Zotter, H; Robinson, N; Zorzoli, M; Schattenberg, L; Saugy, M; Mangin, P
Background: An international, longitudinal medical follow up examination of male professional road cyclists revealed excessively elevated serum ferritin levels. Objective: To evaluate the importance of elevated ferritin values among professional cyclists, their relationship with age and nationality, and their evolution over 3 years. Methods: Over 1000 serum ferritin values were collected. Other parameters were included in order to exclude conditions which might have increased ferritin levels without changing body iron stores. Results: In 1999, over 45% of riders displayed ferritin values above 300 ng/ml and one fourth levels over 500 ng/ml. These percentages had decreased to 27% and 9%, respectively, 3 years later, while the overall average, which was above the normal limits in 1999, had decreased by 33% in 3 years. Older cyclists had higher ferritin values than younger cyclists. There was also a relationship between ferritin levels and the nationality of the cyclists. Analysis of 714 riders in 2000 and 2002 showed only a slight and insignificant decrease in the mean ferritin value although those with initially elevated iron stores had a much greater decrease. Conclusion: Professional road cyclists used excessive iron supplementation leading to high serum ferritin levels correlating with increased body iron stores. Although the situation progressively improved over 3 years, it remains worrying as increased body iron stores are related to health complications. Therefore, prevention in addition to the fight against doping should be a main goal of the UCI. Aggressive therapy for athletes with excessive ferritin values should be carried out at or before the end of their careers. PMID:15562163
Neonatal hypocalcemia is defined as a total serum calcium concentration of <7 mg/dL or an ionized calcium concentration of <4 mg/dL (1mmol/L). In very low birth weight (VLBW) infants, ionized calcium values of 0.8 to 1 mmol/L are common and not usually associated with clinical symptoms. In larger in...
Futatsugi, Akiko; Hidaka, Eiko; Kubota, Noriko; Nishijima, Fumie; Yoshizawa, Katsumi; Ishimine, Nau; Sugano, Mitsutoshi; Hori, Atsushi; Hidaka, Hiroya
Lipoprotein-X (LP-X) in cholestatic jaundice causes abnormal reaction in assays for low-density lipoprotein-cholesterol, but the effects on other test items are unknown. Here, we report an infant with biliary atresia showing abnormal reaction in total serum protein assay using the biuret method, and lipoprotein-X (LP-X) was then detected. In this 11-month-old female infant, jaundice was observed at 2 months old, and a diagnosis of biliary atresia was made. On biochemical tests at 12 months old, the total serum protein concentrations detected by the biuret method were very high, and the response curve and linearity of dilution were abnormal. LP-X was detected by agar electrophoresis. In addition and recovery experiments with normal serum fractionation of the patient's LP-X-rich lipoprotein fraction prepared by ultracentrifugation, normal γ-globulin fractionation showed an abnormal reaction by the biuret method. In infants with biliary atresia, we showed that the total serum protein assay by the biuret method was influenced by LP-X-rich lipoprotein, which may be caused by abnormal reaction of LP-X and γ-globulin. [Case Report].
Lewis, B.; Chait, A.; Oakley, C. M. O.; Wootton, I. D. P.; Krikler, D. M.; Onitiri, A.; Sigurdsson, G.; February, A.
The frequency and nature of abnormalities of serum lipoproteins have been studied, using quantitative techniques, in 143 patients with ischaemic heart disease (I.H.D.). Rigorous selection criteria were used. The findings were related to the distribution of lipoprotein concentrations in a carefully screened control population. Hyperlipoproteinaemia occurred in 55% of patients and in 11 out of 15 patients aged less than 40 years. Raised triglyceride and cholesterol concentrations in very low density lipoprotein were the most frequent abnormalities followed by raised cholesterol content of low density lipoprotein. In young patients high density lipoprotein levels were subnormal. Hyperlipoproteinaemia of W.H.O. types IIa, IIb, III, IV, and V all seemed to be over-represented in I.H.D. I.H.D. patients with type IIa, IIb, and IV abnormalities were all significantly younger than I.H.D. patients with normal lipoprotein levels. PMID:4370367
Law, B.E.; Shah, S.H.A.; Malik, M.A.
Abnormally high formation pressures in the Potwar Plateau of north-central Pakistan are major obstacles to oil and gas exploration. Severe drilling problems associated with high pressures have, in some cases, prevented adequate evaluation of reservoirs and significantly increased drilling costs. Previous investigations of abnormal pressure in the Potwar Plateau have only identified abnormal pressures in Neogene rocks. We have identified two distinct pressure regimes in this Himalayan foreland fold and thrust belt basin: one in Neogene rocks and another in pre-Neogene rocks. Pore pressures in Neogene rocks are as high as lithostatic and are interpreted to be due to tectonic compression and compaction disequilibrium associated with high rates of sedimentation. Pore pressure gradients in pre-Neogene rocks are generally less than those in Neogene rocks, commonly ranging from 0.5 to 0.7 psi/ft (11.3 to 15.8 kPa/m) and are most likely due to a combination of tectonic compression and hydrocarbon generation. The top of abnormally high pressure is highly variable and doesn't appear to be related to any specific lithologic seal. Consequently, attempts to predict the depth to the top of overpressure prior to drilling are precluded.
Polan, M L; Totora, M; Caldwell, B V; DeCherney, A H; Haseltine, F P; Kase, N
A significant portion of human infertility is presumably due to defective ovulation, including patients who fail to conceive despite medical induction of ovulation, those who fail despite repeated timely donor inseminations, and those with "infertility of unknown etiology". All point out the inadequacy of standard criteria for normal ovulation. This investigation correlates preovulatory serum estradiol and gonadotropin concentrations with dominant follicle growth measured ultrasonographically and serum progesterone levels. The data indicate a 35% incidence of cycles with significantly abnormal serum estradiol levels, decreased dominant follicle size, and abnormal progesterone levels despite biphasic basal body temperature curves and normal cycle length. If these cycles represent inadequate or abnormal ovulation, they can be distinguished from adequate cycles prior to follicle rupture and may benefit the treatment of human infertility.
Ledda, Caterina; Loreto, Carla; Matera, Serena; Massimino, Nicoletta; Cannizzaro, Emanuele; Musumeci, Andrea; Migliore, Marcello; Fenga, Concettina; Pomara, Cristoforo; Rapisarda, Venerando
Fluoro-edenite (FE) is a natural mineral asbestos-like fibrous species first isolated in Biancavilla, Sicily. In order to clarify potential involvement of IL-18 in the pathogenesis of FE-induced chest abnormalities, we analyzed IL-18 serum levels in FE-exposed workers (FEEW) and correlated them with pleural and parenchymal abnormalities. A total of 21 FEEWs, residing in Biancavilla for >30 years, with a working seniority of 17 ± 6.1 years were examined. High-resolution computed tomography scans revealed low grade of fibrosis in 8 (38%) FEEWs, and pleural plaques (PPs) in 13 (62%) FEEWs. The mean IL-18 level was 203.13 ± 90.43 pg/ml. Pearson correlation showed a significant association (p < 0.0001) between IL-18 and PPs and parenchymal abnormality scores. Data suggest a potential role of IL-18 in the pathogenesis of these diseases.
Kwan, D; Bartle, W R; Walker, S E
J.M., a healthy, 25-year-old male, volunteered for a study involving warfarin and acetaminophen. Acetaminophen 1 g four times a day was started for 21 days. Liver function tests taken at regular intervals for the first 12 days were unremarkable. On day 18, however, aspartate aminotransferase (AST) was 527 IU/liter and alanine aminotransferase (ALT) was 166 IU/liter. Acetaminophen was discontinued and serum transaminase levels returned to baseline levels two weeks later (AST = 26, ALT = 20). Analysis of J.M.'s urine samples over the first 18 days showed excretion patterns of glucuronide, sulfate, and glutathione derived cysteine and mercapturic acid conjugates were similar to the other subjects in the study. Acetaminophen causes hepatotoxicity in overdose or malnourished or alcoholic patients, none of which applied to our subject. Differences in metabolic activation and capacity for glutathione synthesis can predispose individuals given therapeutic doses of acetaminophen to adverse effects. Failure to detoxify a highly reactive metabolite, formed by P-450 metabolism, via glutathione conjugation is responsible for the development of acute hepatic necrosis. Accumulation of the toxic metabolite due to depleted glutathione stores may have occurred with prolonged high dosing in our subject and been responsible for his abnormal rise in liver enzymes.
von Mandach, U; Huch, R; Huch, A
The purpose of this study was to ascertain whether there is an association between reduced vitamin E levels and an abnormal pregnancy. Levels were measured by HPLC in maternal and, where possible, in paired umbilical cord serum from normal and abnormal pregnancies at delivery and in serial serum samples from healthy women during gestation. Abnormal pregnancies were compared with normals. In normal pregnancies, mean vitamin E levels rose from 12.9 +/- 1.1 micrograms/ml in early pregnancy to 22.5 +/- 1.5 micrograms/ml at term (p < 0.05, n = 11). In pregnancies with fetal complications or maternal risks, levels were lower than in normals at corresponding gestational age (p < 0.005 in smokers, n = 20 at > or = 30 weeks & p < 0.01 in hypertensives, n = 4 at 16-23 weeks). Mean maternal and paired cord serum levels in normal pregnancies at delivery > or = 37 weeks were 21.3 +/- 0.6 and 3.8 +/- 0.1 micrograms/ml respectively (p < 0.001, n = 56). Maternal levels in women with a low birthweight infant and in smokers (> 10 cig/day) were significantly lower (p < 0.05, n = 13 & p < 0.0005, n = 12); levels in women with a malformed infant (n = 6) were also reduced, but just barely below the level of significance (p = 0.06). Cord serum levels in complicated pregnancies, however, were unchanged. The results show lower maternal levels of vitamin E in abnormal pregnancies, suggesting a changed vitamin E metabolism.
Friedman-Mor, Z; Chalon, J; Turndorf, H; Orkin, L R
Significantly elevated numbers of iron laden histiocytes have been shown to appear in the tracheobronchial secretions of subjects in hemorrhagic shock and in patients undergoing open heart-surgery during cardiopulmonary bypass (3,4). Abnormal heme pigments have also been demonstrated in the serum of dogs bled to hemorrhagic shock (6) and have been felt to be toxic. Because the ingestion of abnormal heme pigments by histiocytes may be part of a defense mechanism, we have attempted to correlate the percentage of iron laden histiocytes found in the tracheobronchial secretions of patients in hemorrhagic shock (Prussian blue method) with the presence of degradation of products of hemoglobin found in their serum by scanning spectrophotometry. There were, generally speaking, few iron laden histiocytes when hemoglobin degradation was advanced, and always numerous iron laden histiocytes when abnormal heme pigments were absent or spectrophotometric findings revealed minor degrees of degradation. Our findings probably reflect the process in the reticuloendothelial systems which eliminates toxic products accumulating in the circulation in low-flow states.
Maia, Deborah Bezerra; Marmar, Charles R; Mendlowicz, Mauro V; Metzler, Thomas; Nóbrega, Augusta; Peres, Mhara C; Coutinho, Evandro S; Volchan, Eliane; Figueira, Ivan
Background To measure the serum lipid composition of a sample of Brazilian police officers with and without PTSD regularly exposed to potentially traumatic situations. Methods A cross-sectional survey was conducted with 118 active duty male police officers. Serum concentrations for total cholesterol, LDL-C, HDL-C, and triglycerides were enzymatically determined. Body mass index (BMI) was obtained for each participant. Results Officers with PTSD exhibited significantly higher serum total cholesterol, LDL-C and triglycerides levels than those without PTSD. Total cholesterol and triglycerides, but not LDL-C, remained associated with PTSD diagnosis after controlling for confounding influences (i.e. socio-demographics, BMI, and tobacco, alcohol and medication use). Limitations The sample size was small. A nutritional interview was employed instead of established scales to assess alimentary habits, tobacco or alcohol consumption. A self-report screening tool was used to assess the prevalence of PTSD. Conclusions The association between PTSD and abnormal serum lipid profile and a tendency to exhibit higher BMI suggests that individuals with PTSD may be at increased risk for developing metabolic syndrome, a condition that by itself could account for many of the most serious PTSD-related physical health problems. PMID:17888517
Annerén, G; Magnusson, C G; Lilja, G; Nordvall, S L
Susceptibility to infections is a well known feature of Down's syndrome. The possible relation between this predisposition and the serum concentrations of the IgG subclasses was studied in 38 children with Down's syndrome aged 1-12 years. An age matched group of 50 healthy children served as controls. The serum concentrations of IgG1 and IgG3 were significantly raised among children with Down's syndrome in all three age groups studied (that is 1-2.5, 4-8, and 9-12 years). The serum concentrations of IgG2 were normal in the first two groups but significantly reduced in the third age group. In contrast, the concentrations of IgG4 among children with Down's syndrome were significantly reduced in all three age groups. Moreover, among the children with Down's syndrome aged 4-12 years 68% (15/22) had IgG4 concentrations below 2 SDs of the geometrical mean of the controls. The results may partially explain the proneness of children with Down's syndrome to infections with encapsulated bacteria. Although the underlying cause of these abnormalities is unknown, IgG subclass determination seems relevant in the clinical evaluation of children with Down's syndrome. PMID:1534650
Park, Sora; Kim, Ji Hong
Purpose Kawasaki disease (KD) is an immune-related multisystemic vasculitis that occurs in children, especially ensuing from a coronary artery abnormality. Sodium level is known to be related to vascular injury, which could affect the progress of KD. The purpose of this study was to determine the serum sodium levels that could predict the occurrence of cardiac and coronary artery events in KD. Methods We conducted a retrospective review of medical records for 104 patients with KD from January 2015 to December 2015. Patients with serum Na levels of <135 mEq/L at the time of initial diagnosis were assigned to the hyponatremia group. Laboratory findings and echocardiographic data were analyzed for various aspects. Results Among the 104 patients with KD, 91 were included in the study, of whom 48 (52.7%) had hyponatremia. The degree of fever, white blood cell count, percentage of neutrophils, percentage of lymphocytes, total bilirubin level, brain natriuretic peptide level, erythrocyte sedimentation rate, and C-reactive protein level were higher in the patients with hyponatremia. They also demonstrated a trend of larger coronary artery diameters based on Z scores. Conclusion The severity of vascular inflammation in acute KD with hyponatremia might worsen the prognosis of coronary vasculature. Although no statistically significant correlation was found between the initial serum sodium levels and coronary arteriopathy in the patients with KD in this study, a long-term follow-up study with a larger number of enrolled patients should be designed in the future to elucidate the relationship between serum sodium level and coronary arteriopathy in patients with KD. PMID:28289432
Dote, Tomotaro; Adachi, Kazuya; Yamadori, Emi; Imanishi, Masafumi; Tsuji, Hiroshi; Tanida, Eri; Kono, Koichi
Cadmium fluoride (CdF2, CdF for short) is the most lethal and hepatotoxic of all Cd-containing compounds. The toxic effects of CdF appear to depend on its detoxification and elimination. This study was designed to determine the early dynamics of the absorption, systemic distribution, and metabolism of CdF. The kinetics of cadmium and fluoride were investigated in the blood, bile, and urine of rats as a model of accidental occupational exposure to CdF. The serum concentration-time profiles measured after intravenous CdF (1.34, 2.67 or 4.01 mg/ per kg body weight) administration were analyzed by compartmental modeling using the WinNonlin program. Bile and urine were collected for 300 min after the administration. The kinetic profiles indicate that the clearance of Cd was diminished in the 2.67 and 4.01 mg/kg groups, leading to a persistently high serum Cd level. The mean total biliary excretions of Cd in the 2.67 and 4.01 mg/kg groups were significantly higher than that in the 1.34 mg/kg group. The abnormal kinetics of Cd was attributable to severe hepatic injury that diminished the capacity for Cd accumulation. The elimination of serum F was delayed in the 4.01 mg/kg group. The mean urinary F excretion amount was not significantly higher in the 4.01 mg/kg group than in the 2.67 mg/kg group. The abnormal kinetics of F was attributable to nephrotoxicity that diminished its elimination from the kidney.
Saji, T; Matsuo, N; Shiono, N; Yokomuro, H; Watanabe, Y; Takanashi, Y; Komatsu, H
Immunological features and the production of interleukin-6 (IL-6) in 4 patients with cardiac myxoma were studied. The patients' age ranged from 11 years old to 57 years old; all 4 patients were female. Case 1, an 11-year-old female patient with myxoma located in the right ventricle, was considered to be a familial case. Her mother had myxomas in the right and left atrium, and had undergone removal of both tumors 3 years before. Peripheral blood examination revealed various inflammatory parameters in all of these patients. White blood cell (WBC) count was over 8,000/cmm in 3 of the 4 patients, positive CRP was found in 2 patients, IgG was higher than 1,500 mg/dl in 3 patients, positive anti-nuclear antibody was seen in 1 patient, and positive rheumatoid factor was identified in 1 patient. The OKT 4/8 ratio of lymphocyte subpopulation was 4.65 in one patient. The lymphocyte mitogenic response to PHA was increased in 2 patients. Serum IL-6 increased in 3 of 4 patients, and returned to normal within 3 to 4 weeks after operation. The IL-6 concentration in the homogenized sample remarkably increased in all 4 patients. Tumors larger than 4 cm contained higher tissue IL-6 concentrations than those smaller than 2 cm. The cultured myxoma cells produced abundant IL-6 in the culture medium supernatant. We conclude that inflammatory signs and immunological abnormalities are common in patients with large cardiac myxoma, and, in addition, serum IL-6 levels may increase in such patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Hsieh, Meng-Hsuan; Lin, Wen-Yi; Chien, Hsu-Han; Chien, Li-Ho; Huang, Chao-Kuan; Yang, Jeng-Fu; Chang, Ning-Chia; Huang, Chung-Feng; Wang, Chao-Ling; Chuang, Wan-Long; Yu, Ming-Lung; Dai, Chia-Yen; Ho, Chi-Kung
Several studies have found that metabolic syndrome and uric acid level are related to abnormal liver function test results. The aim of this study was to explore the associations of risk factors [including blood pressure, blood sugar, total cholesterol, triglyceride, uric acid, waist circumference and body mass index (BMI) measurements] with abnormal liver function in the Taiwanese population.In total, 11,411 Taiwanese adults were enrolled in this study. Blood pressure was assessed according to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure criteria, fasting blood sugar level according to the Bureau of Health Promotion, Department of Health, R.O.C., criteria, total cholesterol and triglyceride levels according to the Third Report of the National Cholesterol Education Program Adult Treatment Panel III criteria, BMI according to the Asia-Pacific criteria, and waist circumference according to the Revised Diagnostic Criteria of Metabolic Syndrome in Taiwan. The prevalence of a past history of hypertension and diabetes mellitus was 17.7% and 6.5%, respectively, and the rates of abnormal measurements of blood pressure, BMI, waist circumference, fasting blood sugar, triglyceride, total cholesterol, uric acid (male/female), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were 76.2%, 67.6%, 40.0%, 28.6%, 30.6%, 57.3%, 37.9%/21.9%, 14.6% and 21.3%, respectively. Multivariate analysis showed that waist circumference, BMI, serum uric acid, blood sugar, and triglyceride levels were related to abnormal AST and ALT (p<0.05), but the odds ratio for waist circumference was larger than that for BMI. In conclusion, waist circumference, BMI, serum uric acid, blood sugar, and triglyceride levels are important risk factors for abnormal AST and ALT readings in Taiwanese adults. Waist circumference might be a better indicator of risk of abnormal liver function than BMI.
Brown, T; Kliewer, M A; Hertzberg, B S; Ruiz, C; Stamper, T H; Rosnes, J; Lucas, A; Wright, L N; Chescheir, N C; Farmer, L; Jordan, S; Kay, H H
A prospective multicentre study was performed to identify patients with fetal choroid plexus cysts and examine the association between choroid plexus cysts and chromosome abnormalities in the context of variables such as maternal age, serum triple-screen results, race, other prenatally-identified fetal anomalies and cyst characteristics. A total of 18 437 scans were performed in 5 centres and 257 fetuses were identified with choroid plexus cysts. Outcome was available on 250 patients, and of these, chromosomal abnormalities were detected in a total of 13 (5.2 per cent) fetuses. 26 patients in the group had additional ultrasound abnormalities, and 8 of these had fetal chromosome abnormalities. Among the 224 patients with isolated choroid plexus cysts, 5 (2.2 per cent) were found to have chromosomal abnormalities. All cases with identified chromosomal abnormalities were associated with an additional risk factor, such as other ultrasound findings, advanced maternal age or abnormal maternal serum triple-screen results.
Tzamaloukas, Antonios H; Ing, Todd S; Elisaf, Moses S; Raj, Dominic S C; Siamopoulos, Kostas C; Rohrscheib, Mark; Murata, Glen H
The main difference between dialysis-associated hyperglycemia (DH) and diabetic ketoacidosis (DKA) or nonketotic hyperglycemia (NKH) occurring in patients with preserved renal function is the absence of osmotic diuresis in DH, which eliminates the need for large fluid and solute (including potassium) replacement. We analyzed published reports of serum potassium (K(+)) abnormalities and their treatment in DH. Hyperkalemia was often present at presentation of DH with higher frequency and severity than in hyperglycemic syndromes in patients with preserved renal function. The frequency and severity of hyperkalemia were higher in DH episodes with DKA than those with NKH in both hemodialysis and peritoneal dialysis. For DKA, the frequency and severity of hyperkalemia were similar in hemodialysis and peritoneal dialysis. For NKH, hyperkalemia was more severe and frequent in hemodialysis than in peritoneal dialysis. Insulin infusion corrected the hyperkalemia of DH in most cases. Additional measures for the management of hyperkalemia or modest potassium infusions for hypokalemia were needed in a few DH episodes. The predictors of the decrease in serum K(+) during treatment of DH with insulin included the starting serum K(+) level, the decreases in serum values of glucose concentration and tonicity, and the increase in serum total carbon dioxide level. DH represents a risk factor for hyperkalemia. Insulin infusion is the only treatment for hyperkalemia usually required.
Lee, Seong-Jong; Han, Jong-Min; Lee, Jin-Seok; Son, Chang-Gue; Im, Hwi-Jin; Jo, Hyun-Kyung; Yoo, Ho-Ryong; Kim, Yoon-Sik; Seol, In-Chan
The medicinal plants Artemisia iwayomogi (A. iwayomogi) and Curcuma longa (C. longa) radix have been used to treat metabolic abnormalities in traditional Korean medicine and traditional Chinese medicine (TKM and TCM). In this study we evaluated the effect of the water extract of a mixture of A. iwayomogi and C. longa (ACE) on high-fat diet-induced metabolic syndrome in a mouse model. Four groups of C57BL/6N male mice (except for the naive group) were fed a high-fat diet freely for 10 weeks. Among these, three groups (except the control group) were administered a high-fat diet supplemented with ACE (100 or 200 mg/kg) or curcumin (50 mg/kg). Body weight, accumulation of adipose tissues in abdomen and size of adipocytes, serum lipid profiles, hepatic steatosis, and oxidative stress markers were analyzed. ACE significantly reduced the body and peritoneal adipose tissue weights, serum lipid profiles (total cholesterol and triglycerides), glucose levels, hepatic lipid accumulation, and oxidative stress markers. ACE normalized lipid synthesis-associated gene expressions (peroxisome proliferator-activated receptor gamma, PPARγ; fatty acid synthase, FAS; sterol regulatory element-binding transcription factor-1c, SREBP-1c; and peroxisome proliferator-activated receptor alpha, PPARα). The results from this study suggest that ACE has the pharmaceutical potential reducing the metabolic abnormalities in an animal model. PMID:26508977
Gonzalez-Quintela, A; Alende, R; Gude, F; Campos, J; Rey, J; Meijide, L M; Fernandez-Merino, C; Vidal, C
The present study investigated serum immunoglobulin (Ig) concentrations in relation to demographic factors, common habits (alcohol consumption and smoking) and metabolic abnormalities in an adult population-based survey including 460 individuals. Serum levels of interleukin (IL)-6, a marker of inflammation, were also determined. After adjusting for confounders, male sex was associated positively with IgA levels and negatively with IgM levels. Age was associated positively with IgA and IgG levels. Smoking was associated negatively with IgG levels. Heavy drinking was associated positively with IgA levels. Metabolic abnormalities (obesity and metabolic syndrome) were associated positively with IgA levels. Abdominal obesity and hypertriglyceridaemia were the components of metabolic syndrome associated most strongly with serum IgA. Heavy drinkers with metabolic syndrome showed particularly high serum IgA levels. Serum IL-6 levels were correlated positively with IgA and IgG concentrations. It is concluded that sex, age, alcohol consumption, smoking and common metabolic abnormalities should be taken into account when interpreting serum levels of IgA, IgG and IgM. PMID:18005364
Peris, Pilar; Reverter, Joan Carles; Espinosa, Gerard; Martinez-Ferrer, Angeles; Monegal, Ana; Monteagudo, Juan; Tàssies, Dolors; Guañabens, Nuria
Abstract Multifocal or multiple osteonecrosis (ON), defined by the involvement of 3 or more anatomic sites, is unusual, being observed in only 3%–10% of patients diagnosed with ON. We report the clinical characteristics of a cohort of 29 patients with multifocal ON from a single center and evaluate the prevalence of associated prothrombotic abnormalities in 26 of these patients. We conducted a retrospective study of all patients diagnosed with multifocal ON evaluated in our institution during the last 20 years. We recorded clinical manifestations and underlying diagnoses. A wide thrombophilic profile was performed, including antithrombin, protein C, protein S, lupus anticoagulant, anticardiolipin antibodies, activated protein C resistance, factor V Leiden, mutation G-20210-A of the prothrombin gene, and factor VIII. Coagulation test results were compared with those in a healthy control group and a group of patients with history of lower-extremity deep venous thrombosis. The mean age of the patients was 49.2 ± 15 years (range, 28–81 yr). The mean number of ON localizations per patient was 5.2 ± 2.3 (range, 3–11). Hips were the most commonly affected joint (82%), followed by knees (58%), shoulders (37%), and ankles (13%). Most patients had an underlying disease process, and 12 of 25 (48%) patients had coagulation test abnormalities. The most common alterations were high factor VIII levels and antiphospholipid antibody (aPL) positivity in 24% and 20% of cases, respectively. These abnormalities were more prevalent in patients with multifocal ON compared with patients in the control groups. Sixty-one percent of patients had a history of corticosteroid treatment. Patients with coagulation abnormalities had a higher number of ON localizations per patient (6.5 ± 2.7 vs. 3.88 ± 0.8; p = 0.002) and a higher prevalence of atypical ON localizations (25% vs. 0%; p = 0.05). In conclusion, in the present cohort of patients with multifocal ON, 48% of the patients had at
Gelaye, Bizu; Sumner, Susan J.; McRitchie, Susan; Carlson, James E.; Ananth, Cande V.; Enquobahrie, Daniel A.; Qiu, Chunfang; Sorensen, Tanya K.; Williams, Michelle A.
