long-term parental nutrition. Small intestinal absorption capacity, macronutrient and fluid balance, gastrointestinal transit time, and energy consumption were measured. RESULTS: Data showed that 53% nitrogen, 50% fat, and 32% total energy were malabsorbed. In contrast, the majority (92%) of total carbohydrate was utilized. Fecal short-chain fatty acids (SCFAs) were increased, an indication of increased fermentation. Although only 4% of starch was recovered in stool, it is indicative of considerable starch malabsorption, thus providing the main carbohydrate substrate, for colonic bacterial fermentation. In contrast, nonstarch polysaccharide was a relatively minor fermentation substrate with only 49% utilized. Eighty percent of the pectin was fermented. Supplementation was associated with increased total SCFAs, acetate, and propionate excretion. There was a trend observed toward greater fluid absorption (-5.9% ± 54.4% to 26.9% ± 25.2%) following pectin supplementation. Nonsignificant increases in gastric emptying time and orocolonic transit time were observed. CONCLUSION: Despite malabsorption, starch is the primary carbohydrate substrate for colonic bacterial fermentation in patients with short bowel syndrome, although soluble fiber intake also enhances colonic SCFA production.
Subject(s)
Dietary Carbohydrates/metabolism , Dietary Fiber/therapeutic use , Energy Intake , Fatty Acids, Volatile/biosynthesis , Pectins/therapeutic use , Short Bowel Syndrome/metabolism , Starch/metabolism , Adult , Aged , Colon/metabolism , Colon/pathology , Dietary Fats/metabolism , Dietary Fiber/pharmacology , Female , Humans , Intestinal Absorption , Jejunum/metabolism , Jejunum/pathology , Male , Middle Aged , Nitrogen/metabolism , Pectins/pharmacology , Short Bowel Syndrome/pathology , Short Bowel Syndrome/therapyABSTRACT
The effects of red ginseng extract on circulating angiogenic cell mobilization and improvement of microvascular integrity were evaluated in ST-elevation acute myocardial infarction (AMI) patients during 8-month follow-up. AMI patients (n = 50) were randomly assigned to the red ginseng group (3 g/day, n = 25) or the placebo group (n = 25) after coronary stenting. Coronary flow reserve (CFR) was measured at baseline and at 8 months with an intracoronary Doppler wire. Serial changes in the absolute numbers of circulating angiogenic cells such as CD34(+) , CXCR4(+) , CD117(+) , CD133(+) and C-met(+) were measured at baseline, 1 day, 5 days and at 8 months. CFR were similar between the two groups at baseline, and CFR was significantly higher in the red ginseng group than in the placebo group (2.80 ± 0.91 and 2.56 ± 0.77, p < 0.05, respectively) after 8 months of red ginseng administration. The absolute numbers of circulating CD34(+) , CXCR4(+) and CD117(+) cells were significantly higher in the red ginseng group at 1 and 5 days after stenting. Significant positive correlations were found between the numbers of circulating angiogenic cells at day 1 and the changes from baseline in CFR for CD34(+) , CXCR4(+) , CD117(+) and C-met(+) cells. Red ginseng extract increased CD34(+) , CXCR4(+) and CD117(+) circulating angiogenic cell mobilization and decreased inflammation in AMI patients, thereby improving CFR during the 8-month follow-up.
Subject(s)
Heart/drug effects , Myocardial Infarction/drug therapy , Panax/chemistry , Phytotherapy , Plant Extracts/therapeutic use , Aged , Blood Flow Velocity , Echocardiography, Doppler , Female , Humans , Male , Middle Aged , Neovascularization, Physiologic/drug effects , Plant Extracts/pharmacology , Prospective Studies , Single-Blind MethodABSTRACT
Saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA) show different effects on the development of insulin resistance. In this study, we compared the effect of dietary SFA and MUFA on the insulin signaling pathway in the skeletal muscle of a type 2 diabetic animal model. Twenty-nine-week-old male Otsuka Long-Evans Tokushima fatty (OLETF) rats were randomly divided into three groups and fed one of the following diets for 3 weeks; a normal chow diet, an SFA (lard oil) enriched or a MUFA (olive oil) enriched high-fat diet. The vastus lateralis muscle was used for analyses. Insulin tolerance test showed improved insulin sensitivity in rats fed the MUFA diet, as compared to those fed the SFA diet (p < 0.001). The SFA diet reduced IRS-1 expression and phosphorylated PI3K levels in skeletal muscle, as compared with a chow diet (p < 0.001, respectively). On the contrary, muscle IRS-2 expression and phosphorylated ERK1/2 was significantly increased in rats fed the SFA diet (p < 0.001, respectively). Membrane translocation of glucose transporter type 4 decreased in the skeletal muscle of rats fed the SFA diet, as compared to those fed a chow diet (p < 0.001). These changes in insulin signaling pathway in skeletal muscle were not observed in rats fed the MUFA diet. In conclusion, the beneficial effect of dietary MUFA on insulin sensitivity is associated with a conserved IRS-1/PI3K insulin signaling pathway which was altered by dietary SFA.