Background & Objective Placental abruption, an ischemic placental disorder, complicates about 1 in 100 pregnancies, and is an important cause of maternal and perinatal morbidity and mortality worldwide. Metabolomics holds promise for improving the phenotyping, prediction and understanding of pathophysiologic mechanisms of complex clinical disorders including abruption. We sought to evaluate maternal early pregnancy pre-diagnostic serum metabolic profiles and abnormal vaginal bleeding as predictors of abruption later in pregnancy. Methods Maternal serum was collected in early pregnancy (mean 16 weeks, range 15 to 22 weeks) from 51 abruption cases and 51 controls. Quantitative targeted metabolic profiles of serum were acquired using electrospray ionization liquid chromatography-mass spectrometry (ESI-LC-MS/MS) and the Absolute IDQ® p180 kit. Maternal sociodemographic characteristics and reproductive history were abstracted from medical records. Stepwise logistic regression models were developed to evaluate the extent to which metabolites aid in the prediction of abruption. We evaluated the predictive performance of the set of selected metabolites using a receiver operating characteristics (ROC) curve analysis and area under the curve (AUC). Results Early pregnancy vaginal bleeding, dodecanoylcarnitine/dodecenoylcarnitine (C12 / C12:1), and phosphatidylcholine acyl-alkyl C 38:1 (PC ae C38:1) strongly predict abruption risk. The AUC for these metabolites alone was 0.68, for early pregnancy vaginal bleeding alone was 0.65, and combined the AUC improved to 0.75 with the addition of quantitative metabolite data (P = 0.003). Conclusion Metabolomic profiles of early pregnancy maternal serum samples in addition to the clinical symptom, vaginal bleeding, may serve as important markers for the prediction of abruption. Larger studies are necessary to corroborate and validate these findings in other cohorts. PMID:27300725
LAN, FENG; ZHU, MING; QI, QIUFENG; ZHANG, YAPING; LIU, YONGPING
Aberrant glycosylation of protein occurs in nearly all types of cancers and has been confirmed to be associated with tumor progression, metastasis and the survival rate of patients. The present study aimed to explore the prognostic value of tumor abnormal protein (TAP) in gastric cancer patients. TAP was detected in the blood of 42 gastric cancer patients and 56 healthy volunteers by using the TAP testing kit. Univariate and multivariate Cox regression analysis were performed to evaluate the prognostic value of TAP. In total, 64.3% of gastric cancer patients were positive for TAP, and TAP was significantly correlated with poor prognosis [progression-free survival (PFS), 4.2 vs. 12.6 months; P=0.043]. TAP [hazard ratio (HR), 64.487; P<0.01), differentiation (HR, 17.279; P<0.01) and TNM stage (HR, 45.480; P<0.01) were found to be independent predictive factors for PFS. Furthermore, Kaplan-Meier curves indicated that TAP is associated with a reduced PFS in gastric cancer patients. The results of the present study therefore indicated that the TAP test has significant prognostic value for gastric cancer patients. PMID:27330802
Jain, Manish; Kalsi, Amanpreet Kaur; Srivastava, Amita; Gupta, Yogendra Kumar
Introduction Spermiation is a process of releasing sperm into the lumen of seminiferous tubules. Failure in releasing sperm into the lumen is designated as spermiation defect. Spermiation defect cases present as oligo-azoospermia or azoospermia despite normal gonadotropins and testicular histology/cytology. Human spermiation defect never got attention to investigate infertility practice. Most of the information on spermiation defect, so far is from animal experiments. We assume some cases of non-obstructive azoospermia with normal gonadotropins and testicular histology/cytology could be due to spermiation defect. Aim The aim of the study was to find out the underlying aetiology in cases of human spermiation defect. Materials and Methods A total of 13 cases of spermiation defect and 20 fertile men as control constituted study material. Cases were studied for chromosomal abnormalities by conventional karyotyping, sex chromosome mosaicism by interphase XY FISH, Yq microdeletion by STS PCR, sertoli cell quality (function) and quantity (numbers) by serum Anti-Mullerian Hormone (AMH) and inhibin B besides other hormones like Follicular Stimulating Hormone (FSH), prolactin, testosterone and estradiol. Vitamin A concentration in serum was also measured. Presence of heavy metal was investigated by elemental electron microscopy in seminal cells (eight cases) & by spectrometry in serum as well as seminal plasma. Results Chromosomal and Yq microdeletion study failed to detect any abnormalities. AMH, inhibin B and vitamin A were also normal. Estradiol level was high in 6 out of 13 cases (46%) while platinum in seminal cells was high in 4 cases (50%). High (four times or more) serum level of lead and nickel was observed in 11 (85%) and 6 (46%) cases, respectively. Conclusion High serum concentration of heavy metals like lead & nickel or high platinum accumulation in seminal cells or high serum estradiol alone or in combinations may be underlying aetiologic factors in human
Armanini, Decio; Nacamulli, Davide; Scaroni, Carla; Lumachi, Franco; Selice, Riccardo; Fiore, Cristina; Favia, Gennaro; Mantero, Franco
The study was performed to evaluate the prevalence of thyroid abnormalities detected by ultrasonography and, in particular, of multinodular nontoxic goiter in primary aldosteronism. We analyzed 80 consecutive of patients with primary hyperaldosteronism (40 with unilateral adenoma and 40 with idiopathic hyperaldosteronism) and 80 normotensive healthy controls, comparable for age, sex, iodine intake, and geographical area. Blood pressure, thyroid palpation, thyroid function, and ultrasonography were evaluated. The prevalence of ultrasonographic thyroid abnormalities was 60% in primary aldosteronism and 27% in controls (p < 0.0001). There was a statistically significant difference in prevalence of these abnormalities in unilateral adenoma and idiopathic hyperaldosteronism with respect to controls (p < 0.05 and p < 0.0001, respectively). The prevalence of multinodular nontoxic goiter in idiopathic hyperaldosteronism was higher than in controls (p < 0.001) and, in particular, in female patients. From these data it seems to be worth considering the existence of primary hyperaldosteronism in patients with multinodular goiter and hypertension.
Berg, Kåre; Boman, Helge; Torsvik, Harald; Walker, Suzanne M.
A common antigenic polymorphism of high density lipoprotein (HDL) in rabbit serum is described. The presence or absence of an antigen termed Hl 1 appears to be controlled by autosomal dominant inheritance. The polymorphism should be a useful tool in the study of serum lipoproteins, particularly since genetic polymorphisms within the low density lipoprotein are already known in several species. The Hl polymorphism may make the rabbit more useful for model studies of serum lipoproteins in health and disease. Images PMID:4995822
Bozkurt, N Colak; Cakal, E; Sahin, M; Ozkaya, E Cakir; Firat, H; Delibasi, T
Obstructive sleep apnea (OSA) and 25-hydroxyvitamin-D₃ (25-OH-D) deficiency are two separate disorders associating with obesity, inflammation, and impaired glucose metabolism. We aimed to investigate the vitamin D status of OSA patients regarding to potential links between lower vitamin D levels and abnormal glucose metabolism, which is one of the main adverse outcomes of OSA. Study group is composed of 190 non-diabetic subjects who were suspected of having OSA. Subjects undergone polysomnography and were grouped due to apnea-hypopnea indices (AHI) as controls (AHI < 5, n = 47), mild OSA (5 ≤ AHI < 15, n = 46), moderate OSA (15 ≤ AHI < 30, n = 47), and severe OSA (AHI ≥ 30, n = 50). Serum 25-OH-D, HbA₁c, insulin levels were measured and 75-g oral glucose tolerance test was performed. Serum 25-OH-D level (ng/ml) of OSA patients were lower than control subjects (17.4 ± 6.9 vs. 19.9 ± 7.8), and decrement was parallel to severity of OSA; as 18.2 ± 6.4 (5 ≤ AHI < 15), 17.5 ± 7.4 (15 ≤ AHI < 30), and 16.3 ± 6.9 (AHI > 30), respectively (P = 0.097, r = -0.13). However, severe female OSA patients had significantly lower 25-OH-D levels (11.55 ng/ml), while control males had the highest mean value (21.7 ng/ml) (P < 0.001). Frequency of insulin resistance (IR) was 48%, prediabetes 41%, diabetes 16% in OSA patients. Mean 25-OH-D level of insulin resistant subjects (HOMA-IR ≥ 2.7, n = 77, AHI = 35.5) was lower than non-insulin resistant subjects (HOMA-IR < 2.7, n = 113, AHI = 19.8) as 16.18 ± 7.81 versus 19.2 ± 6.6, respectively (P = 0.004). 25-OH-D level of 91 non-diabetic subjects (n = 91, AHI = 19.7) was 19.5 ± 7.4, prediabetics (n = 75, AHI = 28.7) was 17.45 ± 6.9, and diabetics (n = 24, AHI = 46.3) was 13.8 ± 5.3 (P = 0.02). We showed that subjects with more severe OSA indices (AHI ≥ 15) tended to present lower vitamin D levels correlated to increased prevalence of IR, prediabetes, and diabetes. Vitamin D deficiency may play a role and/or worsen
Kathirvel, Elango; Morgan, Kengathevy; French, Samuel W; Morgan, Timothy R
Mitochondrial abnormalities are suggested to be associated with the development of nonalcoholic fatty liver. Liver mitochondrial content and function have been shown to improve in oral feeding of acetyl-L-carnitine (ALC) to rodents. Carnitine is involved in the transport of acyl-coenzyme A across the mitochondrial membrane to be used in mitochondrial β-oxidation. We hypothesized that oral administration ALC with the antioxidant lipoic acid (ALC + LA) would benefit nonalcoholic fatty liver. To test our hypothesis, we fed Balb/C mice a standard diet (SF) or SF with ALC + LA or high-fat diet (HF) or HF with ALC + LA for 6 months. Acetyl-L-carnitine and LA were dissolved at 0.2:0.1% (wt/vol) in drinking water, and mice were allowed free access to food and water. Along with physical parameters, insulin resistance (blood glucose, insulin, glucose tolerance), liver function (alanine transaminase [ALT], aspartate transaminase [AST]), liver histology (hematoxylin and eosin), oxidative stress (malondialdehyde), and mitochondrial abnormalities (carbamoyl phosphate synthase 1 and electron microscopy) were done. Compared with SF, HF had higher body, liver, liver-to-body weight ratio, white adipose tissue, ALT, AST, liver fat, oxidative stress, and insulin resistance. Coadministration of ALC + LA to HF animals significantly improved the mitochondrial marker carbamoyl phosphate synthase 1 and the size of the mitochondria in liver. Alanine transaminase and AST levels were decreased. In a nonalcoholic fatty liver mice model, ALC + LA combination improved liver mitochondrial content, size, serum ALT, and AST without significant changes in oxidative stress, insulin resistance, and liver fat accumulation.
Azad, Reza Mansourian
Laboratory findings can definitely help the patients not to enter into status, where the damage might be happen due to a miss-diagnosis based on clinical assessment alone. The secondary disease accompanied with thyroid patients should also carefully check out due to the interference which some diseases can cause in the amount of serum thyroid hormone, particularly the free thyroxin. The dilemma over thyroid clinical diagnosis occur due to variation on serum thyroid hormone which initiated by other non-thyroidal disorders which can play an important roles in metabolic disorders of thyroid hormone due to the alteration which occur on the serum level of thyroid hormone transporter proteins. The majority of serum thyroid hormones of up to 95-99% are bound to the carrier proteins mainly to Thyroxin-Binding Globulins (TBG), some transthyretin already known as pre-albumin and albumin which are all synthesis in the liver and any modification which alter their production may alter the status of thyroid hormones. It seems TBG, transthyretin and albumin carries 75, 20, 5% of thyroid hormones within blood circulation, respectively. The dilemma facing the thyroid hormones following disruption of thyroid hormone transporter protein synthesis originate from this fact that any alteration of these protein contribute to the alteration of total thyroid and free serum thyroid hormones which are in fact the biologically active form of thyroid hormones. The subsequent of latter implication result in miss-understanding and miss-diagnosis of thyroid function tests, with possible wrongly thyroid clinical care, followed by undesired therapy of otherwise healthy thyroid.
Rychlak, Joseph F.
This study contrasts a group of mildly'' abnormal high school males with matched normals in a two-session free phantasy procedure. Mildly abnormal boys phantasized more negative contents than normal boys. Normal boys projected more positive phantasies into the future than mildly abnormal boys. A logical learning theory'' embracing the…
Sun, Liyan; Gao, Yanhui; Zhang, Wei; Liu, Hui; Sun, Dianjun
The purpose of this study was to explore the effects of high fluoride and high fat on triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), total antioxidant capacity (T-AOC), lipid peroxide (LPO) and malondialdehyde (MDA) in rabbits. A factorial experimental design was used, with two factors (fluoride and fat) and three levels. Seventy-two male rabbits were randomly assigned into nine groups according to initial weight and serum lipid levels. The rabbits were fed with basic feed, moderate fat feed or high fat feed and drank tap water, fluoridated water at levels of 50 and 100mgfluorion/L freely. Biological materials were collected after 5 months, and serum lipid, T-AOC, LPO, and MDA levels were then measured. Using these data, the separate and interactive effects of high fluoride and high fat were analyzed. High fluoride and high fat both increased serum levels of TC, HDL-C and LDL-C significantly (P<0.05), and there was also a synergistic effect between high fluoride and high fat (P<0.05). High fluoride and high fat had different effects on TG levels: high fat significantly increased TG levels (P<0.01) whereas high fluoride had nothing to do with TG levels (P>0.05). High fat significantly elevated LPO and MDA levels and lowered T-AOC levels in serum (P<0.05). Similarly, high fluoride significantly increased LPO and MDA levels in serum (P<0.05). However, there was no interactive effect between high fat and high fluoride on these indexes. In summary, high fluoride and high fat increased serum TC and LDL-C levels individually and synergistically, and this would cause and aggravate hypercholesterolemia in rabbits. At the same time, high fluoride and high fat both made the accumulation of product of oxidative stress in experimental animals.
Li, Xinli; Chen, Younan; Liu, Jingping; Yang, Guang; Zhao, Jiuming; Liao, Guangneng; Shi, Meimei; Yuan, Yujia; He, Sirong; Lu, Yanrong; Cheng, Jingqiu
Dyslipidemia caused by 'Western-diet pattern' is a strong risk factor for the onset of diabetes. This study aimed to disclose the relationship between the serum metabolite changes induced by habitual intake of high-fat and high-cholesterol (HFHC) diet and the development of impaired glucose tolerance (IGT) and insulin resistance through animal models of Macaca mulatta. Sixteen M. mulatta (six months old) were fed a control diet or a HFHC diet for 18 months. The diet effect on serum metabolic profiles was investigated by longitudinal research. Islet function was assessed by intravenous glucose tolerance and hyperinsulinemic-euglycemic clamp test. Metabonomics were determined by (1)H proton nuclear magnetic resonance spectroscopy. Prolonged diet-dependent hyperlipidemia facilitated visceral fat accumulation in liver and skeletal muscle and disorder of glucose homeostasis in juvenile monkeys. Glucose disappearance rate (K(Glu)) and insulin response to the glucose challenge effects in HFHC monkeys were significantly lower than in control monkeys. Otherwise, serum trimethylamine-N-oxide (TMAO), lactate and leucine/isoleucine were significantly higher in HFHC monkeys. Sphingomyelin and choline were the most positively correlated with K(Glu) (R(2) = 0.778), as well as negative correlation (R(2) = 0.64) with total cholesterol. The HFHC diet induced visceral fat, abnormal lipid metabolism and IGT prior to weight gain and body fat content increase in juvenile monkeys. We suggest that increased serum metabolites, such as TMAO, lactate, branched-chain amino acids and decreased sphingomyelin and choline, may serve as possible predictors for the evaluation of IGT and insulin resistance risks in the prediabetic state.
Qingying, Hou; Kaiyuan, Chen; Zifei, Fan; Libing, Fu; Yefei, Chen
The higher pressure coefficient is the major characteristics of the abnormal high pressure carbonate reservoirs, which the pressure coefficient generally exceeds 1.2 and the initial formation pressure is higher than normal sandstone reservoirs. Due to the large pressure difference between initial formation and saturated pressure, oil wells are capable to production with high flow rate by the natural energy at early production stage. When the formation pressure drops to the saturation pressure, the water or gas is usually injected to stabilize the well productivity and sustain the formation pressure. Based on the characteristics of Kenkiak oilfield, a typical abnormal high pressure carbonate reservoir, a well group model is designed to simulate and analyze the influence factors on water flooding. The conclusion is that permeability, interlayer difference and reserve abundance are the main three factors on the water flooding development in these reservoirs.
Abáigar, María; Robledo, Cristina; Benito, Rocío; Ramos, Fernando; Díez-Campelo, María; Hermosín, Lourdes; Sánchez-del-Real, Javier; Alonso, Jose M.; Cuello, Rebeca; Megido, Marta; Rodríguez, Juan N.; Martín-Núñez, Guillermo; Aguilar, Carlos; Vargas, Manuel; Martín, Ana A.; García, Juan L.; Kohlmann, Alexander; del Cañizo, M. Consuelo; Hernández-Rivas, Jesús M.
To explore novel genetic abnormalities occurring in myelodysplastic syndromes (MDS) through an integrative study combining array-based comparative genomic hybridization (aCGH) and next-generation sequencing (NGS) in a series of MDS and MDS/myeloproliferative neoplasms (MPN) patients. 301 patients diagnosed with MDS (n = 240) or MDS/MPN (n = 61) were studied at the time of diagnosis. A genome-wide analysis of DNA copy number abnormalities was performed. In addition, a mutational analysis of DNMT3A, TET2, RUNX1, TP53 and BCOR genes was performed by NGS in selected cases. 285 abnormalities were identified in 71 patients (23.6%). Three high-risk MDS cases (1.2%) displayed chromothripsis involving exclusively chromosome 13 and affecting some cancer genes: FLT3, BRCA2 and RB1. All three cases carried TP53 mutations as revealed by NGS. Moreover, in the whole series, the integrative analysis of aCGH and NGS enabled the identification of cryptic recurrent deletions in 2p23.3 (DNMT3A; n = 2.8%), 4q24 (TET2; n = 10%) 17p13 (TP53; n = 8.5%), 21q22 (RUNX1; n = 7%), and Xp11.4 (BCOR; n = 2.8%), while mutations in the non-deleted allele where found only in DNMT3A (n = 1), TET2 (n = 3), and TP53 (n = 4). These cryptic abnormalities were detected mainly in patients with normal (45%) or non-informative (15%) karyotype by conventional cytogenetics, except for those with TP53 deletion and mutation (15%), which had a complex karyotype. In addition to well-known copy number defects, the presence of chromothripsis involving chromosome 13 was a novel recurrent change in high-risk MDS patients. Array CGH analysis revealed the presence of cryptic abnormalities in genomic regions where MDS-related genes, such as TET2, DNMT3A, RUNX1 and BCOR, are located. PMID:27741277
Background: Identifying genes that are essential for mouse embryonic development and survival through term is a powerful and unbiased way to discover possible genetic determinants of human developmental disorders. Characterising the changes in mouse embryos that result from ablation of lethal genes is a necessary first step towards uncovering their role in normal embryonic development and establishing any correlates amongst human congenital abnormalities. Methods: Here we present results gathered to date in the Deciphering the Mechanisms of Developmental Disorders (DMDD) programme, cataloguing the morphological defects identified from comprehensive imaging of 220 homozygous mutant embryos from 42 lethal and subviable lines, analysed at E14.5. Results: Virtually all embryos show multiple abnormal phenotypes and amongst the 42 lines these affect most organ systems. Within each mutant line, the phenotypes of individual embryos form distinct but overlapping sets. Subcutaneous edema, malformations of the heart or great vessels, abnormalities in forebrain morphology and the musculature of the eyes are all prevalent phenotypes, as is loss or abnormal size of the hypoglossal nerve. Conclusions: Overall, the most striking finding is that no matter how profound the malformation, each phenotype shows highly variable penetrance within a mutant line. These findings have challenging implications for efforts to identify human disease correlates. PMID:27996060
Baker, Kate C; Bloomsmith, Mollie; Neu, Kimberly; Griffis, Caroline; Maloney, Margaret; Oettinger, Brooke; Schoof, Valerie A M; Martinez, Marni
This study evaluated the application of positive reinforcement training (PRT) as an intervention for abnormal behaviors in singly housed laboratory rhesus macaques at 2 large primate facilities. Training involved basic control behaviors and body-part presentation. The study compared baseline behavioral data on 30 adult males and 33 adult females compared with 3 treatment phases presented in counterbalanced order: 6 min per week of PRT, 20 or 40 min per week of PRT, and 6 min per week of unstructured human interaction (HI). Within-subject parametric tests detected no main or interaction effects involving experimental phase. However, among a subset of subjects with levels of abnormal in the top quartile of the range (n = 15), abnormal behavior was reduced from 35% to 25% of samples with PRT but not with HI. These results suggest that short durations of PRT applied as enrichment for this species and in this context may not in itself be sufficient intervention for abnormal behavior because levels remained high. However, it may be appropriate as an adjunct to other interventions and may be best targeted to the most severely affected individuals.
Baker, Kate C.; Bloomsmith, Mollie; Neu, Kimberly; Griffis, Caroline; Maloney, Margaret; Oettinger, Brooke; Schoof, Valérie A. M.; Martinez, Marni
This study evaluated the application of positive reinforcement training (PRT) as an intervention for abnormal behaviors in singly housed laboratory rhesus macaques at 2 large primate facilities. Training involved basic control behaviors and body-part presentation. The study compared baseline behavioral data on 30 adult males and 33 adult females compared with 3 treatment phases presented in counterbalanced order: 6 min per week of PRT, 20 or 40 min per week of PRT, and 6 min per week of unstructured human interaction (HI). Within-subject parametric tests detected no main or interaction effects involving experimental phase. However, among a subset of subjects with levels of abnormal in the top quartile of the range (n = 15), abnormal behavior was reduced from 35% to 25% of samples with PRT but not with HI. These results suggest that short durations of PRT applied as enrichment for this species and in this context may not in itself be sufficient intervention for abnormal behavior because levels remained high. However, it may be appropriate as an adjunct to other interventions and may be best targeted to the most severely affected individuals. PMID:20183477
By simply adding a high concentration of calcium solution to the surface of the bullfrog heart, we reproduced electrocardiogram (ECG) abnormalities representing those observed in hypercalcemia, such as Osborn waves and shortening of the QT interval. The rise in extracellular calcium concentration may have activated the outward potassium currents during phase 3 of the action potential, and thus decreased its duration. In addition to the known decrease in the duration of phase 2, such changes in phase 3 were also likely to contribute to the shortening of the QT interval. The dual recordings of the action potential in cardiomyocytes and the ECG waves enabled us to demonstrate the mechanisms of ECG abnormalities induced by hypercalcemia.
By simply adding a high concentration of calcium solution to the surface of the bullfrog heart, we reproduced electrocardiogram (ECG) abnormalities representing those observed in hypercalcemia, such as Osborn waves and shortening of the QT interval. The rise in extracellular calcium concentration may have activated the outward potassium currents during phase 3 of the action potential, and thus decreased its duration. In addition to the known decrease in the duration of phase 2, such changes in phase 3 were also likely to contribute to the shortening of the QT interval. The dual recordings of the action potential in cardiomyocytes and the ECG waves enabled us to demonstrate the mechanisms of ECG abnormalities induced by hypercalcemia. PMID:27773880
Vandenput, Liesbeth; Mellström, Dan; Kindmark, Andreas; Johansson, Helena; Lorentzon, Mattias; Leung, Jason; Redlund‐Johnell, Inga; Rosengren, Björn E; Karlsson, Magnus K; Wang, Yi‐Xiang; Kwok, Timothy
ABSTRACT Previous prospective cohort studies have shown that serum levels of sex steroids and sex hormone‐binding globulin (SHBG) associate with nonvertebral fracture risk in men. The predictive value of sex hormones and SHBG for vertebral fracture risk specifically is, however, less studied. Elderly men (aged ≥65 years) from Sweden and Hong Kong participating in the Osteoporotic Fractures in Men (MrOS) study had baseline estradiol and testosterone analyzed by gas chromatography–mass spectrometry (GC‐MS) and SHBG by immunoradiometric assay (IRMA). Incident clinical vertebral fractures (n = 242 cases) were evaluated in 4324 men during an average follow‐up of 9.1 years. In a subsample of these men (n = 2256), spine X‐rays were obtained at baseline and after an average follow‐up of 4.3 years to identify incident radiographic vertebral fractures (n = 157 cases). The likelihood of incident clinical and radiographic vertebral fractures was estimated by Cox proportional hazards models and logistic regression models, respectively. Neither serum estradiol (hazard ratio [HR] per SD increase = 0.93, 95% confidence interval [CI] 0.80–1.08) nor testosterone (1.05, 0.91–1.21) predicted incident clinical vertebral fractures in age‐adjusted models in the combined data set. High serum SHBG, however, associated with increased clinical vertebral fracture risk (1.24, 1.12–1.37). This association remained significant after further adjustment for FRAX with or without bone mineral density (BMD). SHBG also associated with increased incident radiographic vertebral fracture risk (combined data set; odds ratio [OR] per SD increase = 1.23, 95% CI 1.05–1.44). This association remained significant after adjustment for FRAX with or without BMD. In conclusion, high SHBG predicts incident clinical and radiographic vertebral fractures in elderly men and adds moderate information beyond FRAX with BMD for vertebral fracture risk prediction. © 2015 The
Saxena, Ashima; Sun, Wei; Dabisch, Paul A; Hulet, Stanley W; Hastings, Nicholas B; Jakubowski, Edward M; Mioduszewski, Robert J; Doctor, Bhupendra P
Human serum butyrylcholinesterase (Hu BChE) is a stoichiometric bioscavenger that is being developed as a prophylactic countermeasure against organophosphorus nerve agents. This study was designed to evaluate the efficacy of Hu BChE against whole-body inhalation exposure to a lethal dose of sarin (GB) vapor. Male Göttingen minipigs were subjected to: air exposure, GB vapor exposure, or pretreatment with Hu BChE followed by GB vapor exposure. Hu BChE was administered by i.m. injection 24 h prior to exposure to 4.1 mg/m(3) of GB vapor for 60 min. Electrocardiograms (ECG), electroencephalograms (EEG), and pupil size were recorded throughout exposure. Blood drawn before and throughout exposure was analyzed for blood gases, electrolytes, metabolites, acetylcholinesterase and BChE activities, and amount of GB present. Untreated animals exposed to GB vapor exhibited cardiac abnormalities and generalized seizures, ultimately succumbing to respiratory failure. Pretreatment with 3.0 or 6.5 mg/kg of Hu BChE delayed blood gas and acid-base disturbances and the onset of cardiac and neural toxic signs, but failed to increase survivability. Pretreatment with 7.5 mg/kg of Hu BChE, however, completely prevented toxic signs, with blood chemistry and ECG and EEG parameters indistinguishable from control during and after GB exposure. GB bound in plasma was 200-fold higher than plasma from pigs that did not receive Hu BChE, suggesting that Hu BChE scavenged GB in blood and prevented it from reaching other tissues. Thus, prophylaxis with Hu BChE alone not only increased survivability, but also prevented cardiac abnormalities and neural toxicity in minipigs exposed to a lethal dose of GB vapor.
Jastrzebski, Nicola R; Crewther, Sheila G; Crewther, David P
The cause of developmental dyscalculia, a specific deficit in acquisition of arithmetic skills, particularly of enumeration, has never been investigated with respect to the patency of the visual magnocellular system. Here, the question of dysfunction of the afferent magnocellular cortical input and its dorsal stream projections was tested directly using nonlinear analysis of the visual evoked potential (VEP) and through the psychophysical ability to rapidly detect visual change. A group of young adults with self-reported deficiencies of arithmetical ability, showed marked impairment in magnitude estimation and enumeration performance-though not in lexical decision reaction times when compared with an arithmetically capable group controlled for age and handedness. Multifocal nonlinear VEPs were recorded at low (24 %) and high (96 %) contrast. First- and second-order VEP kernels were comparable between groups at low contrast, but not at high contrast. The mathematically impaired group showed an abnormal lack of contrast saturation in the shortest latency first-order peak (N60) and a delayed P100 positivity in the first slice of the second-order kernel. Both features have previously been argued to be physiological markers of magnocellular function. Mathematically impaired participants also performed worse on a gap paradigm change detection for digit task showing increased reaction times for high-contrast stimuli but not for low-contrast stimuli compared with controls. The VEP results give direct evidence of abnormality in the occipital processing of magnocellular information in those with mathematical impairment. The anomalous high visual contrast physiological and psychophysical performance suggests an abnormality in the inhibitory processes that normally result in saturation of contrast gain in the magnocellular system.
Ikemura, Satoshi; Yamamoto, Takuaki; Motomura, Goro; Iwasaki, Kenyu; Yamaguchi, Ryosuke; Zhao, Garida; Iwamoto, Yukihide
The pathogenesis of alcohol-induced osteonecrosis remains unclear. The purpose of the present study was to evaluate the morphological changes in bone marrow fat cells and the changes in the serum lipid levels in alcohol-treated rabbits. Fifteen rabbits were randomly assigned into three groups: Four rabbits intragastrically received low-dose alcohol (LDA) (15 ml/kg per day) containing 15% ethanol for 4 weeks, five rabbits received high-dose alcohol (HDA) (30 ml/kg per day) for 4 weeks and six rabbits received physiologic saline for 4 weeks as a control group. Six weeks after the initial alcohol administration, all rabbits were sacrificed. The mean size of the bone marrow fat cells in rabbits treated with HDA was significantly larger than that in the control group (P = 0.0001). Haematologically, the levels of triglycerides and free fatty acids in the rabbits treated with both low-dose and HDA were significantly higher than those in the control group (P = 0.001 for both comparisons). The results of this study are that there are lipid metabolism abnormalities, both morphologically and haematologically, after alcohol administration. Also these findings were more apparent in rabbits treated with HDA than those treated with LDA. PMID:21645143
Yildiz, Bekir S; Ozkan, Emel; Esin, Fatma; Alihanoglu, Yusuf I; Ozkan, Hayrettin; Bilgin, Murat; Kilic, Ismail D; Ergin, Ahmet; Kaftan, Havane A; Evrengul, Harun
In patients with coronary artery disease (CAD), though aspirin inhibits platelet activation and reduces atherothrombotic complications, it does not always sufficiently inhibit platelet function, thereby causing a clinical situation known as aspirin resistance. As hyperuricemia activates platelet turnover, aspirin resistance may be specifically induced by increased serum uric acid (SUA) levels. In this study, we thus investigated the association between SUA level and aspirin resistance in patients with CAD. We analyzed 245 consecutive patients with stable angina pectoris (SAP) who in coronary angiography showed more than 50% occlusion in a major coronary artery. According to aspirin resistance, two groups were formed: the aspirin resistance group (Group 1) and the aspirin-sensitive group (Group 2). Compared with those of Group 2, patients with aspirin resistance exhibited significantly higher white blood cell counts, neutrophil counts, neutrophil-to-lymphocyte ratios, SUA levels, high-sensitivity C-reactive protein levels, and fasting blood glucose levels. After multivariate analysis, a high level of SUA emerged as an independent predictor of aspirin resistance. The receiver-operating characteristic analysis provided a cutoff value of 6.45 mg/dl for SUA to predict aspirin resistance with 79% sensitivity and 65% specificity. Hyperuricemia may cause aspirin resistance in patients with CAD and high SUA levels may indicate aspirin-resistant patients. Such levels should thus recommend avoiding heart attack and stroke by adjusting aspirin dosage.
Jiang, Qiang; Qiu, Nansheng; Zhu, Chuanqing
It is commonly believed that increase of heat flow caused by a mantle plume is small and transient. Seafloor heat flow data near the Hawaiian hotspot and the Iceland are comparable to that for oceanic lithosphere elsewhere. Numerical modeling of the thermal effect of the Parana large igneous province shows that the added heat flow at the surface caused by the magmatic underplating is less than 5mW/m2. However, the thermal effect of Emeishan mantle plume (EMP) may cause the surface hear-flow abnormally high. The Middle-Late Emeishan mantle plume is located in the western Yangtze Craton. The Sichuan basin, to the northeast of the EMP, is a superimposed basin composed of Paleozoic marine carbonate rocks and Mesozoic-Cenozoic terrestrial clastic rocks. The vitrinite reflectance (Ro) data as a paleogeothermal indicator records an apparent change of thermal regime of the Sichuan basin. The Ro profiles from boreholes and outcrops which are close to the center of the basalt province exhibit a 'dog-leg' style at the unconformity between the Middle and Upper Permian, and they show significantly higher gradients in the lower subsection (pre-Middle Permian) than the Upper subsection (Upper Permian to Mesozoic). Thermal history inversion based on these Ro data shows that the lower subsection experienced a heat flow peak much higher than that of the upper subsection. The abnormal heat flow in the Sichuan basin is consistent with the EMP in temporal and spatial distribution. The high-temperature magmas from deep mantle brought heat to the base of the lithosphere, and then large amount of heat was conducted upwards, resulting in the abnormal high surface heat flow.
Cho, A-Yeon; Yi, Kye Sook; Rhim, Jung-Hyo; Kim, Kyu-Il; Park, Jae-Young; Keum, Eun-Hee; Chung, Junho; Oh, Sangsuk
Amygdalin is a cyanogenic glycoside compound which is commonly found in the pits of many fruits and raw nuts. Although amygdalin itself is not toxic, it can release cyanide (CN) after hydrolysis when the pits and nuts are crushed, moistened and incubated, possibly within the gastrointestinal tract. CN reversibly inhibits cellular oxidizing enzymes and cyanide poisoning generates a range of clinical symptoms. As some pits and nuts may contain unusually high levels of amygdalin such that there is a sufficient amount to induce critical CN poisoning in humans, the detection of abnormal content of amygdalin in those pits and nuts can be a life-saving measure. Although there are various methods to detect amygdalin in food extracts, an enzyme immunoassay has not been developed for this purpose. In this study we immunized New Zealand White rabbits with an amygdalin-KLH (keyhole limpet hemocyanin) conjugate and succeeded in raising anti-sera reactive to amygdalin, proving that amygdalin can behave as a hapten in rabbits. Using this polyclonal antibody, we developed a competition enzyme immunoassay for determination of amygdalin concentration in aqueous solutions. This technique was able to effectively detect abnormally high amygdalin content in various seeds and nuts. In conclusion, we proved that enzyme immunoassay can be used to determine the amount of amygdalin in food extracts, which will allow automated analysis with high throughput.
Konjiki, O; Yoneda, Y; Sato, Y; Oosawa, Y; Imamura, T; Takasaki, M
A 78-year-old man was admitted to our hospital with anemia and jaundice. Hematological studies revealed hyperchromic macrocytic anemia, and biochemical studies revealed findings of hemolysis. The folic acid level was low and megaloblasts were observed in the bone marrow. From these findings, the patient was diagnosed as having megaloblastic anemia due to folic acid deficiency. This patient had been a heavy alcohol drinker in the habit of drinking alcohol without meals. He began to eat regular meals in the hospital, and the anemia and jaundice improved gradually. Since liver cirrhosis was suspected, amino acid analysis of the urine was performed, and abnormal excretion of beta-amino-isobutyric acid (BAIB) was found. According to the amount of BAIB excreted, the Japanese population can be divided into low and high BAIB excretors comprising 65% and 36%, respectively. BAIB is also considered to reflect dissimilation of thymine. The present patient was included in the high excretion group because of the abnormally high urine level of BAIB, which was considered to be caused by ineffective hematopoiesis in the bone marrow as a result of his megaloblastic anemia. For this reason, dissimilation of thymine was considered to have been active in this patient.
... Listen Español Text Size Email Print Share Congenital Abnormalities Page Content Article Body About 3% to 4% ... of congenital abnormalities earlier. 5 Categories of Congenital Abnormalities Chromosome Abnormalities Chromosomes are structures that carry genetic ...
Seo, B. H.; Kim, J. H.; You, S. J.
A controversial problem on the evolution of Ar metastable density as a function of electron density (increasing trend versus decreasing trend) was resolved by discovering the anomalous evolution of the argon metastable density with increasing electron density (discharge power), including both trends of the metastable density [Daltrini et al., Appl. Phys. Lett. 92, 061504 (2008)]. Later, by virtue of an adequate physical explanation based on a simple global model, both evolutions of the metastable density were comprehensively understood as part of the abnormal evolution occurring at low- and high-density regimes, respectively, and thus the physics behind the metastable evolution has seemed to be clearly disclosed. In this study, however, a remarkable result for the metastable density behavior with increasing electron density was observed: even in the same electron density regime, there are both normal and abnormal evolutions of metastable-state density with electron density depending on the measurement position: The metastable density increases with increasing electron density at a position far from the inductively coupled plasma antenna but decreases at a position close to the antenna. The effect of electron temperature, which is spatially nonuniform in the plasma, on the electron population and depopulation processes of Argon metastable atoms with increasing electron density is a clue to understanding the results. The calculated results of the global model, including multistep ionization for the argon metastable state and measured electron temperature, are in a good agreement with the experimental results.
Benlhachemi, A.; Gavarri, J. R.; Musso, J.; Alfred-Duplan, C.; Marfaing, J.
High- Tc 2223-bismuth superconducting pigments have been inserted in a matrix of Fe 3+-doped polyphenylene sulphide (PPS) to obtain new composites with variable properties. The fabrication and the characterization of the various components are briefly described. The electrical resistivity at a low temperature of the composites is reported. In the case of multiphase super-conducting pigments presenting various Tc's and semiconducting fabrication residues inserted in the polymeric matrix, the composites are characterized by abnormal resistivity evolutions between 20 K and 300 K. A new electrical model is proposed to interpret the behavior of such composites in the full 5 K to 300 K temperature range. Percolation features are taken into account through an empirical description of the electrical complex impedances. The computer calculations allow one to characterize fabrication residues and interfaces between insulating, conducting and superconducting areas in the composites.
Fan, Cunxiu; Zhao, Yuhua; Yu, Qian; Yin, Wu; Liu, Haipeng; Lin, Jianzhong; Yang, Tianhe; Fan, Ming; Gesang, Luobu; Zhang, Jiaxing
A large proportion of lowlanders ascending to high-altitude (HA) show no signs of mountain sickness. Whether their brains have indeed suffered from HA environment and the persistent sequelae after return to lowland remain unknown. Thirty-one sea-level college students, who had a 30-day teaching on Qinghai-Tibet plateau underwent MRI scans before, during, and two months after HA exposure. Brain volume, cortical structures, and white matter microstructure were measured. Besides, serum neuron-specific enolase (NSE), C-reactive protein, and interleukin-6 and neuropsychiatric behaviors were tested. After 30-day HA exposure, the gray and white matter volumes and cortical surface areas significantly increased, with cortical thicknesses and curvatures changed in a wide spread regions; Anisotropy decreased with diffusivities increased in multiple sites of white matter tracts. Two months after HA exposure, cortical measurements returned to basal level. However, increased anisotropy with decreased diffusivities was observed. Behaviors and serum inflammatory factor did not significant changed during three time-point tests. NSE significantly decreased during HA but increased after HA exposure. Results suggest brain swelling occurred in people without neurological signs at HA, but no negative sequelae in cortical structures and neuropsychiatric functions were left after the return to lowlands. Reoxygenation changed white matter microstructure. PMID:27633944
Yerkes, R.F.; Levine, P.; Wentworth, C.M.
Abnormally high fluid pressures (AHP's) permitted or aided thrusting of buried tectonic wedges of Franciscan assemblage eastward beneath coeval Great Valley sequence onto mafic basement and thus contributed to the 1983 Coalinga earthquake sequence. Much of the southwestern San Joaquin Valley and adjoining parts of the Diablo Range are underlain by rocks with pressure/depth (P/D) ratios near or greater than 0.5 psi/ft (the hydrostatic gradient for oil-field waters is about 0.47 psi/ft). Plots of P/D ratio versus depth for more than 300 wells show an average ratio of about 0.6 psi/ft above 14,000-ft depth, a lower bound of 0.47 psi/ft, and an upper bound greater than 0.9 psi/ft; ratios greater than 0.60 psi/ft are interpreted to be abnormally high. Several likely sources of AHP's are recognized, but their relative contributions cannot be determined. Chief of these sources are diagenetic-metamorphic generation of fluids in the Great Valley sequence and Franciscan rocks, compaction disequilibrium and aquathermal pressuring in Tertiary strata, and horizontal tectonic compression. Yerkes, Levine, and Wentworth infer the presence of near-lithostatic fluid pressures in the Great Valley sequence and Franciscan rocks below the Coalinga anticline on the basis of (1) a mapped seismic low-velocity zone; (2) active generation of metamorphic fluids in the Great Valley sequence and Franciscan rocks, which pond below relatively impermeable layers and thus increase fluid pressure; and (3) apparent southward and westward propagation of the 1983 main-shock rupture, which indicates rupture on a gently southwest dipping surface and implies an inverse relation between depth and crustal strength.
Carr-Wilkinson, Jane; O' Toole, Kieran; Wood, Katrina M.; Challen, Christine C.; Baker, Angela G.; Board, Julian R.; Evans, Laura; Cole, Michael; Cheung, Nai-Kong V.; Boos, Joachim; Köhler, Gabriele; Leuschner, Ivo; Pearson, Andrew D.J.; Lunec, John; Tweddle, Deborah A.
Purpose: Most neuroblastomas initially respond to therapy but many relapse with chemoresistant disease. p53 mutations are rare in diagnostic neuroblastomas, but we have previously reported inactivation of the p53/MDM2/p14ARF pathway in 9/17 (53%) neuroblastoma cell lines established at relapse. Hypothesis: Inactivation of the p53/MDM2/p14ARF pathway develops during treatment and contributes to neuroblastoma relapse. Methods: Eighty-four neuroblastomas were studied from 41 patients with relapsed neuroblastoma including 38 paired neuroblastomas at different stages of therapy. p53 mutations were detected by automated sequencing, p14ARF methylation and deletion by methylation-specific PCR and duplex PCR respectively, and MDM2 amplification by fluorescent in-situ hybridisation. Results: Abnormalities in the p53 pathway were identified in 20/41(49%) cases. Downstream defects due to inactivating missense p53 mutations were identified in 6/41 (15%) cases, 5 following chemotherapy and/or at relapse and 1 at diagnosis, post chemotherapy and relapse. The presence of a p53 mutation was independently prognostic for overall survival (hazard ratio 3.4, 95% confidence interval 1.2, 9.9; p = 0.02). Upstream defects were present in 35% cases: MDM2 amplification in 3 cases, all at diagnosis & relapse and p14ARF inactivation in 12/41 (29%) cases: 3 had p14ARF methylation, 2 after chemotherapy, and 9 had homozygous deletions, 8 at diagnosis and relapse. Conclusions: These results show that a high proportion of neuroblastomas which relapse have an abnormality in the p53 pathway. The majority have upstream defects suggesting that agents which reactivate wild-type p53 would be beneficial, in contrast to those with downstream defects where p53 independent therapies are indicated. PMID:20145180
Gliske, Stephen; Catoni, Nicholas
Abstract High-frequency oscillations (HFOs) are an intriguing potential biomarker for epilepsy, typically categorized according to peak frequency as either ripples (100–250 Hz) or fast ripples (>250 Hz). In the hippocampus, fast ripples were originally thought to be more specific to epileptic tissue, but it is still very difficult to distinguish which HFOs are caused by normal versus pathological brain activity. In this study, we use a computational model of hippocampus to investigate possible network mechanisms underpinning normal ripples, pathological ripples, and fast ripples. Our results unify several prior findings regarding HFO mechanisms, and also make several new predictions regarding abnormal HFOs. We show that HFOs are generic, emergent phenomena whose characteristics reflect a wide range of connectivity and network input. Although produced by different mechanisms, both normal and abnormal HFOs generate similar ripple frequencies, underscoring that peak frequency is unable to distinguish the two. Abnormal ripples are generic phenomena that arise when input to pyramidal cells overcomes network inhibition, resulting in high-frequency, uncoordinated firing. In addition, fast ripples transiently and sporadically arise from the precise conditions that produce abnormal ripples. Lastly, we show that such abnormal conditions do not require any specific network structure to produce coherent HFOs, as even completely asynchronous activity is capable of producing abnormal ripples and fast ripples in this manner. These results provide a generic, network-based explanation for the link between pathological ripples and fast ripples, and a unifying description for the entire spectrum from normal ripples to pathological fast ripples. PMID:26146658
Song, Jun; Chang, Insoon; Chen, Zhuo; Kang, Mo; Wang, Cun-Yu
Side Population (SP) cells, a subset of Hoechst-low cells, are enriched with stem cells. Originally, SP cells were isolated from bone marrow but recently have been found in various solid tumors and cancer cell lines that are clonogenic in vitro and tumorigenic in vivo. In this study, SP cells from lymph node metastatic head and neck squamous cell carcinoma (HNSCC) cell lines were examined using flow cytometry and Hoechst 3342 efflux assay. We found that highly metastatic HNSCC cell lines M3a2 and M4e contained more SP cells compared to the low metastatic parental HNSCC cell line 686LN. SP cells in HNSCC were highly invasive in vitro and tumorigenic in vivo compared to non-SP cells. Furthermore, SP cells highly expressed ABCG2 and were chemoresistant to Bortezomib and etoposide. Importantly, we found that SP cells in HNSCC had abnormal activation of Wnt/β-catenin signaling as compared to non-SP cells. Together, these findings indicate that SP cells might be a major driving force of head and neck tumor formation and metastasis. The Wnt/β-catenin signaling pathway may be an important target for eliminating cancer stem cells in HNSCC. PMID:20625515
Sotto, A; Peray, P; Geny, F; Brunschwig, C; Carrière, C; Galtier, M; Ramuz, M; Jourdan, J
An enzymatic method using nitrocefin as substrate was developed to assay sulbactam in human serum. Serum containing sulbactam was incubated with purified titrated TEM-1 beta-lactamase and nitrocefin was then added to the mixture to determine the remaining beta-lactamase activity and consequently the concentration of sulbactam. Assays were carried out on five patients with pulmonary infections receiving sulbactam plus amoxycillin iv. The values for serum sulbactam concentrations determined by the enzymatic method were compared with those determined by high performance liquid chromatography (HPLC). The correlation coefficient was 0.990 for serum sulbactam concentrations below 15 mg/L.
Dekker, Marijke; Pasch, Andreas; van der Sande, Frank; Konings, Constantijn; Bachtler, Matthias; Dionisi, Mauro; Meier, Matthias; Kooman, Jeroen; Canaud, Bernard
Background Calciprotein particles (CPPs) may play an important role in the calcification process. The calcification propensity of serum (T50) is highly predictive of all-cause mortality in chronic kidney disease patients. Whether T50 is therapeutically improvable, by high-flux hemodialysis (HD) or hemodiafiltration (HDF), has not been studied yet. Methods We designed a cross-sectional single center study, and included stable prevalent in-center dialysis patients on HD or HDF. Patients were divided into two groups based on dialysis modality, were on a thrice-weekly schedule, had a dialysis vintage of > 3 months and vascular access providing a blood flow rate > 300 ml/min. Calcification propensity of serum was measured by the time of transformation from primary to secondary CPP (T50 test), by time-resolved nephelometry. Results We included 64 patients, mean convective volume was 21.7L (SD 3.3L). In the pooled analysis, T50 levels increased in both the HD and HDF group with pre- and post-dialysis (mean (SD)) of 244(64) - 301(57) and 253(55) - 304(61) min respectively (P = 0.43(HD vs. HDF)). The mean increase in T50 was 26.29% for HD and 21.97% for HDF patients (P = 0.61 (HD vs. HDF)). The delta values (Δ) of calcium, phosphate and serum albumin were equal in both groups. Baseline T50 was negatively correlated with phosphate, and positively correlated with serum magnesium and fetuin-A. The ΔT50 was mostly influenced by Δ phosphate (r = -0.342; P = 0.002 HD and r = -0.396; P<0.001 HDF) in both groups. Conclusions HD and HDF patients present with same baseline T50 calcification propensity values pre-dialysis. Calcification propensity is significantly improved during both HD and HDF sessions without significant differences between both modalities. PMID:27064679
Maes, M; Smith, R; Christophe, A; Vandoolaeghe, E; Van Gastel, A; Neels, H; Demedts, P; Wauters, A; Meltzer, H Y
Recently, there have been some reports that changes in serum lipid composition may be related to suicide, major depression and immune-inflammatory responses. Findings from our laboratory suggest that major depression is accompanied by reduced formation of cholesteryl esters and perhaps by impairment of reverse cholesterol transport. The latter is reportedly accompanied by lower serum high-density lipoprotein cholesterol (HDL-C). The aim of this study was to examine whether (i) major depression is accompanied by lower serum HDL-C or by abnormal levels of serum total cholesterol, triglycerides, low-density lipoprotein-C (LDL-C) or vitamin E, (ii) suicidal attempts are related to lower serum HDL-C and (iii) there are significant associations between serum HDL-C and immune/inflammatory markers. A total of 36 subjects with major depression, of whom 28 patients showed treatment resistance, as well as 28 normal control subjects, had blood sampled for the assay of the above lipids, serum zinc (Zn), albumin (Alb) and flow cytometric determination of the T-helper/T-suppressor (CD4+/CD8+) T-cell ratio. In total, 28 depressed subjects had repeated measures of these variables both before and after treatment with antidepressants. Serum HDL-C and total cholesterol, as well as the HDL-C/cholesterol ratio, were significantly lower in subjects with major depression than in normal controls. Serum HDL-C levels were significantly lower in depressed men who had at some time made serious suicidal attempts than in those without such suicidal behaviour. Treatment with antidepressants for 5 weeks did not significantly alter either serum HDL-C or other lipid variables. Serum HDL-C levels were significantly and negatively correlated with the (CD4+/CD8+) T-cell ratio, and positively correlated with serum Alb and Zn. These results suggest that (i) lower serum HDL-C levels are a marker for major depression and suicidal behaviour in depressed men, (ii) lower serum HDL-C levels are probably
Yuksel, C; Du, F; Ravichandran, C; Goldbach, J R; Thida, T; Lin, P; Dora, B; Gelda, J; O'Connor, L; Sehovic, S; Gruber, S; Ongur, D; Cohen, B M
Converging evidence suggests bioenergetic abnormalities in bipolar disorder (BD). In the brain, phosphocreatine (PCr) acts a reservoir of high-energy phosphate (HEP) bonds, and creatine kinases (CK) catalyze the transfer of HEP from adenosine triphosphate (ATP) to PCr and from PCr back to ATP, at times of increased need. This study examined the activity of this mechanism in BD by measuring the levels of HEP molecules during a stimulus paradigm that increased local energy demand. Twenty-three patients diagnosed with BD-I and 22 healthy controls (HC) were included. Levels of phosphorus metabolites were measured at baseline and during visual stimulation in the occipital lobe using (31)P magnetic resonance spectroscopy at 4T. Changes in metabolite levels showed different patterns between the groups. During stimulation, HC had significant reductions in PCr but not in ATP, as expected. In contrast, BD patients had significant reductions in ATP but not in PCr. In addition, PCr/ATP ratio was lower at baseline in patients, and there was a higher change in this measure during stimulation. This pattern suggests a disease-related failure to replenish ATP from PCr through CK enzyme catalysis during tissue activation. Further studies measuring the CK flux in BD are required to confirm and extend this finding.
McCarty, J. |; Secord, A.; Tillitt, D.
Tree Swallows (Tachycineta bicolor) breeding along the Hudson River forage extensively on PCB contaminated insects that emerge from the river. The authors studied the reproductive ecology and behavior of tree swallows breeding at several sites along the Hudson River. These sites vary in the severity of PCB contamination. PCB levels in both eggs and chicks were found to be among the highest ever reported in this species, with concentrations comparable to those found in aquatic organisms in the Hudson River. In 1994 reproductive success at PCB contaminated sites was significantly impaired, relative to other sites in New York. Reduced reproductive success was largely attributed to high levels of nest abandonment during incubation and reduced hatchability of eggs. Growth and development of nestlings was not significantly impaired. Abnormal nest building behavior was also noted in 1994, and this was studied in detail in 1995. Nests from contaminated areas are significantly smaller than those at a nearby reference site and at other sites in New York. The authors suggest that the reduced reproductive outputs at these sites are, in large part, a result of effects on the behavior of incubating females. The population-level implications of these patterns are unknown.
He, Binfeng; Li, Hongli; Hu, Mingdong; Dong, Weijie; Wei, Zhenghua; Li, Jin; Yao, Wei; Guo, Xiaolan
High-altitude deacclimatization syndrome (HADAS) is emerging as a severe public health issue that threatens the quality of life of individuals who return to lower altitude from high altitude. In this study, we measured serum levels of SOD, MDA, IL-17A, IL-10, TNF-α, and HADAS score in HADAS subjects at baseline and 50th and 100th days and to evaluate the relationship between interleukins, including IL-17A, and HADAS. Our data showed that and the serum IL-17A levels and HADAS score decreased over time in the HADAS group, and serum IL-17A levels were significantly higher in the HADAS group at baseline and 50th day compared with controls (p < 0.05). Furthermore, baseline serum levels of MDA and TNF-α were significantly higher, while SOD and IL-10 levels were lower in HADAS subjects compared with controls (p < 0.05). It is interesting that serum levels of IL-17A were clearly interrelated with HADAS incidence and severity (p < 0.05). ROC curve analysis showed that combined serum IL-17A and IL-10 levels were a better predictor of HADAS incidence than serum levels of IL-17A or IL-10 alone. These data suggest that serum levels of IL-17A are a novel predictive index of HADAS. PMID:27190491
Leggett, J E; Wolz, S A; Craig, W A
Although pooled human serum diluent is advocated in the serum dilution test, its use may compensate for protein binding defects in patients and yield nonrepresentative titers. To test this hypothesis, comparison was made of serum ultrafiltrate (molecular weight cutoff less than or equal to 30,000) serially diluted into either pooled serum ultrafiltrate or Mueller-Hinton broth with patient serum samples diluted into pooled human serum in 111 assays from 55 patients and 6 volunteers. Of 111 bactericidal titers in ultrafiltrate and/or Mueller-Hinton broth, 101 were within a single twofold dilution of titers in pooled human serum. Nine of 10 discordant titers involved highly bound drugs and were usually higher in ultrafiltrate than in pooled human serum. In seven additional volunteers with renal failure, titers in ultrafiltrate and in each volunteer's serum were higher than those diluted in pooled human serum (P = .002). Recommended methods using pooled serum diluent may not accurately predict actual bactericidal titers in patients with abnormal protein binding.
Di Minno, G; Davì, G; Margaglione, M; Cirillo, F; Grandone, E; Ciabattoni, G; Catalano, I; Strisciuglio, P; Andria, G; Patrono, C
Homocystinuria due to homozygous cystathionine beta-synthase deficiency is an inborn error of metabolism characterized by a high incidence of thrombosis and premature atherosclerosis. We evaluated TXA2 biosynthesis in vivo and several in vitro tests of platelet function in 11 homocystinuric patients and 12 healthy controls. In vitro, patients' platelet aggregation was within control values as were TXB2 formation, fibrinogen binding, and ATP secretion in response to thrombin. In contrast, the urinary excretion of 11-dehydro-TXB2, a major enzymatic derivative of TXA2, was > 2 SD of controls in all patients (1,724 +/- 828 pg/mg creatinine, mean +/- SD, in patients vs. 345 +/- 136 in controls, P < 0.001). The administration to four patients of low-dose aspirin (50 mg/d for 1 wk) reduced metabolite excretion by > 80%. The recovery of 11-dehydro-TXB2 excretion over the 10 d that followed aspirin cessation occurred with a pattern consistent with the entry into the circulation of platelets with intact cyclooxygenase activity. Prolonged partial reduction in the abnormally high excretion of both 11-dehydro-TXB2 and 2,3-dinor-TXB2, was also observed in seven patients who ingested 500 mg daily for 3 wk of the antioxidant drug probucol. These results provide evidence for enhanced thromboxane biosynthesis in homocystinuria and for its partial dependence on probucol-sensitive mechanisms. Furthermore, the elevated TXA2 formation in homocystinuria is likely to reflect, at least in part, in vivo platelet activation. PMID:8376592
Lee, Dongjun; Joo, Ikhyung; Lee, Changsub; Song, Duheon; Choi, Byoungdeog
We investigated the abnormal degradation of high-voltage p-type MOSFET (HV pMOSFET) under negative AC gate bias stress. In HV pMOSFET with n+ polycrystalline silicon (poly-Si) gate, the abnormal degradation occurs after the gradual degradation during negative AC stress. The abnormal degradation is suppressed by changing the gate material from n+ poly-Si to p+ poly-Si, and it is caused by hot holes produced by the impact ionization near the surface when electrons move from the gate toward the gate oxide. We suggest a possible mechanism to explain the improvement of degradation by using p+ poly-Si as a gate material.
Kunjithapatham, Rani; Geschwind, Jean-Francois; Devine, Lauren; Boronina, Tatiana N; O'Meally, Robert N; Cole, Robert N; Torbenson, Michael S; Ganapathy-Kanniappan, Shanmugasundaram
Cellular glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a phylogenetically conserved, ubiquitous enzyme that plays an indispensable role in energy metabolism. Although a wealth of information is available on cellular GAPDH, there is a clear paucity of data on its extracellular counterpart (i.e., the secreted or extracellular GAPDH). Here, we show that the extracellular GAPDH in human serum is a multimeric, high-molecular-weight, yet glycolytically active enzyme. The high-molecular-weight multimers of serum GAPDH were identified by immunodetection on one- and two-dimensional gel electrophoresis using multiple antibodies specific for various epitopes of GAPDH. Partial purification of serum GAPDH by DEAE Affigel affinity/ion exchange chromatography further established the multimeric composition of serum GAPDH. In vitro data demonstrated that human cell lines secrete a multimeric, high-molecular-weight enzyme similar to that of serum GAPDH. Furthermore, LC-MS/MS analysis of extracellular GAPDH from human cell lines confirmed the presence of unique peptides of GAPDH in the high-molecular-weight subunits. Furthermore, data from pulse-chase experiments established the presence of high-molecular-weight subunits in the secreted, extracellular GAPDH. Taken together, our findings demonstrate the presence of a high-molecular-weight, enzymatically active secretory GAPDH in human serum that may have a hitherto unknown function in humans.
Noguchi, H; Yoshida, K; Murano, M; Naruto, S
A sensitive high-performance liquid chromatographic method for a routine assay of nadolol in serum is described. Serum samples spiked with atenolol (internal standard) were extracted with diethyl ether. After centrifugation, the organic layer was evaporated to dryness. The residue was redissolved in the mobile phase and injected onto an octadecyl silica column (150 mm x 4.6 mm I.D.). The mobile phase was 0.05 M ammonium acetate (pH 4.5)-acetonitrile (85:15, v/v). Fluorometric detection (excitation 230 nm, emission 300 nm) was used. The minimum detectable level of nadolol in serum was 1 ng/ml.
Beau's lines; Fingernail abnormalities; Spoon nails; Onycholysis; Leukonychia; Koilonychia; Brittle nails ... 2012:chap 71. Zaiac MN, Walker A. Nail abnormalities associated with systemic pathologies. Clin Dermatol . 2013;31: ...
Yang, Juan; Li, Wenhua; Liu, Siyuan; Yuan, Dongya; Guo, Yijiao; Jia, Cheng; Song, Tusheng; Huang, Chen
We aimed to identify serum biomarkers for screening individuals who could adapt to high-altitude hypoxia at sea level. HHA (high-altitude hypoxia acclimated; n = 48) and HHI (high-altitude hypoxia illness; n = 48) groups were distinguished at high altitude, routine blood tests were performed for both groups at high altitude and at sea level. Serum biomarkers were identified by comparing serum peptidome profiling between HHI and HHA groups collected at sea level. Routine blood tests revealed the concentration of hemoglobin and red blood cells were significantly higher in HHI than in HHA at high altitude. Serum peptidome profiling showed that ten significantly differentially expressed peaks between HHA and HHI at sea level. Three potential serum peptide peaks (m/z values: 1061.91, 1088.33, 4057.63) were further sequence identified as regions of the inter-α trypsin inhibitor heavy chain H4 fragment (ITIH4 347–356), regions of the inter-α trypsin inhibitor heavy chain H1 fragment (ITIH1 205–214), and isoform 1 of fibrinogen α chain precursor (FGA 588–624). Expression of their full proteins was also tested by ELISA in HHA and HHI samples collected at sea level. Our study provided a novel approach for identifying potential biomarkers for screening people at sea level who can adapt to high altitudes.
Heuch, Ingrid; Heuch, Ivar; Hagen, Knut; Zwart, John-Anker
Background Cross-sectional studies suggest associations between abnormal lipid levels and prevalence of low back pain (LBP), but it is not known if there is any causal relationship. Objective The objective was to determine, in a population-based prospective cohort study, whether there is any relation between levels of total cholesterol, high density lipoprotein (HDL) cholesterol and triglycerides and the probability of experiencing subsequent chronic (LBP), both among individuals with and without LBP at baseline. Methods Information was collected in the community-based HUNT 2 (1995–1997) and HUNT 3 (2006–2008) surveys of an entire Norwegian county. Participants were 10,151 women and 8731 men aged 30–69 years, not affected by chronic LBP at baseline, and 3902 women and 2666 men with LBP at baseline. Eleven years later the participants indicated whether they currently suffered from chronic LBP. Results Among women without LBP at baseline, HDL cholesterol levels were inversely associated and triglyceride levels positively associated with the risk of chronic LBP at end of follow-up in analyses adjusted for age only. Adjustment for the baseline factors education, work status, physical activity, smoking, blood pressure and in particular BMI largely removed these associations (RR: 0.96, 95% CI: 0.85–1.07 per mmol/l of HDL cholesterol; RR: 1.16, 95% CI: 0.94–1.42 per unit of lg(triglycerides)). Total cholesterol levels showed no associations. In women with LBP at baseline and men without LBP at baseline weaker relationships were observed. In men with LBP at baseline, an inverse association with HDL cholesterol remained after complete adjustment (RR: 0.83, 95% CI: 0.72–0.95 per mmol/l). Conclusion Crude associations between lipid levels and risk of subsequent LBP in individuals without current LBP are mainly caused by confounding with body mass. However, an association with low HDL levels may still remain in men who are already affected and possibly experience a
Smieskova, R; Marmy, J; Schmidt, A; Bendfeldt, K; Riecher-Rössler, A; Walter, M; Lang, UE; Borgwardt, S
Introduction: Pre-psychotic and early psychotic characteristics are investigated in the high-risk (HR) populations for psychosis. There are two different approaches based either on hereditary factors (genetic high risk, G-HR) or on the clinically manifested symptoms (clinical high risk, C-HR). Common features are an increased risk for development of psychosis and similar cognitive as well as structural and functional brain abnormalities. Methods: We reviewed the existing literature on longitudinal structural, and on functional imaging studies, which included G-HR and/or C-HR individuals for psychosis, healthy controls (HC) and/or first episode of psychosis (FEP) or schizophrenia patients (SCZ). Results: With respect to structural brain abnormalities, vulnerability to psychosis was associated with deficits in frontal, temporal, and cingulate regions in HR, with additional insular and caudate deficits in C-HR population. Furthermore, C-HR had progressive prefrontal deficits related to the transition to psychosis. With respect to functional brain abnormalities, vulnerability to psychosis was associated with prefrontal, cingulate and middle temporal abnormalities in HR, with additional parietal, superior temporal, and insular abnormalities in C-HR population. Transition-to-psychosis related differences emphasized prefrontal, hippocampal and striatal components, more often detectable in C-HR population. Multimodal studies directly associated psychotic symptoms displayed in altered prefrontal and hippocampal activations with striatal dopamine and thalamic glutamate functions. Conclusion: There is an evidence for similar structural and functional brain abnormalities within the whole HR population, with more pronounced deficits in the C-HR population. The most consistent evidence for abnormality in the prefrontal cortex reported in structural, functional and multimodal studies of HR population may underlie the complexity of higher cognitive functions that are impaired
Fernández, Carolina; Santos, Hugo M; Ruíz-Romero, Cristina; Blanco, Francisco J; Capelo-Martínez, José-Luis
In this work three methods to diminish the content of most highly abundant proteins in human serum have been studied and compared. Protein depletion with ACN or DTT and protein equalization with the ProteoMiner(™) (PM) have been assessed by 1-D gel electrophoresis and MS. After treatment 5, 18 and 9 major proteins within the 20 most abundant proteins in serum were identified for the ACN, DTT and PM methods, respectively. The ACN method was efficient for depleting high molecular weight proteins, over 75 KDa, resulting in 10±4% (n=3) of the total protein content remaining in the depleted serum. In addition, 75% of the proteins belonging to the group of the 20 most abundant proteins were not detected, making this depletion strategy a cheap alternative to expensive commercial tools regularly used for removing high abundance proteins from serum. The ACN extract was found rich in apolipoproteins. The dithithreitol method promotes the precipitation of proteins rich in disulfide bonds, mainly albumin, with 73±7% (n=3) of the total protein content remaining in the depleted serum, which was found rich in immunoglobulins. The PM method compresses the dynamic range of the serum proteins, rendering an extract containing 16±2% (n=3) of the total initial protein content. The extract was found to be rich in both apolipoproteins and immunoglobulins. As a general rule the DTT and PM methods provide a compression of the dynamic range of serum protein concentrations while the ACN method allows an effective depletion of the protein fraction above 72 KDa.
Ide, H; Tsuji, M; Shimada, M; Kondo, T; Fujiya, S; Asanuma, Y; Agishi, Y
Phospholipids in high density lipoproteins (HDL) is being used as a negative risk indicator of atherosclerosis. Phospholipids in HDL may not demonstrate the actual level of HDL-phospholipids when determined by the precipitation or ultracentrifugal methods, because HDL fractions contain very high density lipoproteins (VHDL) and albumin. In the present study, the true level of phospholipids in HDL was estimated using high performance liquid chromatography (HPLC), and it was compared with the level of phospholipids in HDL determined by the precipitation method. Sera from 18 healthy subjects were used as materials. In the HPLC method, the HDL fraction was extracted making sure that it contained no free albumin, which is albumin not bound to phospholipids. The HDL fraction was separated into subfractions. It was found that phospholipids in the VHDL fraction make a 20.2 +/- 7.3% (mean +/- S.D.) part of the total HDL-phospholipids. A large part of the VHDL fraction was constituted of albumin-bound phospholipids. A significant correlation was observed between HDL-phospholipids determined by the precipitation method, which contain albumin, and the actual HDL fraction phospholipids determined by HPLC, which do not contain VHDL (r = 0.903, p less than 0.01). These results suggest that HDL-phospholipids values determined by the precipitation method give useful clinical data.
Venkatasubramanian, Ganesan; Puthumana, Dawn Thomas K.; Jayakumar, Peruvumba N.; Gangadhar, B. N.
Background: Emotion processing abnormalities are considered among the core deficits in schizophrenia. Subjects at high risk (HR) for schizophrenia also show these deficits. Structural neuroimaging studies examining unaffected relatives at high risk for schizophrenia have demonstrated neuroanatomical abnormalities involving neo-cortical and sub-cortical brain regions related to emotion processing. The brain functional correlates of emotion processing in these HR subjects in the context of ecologically valid, real-life dynamic images using functional Magnetic Resonance Imaging (fMRI) has not been examined previously. Aim: To examine the neurohemodynamic abnormalities during emotion processing in unaffected subjects at high risk for schizophrenia in comparison with age-, sex-, handedness- and education-matched healthy controls, using fMRI. Materials and Methods: HR subjects for schizophrenia (n=17) and matched healthy controls (n=16) were examined. The emotion processing of fearful facial expression was examined using a culturally appropriate and valid tool for Indian subjects. The fMRI was performed in a 1.5-T scanner during an implicit emotion processing paradigm. The fMRI analyses were performed using the Statistical Parametric Mapping 2 (SPM2) software. Results: HR subjects had significantly reduced brain activations in left insula, left medial frontal gyrus, left inferior frontal gyrus, right cingulate gyrus, right precentral gyrus and right inferior parietal lobule. Hypothesis-driven region-of-interest analysis revealed hypoactivation of right amygdala in HR subjects. Conclusions: Study findings suggest that neurohemodynamic abnormalities involving limbic and frontal cortices could be potential indicators for increased vulnerability toward schizophrenia. The clinical utility of these novel findings in predicting the development of psychosis needs to be evaluated. PMID:21267363
Shahin, Amira; Elsawaf, Amani; Ramadan, Shahira; Shaker, Olfat; Amin, Mona; Taha, Mohamed
In this study, we measured the serum concentration of TIMP-2 in patients with systemic sclerosis (SSc) and explored its possible correlation with cardiac and pulmonary lesions. We studied 42 patients with SSc, with duration equal to or more than 2 years. CT chest, ECG, echocardiography, and serum TIMP-2 concentration measurement using ELISA technique were performed in all patients and in 25 normal controls. The mean serum levels of TIMP-2 in patients was higher than in controls (P = .005). The mean CT score of dSSc patients with elevated TIMP-2 levels was significantly higher than dSSc patients with normal levels (P = .013). Four patients out of five with elevated TIMP-2 levels showed diastolic dysfunction (80%), compared to 2 out of 15 lSSc patients with normal levels (13.3%), with P = .014. Our research, though involving a small group of patients, points to the probable role of TIMP-2 in the development of pulmonary lesions in dSSc patients and cardiac lesions in lSSc patients with duration equal to or more than 2 years. PMID:17392585
Bharti, Vijay K; Gupta, Meenakshi; Lall, D
An experiment was undertaken to evaluate the protective role of boron on the serum profile of buffalo calves fed a high fluoride ration. Twelve male Murrah buffalo (Bubalus bubalis) calves of 6-8 months age, divided into three groups of four calves in each, were fed basal diets and supplemented with sodium fluoride (NaF, 60 ppm) alone or in combination with borax (Na2B4O7.10H2O, 140 ppm) for 90 days. Boron (B) was added in the ration as borax to make @140 ppm boron (elemental B) on DM basis in treatment II. Dietary F caused a significant (p<0.05) depressing effect on serum Ca and Zn on day 90 which was improved with B supplementation. However, serum Fe and Cu did not show any significant change on F or F+B supplementation. The serum ALP and phosphorus level were increased significantly (p<0.05) on F feeding but declined significantly (p<0.05) when B was fed. The findings suggested beneficial effect of boron on serum minerals and ALP in buffalo calves fed high fluoride ration.
Hage, David S.; Anguizola, Jeanethe; Barnaby, Omar; Jackson, Abby; Yoo, Michelle J.; Papastavros, Efthimia; Pfaunmiller, Erika; Sobansky, Matt; Tong, Zenghan
The binding of drugs with serum proteins can affect the activity, distribution, rate of excretion, and toxicity of pharmaceutical agents in the body. One tool that can be used to quickly analyze and characterize these interactions is high-performance affinity chromatography (HPAC). This review shows how HPAC can be used to study drug-protein binding and describes the various applications of this approach when examining drug interactions with serum proteins. Methods for determining binding constants, characterizing binding sites, examining drug-drug interactions, and studying drug-protein dissociation rates will be discussed. Applications that illustrate the use of HPAC with serum binding agents such as human serum albumin, α1-acid glycoprotein, and lipoproteins will be presented. Recent developments will also be examined, such as new methods for immobilizing serum proteins in HPAC columns, the utilization of HPAC as a tool in personalized medicine, and HPAC methods for the high-throughput screening and characterization of drug-protein binding. PMID:21395530
Chapter 19, describes meiotic abnormalities. These include nondisjunction of autosomes and sex chromosomes, genetic and environmental causes of nondisjunction, misdivision of the centromere, chromosomally abnormal human sperm, male infertility, parental age, and origin of diploid gametes. 57 refs., 2 figs., 1 tab.
Than, Nwe Ni; Neuberger, James
Abnormalities of liver function (notably rise in alkaline phosphatase and fall in serum albumin) are common in normal pregnancy, whereas rise in serum bilirubin and aminotransferase suggest either exacerbation of underlying pre-existing liver disease, liver disease related to pregnancy or liver disease unrelated to pregnancy. Pregnant women appear to have a worse outcome when infected with Hepatitis E virus. Liver diseases associated with pregnancy include abnormalities associated hyperemesis gravidarum, acute fatty liver disease, pre-eclampsia, cholestasis of pregnancy and HELLP syndrome. Prompt investigation and diagnosis is important in ensuring a successful maternal and foetal outcome. In general, prompt delivery is the treatment of choice for acute fatty liver, pre-eclampsia and HELLP syndrome and ursodeoxycholic acid is used for cholestasis of pregnancy although it is not licenced for this indication.
Wang, Dan; Luo, Jian; Du, Wen; Zhang, Lan-Lan; He, Li-Xiu
Background Airway structure changes, termed as airway remodeling, are common in asthma patients due to chronic inflammation, which can be assessed by high-resolution computed tomography (HRCT). Considering the controversial conclusions in the correlation of morphologic abnormalities with clinical feature and outcome, we aimed to further specify and evaluate the structural abnormalities of Chinese asthmatics by HRCT. Methods From August 2012 to February 2015, outpatients with asthma were recruited consecutively in the Asthma Center of West China Hospital, Sichuan University. Standard HRCT and pulmonary function test (PFT) were performed to collect information of bronchial wall thickening, bronchial dilatation, mucus impaction, emphysema, mosaic perfusion, atelectasis, and spirometric parameters. We reported the incidence of each structural abnormality in HRCT and compared it among different asthmatic severities. Results A total of 123 asthmatics were enrolled, among which 84 (68.3%) were female and 39 (31.7%) were male. At least one structural abnormality was detected by HRCT in 85.4% asthmatics, and the incidence of bronchial wall thickening, bronchial dilatation, mucus impaction, emphysema, mosaic perfusion, and atelectasis was 57.7%, 51.2%, 22%, 24.4%, 5.7% and 1.6%, respectively. The incidences of bronchial wall thickening, bronchial dilation and emphysema were significantly increased by asthma severity (P<0.05), while incidences of mucus impaction (26/27, 96.30%), mosaic perfusion (6/7, 85.71%) and atelectasis (2/2, 100%) were mainly found in severe asthma. We found a longer asthma history (28.13±18.55 years, P<0.001, P=0.003), older age (51.30±10.70 years, P=0.022, P=0.006) and lower predicted percentage of forced expiratory volume in one second (FEV1%) (41.97±15.19, P<0.001, P<0.001) and ratio of forced expiratory volume to forced vital capacity (FEV1/FVC) (48.01±9.55, P<0.001, P<0.001) in patients with severe bronchial dilation compared with those in
Hayakawa, K; Masuko, M; Mineta, M; Yoshikawa, K; Yamauchi, K; Hirano, M; Katsumata, N; Tanaka, T
A general high-performance gel-permeation chromatography (HPGPC) method was developed to determine protein in human serum with improved sensitivity and speed. The optimum UV wavelength for protein detection was found to be 210 nm, by comparing the protein values obtained by varying the UV wavelength of the HPLC detection system with the protein values obtained from spectrophotometric protein assays, i.e., the bicinchoninic acid (BCA) method and the biuret method. The analysis time was less than 1 min. Since this HPGPC serum protein assay method is simple and rapid, it is expected to be particularly well adapted for use in clinical laboratories.
Zhang, Hui; Yi, Eugene C.; Li, Xiao-jun; Mallick, Parag; Kelly-Spratt, Karen S.; Masselon, Christophe D.; Camp, David G.; Smith, Richard D.; Kemp, Christopher J.; Aebersold, Reudi
It is expected that the composition of the serum proteome can provide valuable information about the state of the human body in health and disease and that this information can be extracted via quantitative proteomic measurements. Suitable proteomic techniques need to be sensitive, reproducible, and robust to detect potential biomarkers below the level of highly expressed proteins, generate data sets that are comparable between experiments and laboratories, and have high throughput to support statistical studies. Here we report a method for high throughput quantitative analysis of serum proteins. It consists of the selective isolation of peptides that are N-linked glycosylated in the intact protein, the analysis of these now deglycosylated peptides by liquid chromatography electrospray ionization mass spectrometry, and the comparative analysis of the resulting patterns. By focusing selectively on a few formerly N-linked glycopeptides per serum protein, the complexity of the analyte sample is significantly reduced and the sensitivity and throughput of serum proteome analysis are increased compared with the analysis of total tryptic peptides from unfractionated samples. We provide data that document the performance of the method and show that sera from untreated normal mice and genetically identical mice with carcinogen-induced skin cancer can be unambiguously discriminated using unsupervised clustering of the resulting peptide patterns. We further identify, by tandem mass spectrometry, some of the peptides that were consistently elevated in cancer mice compared with their control littermates.
Patil, Kuldeep M; Bodhankar, Subhash L
A simple and rapid high-performance thin-layer chromatographic (HPTLC) determination of lamotrigine (LTG) in serum is reported. The method involves extraction of the drug by ethyl acetate followed by separation on TLC silica plates using a mixture of toluene-acetone-ammonia (7:3:0.5), as eluting solvent. Densitometric analysis was carried out at 312 nm with lamotrigine being detected at Rf of 0.54. The analytical method has excellent linearity (r=0.998) in the range of 20-300 ng/spot. This assay range is adequate for analyzing human serum, as it corresponds to lamotrigine concentrations measured in human serum from epileptic patients. The method was validated for sensitivity, selectivity, extraction efficiency, accuracy and intra and inter-day reproducibility. The limit of detection and limit of quantification were found to be 6.4 and 10.2 ng, respectively. Good accuracy is reported in the range of 92.06-97.12% and high precision with %CV in range of 0.53-2.59. The method was applied for determination of serum lamotrigine levels in epileptic patients and in pharmacokinetic study of lamotrigine administered orally to rabbits.
Hisano, Ryohei; Sornette, Didier; Mizuno, Takayuki; Ohnishi, Takaaki; Watanabe, Tsutomu
Understanding the mutual relationships between information flows and social activity in society today is one of the cornerstones of the social sciences. In financial economics, the key issue in this regard is understanding and quantifying how news of all possible types (geopolitical, environmental, social, financial, economic, etc.) affects trading and the pricing of firms in organized stock markets. In this article, we seek to address this issue by performing an analysis of more than 24 million news records provided by Thompson Reuters and of their relationship with trading activity for 206 major stocks in the S&P US stock index. We show that the whole landscape of news that affects stock price movements can be automatically summarized via simple regularized regressions between trading activity and news information pieces decomposed, with the help of simple topic modeling techniques, into their “thematic” features. Using these methods, we are able to estimate and quantify the impacts of news on trading. We introduce network-based visualization techniques to represent the whole landscape of news information associated with a basket of stocks. The examination of the words that are representative of the topic distributions confirms that our method is able to extract the significant pieces of information influencing the stock market. Our results show that one of the most puzzling stylized facts in financial economies, namely that at certain times trading volumes appear to be “abnormally large,” can be partially explained by the flow of news. In this sense, our results prove that there is no “excess trading,” when restricting to times when news is genuinely novel and provides relevant financial information. PMID:23762258
Hisano, Ryohei; Sornette, Didier; Mizuno, Takayuki; Ohnishi, Takaaki; Watanabe, Tsutomu
Understanding the mutual relationships between information flows and social activity in society today is one of the cornerstones of the social sciences. In financial economics, the key issue in this regard is understanding and quantifying how news of all possible types (geopolitical, environmental, social, financial, economic, etc.) affects trading and the pricing of firms in organized stock markets. In this article, we seek to address this issue by performing an analysis of more than 24 million news records provided by Thompson Reuters and of their relationship with trading activity for 206 major stocks in the S&P US stock index. We show that the whole landscape of news that affects stock price movements can be automatically summarized via simple regularized regressions between trading activity and news information pieces decomposed, with the help of simple topic modeling techniques, into their "thematic" features. Using these methods, we are able to estimate and quantify the impacts of news on trading. We introduce network-based visualization techniques to represent the whole landscape of news information associated with a basket of stocks. The examination of the words that are representative of the topic distributions confirms that our method is able to extract the significant pieces of information influencing the stock market. Our results show that one of the most puzzling stylized facts in financial economies, namely that at certain times trading volumes appear to be "abnormally large," can be partially explained by the flow of news. In this sense, our results prove that there is no "excess trading," when restricting to times when news is genuinely novel and provides relevant financial information.
Sayagués, José María; Fontanillo, Celia; Abad, María del Mar; González-González, María; Sarasquete, María Eugenia; del Carmen Chillon, Maria; Garcia, Eva; Bengoechea, Oscar; Fonseca, Emilio; Gonzalez-Diaz, Marcos; De Las Rivas, Javier
Background For years, the genetics of metastatic colorectal cancer (CRC) have been studied using a variety of techniques. However, most of the approaches employed so far have a relatively limited resolution which hampers detailed characterization of the common recurrent chromosomal breakpoints as well as the identification of small regions carrying genetic changes and the genes involved in them. Methodology/Principal Findings Here we applied 500K SNP arrays to map the most common chromosomal lesions present at diagnosis in a series of 23 primary tumours from sporadic CRC patients who had developed liver metastasis. Overall our results confirm that the genetic profile of metastatic CRC is defined by imbalanced gains of chromosomes 7, 8q, 11q, 13q, 20q and X together with losses of the 1p, 8p, 17p and 18q chromosome regions. In addition, SNP-array studies allowed the identification of small (<1.3 Mb) and extensive/large (>1.5 Mb) altered DNA sequences, many of which contain cancer genes known to be involved in CRC and the metastatic process. Detailed characterization of the breakpoint regions for the altered chromosomes showed four recurrent breakpoints at chromosomes 1p12, 8p12, 17p11.2 and 20p12.1; interestingly, the most frequently observed recurrent chromosomal breakpoint was localized at 17p11.2 and systematically targeted the FAM27L gene, whose role in CRC deserves further investigations. Conclusions/Significance In summary, in the present study we provide a detailed map of the genetic abnormalities of primary tumours from metastatic CRC patients, which confirm and extend on previous observations as regards the identification of genes potentially involved in development of CRC and the metastatic process. PMID:21060790
Griffiths, Pamela S.; Walton, Cheryl; Samsell, Lennie; Perez, Miriam K.; Piedimonte, Giovanni
Background: We have shown in a previous population-based study significant correlation between childhood asthma and early abnormalities of lipid and glucose metabolism. This study's specific aim was to determine whether maternal nutrition in pregnancy affects postnatal metabolic and respiratory outcomes in the offspring. Methods: On gestation day 1, dams were switched from standard chow to either high-fat hypercaloric diet or control diet. Terminal experiments were performed on newborn and weanling offspring of dams fed the study diet during gestation and lactation, and on adult offspring maintained on the same diet as their mother. Results: Pups born from high-fat hypercaloric diet (HFD) dams developed metabolic abnormalities persistent throughout development. Cytokine expression analysis of lung tissues from newborns born to HFD dams revealed a strong proinflammatory pattern. Gene expression of neurotrophic factors and receptors was upregulated in lungs of weanlings born to HFD dams, and this was associated to higher respiratory system resistance and lower compliance at baseline, as well as hyperreactivity to aerosolized methacholine. Furthermore, HFD dams delivered pups prone to develop more severe disease after respiratory syncytial virus (RSV) infection. Conclusion: Maternal nutrition in pregnancy is a critical determinant of airway inflammation and hyperreactivity in offspring and also increases risk for bronchiolitis independent from prepregnancy nutrition. PMID:26539661
Zhang, Ting; Li, He; Zhang, Junying; Li, Xin; Qi, Di; Wang, Nuo; Zhang, Zhanjun
Epidemiological and clinical studies suggest that high serum cholesterol is a risk factor of dementia. However, the effects of cholesterol on cognition and brain remain largely unclear. This study aims to investigate the associations between serum total cholesterol (TC) and neuropsychological performance, and intrinsic functional networks in non-demented elderly. Among a cohort of 120 community-dwelling Beijing residents, 29 subjects in the high-TC group (1st quartile) and 31 in the low-TC group (4th quartile) were included in this study, and underwent a battery of neuropsychological tests and magnetic resonance imaging (MRI) scans, including T2- and T1-weighted imaging, and resting-state functional MRI. No significant group difference was found in any of the neuropsychological tests used. Stronger connectivity in the default mode network was observed in the high-TC group compared to that in the low-TC group (p < 0.001, uncorrected). While in the salience network (SN), the high-TC group showed lower connectivity in the anterior cingulate cortex and frontal regions, compared to the low-TC group (p < 0.05, FWE corrected). Our findings suggest that in non-demented elderly persons, high serum cholesterol is associated with disruption of functional connectivity in the SN. The results not only deepen our understanding of how cholesterol affects the brain, but are also significant for selecting sensitive indicators for monitoring the impairments of cholesterol on the neural system.
Fusar-Poli, Paolo; Crossley, Nicolas; Woolley, James; Carletti, Francesco; Perez-Iglesias, Rocio; Broome, Matthew; Johns, Louise; Tabraham, Paul; Bramon, Elvira; McGuire, Philip
Background Psychosis onset is characterized by white matter and electrophysiologic abnormalities. The relation between these factors in the development of illness is almost unknown. We studied the relation between white matter volumes and P300 in prodromal psychosis. Methods We assessed white matter volume (detected using magnetic resonance imaging) and electrophysiologic response during an oddball task (P300) in healthy controls and individuals at high clinical risk for psychosis (with an “at-risk mental state” [ARMS]). Results We included 41 controls and 39 patients with an ARMS in our study. A psychotic disorder developed in 26% of the ARMS group within the follow-up period of 2 years. The P300 amplitude was significantly lower in the ARMS group than in the control group. The ARMS group showed reduced volume of white matter underlying the left superior temporal gyrus and the left superior frontal gyrus and increased volume of white matter underlying the right insula and the right angular gyrus compared with controls. Relative to individuals who did not later become psychotic, the subgroup in whom psychosis subsequently developed had a smaller volume of white matter underlying the left precuneus and the right middle temporal gyrus and increased volume in the white matter underlying the right middle frontal gyrus. We observed a significant interaction in the right middle frontal gyrus: white matter volume was negatively associated with P300 amplitude in the ARMS group and positively associated with P300 amplitude in the control group. Limitations The voxel-based morphometry method alone cannot determine whether abnormal white matter volumes are due to an altered number of axonal connections or decreased myelination. Conclusion P300 abnormalities precede the onset of psychosis and are directly related to white matter alterations, representing a correlate of an increased vulnerability to disease. PMID:21299920
Jim, L K; el-Sayed, N; al-Khamis, K I
A simple and selective high-performance liquid chromatographic (HPLC) method for the determination of ciprofloxacin in serum has been developed and evaluated. Serum protein was precipitated with acetonitrile. The drug and the internal standard (quinine) were evaluated from a 10 microns U-Bondapack C-18 cartridge at ambient temperature with a mobile phase consisting of acetonitrile: 0.1 M sodium dihydrogen phosphate (20:80%, v/v) adjusted to pH 3.9 with phosphoric acid, and at a flow rate of 2.5 ml/min. The effluent was monitored on a fluorescence detector using an excitation and emission wavelength of 280 and 455 nm, respectively. Each analysis required no longer than 6 min. Quantification was achieved by the measurement of the peak-height ratio and the limit of quantification for ciprofloxacin in serum is 25 ng/ml. The intraday coefficient of variation (CV) ranged from 0.4 to 5.8%, and interday CV from 4.6 to 8.8% at three different concentrations. Relative recovery ranged from 98 to 100.2% at three different concentrations. Preliminary stability tests show that ciprofloxacin is stable for at least 3 weeks in serum after freezing.
Buice, R G; Sidhu, P; Gurley, B J; Niell, H B
A reversed-phase high-performance liquid chromatographic method is presented by which the cancer chemotherapeutic agent, mitomycin C, may be measured in human serum. A mobile phase of methanol:water (35:65) passed through a mu-Bondapak C-18 column at a rate of 1.0 ml/min produced a sharp, symmetrical band for mitomycin C. An improved serum extraction procedure, using a reversed-phase sample preparation cartridge, proved to be efficient and reproducible. Recovery over a concentration range of 10-100 ng/ml was 81.6% with a between-day coefficient of variation of 4.6% (n = 5). The within-day coefficient of variation at 50 ng/ml was 5.6% (n = 10). Ultraviolet detection at a wavelength of 365 nm was sensitive to serum concentrations of 10 ng/ml. Serum concentration-time course data from lung cancer patients receiving mitomycin C by rapid intravenous injection are presented.
Rossi, Settimio; Gesualdo, Carlo; Maisto, Rosa; Trotta, Maria Consiglia; Di Carluccio, Nadia; Brigida, Annalisa; Di Iorio, Valentina; Testa, Francesco; Simonelli, Francesca; D’Amico, Michele; Di Filippo, Clara
In this paper, the authors describe a case of high serum levels of ubiquitin and proteasome in a woman under an acute attack of autoimmune uveitis. The woman was 52 years old, diagnosed as positive for the Human leukocyte antigen-B27 gene, and came to our observation in January 2013 claiming a severe uveitis attack that involved the right eye. During the acute attack of uveitis, this woman had normal serum biochemical parameters but higher levels of serum ubiquitin and proteasome 20S subunit, with respect to a healthy volunteer matched for age and sex. These levels correlated well with the clinical score attributed to uveitis. After the patient was admitted to therapy, she received oral prednisone in a de-escalation protocol (doses from 50 to 5 mg/day) for four weeks. Following this therapy, she had an expected reduction of clinical signs and score for uveitis, but concomitantly she had a reduction of the serum levels of ubiquitin, poliubiquitinated proteins (MAb-FK1) and proteasome 20S activity. Therefore, a role for ubiquitin and proteasome in the development of human autoimmune uveitis has been hypothesized. PMID:28245629
Wells, J. V.; Fudenberg, H. H.
Metabolic turnover studies were performed with radio-iodinated IgG in twelve patients with a serum IgG level greater than 1600 mg/100 ml (six with monoclonal gammopathy and six with a polyclonal increase in IgG associated with liver disease). The six patients with an IgG monoclonal protein comprised four multiple myeloma, one benign monoclonal gammopathy and one biclonal gammopathy presenting as Waldenström's macroglobulinaemia. The six patients with liver disease comprised two patients with cirrhosis, two with infective hepatitis and two with chronic active hepatitis. The injected IgG was either autologous normal IgG (five cases), autologous monoclonal IgG (five cases), homologous normal IgG (one case) or therapeutic intravenous HGG (two cases). The plasma volume was increased in six patients; the plasma IgG pool in nine; and the total body IgG pool in seven. The plasma T½ was normal in one patient with monoclonal and one patient with polyclonal gammopathy but shortened in the other ten studies with mean values of 11·3 and 11·0 days in monoclonal and polyclonal gammopathy respectively. The fractional turnover rate was normal in two studies in polyclonal gammopathy and increased in the other ten with mean values of 13·6% per day in both groups of patients. The IgG synthesis rate was significantly increased in all studies except for a reduced synthesis of normal IgG in one patient with multiple myeloma. The mean synthesis rates in monoclonal and polyclonal gammopathy were respectively 6·7 and 4·1 times the mean synthesis rate in normal controls. The pattern of increased synthesis and increased catabolism in such patients confirms published reports in some diseases and demonstrates a similar pattern in chronic active hepatitis. The findings are consistent with the `concentration-catabolism' effect. PMID:5003444
Brandtzaeg, Ole Kristian; Johnsen, Elin; Roberg-Larsen, Hanne; Seip, Knut Fredrik; MacLean, Evan L.; Gesquiere, Laurence R.; Leknes, Siri; Lundanes, Elsa; Wilson, Steven Ray
The neuropeptide oxytocin (OT) is associated with a plethora of social behaviors, and is a key topic at the intersection of psychology and biology. However, tools for measuring OT are still not fully developed. We describe a robust nano liquid chromatography-mass spectrometry (nanoLC-MS) platform for measuring the total amount of OT in human plasma/serum. OT binds strongly to plasma proteins, but a reduction/alkylation (R/A) procedure breaks this bond, enabling ample detection of total OT. The method (R/A + robust nanoLC-MS) was used to determine total OT plasma/serum levels to startlingly high concentrations (high pg/mL-ng/mL). Similar results were obtained when combining R/A and ELISA. Compared to measuring free OT, measuring total OT can have advantages in e.g. biomarker studies. PMID:27528413
Brandtzaeg, Ole Kristian; Johnsen, Elin; Roberg-Larsen, Hanne; Seip, Knut Fredrik; Maclean, Evan L.; Gesquiere, Laurence R.; Leknes, Siri; Lundanes, Elsa; Wilson, Steven Ray
The neuropeptide oxytocin (OT) is associated with a plethora of social behaviors, and is a key topic at the intersection of psychology and biology. However, tools for measuring OT are still not fully developed. We describe a robust nano liquid chromatography-mass spectrometry (nanoLC-MS) platform for measuring the total amount of OT in human plasma/serum. OT binds strongly to plasma proteins, but a reduction/alkylation (R/A) procedure breaks this bond, enabling ample detection of total OT. The method (R/A + robust nanoLC-MS) was used to determine total OT plasma/serum levels to startlingly high concentrations (high pg/mL-ng/mL). Similar results were obtained when combining R/A and ELISA. Compared to measuring free OT, measuring total OT can have advantages in e.g. biomarker studies.
Li, Ning; Perea, José Darío; Kassar, Thaer; Richter, Moses; Heumueller, Thomas; Matt, Gebhard J.; Hou, Yi; Güldal, Nusret S.; Chen, Haiwei; Chen, Shi; Langner, Stefan; Berlinghof, Marvin; Unruh, Tobias; Brabec, Christoph J.
The performance of organic solar cells is determined by the delicate, meticulously optimized bulk-heterojunction microstructure, which consists of finely mixed and relatively separated donor/acceptor regions. Here we demonstrate an abnormal strong burn-in degradation in highly efficient polymer solar cells caused by spinodal demixing of the donor and acceptor phases, which dramatically reduces charge generation and can be attributed to the inherently low miscibility of both materials. Even though the microstructure can be kinetically tuned for achieving high-performance, the inherently low miscibility of donor and acceptor leads to spontaneous phase separation in the solid state, even at room temperature and in the dark. A theoretical calculation of the molecular parameters and construction of the spinodal phase diagrams highlight molecular incompatibilities between the donor and acceptor as a dominant mechanism for burn-in degradation, which is to date the major short-time loss reducing the performance and stability of organic solar cells.
Li, Ning; Perea, José Darío; Kassar, Thaer; Richter, Moses; Heumueller, Thomas; Matt, Gebhard J.; Hou, Yi; Güldal, Nusret S.; Chen, Haiwei; Chen, Shi; Langner, Stefan; Berlinghof, Marvin; Unruh, Tobias; Brabec, Christoph J.
The performance of organic solar cells is determined by the delicate, meticulously optimized bulk-heterojunction microstructure, which consists of finely mixed and relatively separated donor/acceptor regions. Here we demonstrate an abnormal strong burn-in degradation in highly efficient polymer solar cells caused by spinodal demixing of the donor and acceptor phases, which dramatically reduces charge generation and can be attributed to the inherently low miscibility of both materials. Even though the microstructure can be kinetically tuned for achieving high-performance, the inherently low miscibility of donor and acceptor leads to spontaneous phase separation in the solid state, even at room temperature and in the dark. A theoretical calculation of the molecular parameters and construction of the spinodal phase diagrams highlight molecular incompatibilities between the donor and acceptor as a dominant mechanism for burn-in degradation, which is to date the major short-time loss reducing the performance and stability of organic solar cells. PMID:28224984
Ando, M; Yokozawa, T; Sawada, J; Takaue, Y; Togitani, K; Kawahigashi, N; Narabayashi, M; Takeyama, K; Tanosaki, R; Mineishi, S; Kobayashi, Y; Watanabe, T; Adachi, I; Tobinai, K
Cardiac toxicities in 39 consecutive patients with breast cancer receiving high-dose chemotherapy (HDC) with stem cell transplantation were reviewed. All 39 patients received various anthracycline-containing regimens in adjuvant settings and/or for metastatic disease before HDC. As a cytoreductive regimen, all received cyclophosphamide 2000 mg/m2 and thiotepa 200 mg/m2 for 3 consecutive days. No immediate fatal toxicities were observed, but one patient developed chronic congestive heart failure and two had transient left ventricular dysfunction. Pericardial effusion was observed in another three patients. ST-T abnormalities during HDC were observed in two patients and arrhythmias were observed in nine, four of which occurred during stem cell infusion (SCI). There were three atrial arrhythmias, two ventricular arrhythmias, and four atrioventricular (AV)-block episodes. Two patients developed advanced and complete AV-block with an asystolic pause. Notably, three patients experienced AV-block with uncontrolled vomiting. No relationship was observed between the cumulative dose of anthracycline and cardiac toxicities during HDC. These results suggest that abnormalities in the conduction system during HDC may be more frequent than previously reported. Vagal reflex secondary to emesis may play an important role in the development of AV-block. Bone Marrow Transplantation (2000) 25, 185-189.
Guo Baonian; Gossmann, Hans-Joachim; Toh, Terry; Colombeau, Benjamin; Todorov, Stan; Sinclair, Frank; Shim, Kyu-Ha; Henry, Todd
Angle control has been widely accepted as the key requirement for ion implantation in semiconductor device processing. From an ion implanter point of view, the incident ion direction should be measured and corrected by suitable techniques, such as XP-VPS for the VIISta implanter platform, to ensure precision ion placement in device structures. So called V-curves have been adopted to generate the wafer-based calibration using channeling effects as the Si lattice steer ions into a channeling direction. Thermal Wave (TW) or sheet resistance (Rs) can be used to determine the minimum of the angle response curve. Normally it is expected that the TW and Rs have their respective minima at identical angles. However, the TW and Rs response to the angle variations does depend on factors such as implant species, dose, and wafer temperature. Implant damage accumulation effects have to be considered for data interpretation especially for some 'abnormal' V-curve data. In this paper we will discuss some observed 'abnormal' angle responses, such as a) TW/Rs reverse trend for Arsenic beam, 2) 'W' shape of Rs Boron, and 3) apparent TW/Rs minimum difference for high tilt characterization, along with experimental data and TCAD simulations.
Fernandez, Christian A; Cai, Xiangjun; Elozory, Allie; Liu, Chengcheng; Panetta, J Carl; Jeha, Sima; Molinelli, Alejandro R; Relling, Mary V
Asparaginase is an antineoplastic agent used in combination therapy for acute lymphoblastic leukemia (ALL). The asparaginase activity measured in serum reflects the effectiveness of the drug. However, the wide inter-individual variability in the pharmacokinetics of asparaginase suggests that the serum activity should be closely monitored in patients during therapy. In order to identify patients with low asparaginase exposure during treatment, a fast, sensitive, and high-throughput assay is required for measuring asparaginase activity in patient sera. In this study, asparaginase activity was determined by monitoring the enzymatically-coupled oxidation of reduced nicotinamide adenine dinucleotide (NADH) to NAD+ in a 96-well format. The rate of disappearance of NADH (ΔmOD/minute) was directly proportional to the activity of asparaginase, and the linear range of the assay was established from 0.025 to 2.2 IU/mL (R2 = 0.998) with a reportable range that was extended to 4.0 IU/mL by dilution with serum albumin. Inter-assay precision was established (low control CV% = 8.8, high control CV% = 9.0), as was intra-assay precision (low control CV% = 3.3, high control CV% = 2.7). The method is high-throughput and provides a broader linear range of detection compared to previously described assays. The speed, ease, and accuracy of the assay make it suitable for assessing serum asparaginase activity after standard doses of native E. coli, Erwinia, and PEGylated E. coli asparaginase given to children during the treatment of leukemia. PMID:23936585
Li, Wei; Lin, Hong; Fan, Rui; Li, Cuiling; Liu, Donghong; Yao, Fengjuan
Objectives We initiated this study to explore the relationships of serum phosphorus level with left ventricular ultrasound features and diastolic function in peritoneal dialysis (PD) patients. Methods 174 patients with end-stage renal disease (ESRD) receiving PD were enrolled in this retrospective observational study. Conventional echocardiography examination and tissue Doppler imaging (TDI) were performed in each patient. Clinical information and laboratory data were also collected. Analyses of echocardiographic features were performed according to phosphorus quartiles groups. And multivariate regression models were used to determine the association between serum phosphorus and Left ventricular diastolic dysfunction (LVDD). Results With the increase of serum phosphorus levels, patients on PD showed an increased tissue Doppler-derived E/e’ ratio of lateral wall (P < 0.001), indicating a deterioration of left ventricular diastolic function. Steady growths of left atrium and left ventricular diameters as well as increase of left ventricular muscle mass were also observed across the increasing quartiles of phosphorus, while left ventricular ejection fraction remained normal. In a multivariate analysis, the regression coefficient for E/e’ ratio in the highest phosphorus quartile was almost threefold higher relative to those in the lowest quartile group. And compared with patients in the lowest phosphorus quartile (<1.34 mmol/L) those in the highest phosphorus quartile (>1.95 mmol/L) had a more than fivefold increased odds of E/e’ ratio >15. Conclusions Our study showed an early impairment of left ventricular diastolic function in peritoneal dialysis patients. High serum phosphorus level was independently associated with greater risk of LVDD in these patients. Whether serum phosphorus will be a useful target for prevention or improvement of LVDD remains to be proved by further studies. PMID:27661984
Oikonomou, Theodora; Goulis, Ioannis; Soulaidopoulos, Stergios; Karasmani, Areti; Doumtsis, Petros; Tsioni, Konstantina; Mandala, Eudokia; Akriviadis, Evangelos; Cholongitas, Evangelos
Background Studies in patients with decompensated cirrhosis showed a correlation between serum ferritin levels and patients’ prognosis. Besides, red blood cell distribution width (RDW) and mean platelet volume (MPV) have been associated with the severity of hepatic function. The aim of this study was to evaluate the prognostic impact of serum ferritin and RDW/MPV in the outcome [survival, death, or liver transplantation (LT)] of patients with stable decompensated cirrhosis. Methods Consecutive adult patients with stable decompensated cirrhosis admitted to our department between September 2010 and February 2016 were included. Serum ferritin, RDW and MPV were recorded in every patient. They were followed up and their outcome (alive, death, or LT) was evaluated. Results 192 consecutive patients with stable decompensated cirrhosis (142 men, age 54.2±12 years); at the end of follow up [12 (range: 1-64) months] 62 patients remained alive and 130 died or underwent LT. In multivariate analysis, serum ferritin (HR 1.001, 95%CI 1.00-1.002, P=0.005) and GFR (HR 0.96, 95%CI 0.92-0.99, P=0.035) were the only independent factors significantly associated with the outcome. Ferritin had low discriminative ability (AUC: 0.61) to the outcome yielding a sensitivity and specificity of 85.3% and 44.2%, respectively, at the best cut-off point (>55 ng/mL), while patients with ferritin >55 ng/mL (n=145) had a worse outcome compared to those with ferritin ≤55 ng/mL (n=47) (log rank P=0.001). RDW and MPV were not associated with the outcome. Conclusion High serum ferritin, but not RDW/MPV, is associated with worse outcome in patients with established decompensated cirrhosis. However, further studies are needed to elucidate better this issue. PMID:28243043
Jehl, F; Gallion, C; Thierry, R C; Monteil, H
A rapid, accurate, reverse-phase high-pressure liquid chromatographic procedure for vancomycin quantitation in human serum, cerebrospinal fluid, and peritoneal fluid was developed. This procedure involves a simple chemical extraction of the antibiotic and is suitable for each of these body fluids. The column and mobile phase used provided a good resolution of the vancomycin peak with a retention time of 6.1 min. The precision of the assay was within the requirement for a daily routine clinical application. Coefficients of variation for within-day reproducibility were 5.80 and 6.28%, respectively, for samples at 50 and 25 micrograms/ml, and for between-day reproducibility they were 11.4 and 11.1%, respectively. No interference was found with respect to beta-lactam and aminoglycoside antibiotics and many other currently used drugs, indicating a good specificity for the procedure. The detection limit of 100 ng/ml has proven to be sufficient for monitoring drug levels in serum obtained after usual dosages. Drug levels in 112 clinical serum specimens assayed by high-pressure liquid chromatography were regressed against the levels obtained for the same samples by radioimmunoassay and fluorescent polarization immunoassay. Correlation coefficients were 0.945 and 0.967, respectively, and were highly significant (alpha less than 0.001). PMID:3890726
Duarte, Raquel; Naicker, Saraladevi
Objective. To determine the association between serum total alkaline phosphatase (TAP) and mortality in African maintenance haemodialysis patients (MHD). Patients and Methods. The study enrolled a total of 213 patients on MHD from two dialysis centers in Johannesburg between January 2009 and March 2016. Patients were categorized into a low TAP group (≤112 U/L) versus a high TAP group (>112 U/L) based on a median TAP of 112 U/L. Results. During the follow-up period of 7 years, there were 55 (25.8%) deaths. After adjusting for cofounders such as age, other markers of bone disorder, and comorbidity (diabetes mellitus), patients in the high TAP group had significantly higher risk of death compared to patients in the low TAP group (hazard ratio, 2.50; 95% CI 1.24–5.01, P = 0.01). Similarly, serum calcium >2.75 mmol/L was associated with increased risk of death compared to patients within levels of 2.10–2.37 mmol/L (HR 6.34, 95% CI 1.40–28.76; P = 0.02). The HR for death in white patients compared to black patients was 6.88; 95% CI 1.82–25.88; P = 0.004. Conclusion. High levels of serum alkaline phosphatase, hypercalcaemia, and white race are associated with increased risk of death in MHD patients. PMID:28168054
Waziri, Bala; Duarte, Raquel; Naicker, Saraladevi
Objective. To determine the association between serum total alkaline phosphatase (TAP) and mortality in African maintenance haemodialysis patients (MHD). Patients and Methods. The study enrolled a total of 213 patients on MHD from two dialysis centers in Johannesburg between January 2009 and March 2016. Patients were categorized into a low TAP group (≤112 U/L) versus a high TAP group (>112 U/L) based on a median TAP of 112 U/L. Results. During the follow-up period of 7 years, there were 55 (25.8%) deaths. After adjusting for cofounders such as age, other markers of bone disorder, and comorbidity (diabetes mellitus), patients in the high TAP group had significantly higher risk of death compared to patients in the low TAP group (hazard ratio, 2.50; 95% CI 1.24-5.01, P = 0.01). Similarly, serum calcium >2.75 mmol/L was associated with increased risk of death compared to patients within levels of 2.10-2.37 mmol/L (HR 6.34, 95% CI 1.40-28.76; P = 0.02). The HR for death in white patients compared to black patients was 6.88; 95% CI 1.82-25.88; P = 0.004. Conclusion. High levels of serum alkaline phosphatase, hypercalcaemia, and white race are associated with increased risk of death in MHD patients.
Moore, E; Magee, H; Coyne, J; Gorey, T; Dervan, P A
For a variety of technical reasons it is rarely possible to study cytogenetic abnormalities in ductal carcinoma in situ (DCIS) using traditional techniques. However, by combining molecular biology and computerized image analysis it is possible to carry out cytogenetic analyses on formalin-fixed, paraffin-embedded tissue, using comparative genomic hybridization (CGH). The purpose of this study was to identify the prevalence of chromosomal amplifications and deletions in high-grade DCIS and to look specifically for unique or consistent abnormalities in this pre-invasive cancer. Twenty-three cases of asymptomatic, non-palpable, screen-detected, high-grade DCIS were examined using CGH on tumour cells obtained from histology slides. All cases showed chromosomal abnormalities. A wide variety of amplifications and deletions were spread across the genome. The most frequent changes were gains of chromosomes 17 (13 of 23), 16p (13 of 23), and 20q (9 of 23) and amplifications of 11q13 (22 of 23), 12q 24.1-24.2 (12 of 23), 6p21.3 (11 of 23), and 1q31-qter (6 of 23). The most frequent deletions were on 13q 21.3-q33 (7 of 23), 9p21 (4 of 23), and 6q16.1 (4 of 23). These findings indicate that high-grade DCIS is, from a cytogenetic viewpoint, an advanced lesion. There was no absolutely consistent finding in every case, but amplification of 11q13 was found in 22 of the 23 cases. The precise significance of this is unknown at present. This region of chromosome 11q harbours a number of known oncogenes, including cyclin D1 andINT2. It is likely that many of these findings are the result of accumulated chromosomal abnormalities, reflecting an unstable genome in established malignancy.
Unruh, J.R.; Davisson, M.L.; Criss, R.E.; Moores, E.M. )
Perennial saline springs in the Rumsey Hills area, southwestern Sacramento Valley, California, locally discharge at high elevations and near ridgetops. The springs are cold, are commonly associated with natural gas seeps, and typically emerge along west-vergent thrust faults. Stable isotope analyses indicate that the spring waters are similar to oil-field formation fluids and they have had a significant residence time in the subsurface at moderate temperatures. The nonmeteoric character of the springs demonstrates that they are not being fed by perched water tables. The authors propose that these subsurface formation waters are being forced to the surface by anomalously high porefluid pressures. The Rumsey Hills area is one of Quaternary uplift, thrusting, and crustal shortening, and prospect wells drilled there have encountered anomalously high fluid pressures at shallow depths. They attribute these high fluid pressures to active tectonic compression and shortening of Cretaceous marine sedimentary rocks. The widespread occurrence of anomalously high pore-fluid pressures and perennial saline springs in the Coast Ranges and western Great Valley suggests that much of western California may be characterized as a seismically active, overpressured thrust belt. The emergence of formation waters along thrust faults further suggests that patterns of subsurface fluid flow in western California may be similar to those in overpressured accretionary prisms, and that excess fluid pressures may also play a role in the distribution of seismicity.
Bobjer, J; Naumovska, M; Giwercman, Y L; Giwercman, A
In men with non-obstructive azoospermia (NOA), the risk of hypogonadism is often overlooked. Testicular sperm extraction (TESE) may increase this risk. The objective of this study was to elucidate the prevalence of hypogonadism in NOA-patients, the impact of TESE on hormone balance and the association between testosterone deficiency and dyslipidaemia. Men with NOA who had undergone TESE during the period 2004-2009 were eligible. Hypogonadism was defined as total testosterone <10 nmol/L and/or LH >10 IU/L and/or ongoing androgen replacement therapy. Sixty-five consecutive men who had undergone TESE owing to NOA and from whom post-TESE serum testosterone levels measured before 1100 h were available. Furthermore, 141 fertile men served as controls. Serum concentrations of testosterone, LH and lipids were assessed. Odds ratios (OR) for biochemical hypogonadism were calculated. Pre- and post-TESE hormone levels were compared. Lipid profile was related to testosterone levels. Hypogonadism was found in 47% (95% CI, 0.36, 0.59) of the NOA-men. As compared with fertile controls, the OR for hypogonadism post-TESE was 17 (95% CI 6.6-45). Serum LH (p = 0.03), but not testosterone (p = 0.43), differed significantly pre- and post-TESE. Compared with eugonadal NOA-men, the OR for having deviations in lipid profile was 3.3 (95% CI 1.3-8.8) for the hypogonadal NOA-men. NOA-men are at very high risk of androgen deficiency, which even in young subjects is associated with dyslipidaemia. Medical management of these men should therefore include endocrinological evaluation and follow-up after completion of infertility treatment.
Lin, Yi-Hsin; Chang, Kai-Han; Chu, Wei-Lin; Tsou, Yu-Shih; Wu, Li-Ching; Li, Chien-Feng
A biosensor for the concentration of high-density lipoprotein (HDL) in human serum on a liquid crystal and polymer composite film (LCPCF) is demonstrated. The sensing mechanism is based on a polar-polar interaction between orientation of LC directors and HDL in human serum. The concentration of polar HDL in human serum affects the orientations of LC directors at the interface between LCPCF and the human serum. In addition, the surface free energy of LCPCF changes with the applied voltage due to the electrically tunable orientations of LC directors anchored among the polymer grains of LCPCF. As a result, the droplet motion of human serum on LCPCF under applied voltages can sense the concentration of HDL in human serum.
McAlonan, Grainne M.; Suckling, John; Wong, Naikei; Cheung, Vinci; Lienenkaemper, Nina; Cheung, Charlton; Chua, Siew E.
Background: Autism exists across a wide spectrum and there is considerable debate as to whether children with Asperger's syndrome, who have normal language milestones, should be considered to comprise a subgroup distinct other from high-functioning children with autism (HFA), who have a history of delayed language development. Magnetic resonance…
Gabig, T G
Certain qualitative abnormalities in neutrophils and blood monocytes are associated with frequent, severe, and recurrent bacterial infections leading to fatal sepsis, while other qualitative defects demonstrated in vitro may have few or no clinical sequelae. These qualitative defects are discussed in terms of the specific functions of locomotion, phagocytosis, degranulation, and bacterial killing.
Salehi, Negar; Abdi, Seyfollah; Pouraliakba, Hamid Reza; Vakili-Zarch, Anoushiravan
Coronary anomalies are rare congenital disorders with mostly benign course. We report a case of 54-year-old white male who was with stable angina scheduled for coronary angiography. Due to the difficulty of catheterization, patient underwent CT angiography and high take off left main and right coronary arteries were revealed. We conclude that anomalous coronary arteries are important and coronary interventions may be difficult in their presence.
Gonzales, Gustavo F
Populations living at high altitudes (HAs), particularly in the Peruvian Andes, are characterized by a mixture of subjects with erythrocytosis (16 g dl−1
Bhattacharya, Sankhya; Sasmal, Milan
We present a high-speed humidity sensor based on immobilization of bovine serum albumin upon multiwall carbon nanotube (IBC). A simple and versatile drop casting technique was employed to make the humidity sensor using novel material IBC at room temperature. IBC was synthesized using easy solution process technique. The working principle of the IBC humidity sensor depends upon the variation of output current or conductance with the exposure of different humidity level. Humidity sensing properties of our device is explained on the basis of charge transfer from water molecules to IBC and bovine serum albumin to multiwall carbon nanotube (MWCNT). Our sensor exhibits faster response time around 1.2 s and recovery time 1.5 s respectively.
Wieland, E; Schettler, V; Diedrich, F; Schuff-Werner, P; Oellerich, M
It is postulated that lipid peroxidation plays a role in the pathogenesis of a variety of diseases. Efforts have therefore been made to develop reliable and practicable procedures for quantifying lipid peroxidation products such as lipid hydroperoxides in biological specimens. An iodometric cholesterol colour reagent (Merck, Darmstadt, Germany) can be used to measure lipid hydroperoxides in isolated low density lipoproteins without lipid extraction. This method has been validated with respect to its analytical performance and suitability for serum samples by comparing it with a high performance liquid chromatography technique. The method was found to have acceptable performance characteristics with aqueous fatty acid hydroperoxide solutions (linoleic acid) and isolated low density lipoproteins, but it cannot be applied to native serum samples without extraction of lipids.
Houzé, Pascal; Borron, Stephen W; Scherninski, François; Bousquet, Bernard; Gourmel, Bernard; Baud, Frédéric
Pralidoxime methylsulfate (Contrathion) is widely used to treat organophosphate poisoning. Despite animal and human studies, the usefulness of Contrathion therapy remains a matter of debate. Therapeutic dosage regimens need to be clarified and availability of a reliable method for plasma pralidoxime quantification would be helpful in this process. We here describe a high-performance liquid chromatography technique with electrochemical detection to measure pralidoxime concentrations in human serum using guanosine as an internal standard. The assay was linear between 0.25 and 50 microg mL(-1) with a quantification limit of 0.2 microg mL(-1). The analytical precision was satisfactory, with variation coefficients lower 10%. This assay was applied to the analysis of a serum from an organophosphorate poisoned patient and treated by Contrathion infusions (100 and 200 mg h(-1)) after a loading dose (400 mg).
Chiba, Ryoko; Ogasawara, Ayako; Kubo, Teppei; Yamazaki, Hiroyuki; Umino, Masuo; Ishizuka, Yoichi
A column-switching high-performance liquid chromatographic method with fluorescence detection was developed for the simultaneous determination of four benzamide-type anti-psychotic drugs: sulpiride, tiapride, sultopride and metoclopramide in human serum. In this method, a TSKgel Super-ODS column was used as an analytical column, and a TSKgel G 2000SW was prepared as a pretreatment column. Under the optimized analytical conditions, four benzamide-type anti-psychotic drugs were eluted within 18 min. The detection limits (S/N = 3) for sulpiride, tiapride, sultopride and metoclopramide are 1 ng/ml, 4 ng/ml, 2 ng/ml and 0.5 ng/ml, respectively. Finally, the method was applied to the determination of sulpiride in human serum samples obtained after a single oral dose of sulpiride.
Yapo, Paul Angoué; Datté, Jacques Y; Yapo, Ayekoé; Wachman, Henri
Rare abnormal haemoglobin (Hb) often poses a problem in the diagnosis of relative electrophoresis mobility. The rare neutral Hbs interact with the Hb S and thus can increase the severity of sickle cell anaemia. In the present study, we investigated the use of reversed-phase high-performance liquid chromatography (RP-HPLC) as a method for the identification of neutral or unstable Hb, and compared it with the well-known techniques urea-triton electrophoresis (UT) and isoelectrofocusing (IEF). The results of our experiments showed that Bucuresti Hb was separated without ambiguity by RP-HPLC. To date, no other electrophoresis techniques have been able to isolate this Hb. We also examined the Hb Nouakchott, which was the most hydrophobic Hb. Moreover, the adult and foetal chains of globins (especially the Agamma(t) and Agamma(i) chains) were quantified on the same chromatogram.
Arnold, Steven E; Lucki, Irwin; Brookshire, Bethany R; Carlson, Gregory C; Browne, Caroline A; Kazi, Hala; Bang, Sookhee; Choi, Bo-Ran; Chen, Yong; McMullen, Mary F; Kim, Sangwon F
Insulin resistance and other features of the metabolic syndrome are increasingly recognized for their effects on cognitive health. To ascertain mechanisms by which this occurs, we fed mice a very high fat diet (60% kcal by fat) for 17days or a moderate high fat diet (HFD, 45% kcal by fat) for 8weeks and examined changes in brain insulin signaling responses, hippocampal synaptodendritic protein expression, and spatial working memory. Compared to normal control diet mice, cerebral cortex tissues of HFD mice were insulin-resistant as evidenced by failed activation of Akt, S6 and GSK3β with ex-vivo insulin stimulation. Importantly, we found that expression of brain IPMK, which is necessary for mTOR/Akt signaling, remained decreased in HFD mice upon activation of AMPK. HFD mouse hippocampus exhibited increased expression of serine-phosphorylated insulin receptor substrate 1 (IRS1-pS(616)), a marker of insulin resistance, as well as decreased expression of PSD-95, a scaffolding protein enriched in post-synaptic densities, and synaptopodin, an actin-associated protein enriched in spine apparatuses. Spatial working memory was impaired as assessed by decreased spontaneous alternation in a T-maze. These findings indicate that HFD is associated with telencephalic insulin resistance and deleterious effects on synaptic integrity and cognitive behaviors.
Arnold, Steven E.; Lucki, Irwin; Brookshire, Bethany R.; Carlson, Gregory C.; Browne, Carolyn A.; Kazi, Hala; Bang, Sookhee; Choi, Bo-Ran; Chen, Yong; McMullen, Mary F.; Kim, Sangwon F.
Insulin resistance and other features of the metabolic syndrome are increasingly recognized for their effects on cognitive health. To ascertain mechanisms by which this occurs, we fed mice a very high fat diet (60% kcal by fat) for 17 days or a moderate high fat diet (HFD, 45% kcal by fat) for 8 weeks and examined changes in brain insulin signaling responses, hippocampal synaptodendritic protein expression, and spatial working memory. Compared to normal control diet mice, cerebral cortex tissues of HFD mice were insulin-resistant as evidenced by failed activation of Akt, S6 and GSK3β with ex-vivo insulin stimulation. Importantly, we found that expression of brain IPMK, which is necessary for mTOR/Akt signaling, remained decreased in HFD mice upon activation of AMPK. HFD mouse hippocampus exhibited increased expression of serine-phosphorylated insulin receptor substrate 1 (IRS1-pS616), a marker of insulin resistance, as well as decreased expression of PSD-95, a scaffolding protein enriched in post-synaptic densities, and synaptopodin, an actin-associated protein enriched in spine apparatuses. Spatial working memory was impaired as assessed by decreased spontaneous alternation in a T-maze. These findings indicate that HFD is associated with telencephalic insulin resistance and deleterious effects on synaptic integrity and cognitive behaviors. PMID:24686304
Uchida, S.; Iramina, K.; Goto, K.; Ueno, S.
The purpose of our study was to identify the current source produced by acute ischemia and infarction. We measured magnetocardiograms (MCG) and electrocardiograms (ECG) of five male rats using a high-resolution dc superconducting quantum interference device gradiometer in a magnetically shielded room after performing coronary artery occlusion. The spatial resolution of the detecting magnetic field of our system is higher than the typical system, thus permitting the measurement of magnetic fields in small animals. Distribution of the magnetic fields B(t) and distribution of |rot B(t)|, which corresponded to the distribution of the current source, were imaged by 12-channel MCGs. As a result, the distribution of current source changes in the affected area of the myocardium during the ST segment, and amplitude of the peak significantly increased after occlusion. Our system can be used to help clarify the mechanism of the ST shift related to severe heart disease.
Hunt, Walter A.; Joseph, James A.; Rabin, Bernard M.
Exposure of rats to high-energy iron particles (600 MeV/amu) has been found to alter behavior after doses as low as 10 rads. The performance of a task that measures upper body strength was significantly degraded after irradiation. In addition, an impairment in the regulation of dopamine release in the caudate nucleus (a motor center in the brain), lasting at least 6 months, was also found and correlated with the performance deficits. A general indication of behavioral toxicity and an index of nausea and emesis, the conditioned taste aversion, was also evident. The sensitivity to iron particles was 10-600 times greater than to gamma photons. These results suggest that behavioral and neurobiological damage may be a consequence of exposure to low doses of heavy particles and that this possibility should be extensively studied.
Hernández-Romero, Diana; Sanchez-Amat, Antonio; Solano, Francisco
The sequencing of the genome of Ralstonia solanacearum[Salanoubat M, Genin S, Artiguenave F, et al. (2002) Nature 415, 497-502] revealed several genes that putatively code for polyphenol oxidases (PPOs). This soil-borne pathogenic bacterium withers a wide range of plants. We detected the expression of two PPO genes (accession numbers NP_518458 and NP_519622) with high similarity to tyrosinases, both containing the six conserved histidines required to bind the pair of type-3 copper ions at the active site. Generation of null mutants in those genes by homologous recombination mutagenesis and protein purification allowed us to correlate each gene with its enzymatic activity. In contrast with all tyrosinases so far studied, the enzyme NP_518458 shows higher monophenolase than o-diphenolase activity and its initial activity does not depend on the presence of l-dopa cofactor. On the other hand, protein NP_519622 is an enzyme with a clear preference to oxidize o-diphenols and only residual monophenolase activity, behaving as a catechol oxidase. These catalytic characteristics are discussed in relation to two other characteristics apart from the six conserved histidines. One is the putative presence of a seventh histidine which interacts with the carboxy group on the substrate and controls the preference for carboxylated and decarboxylated substrates. The second is the size of the residue isosteric with the aromatic F261 reported in sweet potato catechol oxidase which acts as a gate to control accessibility to CuA at the active site.
Makarova, Elena N; Chepeleva, Elena V; Panchenko, Polina E; Bazhan, Nadezhda M
Maternal obesity increases the risk of obesity in offspring, and obesity is accompanied by an increase in blood leptin levels. The "yellow" mutation at the mouse agouti locus (A(y)) increases blood leptin levels in C57BL preobese pregnant mice without affecting other metabolic characteristics. We investigated the influence of the A(y) mutation or leptin injection at the end of pregnancy in C57BL mice on metabolic phenotypes and the susceptibility to diet-induced obesity (DIO) in offspring. In both C57BL-A(y) and leptin-treated mice, the maternal effect was more pronounced in male offspring. Compared with males born to control mothers, males born to A(y) mothers displayed equal food intake (FI) but decreased body weight (BW) gain after weaning, equal glucose tolerance, and enhanced FI-to-BW ratios on the standard diet but the same FI and BW on the high-fat diet. Males born to A(y) mothers were less responsive to the anorectic effect of exogenous leptin and less resistant to fasting (were not hyperphagic and gained less weight during refeeding after food deprivation) compared with males born to control mothers. However, all progeny displayed equal hypothalamic expression of Agouti gene-related protein (AgRP), neuropeptide Y (NPY), and proopiomelanocortin (POMC) and equal plasma leptin and glucose levels after food deprivation. Leptin injections in C57BL mice on day 17 of pregnancy decreased BW in both male and female offspring but inhibited FI and DIO only in male offspring. Our results show that hyperleptinemia during pregnancy has sex-specific long-term effects on energy balance regulation in progeny and does not predispose offspring to developing obesity.
Krzyzanowska, K; Schnack, C; Mittermayer, F; Kopp, H P; Hofer, M; Kann, T; Schernthaner, G
Patients with hypopituitarism have an increased mortality from cardiovascular events. Reduced nocturnal blood pressure decline (non-dipping) and impaired glucose tolerance are considered as cardiovascular risk factors. To evaluate the role of these risk factors in patients with hypopituitarism we determined the 24-hour blood pressure regulation and glucose tolerance status in hypopituitary patients with and without growth hormone (GH) deficiency. Sixty-one hypopituitary subjects 5 +/- 3 years after brain surgery because of macroadenoma, 61 patients with type 2 diabetes mellitus (T2DM), and 20 healthy controls were included. Forty-four hypopituitary patients were GH deficient and 28 of these on GH treatment. Non-dipping was observed in 41 % (n = 7) of hypopituitary subjects with normal GH release, in 46 % (n = 13) of patients on GH therapy, and in 69 % (n = 11) of untreated GH deficient patients. Untreated GH deficient patients had a higher systolic night/day ratio (1.00 +/- 0.03) compared to non GH deficient (0.92 +/- 0.02; p < 0.02) and GH treated hypopituitary patients (0.93 +/- 0.01; p < 0.02). The rate of non-dipping in hypopituitarism was comparable to that in T2DM. Pathologic glucose tolerance was diagnosed in 30 % of the hypopituitary patients. The prevalence of non-dipping was independent of glucose metabolism in hypopituitary patients. All controls had normal night time blood pressure fall and glucose metabolism. The high prevalence of nocturnal non-dipping and glucose intolerance detected in this cohort might contribute to the increased cardiovascular risk of hypopituitary patients.
Trascasa, M L; Egido, J; Sancho, J; Hernando, L
Eleven out of 15 patients with IgA mesangial glomerulonephritis (Berger's disease) had an increased proportion of serum IgA in 9-21S fractions on 5-40% sucrose density-gradient ultracentrifugation; the heavier fractions decreased at acid pH. Serum IgA purified by starch electrophoresis was subjected to reduction-alkylation yielding fragments of lower molecular weight. J chain was detected on urea alkaline polyacrylamide electrophoresis and the high-molecular weight IgA bound the human secretory component. In six patients treated with phenytoin for 1 year there was a decrease in polymeric IgA and an increase in monomeric IgA adopting a pattern similar to that of the controls. Our results show the presence of a large amount of true IgA polymers, partially as immune complexes, in the serum of patients with Berger's disease. These data together with their normalization after phenytoin treatment may open a new pathogenic and therapeutic approach to this entity.
Boshtam, Maryam; Pourfarzam, Morteza; Ani, Mohsen; Naderi, Gholam Ali; Basati, Gholam; Mansourian, Marjan; Dinani, Narges Jafari; Asgary, Seddigheh; Abdi, Soheila
Introduction. Cardioprotective effect of high density lipoprotein (HDL) is, in part, dependent on its related enzyme, paraoxonase 1 (PON1). Fatty acid composition of HDL could affect its size and structure. On the other hand, PON1 activity is directly related to the structure of HDL. This study was designed to investigate the association between serum PON1 activity and fatty acid composition of HDL in healthy men. Methods. One hundred and forty healthy men participated in this research. HDL was separated by sequential ultracentrifugation, and its fatty acid composition was analyzed by gas chromatography. PON1 activity was measured spectrophotometrically using paraxon as substrate. Results. Serum PON1 activity was directly correlated with the amount of stearic acid and dihomo-gamma-linolenic acid (DGLA). PON1/HDL-C was directly correlated with the amount of miristic acid, stearic acid, and DGLA and was inversely correlated with total amount of ω6 fatty acids of HDL. Conclusion. The fatty acid composition of HDL could affect the activity of its associated enzyme, PON1. As dietary fats are the major determinants of serum lipids and lipoprotein composition, consuming some special dietary fatty acids may improve the activity of PON1 and thereby have beneficial effects on health. PMID:24167374
Tan, Guangguo; Wang, Haibo; Yuan, Jianlin; Qin, Weijun; Dong, Xin; Wu, Hong; Meng, Ping
To address the shortcomings of cystoscopy and urine cytology for detecting and grading bladder cancer (BC), ultrahigh performance liquid chromatography (UHPLC) coupled with Q-TOF mass spectrometry in conjunction with univariate and multivariate statistical analyses was employed as an alternative method for the diagnosis of BC. A series of differential serum metabolites were further identified for low-grade(LG) and high-grade(HG) BC patients, suggesting metabolic dysfunction in malignant proliferation, immune escape, differentiation, apoptosis and invasion of cancer cells in BC patients. In total, three serum metabolites including inosine, acetyl-N-formyl-5-methoxykynurenamine and PS(O-18:0/0:0) were selected by binary logistic regression analysis, and receiver operating characteristic (ROC) test based on their combined use for HG BC showed that the area under the curve (AUC) was 0.961 in the discovery set and 0.950 in the validation set when compared to LG BC. Likewise, this composite biomarker panel can also differentiate LG BC from healthy controls with the AUC of 0.993 and 0.991 in the discovery and validation set, respectively. This finding suggested that this composite serum metabolite signature was a promising and less invasive classifier for probing and grading BC, which deserved to be further investigated in larger samples. PMID:28382976
Tiwari, Priya; Thomas, M K; Pathania, Subha; Dhawan, Deepa; Gupta, Y K; Vishnubhatla, Sreenivas; Bakhshi, Sameer
Facilities for measuring methotrexate (MTX) levels are not available everywhere, potentially limiting administration of high-dose methotrexate (HDMTX). We hypothesized that serum creatinine alteration after HDMTX administration predicts MTX clearance. Overall, 122 cycles in 50 patients of non-Hodgkin lymphoma or acute lymphoblastic leukemia aged ≤18 years receiving HDMTX were enrolled prospectively. Plasma MTX levels were measured at 12, 24, 36, 48, 60, and 72 hours; serum creatinine was measured at baseline, 24, 48, and 72 hours. Correlation of plasma MTX levels with creatinine levels and changes in creatinine from baseline (Δ creatinine) were evaluated. Plasma MTX levels at 72 hours showed positive correlation with serum creatinine at 48 hours (P = .011) and 72 hours (P = .013) as also Δ creatinine at 48 hours (P = .042) and 72 hours (P = .045). However, cut-off value of either creatinine or Δ creatinine could not be established to reliably predict delayed MTX clearance. Greater than 50% Δ creatinine at 48 and 72 hours significantly predicted grade 3/4 leucopenia (P = .036 and P = .001, respectively) and thrombocytopenia (P = .012 and P = .009, respectively) but not mucositis (P = .827 and P = .910, respectively). Delayed MTX elimination did not predict any grade 3/4 toxicity. In spite of demonstration of significant correlation between serum creatinine and Δ creatinine with plasma MTX levels at 72 hours, cut-off value of either variable to predict MTX delay could not be established. Thus, either of these cannot be used as a surrogate for plasma MTX estimation. Interestingly, Δ creatinine effectively predicted hematological toxicities, which were not predicted by delayed MTX clearance.
Ishikawa, Hiroaki; Yamada, Hiroya; Taromaru, Nao; Kondo, Kanako; Nagura, Ayuri; Yamazaki, Mirai; Ando, Yoshitaka; Munetsuna, Eiji; Suzuki, Koji; Ohashi, Koji; Teradaira, Ryoji
Background Recently, several studies have shown that microRNAs are present in high-density lipoprotein, and high-density lipoprotein-microRNA may be a promising disease biomarker. We investigated the stability of high-density lipoprotein-microRNAs in different storage conditions as this is an important issue for its application to the field of clinical research. Methods microRNAs were extracted from the high-density lipoprotein fraction that was purified from the serum. miR-135 a and miR-223, which are known to be present in high-density lipoprotein, were quantified by quantitative real-time PCR. The influence of preanalytical parameters on the analysis of high-density lipoprotein-miRNAs was examined by the effect of RNase, storage conditions, and freezing and thawing. Results The concentrations of microRNA in high-density lipoprotein were not altered by RNase A treatment (0-100 U/mL). No significant change in these microRNAs was observed after storing serum at room temperature or 4℃ for 0-24 h, and there was a similar result in the cryopreservation for up to two weeks. Also, high-density lipoprotein-microRNAs were stable for, at least, up to five freeze-thaw cycles. Conclusions These results demonstrated that high-density lipoprotein-microRNAs are relatively resistant to various storage conditions. This study provides new and important information on the stability of high-density lipoprotein-microRNAs.
Blacker, Bryan C; Snyder, Shannon M; Eggett, Dennis L; Parker, Tory L
We sought to determine whether consumption of blueberries could reduce postprandial oxidation when consumed with a typical high-carbohydrate, low-fat breakfast. Participants (n 14) received each of the three treatments over 3 weeks in a cross-over design. Treatments consisted of a high blueberry dose (75 g), a low blueberry dose (35 g) and a control (ascorbic acid and sugar content matching that of the high blueberry dose). Serum oxygen radical absorbance capacity (ORAC), serum lipoprotein oxidation (LO) and serum ascorbate, urate and glucose were measured at fasting, and at 1, 2 and 3 h after sample consumption. The mean serum ORAC was significantly higher in the 75 g group than in the control group during the first 2 h postprandially, while serum LO lag time showed a significant trend over the 3 h for both blueberry doses. Changes in serum ascorbate, urate and glucose were not significantly different among the groups. To our knowledge, this is the first report that has demonstrated that increased serum antioxidant capacity is not attributable to the fructose or ascorbate content of blueberries. In summary, a practically consumable quantity of blueberries (75 g) can provide statistically significant oxidative protection in vivo after a high-carbohydrate, low-fat breakfast. Though not tested directly, it is likely that the effects are due to phenolic compounds, either directly or indirectly, as they are a major family of compounds in blueberries with potential bioactive activity.
Misra, Santosh K.; Biswas, Joydeep; Kondaiah, Paturu; Bhattacharya, Santanu
Background Six new cationic gemini lipids based on cholesterol possessing different positional combinations of hydroxyethyl (-CH2CH2OH) and oligo-oxyethylene -(CH2CH2O)n- moieties were synthesized. For comparison the corresponding monomeric lipid was also prepared. Each new cationic lipid was found to form stable, clear suspensions in aqueous media. Methodology/Principal Findings To understand the nature of the individual lipid aggregates, we have studied the aggregation properties using transmission electron microscopy (TEM), dynamic light scattering (DLS), zeta potential measurements and X-ray diffraction (XRD). We studied the lipid/DNA complex (lipoplex) formation and the release of the DNA from such lipoplexes using ethidium bromide. These gemini lipids in presence of a helper lipid, 1, 2-dioleoyl phophatidyl ethanol amine (DOPE) showed significant enhancements in the gene transfection compared to several commercially available transfection agents. Cholesterol based gemini having -CH2-CH2-OH groups at the head and one oxyethylene spacer was found to be the most effective lipid, which showed transfection activity even in presence of high serum levels (50%) greater than Effectene, one of the potent commercially available transfecting agents. Most of these geminis protected plasmid DNA remarkably against DNase I in serum, although the degree of stability was found to vary with their structural features. Conclusions/Significance -OH groups present on the cationic headgroups in combination with oxyethylene linkers on cholesterol based geminis, gave an optimized combination of new genera of gemini lipids possessing high transfection efficiency even in presence of very high percentage of serum. This property makes them preferential transfection reagents for possible in vivo studies. PMID:23861884
Kai, M; Ogata, T; Haraguchi, K; Ohkura, Y
A highly sensitive and simple fluorimetric method for the determination of free and total polyamines, spermidine, spermine, putrescine and cadaverine, in human serum by high-performance liquid chromatography is described. The polyamines, obtained after clean-up of deproteinized serum by Cellex P column chromatography, are converted to their fluorescamine derivatives in the presence of nickel ion which inhibits the reaction of interfering amines with fluorescamine, and the derivatives are separated simultaneously by reversed-phase chromatography (LiChrosorb RP-18) with a linear gradient elution. The lower limits of detection are 10 and 15 pmole for spermine and the others in 0.5 ml of serum, respectively.
This presentation, Suspect Screening of Environmental Organic Acids in Human Serum Using High-resolution Mass Spectrometry (HRMS), was given at the NIEHS/EPA Children's Centers 2016 Webinar Series: Exposome held on May 11, 2016.
Huang, Ya-Kai; Kang, Wei-Ming; Ma, Zhi-Qiang; Liu, Yu-Qin; Zhou, Li; Yu, Jian-Chun
Abstract Obesity is related to an increased risk of gastric cardia cancer. However, the influences of excess body weight and serum total cholesterol on the risk of gastric high-grade dysplasia have not been fully characterized. A case–control study was conducted to explore the relationships between body mass index (BMI), serum total cholesterol level, and the risk of gastric high-grade dysplasia in Chinese adults. A total of 893 consecutive patients with gastric high-grade dysplasia (537 men and 356 women) and 902 controls (543 men and 359 women) were enrolled from January 2000 to October 2015. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated, and a multivariate analysis was conducted. After adjusting for age, alcohol consumption, smoking status, family history of gastric cancer or esophageal cancer, and serum total cholesterol level, a BMI ranging from 27.5 to 29.9 was significantly related to an increased risk of gastric high-grade dysplasia in both men (adjusted OR = 1.87, 95% CI = 1.24–2.81) and women (adjusted OR = 2.72, 95% CI = 1.44–5.16). The 2 highest BMI categories (27.5–29.9 and ≥30.0) were identified as risk factors for gastric cardia high-grade dysplasia in both men (BMI = 27.5–29.9: adjusted OR = 1.78, 95% CI = 1.02–3.10; BMI ≥ 30.0: adjusted OR = 2.54, 95% CI = 1.27–5.08) and women (BMI = 27.5–29.9: adjusted OR = 2.88, 95% CI = 1.27–6.55; BMI ≥ 30.0: adjusted OR = 2.77, 95% CI = 1.36–5.64), whereas only a BMI ranging from 27.5 to 29.9 was a risk factor for gastric noncardia high-grade dysplasia in both men (adjusted OR = 1.98, 95% CI = 1.25–3.14) and women (adjusted OR = 2.88, 95% CI = 1.43–5.81). In addition, higher serum total cholesterol was associated with an increased risk of gastric noncardia high-grade dysplasia (adjusted OR = 1.83, 95% CI = 1.25–2.69) in women. Increased BMI was associated with an increased risk
de Haas, C J; Poppelier, M J; van Kessel, K P; van Strijp, J A
Lipopolysaccharide (LPS) is an amphipathic macromolecule that is highly aggregated in aqueous preparations. LPS-binding protein (LBP) catalyzes the transfer of single LPS molecules, segregated from an LPS aggregate, to high-density lipoproteins (HDL), which results in the neutralization of LPS. When fluorescein isothiocyanate-labeled LPS (FITC-LPS) is used, this transfer of LPS monomers to HDL can be measured as an increase in fluorescence due to dequenching of FITC-LPS. Recently, serum amyloid P component (SAP) was shown to neutralize LPS in vitro, although only in the presence of low concentrations of LBP. In this study, we show that SAP prevented HDL-mediated dequenching of FITC-LPS, even in the presence of high concentrations of LBP. Human bactericidal/permeability-increasing protein (BPI), a very potent LPS-binding and -neutralizing protein, also prevented HDL-mediated dequenching of FITC-LPS. Furthermore, SAP inhibited HDL-mediated neutralization of both rough and smooth LPS in a chemiluminescence assay quantifying the LPS-induced priming of neutrophils in human blood. SAP bound both isolated HDL and HDL in serum. Using HDL-coated magnetic beads prebound with SAP, we demonstrated that HDL-bound SAP prevented the binding of LPS to HDL. We suggest that SAP, by preventing LPS binding to HDL, plays a regulatory role, balancing the amount of LPS that, via HDL, is directed to the adrenal glands.
Croci, D; Salmaggi, A; de Grazia, U; Bernardi, G
Lamotrigine is an anticonvulsant drug recently approved in Italy for clinical use. Therapeutic monitoring of lamotrigine is relevant for patient management and avoidance of toxicity. The authors describe a simple, sensitive, and highly selective high-performance liquid chromatography method that does not involved extraction for analysis of serum lamotrigine. Serum (20 microL) with internal standard (BW 725 C) was injected directly into a column (25 cm x 4.6 mm) with an internal surface reversed phase (ISRP). The mobile phase consisted of 0.01 mol/L potassium phosphate bibasic (pH 6.0) and acetonitrile (82:18), the flow rate was 1.0 mL/min, and UV detection was optimized at 330 nm. The overall between-run coefficient of variance ranged from 1.89% to 3.25% and the lowest limit of detection was 0.05 mg/L. High linearity (r = 0.9996) in a wide range of concentrations (0.1-20.0 mg/L) and no interference with other antiepileptic drugs, benzodiazepines, and tricyclic antidepressants were the other characteristics of the method. The innovation of this method is the use of ISRP column and the choice of detection wavelength, which allow a shorter analysis time (5-6 minutes). The possibility of direct injection of plasma samples into the column permits a reduction in reagent consumption and in analytic steps, and hence in analytic error.
Inoue, Naoto; Takai, Eisuke; Arakawa, Tsutomu; Shiraki, Kentaro
Therapeutic protein solutions for subcutaneous injection must be very highly concentrated, which increases their viscosity through protein-protein interactions. However, maintaining a solution viscosity below 50 cP is important for the preparation and injection of therapeutic protein solutions. In this study, we examined the effect of various amino acids on the solution viscosity of very highly concentrated bovine serum albumin (BSA) and human serum albumin (HSA) at a physiological pH. Among the amino acids tested, l-arginine hydrochloride (ArgHCl) and l-lysine hydrochloride (LysHCl) (50-200 mM) successfully reduced the viscosity of both BSA and HSA solutions; guanidine hydrochloride (GdnHCl), NaCl, and other sodium salts were equally as effective, indicating the electrostatic shielding effect of these additives. Fourier transform infrared spectroscopy showed that BSA is in its native state even in the presence of ArgHCl, LysHCl, and NaCl at high protein concentrations. These results indicate that weakened protein-protein interactions play a key role in reducing solution viscosity. ArgHCl and LysHCl, which are also non-toxic compounds, will be used as additives to reduce the solution viscosity of concentrated therapeutic proteins.
Caron, F; Alexandre, K; Pestel-Caron, M; Chassagne, P; Grise, P; Etienne, M
Urine bacterial titers (BTs) are influenced by bacterial and host factors. The impact of an abnormal postvoid residual (PVR) on BT in urine was investigated. A total of 103 inpatients with a urine growing Enterobacteriacae (≥ 10(2) CFU/mL) and a PVR measure were analyzed, mostly female (62%), elderly (mean age: 72 years), with urinary tract infection (25% of asymptomatic bacteriuria) due to Escherichia coli (85%). Fifty-two subjects (56%) had BT ≥ 10(6) CFU/mL; 48 (53%) had a PVR ≤ 100 mL, while 26 (25%) had a PVR >250 mL. PVR increased with BT, and a significant (P<0.0001) threshold was reached for 10(6) CFU/mL: 100mL mean PVR for patients with BT ≤ 10(5) CFU/mL versus 248 mL for patients with BT >10(5) CFU/mL. High PVR and BT were associated with complicated infections, concomitant bacteremia, and delayed apyrexia. Screening for patients with BT ≥ 10(6) CFU/mL is an easy way to identify patients at high risk for acute retention and voiding disorders.
Hue-Beauvais, C; Koch, E; Chavatte-Palmer, P; Galio, L; Chat, S; Letheule, M; Rousseau-Ralliard, D; Jaffrezic, F; Laloë, D; Aujean, E; Révillion, F; Lhotellier, V; Gertler, A; Devinoy, E; Charlier, M
Alterations to the metabolic endocrine environment during early life are crucial to mammary gland development. Among these environmental parameters, the initial nutritional event after birth is the consumption of milk, which represents the first maternal support provided to mammalian newborns. Milk is a complex fluid that exerts effects far beyond its immediate nutritional value. The present study, therefore, aimed to determine the effect of the nutritional changes during the neonatal and prepubertal periods on the adult mammary phenotype. Newborn rabbits were suckled by dams fed a high-fat/high-sugar obesogenic (OD) or a control (CON) diet and then subsequently fed either the OD or CON diets from the onset of puberty and throughout early pregnancy. Mammary glands were collected during early pregnancy (Day 8 of pregnancy). Rabbits fed with OD milk and then subjected to an OD diet displayed an abnormal development of the mammary gland: the mammary ducts were markedly enlarged (P < 0.05) and filled with abundant secretory products. Moreover, the alveolar secretory structures were disorganized, with an abnormal aspect characterized by large lumina. Mammary epithelial cells contained numerous large lipid droplets and exhibited fingering of the apical membrane and abnormally enlarged intercellular spaces filled with casein micelles. Leptin has been shown to be involved in modulating several developmental processes. We therefore analyzed its expression in the mammary gland. Mammary leptin mRNA was strongly expressed in rabbits fed with OD milk and subjected to an OD diet by comparison with the CON rabbits. Leptin transcripts and protein were localized in the epithelial cells, indicating that the increase in leptin synthesis occurs in this compartment. Taken together, these findings suggest that early-life nutritional history, in particular through the milking period, can determine subsequent mammary gland development. Moreover, they highlight the potentially important
Sahoo, S.; Raghavendra, K. M.; Biswas, S.
Moringa oleifera Lam. has been an important plant in the history of mankind, both for its nutritional and medicinal uses. Apart from bactericidal effects, the parts of this plant have been effectively used in the treatment of circulatory, respiratory, endocrine, digestive as well as neural disorders. Till date, though, there has been no reported activity of the involvement of any proteinaceous extract from M. oleifera on high levels of serum creatinine. To address this issue, blood samples with high levels of serum creatinine (2 mg/dl and above) were treated with leaf extract from M. oleifera. The crude extract was partially purified initially and eventually purified to completion as well. All these proteinaceous fractions were used to treat samples with high levels of serum creatinine as mentioned above. While the treatment of serum sample having high creatinine with crude extract and partially purified protein fractions showed a decrease of approximately 20% in the levels of serum creatinine over a period of 24 h, the samples treated with purified protein fraction reduced the serum creatinine level by 50%. In light of the fact that increased level of serum creatinine levels have adverse downstream effects on the heart, lungs and other organs, this communication assumes significance because it suggests a way of reducing the level of serum creatinine as an emergency measure. Further, the identification and characterisation of this proteinaceous component and possible in vivo experiments would provide a major tool for the treatment of downstream complications associated with increased serum creatinine via a new sources, albeit a natural one. PMID:24799742
Kohno, Kei; Narimatsu, Hiroto; Shiono, Yosuke; Suzuki, Ikuko; Kato, Yuichi; Sho, Ri; Otani, Katsumi; Ishizawa, Kenichi; Yamashita, Hidetoshi; Kubota, Isao; Ueno, Yoshiyuki; Kato, Takeo; Fukao, Akira; Kayama, Takamasa
Erythroid abnormalities including anemia and polycythemia are often observed in the general clinical setting. Because recent studies reported that adiponectin negatively affects hematopoiesis, we performed a prospective observational study to assess the relationship between anemia and adiponectin, as well as other parameters, in 1029 Japanese subjects (477 men and 552 women) 40 years of age and older. Body measurements, blood tests, and nutrition intake studies were performed at baseline, and 5 to 7 years later (follow-up). Hemoglobin (Hb) and hematocrit (Hct) levels in men with high serum adiponectin levels were lower at follow-up than at baseline. Multiple regression analysis showed that age, body mass index, adiponectin, and glutamic-pyruvic transaminase were significantly associated with erythroid-related variables (red blood cells, Hb, and Hct) in both men and women (P <0.05). In a logistic regression analysis, adiponectin, fasting blood glucose, and β-natriuretic peptide were significant risk factors for anemia in men, and blood urea nitrogen and amylase were significant risk factors in women. Physical features and nutrient intake were not risk factors for anemia. Our study demonstrates, both clinically and epidemiologically, that a high serum adiponectin level decreases the amounts of erythroid-related variables and is a risk factor for anemia in Japanese men. PMID:27918575
Assessing the Association between Serum Ferritin, Transferrin Saturation, and C-Reactive Protein in Northern Territory Indigenous Australian Patients with High Serum Ferritin on Maintenance Haemodialysis
Lawton, Paul D.; Barzi, Federica; Cass, Alan; Hughes, Jaquelyne T.
Objective. To determine the significance of high serum ferritin observed in Indigenous Australian patients on maintenance haemodialysis in the Northern Territory, we assessed the relationship between ferritin and transferrin saturation (TSAT) as measures of iron status and ferritin and C-reactive protein (CRP) as markers of inflammation. Methods. We performed a retrospective cohort analysis of data from adult patients (≥18 years) on maintenance haemodialysis (>3 months) from 2004 to 2011. Results. There were 1568 patients. The mean age was 53.9 (11.9) years. 1244 (79.3%) were Indigenous. 44.2% (n = 693) were male. Indigenous patients were younger (mean age [52.3 (11.1) versus 57.4 (15.2), p < 0.001]) and had higher CRP [14.7 mg/l (7–35) versus 5.9 mg/l (1.9–17.5), p < 0.001], higher median serum ferritin [1069 µg/l (668–1522) versus 794.9 µg/l (558.5–1252.0), p < 0.001], but similar transferrin saturation [26% (19–37) versus 28% (20–38), p = 0.516]. We observed a small positive correlation between ferritin and TSAT (r2 = 0.11, p < 0.001), no correlation between ferritin and CRP (r2 = 0.001, p < 0.001), and positive association between high serum ferritin and TSAT (p < 0.001), Indigenous ethnicity (p < 0.001), urea reduction ratio (p = 0.001), and gender (p < 0.001) after adjustment in mixed regression analysis. Conclusion. Serum ferritin and TSAT may inadequately reflect iron status in this population. The high ferritin was poorly explained by inflammation. PMID:28243472
Shimizu, M; Yamauchi, K; Miyauchi, Y; Sakurai, T; Tokugawa, K; McIlhinney, R A
Gradient-polyacrylamide-gel electrophoresis of human milk serum separated three high-Mr glycoprotein bands. The properties of the components corresponding to the three bands (tentatively termed 'Components C, B and A' in their order of migration) were compared by staining with four monoclonal antibodies and lectins. Components B and C both reacted with the four antibodies, but Component A did not. Components B and C were stained with peanut (Arachis hypogaea) agglutinin (PNA) and wheat (Triticum)-germ agglutinin (WGA), Component A being stained with soya-bean (Glycine max) agglutinin as well as PNA and WGA. These results suggest that Components B and C were related molecules, whereas Component A was markedly different from them. The reactivities of Components B and C were the same as those of PAS-0, a high-Mr periodate/Schiff (PAS)-positive glycoprotein previously isolated from human milk fat-globule membrane (MFGM). Component C, whose electrophoretic mobility was the same as PAS-0, could have been a soluble form of PAS-0. A high-Mr glycoprotein having the same properties as Component A was also observed in MFGM. The amino acid composition of the isolated Component A was significantly different from that of Component C and PAS-0, high threonine and serine contents being characteristic of Component A. The carbohydrate content of Component A was 65-80%, and was much higher than that of Component C and PAS-0. Fucose, galactose, N-acetylglucosamine, N-acetylgalactosamine and sialic acid were each detected as constituent sugars of Component A. Component A represents, therefore, a new high-Mr glycoprotein species in human milk serum and MFGM. Since these glycoproteins were high-Mr mucin-like glycoproteins, the names 'HM glycoprotein-A' and 'HM glycoprotein-C' were proposed for Component A and Component C (PAS-O) respectively.
Tessitore, Alessandra; Gaggiano, Agata; Cicciarelli, Germana; Verzella, Daniela; Capece, Daria; Fischietti, Mariafausta; Zazzeroni, Francesca; Alesse, Edoardo
Cancer affects millions of people worldwide. Tumor mortality is substantially due to diagnosis at stages that are too late for therapies to be effective. Advances in screening methods have improved the early diagnosis, prognosis, and survival for some cancers. Several validated biomarkers are currently used to diagnose and monitor the progression of cancer, but none of them shows adequate specificity, sensitivity, and predictive value for population screening. So, there is an urgent need to isolate novel sensitive, specific biomarkers to detect the disease early and improve prognosis, especially in high-mortality tumors. Proteomic techniques are powerful tools to help in diagnosis and monitoring of treatment and progression of the disease. During the last decade, mass spectrometry has assumed a key role in most of the proteomic analyses that are focused on identifying cancer biomarkers in human serum, making it possible to identify and characterize at the molecular level many proteins or peptides differentially expressed. In this paper we summarize the results of mass spectrometry serum profiling and biomarker identification in high mortality tumors, such as ovarian, liver, lung, and pancreatic cancer. PMID:23401773
Okazaki, Yukako; Kakehi, Shoko; Xu, Yonghui; Tsujimoto, Kazuhisa; Sasaki, Masahiro; Ogawa, Hiroshi; Kato, Norihisa
The effect was examined of dietary sericin on the lipid and carbohydrate metabolism in rats fed with a high-fat diet. The rats were fed with a 20% beef tallow diet with or without sericin at the level of 4% for 5 weeks. The final body weight and white adipose tissue weight were unaffected by dietary manipulation. The consumption of sericin significantly reduced the serum levels of triglyceride, cholesterol, phospholipids and free fatty acids. Serum very-low-density lipoprotein (VLDL)-triglyceride, VLDL-cholesterol, low-density lipoprotein (LDL)-cholesterol and LDL-phospholipids were also significantly reduced by the sericin intake. Liver triglyceride and the activities of glucose 6-phosphate dehydrogenase and malic enzyme, the lipogenic enzymes, were also reduced by the sericin intake. Dietary sericin caused a marked elevation in serum adiponectin. The consumption of sericin suppressed the increases in plasma glucose and insulin levels after an intraperitoneal glucose injection. These results imply the usefulness of sericin for improving the lipid and carbohydrate metabolism in rats fed on a high-fat diet.
Jones, Laundette P; Buelto, Destiney; Tago, Elaine; Owusu-Boaitey, Kwadwo E
A major challenge to breast cancer research is the identification of alterations in the architecture and composition of the breast that are associated with breast cancer progression. The aim of the present investigation was to characterize the mammary adipose phenotype from Brca1 mutant mice in the expectation that this would shed light on the role of the mammary tissue environment in the early stages of breast tumorigenesis. We observed that histological sections of mammary tissue from adult Brca1 mutant mice abnormally display small, multilocular adipocytes that are reminiscent of brown adipose tissue (BAT) as compared to wildtype mice. Using a marker for BAT, the uncoupling protein 1 (UCP1), we demonstrated that these multilocular adipose regions in Brca1 mutant mice stain positive for UCP1. Transcriptionally, UCP1 mRNA levels in the Brca1 mutant mice were elevated greater than 50-fold compared to age-matched mammary glands from wildtype mice. Indeed, BAT has characteristics that are favorable for tumor growth, including high vascularity. Therefore, we also demonstrated that the multilocular brown adipose phenotype in the mammary fat pad of Brca1 mutant mice displayed regions of increased vascularity as evidenced by a significant increase in the protein expression of CD31, a marker for angiogenesis. This Brca1 mutant mouse model should provide a physiologically relevant context to determine whether brown adipose tissue can play a role in breast cancer development.
Zhang, Zhiying; Lanza, Elaine; Kris-Etherton, Penny M.; Colburn, Nancy H.; Bagshaw, Deborah; Rovine, Michael J.; Ulbrecht, Jan S.; Bobe, Gerd; Chapkin, Robert S.; Hartman, Terryl J.
Clinical studies have shown that fiber consumption facilitates weight loss and improves lipid profiles; however, the beneficial effects of high fermentable fiber low glycemic index (GI) diets under conditions of weight maintenance are unclear. In the Legume Inflammation Feeding Experiment, a randomized controlled cross-over feeding study, 64 middle-aged men who had undergone colonoscopies within the previous 2 years received both a healthy American (HA) diet (no legume consumption, fiber consumption = 9 g/1,000 kcal, and GI = 69) and a legume enriched (1.5 servings/1,000 kcal), high fiber (21 g/1,000 kcal), low GI (GI = 38) diet (LG) in random order. Diets were isocaloric and controlled for macronutrients including saturated fat; they were consumed each for 4 weeks with a 2–4 week break separating dietary treatments. Compared to the HA diet, the LG diet led to greater declines in both fasting serum total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) (P <0.001 and P <0.01, respectively). Insulin-resistant (IR) subjects had greater reductions in high density lipoprotein cholesterol (HDL-C; P <0.01), and triglycerides (TAG)/HDL-C (P = 0.02) after the LG diet, compared to the HA diet. Insulin-sensitive (IS) subjects had greater reductions in TC (P <0.001), LDL-C (P <0.01), TC/HDL-C (P <0.01), and LDL-C/HDL-C (P = 0.02) after the LG diet, compared to the HA diet. In conclusion, a high legume, high fiber, low GI diet improves serum lipid profiles in men, compared to a healthy American diet. However, IR individuals do not achieve the full benefits of the same diet on cardiovascular disease (CVD) lipid risk factors. PMID:20734238
Zhang, Jun; Shou, Wilson Z; Vath, Marianne; Kieltyka, Kasia; Maloney, Jennifer; Elvebak, Larry; Stewart, Jeremy; Herbst, John; Weller, Harold N
Quantification of small molecules using liquid chromatography/tandem mass spectrometry (LC/MS/MS) on a triple quadrupole mass spectrometer has become a common practice in bioanalytical support of in vitro adsorption, distribution, metabolism and excretion (ADME) screening. The bioanalysis process involves primarily three indispensable steps: MS/MS optimization for a large number of new chemical compounds undergoing various screening assays in early drug discovery, high-throughput sample analysis with LC/MS/MS for those chemically diverse compounds using the optimized MS/MS conditions, and post-acquisition data review and reporting. To improve overall efficiency of ADME bioanalysis, an integrated system was proposed featuring an automated and unattended MS/MS optimization, a staggered parallel LC/MS/MS for high-throughput sample analysis, and a sophisticated software tool for LC/MS/MS raw data review as well as biological data calculation and reporting. The integrated platform has been used in bioanalytical support of a serum protein binding screening assay with high speed, high capacity, and good robustness. In this new platform, a unique sample dilution scheme was also introduced. With this dilution design, the total number of analytical samples was reduced; therefore, the total operation time was reduced and the overall throughput was further improved. The performance of the protein binding screening assay was monitored with two controls representing high and low binding properties and an acceptable inter-assay consistency was achieved. This platform has been successfully used for the determination of serum protein binding in multiple species for more than 4000 compounds.
Cummins, D; Bennett, D; Fisher-Hoch, S P; Farrar, B; McCormick, J B
Electrocardiograms from 32 patients with acute Lassa fever were abnormal in over 70% of cases. The changes noted included non-specific ST-segment and T-wave abnormalities, ST-segment elevation, generalized low-voltage complexes, and changes reflecting electrolyte disturbance. None of the abnormalities correlated with clinical severity of infection, serum transaminase levels, or eventual outcome. ECG changes are common in Lassa fever, but usually unassociated with clinical manifestations of myocarditis.
Chihara, Ichiro; Nitta, Satoshi; Kimura, Tomokazu; Kandori, Shuya; Kawahara, Takashi; Waku, Natsui; Kojima, Takahiro; Joraku, Akira; Miyazaki, Jun; Iwasaki, Hitoshi; Suzuki, Hiroaki; Kawai, Koji; Nishiyama, Hiroyuki
We reported two cases of hyperthyroidism that developed during induction chemotherapy for advanced germ cell tumors with high serum human chorionic gonadotropin (hCG) levels. Case 1 : An 18-year-old man with mediastinal choriocarcinoma complained of tachycardia and tremor. His pretreatment serum hCG level was 1.37 million mIU/ml. The free thyroxine (fT4) level measured on day 2 of the first course of bleomycin, etoposide and cisplatin (BEP) was elevated to 7.8 ng/dl (＜1.7 ng/dl), whereasthe thyroidstimulating hormone (TSH) level was undetectable. We diagnosed the patient with hyperthyroidism and started oral propranolol and thiamazole. Subsequently, his tachycardia and tremor disappeared. On day 12 of the first course of BEP, his hCG level decreased to less than 50,000 mIU/ml. Also, his fT4 level returned to the normal range. Case 2 : A 29-year-old man presented with a left scrotal mass. He was diagnosed with non-seminoma testicular cancer (embryonal carcinoma and choriocarcinoma) with multiple lung, liver and lymph node metastases. On the admission day, his serum hCG and fT4 levels were high ; 3.23 million mIU/ml and 2.2 ng/dl, respectively. The TSH level was low at 0.011 mIU/ml. On day 3 of the first course of BEP, his hCG and fT4 levels increased to 4.5 million mIU/ml and 3.0 ng/dl, respectively. He complained of tachycardia, tremor and hyperhydrosis. He was started on propranolol and potassium iodide. After the treatment, histachycardia, tremor and hyperhidrosisdis appeared. HisfT4 level normalized on day 17 of the first course of BEP. The TSH-like activity of hCG is considered to be responsible for paraneoplastic hyperthyroidism among germ cell cancer patients with high hCG levels. To our knowledge, thisisthe first report of such a case in Japan. However, thisphenomenon isnot rare among patients with extremely high hCG levels. Therefore, we should be careful of these patients.
Davenport, Elizabeth M; Whitlow, Christopher T; Urban, Jillian E; Espeland, Mark A; Jung, Youngkyoo; Rosenbaum, Daryl A; Gioia, Gerard A; Powers, Alexander K; Stitzel, Joel D; Maldjian, Joseph A
The aim of this study was to determine whether the cumulative effects of head impacts from a season of high school football produce magnetic resonance imaging (MRI) measureable changes in the brain in the absence of clinically diagnosed concussion. Players from a local high school football team were instrumented with the Head Impact Telemetry System (HITS™) during all practices and games. All players received pre- and postseason MRI, including diffusion tensor imaging (DTI). Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) was also conducted. Total impacts and risk-weighted cumulative exposure (RWE), including linear (RWELinear), rotational (RWERotational), and combined components (RWECP), were computed from the sensor data. Fractional, linear, planar, and spherical anisotropies (FA, CL, CP, and CS, respectively), as well as mean diffusivity (MD), were used to determine total number of abnormal white matter voxels defined as 2 standard deviations above or below the group mean. Delta (post-preseason) ImPACT scores for each individual were computed and compared to the DTI measures using Spearman's rank correlation coefficient. None of the players analyzed experienced clinical concussion (N=24). Regression analysis revealed a statistically significant linear relationship between RWECP and FA. Secondary analyses demonstrated additional statistically significant linear associations between RWE (RWECP and RWELinear) and all DTI measures. There was also a strong correlation between DTI measures and change in Verbal Memory subscore of the ImPACT. We demonstrate that a single season of football can produce brain MRI changes in the absence of clinical concussion. Similar brain MRI changes have been previously associated with mild traumatic brain injury.
Deji, Shizuhiko; Nishizawa, Kunihide
High frequency electromagnetic fields emitted from digital cellular telephones (cell phones) occasionally cause abnormally high and erroneous indicated dose readings on electronic pocket dosimeters (EPDs). Electric field strength distribution around a cell phone transmitting 1.5 GHz band with a maximum power of 0.8 W was analyzed by using an isotropic probe with tri-axial dipole antennas. Five types of EPDs were exposed to the fields for 50 s under configurations relative to the cell phone. The electric field distribution expanded around the phone's antenna and had a maximum electric field strength of 36.5 +/- 0.3 V m(-1). The cell phone gave rise to erroneous indicated dose readings on four out of five EPDs. The maximum value of erroneous indicated dosage for 50 s reached 1,283 microSv, which was about 2.6% of the annual effective dose limit of 50 mSv. The electromagnetic susceptibility of the EPDs was higher in the sections where the semiconductor detectors or electric circuit boards were located. The distance required to prevent electromagnetic interference differed for each EPD and ranged from 2.0 to 21.0 cm from the cell phone. The electric and magnetic field immunity levels of the EPDs varied from 9.2 V m(-1) to greater than 37.6 V m(-1), and from 0.03 A m(-1) to greater than 0.51 A m(-1). The EPDs displayed erroneous dose readings during exposure but recovered their normal performance after the cell phone ceased transmitting. The electromagnetic immunity levels of the EPDs were either equal to or greater than the IEC-standard. The immunity levels should be enhanced greater than the IEC-standard from the standpoint of radiation protection. The simplest and most reliable measure to prevent potential malfunction is to prohibit the radiation workers from carrying cell phones to their workplace.
Cao, Yan; Wang, Liang; Zhao, Junhong; Zhang, Hongbing; Tian, Ying; Liang, Houcheng; Ma, Qiang
Serum response factor (SRF), which encodes the MADS-box family of related proteins, is a common transcription factor related to the expression of genes associated with cell survival. However, SRF's role in retinal ganglion cells (RGCs) after high-glucose injury remains unclear. In this study, we investigate the protective role of SRF after high-glucose injury and its underlying mechanism. The in vitro RGC model subjected to high glucose was established by employing a 50 mmol/L glucose culture environment. As detected by real-time quantitative PCR and Western blot, SRF was significantly upregulated in RGCs treated with high glucose. Overexpression of SRF significantly promoted survival among RGCs exposed to high glucose and inhibited RGC apoptosis. Knockdown of SRF exerted an inverse effect. Moreover, SRF upregulation enhanced expression of an antioxidant protein, nuclear factor erythroid 2-related factor (Nrf2), via control of the Fos-related antigen 1 (Fra-1). SRF upregulation also affected RGC survival after high-glucose treatment. Our findings showed that overexpression of SRF promoted survival of RGCs after high-glucose injury by regulating Fra-1 and Nrf2.
Li, W Y; Seah, S K; Koda, R T
Mitomycin C (MMC) is used in the treatment of disseminated adenocarcinoma of the stomach and pancreas and is used in ophthalmology as adjunctive therapy in trabeculectomy. Since only small volumes of aqueous humor are available for analysis, a sensitive method requiring limited sample preparation was developed. An internal standard, 4-aminoacetophenone, was added to aqueous humor specimens, and the solution was directly injected into the high-performance liquid chromatographic (HPLC) column. The use of a short 50-mm C18 reversed-phase column gave adequate resolution of peaks with improved sensitivity. The method was applicable for determination of MMC in serum, although solid-phase extraction for sample clean-up was required prior to injection into the HPLC column, and analytical columns of 150-250 mm were necessary for adequate resolution of peaks. The method has been validated and is linear from 6.25 to 50 ng/ml in aqueous humor and from 10 to 500 ng/ml in serum.
Ariza, Adriana; Garzon, Davide; Abánades, Daniel R; de los Ríos, Vivian; Vistoli, Giulio; Torres, María J; Carini, Marina; Aldini, Giancarlo; Pérez-Sala, Dolores
Allergy towards wide spectrum antibiotics such as amoxicillin (AX) is a major health problem. Protein haptenation by covalent conjugation of AX is considered a key process for the allergic response. However, the nature of the proteins involved has not been completely elucidated. Human serum albumin (HSA) is the most abundant protein in plasma and is considered a major target for haptenation by drugs, including β-lactam antibiotics. Here we report a procedure for immunological detection of AX-protein adducts with antibodies recognizing the lateral chain of the AX molecule. With this approach we detected human serum proteins modified by AX in vitro and identified HSA, transferrin and immunoglobulins heavy and light chains as prominent AX-modified proteins. Since HSA was the major AX target, we characterized AX-HSA interaction using high resolution LTQ orbitrap MS. At 0.5mg/mL AX, we detected one main AX-HSA adduct involving residues Lys 190, 199 or 541, whereas higher AX concentrations elicited a more extensive modification. In molecular modeling studies Lys190 and Lys 199 were found the most reactive residues towards AX, with surrounding residues favoring adduct formation. These findings provide novel tools and insight for the study of protein haptenation and the mechanisms involved in AX-elicited allergic reactions.
Montskó, Gergely; Tarjányi, Zita; Mezősi, Emese; Kovács, Gábor L
Blood cortisol level is routinely analysed in laboratory medicine, but the immunoassays in widespread use have the disadvantage of cross-reactivity with some commonly used steroid drugs. Mass spectrometry has become a method of increasing importance for cortisol estimation. However, current methods do not offer the option of accurate mass identification. Our objective was to develop a mass spectrometry method to analyse salivary, serum total, and serum free cortisol via accurate mass identification. The analysis was performed on a Bruker micrOTOF high-resolution mass spectrometer. Sample preparation involved protein precipitation, serum ultrafiltration, and solid-phase extraction. Limit of quantification was 12.5 nmol L(-1) for total cortisol, 440 pmol L(-1) for serum ultrafiltrate, and 600 pmol L(-1) for saliva. Average intra-assay variation was 4.7%, and inter-assay variation was 6.6%. Mass accuracy was <2.5 ppm. Serum total cortisol levels were in the range 35.6-1088 nmol L(-1), and serum free cortisol levels were in the range 0.5-12.4 nmol L(-1). Salivary cortisol levels were in the range 0.7-10.4 nmol L(-1). Mass accuracy was equal to or below 2.5 ppm, resulting in a mass error less than 1 mDa and thus providing high specificity. We did not observe any interference with routinely used steroidal drugs. The method is capable of specific cortisol quantification in different matrices on the basis of accurate mass identification.
Binding of warfarin, digitoxin, diazepam, salicylate and Phenol Red, individually or in different pair combinations, to defatted human serum albumin at ligand/protein molar ratios less than 1:1 was studied at pH 7.0. The binding was determined by ultrafiltration. Some of the experiments were repeated with the use of equilibrium dialysis in order to strengthen the results. Irrespective of the method used, all ligands bind to one high-affinity binding site with an association constant in the range 10(4)-10(6) M-1. High-affinity binding of the following pair of ligands took place independently: warfarin-Phenol Red, warfarin-diazepam, warfarin-digitoxin and digitoxin-diazepam. Simultaneous binding of warfarin and salicylate led to a mutual decrease in binding of one another, as did simultaneous binding of digitoxin and Phenol Red. Both effects could be accounted for by a coupling constant. The coupling constant is the factor by which the primary association constants are affected; in these examples of anti-co-operativity the factor has a value between 0 and 1. In the first example it was calculated to be 0.8 and in the latter 0.5. Finally, digitoxin and salicylate were found to compete for a common high-affinity binding site. The present findings support the proposal of four separate primary binding sites for warfarin, digitoxin (and salicylate), diazepam and Phenol Red. An attempt to correlate this partial binding model for serum albumin with other models in the literature is made. PMID:3977850
Kubomura, Daiki; Yamada, Masanori; Masui, Ayano
Long-term reduction of serum urate levels is vital in the treatment of gout. However, it is difficult to convince gout-free individuals of the necessity of treatment as few appropriate over-the-counter remedies and dietary supplements are available. Therefore, the present study aimed to investigate the antihyperuricemic efficacy and safety of a tuna extract containing the imidazole compounds to evaluate its potential as a functional food ingredient. A randomized, 4-week, double-blind, placebo-controlled study was conducted. A total of 48 male gout-free subjects with insignificantly high serum uric acid were randomly assigned to low- and high-dose tuna extract groups or a placebo group. The efficacy of the extract was assessed by measuring serum uric acid levels. Furthermore, a safety assessment was performed by physical parameters, hematology, blood biochemistry and urinalysis. The results indicated that the uric acid level was decreased at week 4 during the intervention in the tuna extract groups (low and high dose, −0.23 and −0.34 mg/dl, respectively) compared to the placebo group (−0.07 mg/dl). At week 4 after the intervention, a significant reduction in uric acid levels (−0.41 mg/dl; P<0.05) was observed in the high-dose tuna extract group compared with the placebo group (+0.11 mg/dl). No dose-related adverse events were observed during and following the intervention. Therefore, the present results suggest that oral administration of tuna extract containing the imidazole compounds has hypouricemic activity with no undesirable side effects. PMID:27446553
Chaze, Thibault; Slomianny, Marie-Christine; Milliat, Fabien; Tarlet, Georges; Lefebvre-Darroman, Tony; Gourmelon, Patrick; Bey, Eric; Benderitter, Marc; Michalski, Jean-Claude; Guipaud, Olivier
Exposure of the skin to ionizing radiation leads to characteristic reactions that will often turn into a pathophysiological process called the cutaneous radiation syndrome. The study of this disorder is crucial to finding diagnostic and prognostic bioindicators of local radiation exposure or radiation effects. It is known that irradiation alters the serum proteome content and potentially post-translationally modifies serum proteins. In this study, we investigated whether localized irradiation of the skin alters the serum glycome. Two-dimensional differential in-gel electrophoresis of serum proteins from a man and from mice exposed to ionizing radiation showed that potential post-translational modification changes occurred following irradiation. Using a large-scale quantitative mass-spectrometry-based glycomic approach, we performed a global analysis of glycan structures of serum proteins from non-irradiated and locally irradiated mice exposed to high doses of γ-rays (20, 40, and 80 Gy). Non-supervised descriptive statistical analyses (principal component analysis) using quantitative glycan structure data allowed us to discriminate between uninjured/slightly injured animals and animals that developed severe lesions. Decisional statistics showed that several glycan families were down-regulated whereas others increased, and that particular structures were statistically significantly changed in the serum of locally irradiated mice. The observed increases in multiantennary N-glycans and in outer branch fucosylation and sialylation were associated with the up-regulation of genes involved in glycosylation in the liver, which is the main producer of serum proteins, and with an increase in the key proinflammatory serum cytokines IL-1β, IL-6, and TNFα, which can regulate the expression of glycosylation genes. Our results suggest for the first time a role of serum protein glycosylation in response to irradiation. These protein-associated glycan structure changes might
Gao, Hua-Jun; Chen, Ya-Jing; Zuo, Duo; Xiao, Ming-Ming; Li, Ying; Guo, Hua; Zhang, Ning; Chen, Rui-Bing
Objective Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths. Novel serum biomarkers are required to increase the sensitivity and specificity of serum screening for early HCC diagnosis. This study employed a quantitative proteomic strategy to analyze the differential expression of serum glycoproteins between HCC and normal control serum samples. Methods Lectin affinity chromatography (LAC) was used to enrich glycoproteins from the serum samples. Quantitative mass spectrometric analysis combined with stable isotope dimethyl labeling and 2D liquid chromatography (LC) separations were performed to examine the differential levels of the detected proteins between HCC and control serum samples. Western blot was used to analyze the differential expression levels of the three serum proteins. Results A total of 2,280 protein groups were identified in the serum samples from HCC patients by using the 2D LC-MS/MS method. Up to 36 proteins were up-regulated in the HCC serum, whereas 19 proteins were down-regulated. Three differential glycoproteins, namely, fibrinogen gamma chain (FGG), FOS-like antigen 2 (FOSL2), and α-1,6-mannosylglycoprotein 6-β-N-acetylglucosaminyltransferase B (MGAT5B) were validated by Western blot. All these three proteins were up-regulated in the HCC serum samples. Conclusion A quantitative glycoproteomic method was established and proven useful to determine potential novel biomarkers for HCC. PMID:26487969
Bernasconi, C.F.; Kanavarioti, A.
The title reaction leads to the formation of the zwitterionic Michael adduct T/sup +/-/ (PhCH(R/sub 2/NH/sup +/)C(COCH/sub 3/)/sub 2//sup -/) which is in rapid acid-base equilibrium with its anionic form T/sup -/ (PhCH(R/sub 2/N)C(COCH/sub 3/)/sub 2//sup -/). Rate (K/sub 1/, k/sub -1/) and equilibrium constants (K/sub 1/) for nucleophilic addition and the pK/sub a/ of the T/sup +/-/-adducts were determined in 50% Me/sub 2/SO-50% water at 20/sup 0/C. From an interpolation of the rate constants to K/sub 1/ = 1 an intrinsic rate constant, log k/sub 0/ = 0.3, was determined. This value deviates negatively by approximately 2.5 log units from a correlation of log k/sub 0/ for amine addition to five olefins of the type PhCH=CXY, with log k/sub 0/ for the deprotonation of the corresponding carbon acids CH/sub 2/XY. Two major factors are believed to contribute to this depressed intrinsic rate constant or enhanced intrinsic barrier: (1) steric inhibition of resonance in T/sup +/-/ with the steric effect developing ahead of C-N bond formation (this conclusion is supported by an X-ray crystallographic study of p-methoxybenzylideneacetylacetone which shows that steric hindrance to optimal ..pi..-overlap in the adduct T/sup+/-/ is already present in the substrate); (2) intramolecular hydrogen bonding in T/sup +/-/, which is inferred from abnormally high pK/sub a/ values and whose development lags behind C-N bond formation. These effects are shown to be manifestations of the Principle of Nonperfect Synchronization.
Yeh, Fawn; Dixon, Anne E; Best, Lyle G; Marion, Susan M; Lee, Elisa T; Ali, Tauqeer; Yeh, Jeunliang; Rhoades, Everett R; Howard, Barbara V; Devereux, Richard B
The associations of pulmonary function with cardiovascular disease (CVD) independent of diabetes mellitus (DM) and metabolic syndrome have not been examined in a population-based setting. We examined prevalence and incidence CVD in relation to lower pulmonary function in the Strong Heart Study second examination (1993 to 1995) in 352 CVD and 2,873 non-CVD adults free of overt lung disease (mean age 60 years). Lung function was assessed by standard spirometry. Participants with metabolic syndrome or DM with or without CVD had lower pulmonary function than participants without these conditions after adjustment for hypertension, age, gender, abdominal obesity, smoking, physical activity index, and study field center. CVD participants with DM had significantly lower forced vital capacity than participants with CVD alone. Significant associations were observed between reduced pulmonary function, preclinical CVD, and prevalent CVD after adjustment for multiple CVD risk factors. During follow-up (median 13.3 years), pulmonary function did not predict CVD incidence, it predicted CVD mortality. Among 3,225 participants, 412 (298 without baseline CVD) died from CVD by the end of 2008. In models adjusted for multiple CVD risk factors, DM, metabolic syndrome, and baseline CVD, compared with highest quartile of lung function, lower lung function predicted CVD mortality (relative risk up to 1.5, 95% confidence interval 1.1 to 2.0, p<0.05). In conclusion, a population with a high prevalence of DM and metabolic syndrome and lower lung function was independently associated with prevalent clinical and preclinical CVD, and its impairment predicted CVD mortality. Additional research is needed to identify mechanisms linking metabolic abnormalities, low lung function, and CVD.
Kawashima, Yusuke; Fukutomi, Toshiyuki; Tomonaga, Takeshi; Takahashi, Hiroki; Nomura, Fumio; Maeda, Tadakazu; Kodera, Yoshio
Serum proteins/peptides reflect physiological or pathological states in humans and are an attractive target for the discovery of disease biomarkers. However, the existence of high-abundance proteins and the large dynamic range of serum proteins/peptides make any quantitative analysis of low-abundance proteins/peptides challenging. Furthermore, analyses of peptides, including the cleaved fragments of proteins, are difficult because of carrier protein binding. Here, we developed a differential solubilization (DS) method to extract low-molecular-weight proteins/peptides in serum with good reproducibility and yield as compared to typical peptide-extraction methods such as organic solvent precipitation and ultrafiltration. Using the DS method combined with reverse-phase HPLC fractionation followed by MALDI-TOF-MS, we performed high-quality comparative analyses of more than 1500 peptides from 1 microL of serum samples, including low-abundance peptides in the subnanomolar range and containing many peptides bound to carrier proteins such as albumin. We applied this method and successfully discovered four new biomarker candidates of colon cancer, none of which have previously been observed in serum and one of which is a fragment of the protein zyxin that possibly originated from tumor cells. Our results indicate that serum peptide analyses based on the DS method should greatly contribute to the discovery of novel low-abundance biomarkers.
Bookhagen, Bodo; Thiede, Rasmus C.; Strecker, Manfred R.
The interplay between topography and Indian summer monsoon circulation profoundly controls precipitation distribution, sediment transport, and river discharge along the Southern Himalayan Mountain Front (SHF). The Higher Himalayas form a major orographic barrier that separates humid sectors to the south and arid regions to the north. During the Indian summer monsoon, vortices transport moisture from the Bay of Bengal, swirl along the SHF to the northwest, and cause heavy rainfall when colliding with the mountain front. In the eastern and central parts of the Himalaya, precipitation measurements derived from passive microwave analysis (SSM/I) show a strong gradient, with high values at medium elevations and extensive penetration of moisture along major river valleys into the orogen. The end of the monsoonal conveyer belt is near the Sutlej Valley in the NW Himalaya, where precipitation is lower and rainfall maxima move to lower elevations. This region thus comprises a climatic transition zone that is very sensitive to changes in Indian summer monsoon strength. To constrain magnitude, temporal, and spatial distribution of precipitation, we analyzed high-resolution passive microwave data from the last decade and identified an abnormal monsoon year (AMY) in 2002. During the 2002 AMY, violent rainstorms conquered orographic barriers and penetrated far into otherwise arid regions in the northwest Himalaya at elevations in excess of 3 km asl. While precipitation in these regions was significantly increased and triggered extensive erosional processes (i.e., debris flows) on sparsely vegetated, steep hillslopes, mean rainfall along the low to medium elevations was not significantly greater in magnitude. This shift may thus play an important role in the overall sediment flux toward the Himalayan foreland. Using extended precipitation and sediment flux records for the last century, we show that these events have a decadal recurrence interval during the present-day monsoon
Changes in testosterone and dihydrotestosterone levels in male rat accessory sex organs, serum, and seminal fluid after castration: establishment of a new highly sensitive simultaneous androgen measurement method.
Kashiwagi, Bunzo; Shibata, Yasuhiro; Ono, Yoshihiro; Suzuki, Ryota; Honma, Seijiro; Suzuki, Kazuhiro
It is known that abnormal androgen dynamics in the tissues is a cause of androgen-dependent disorders. Investigation of tissue androgen levels could provide a clue to the elucidation of disorders. However, it is difficult to measure a trace amount of androgen in the tissues. We established a highly sensitive simultaneous quantification method of testosterone and dihydrotestosterone (DHT), which play the most important roles in the body among androgenic steroids in trace amounts, and investigated time course changes in testosterone and DHT levels in male accessory sex organs, serum, and seminal fluid after castration in rat models. In addition, changes in the testosterone/DHT ratio of male accessory sex organs and seminal fluid were observed. The simultaneous testosterone and DHT measurement method established by us was validated. Intra-assay variation and interassay precision and accuracy were all within +/-20%, and the quantification limits of testosterone and DHT were both 15.6 pg/g. With the use of this method, the testosterone and DHT levels in the prostate, seminal vesicles, and serum immediately after castration were similar to those previously reported. The testosterone and DHT levels were 350 pg/g and 605 pg/g, respectively; which showed dominance of DHT in seminal fluid, although it was not as marked as that in the male accessory sex organs. Androgens decreased with time after castration in the accessory sex organs, serum, and seminal fluid. In the prostate and seminal vesicles, testosterone and DHT decreased to about 50% and about 2% of the normal levels, respectively, 72 hours after castration. The serum levels were under the quantification limits 6 hours after castration and thereafter. In seminal fluid, the testosterone and DHT levels decreased to 49% and 35% of normal levels, respectively, 72 hours after castration. The testosterone/DHT ratio in the male accessory sex organs was lower in the prostate (0.06) than in the seminal vesicles (0
Sukumar, D.; Partridge, N. C.; Wang, X.
Context: Chronic high levels of PTH may be associated with up-regulation of proteases and cytokines. Monocyte chemoattractant protein-1 (MCP-1) is an inflammatory cytokine, produced predominantly by macrophages and endothelial cells, and is expressed in adipose tissue. More recently it has been shown that PTH administration increases MCP-1 expression in osteoblasts. Objectives: Because both PTH and MCP-1 levels are higher in obesity, the goal was to determine whether the high MCP-1 occurs only in the presence of high serum PTH and is independent of adiposity and examine its relationship with bone mineral density (BMD) and turnover. Design, Setting, and Participants: In this case-control clinical design, 111 eligible women were categorized into four groups: leaner women [body mass index (BMI) 23 ± 2 kg/m2] with normal or higher PTH and obese (BMI 44 ± 7 kg/m2) with normal or higher PTH. Results: Serum MCP-1 levels were higher (P < 0.01) in the high (PTH = 74.9 ± 27.0 pg/ml, MCP-1 = 421.5 ± 157.0 pg/ml) compared with normal PTH (PTH = 32.5 ± 10.4 pg/ml, MCP-1 = 322.5 ± 97.8 pg/ml) group, independent of BMI. C-reactive protein and adiponectin were influenced only by BMI and not PTH. MCP-1 was positively associated with osteocalcin and propeptide of type 1 collagen in the leaner (r > 0.3, P < 0.05) but not the obese women and was not associated with BMD in either group. Conclusions: Together these data suggest that MCP-1 is higher only in the presence of increased PTH and that adiposity alone cannot explain the higher MCP-1 levels in obesity. PMID:21508136
Chan, Raymond C. K.; Di, Xin; McAlonan, Grainne M.; Gong, Qi-yong
Objective: The present study reviewed voxel-based morphometry (VBM) studies on high-risk individuals with schizophrenia, patients experiencing their first-episode schizophrenia (FES), and those with chronic schizophrenia. We predicted that gray matter abnormalities would show progressive changes, with most extensive abnormalities in the chronic group relative to FES and least in the high-risk group. Method: Forty-one VBM studies were reviewed. Eight high-risk studies, 14 FES studies, and 19 chronic studies were analyzed using anatomical likelihood estimation meta-analysis. Results: Less gray matter in the high-risk group relative to controls was observed in anterior cingulate regions, left amygdala, and right insula. Lower gray matter volumes in FES compared with controls were also found in the anterior cingulate and right insula but not the amygdala. Lower gray matter volumes in the chronic group were most extensive, incorporating similar regions to those found in FES and high-risk groups but extending to superior temporal gyri, thalamus, posterior cingulate, and parahippocampal gryus. Subtraction analysis revealed less frontotemporal, striatal, and cerebellar gray matter in FES than the high-risk group; the high-risk group had less gray matter in left subcallosal gyrus, left amygdala, and left inferior frontal gyrus compared with FES. Subtraction analysis confirmed lower gray matter volumes through ventral-dorsal anterior cingulate, right insula, left amygdala and thalamus in chronic schizophrenia relative to FES. Conclusions: Frontotemporal brain structural abnormalities are evident in nonpsychotic individuals at high risk of developing schizophrenia. The present meta-analysis indicates that these gray matter abnormalities become more extensive through first-episode and chronic illness. Thus, schizophrenia appears to be a progressive cortico-striato-thalamic loop disorder. PMID:19633214
El-Alameey, Inas R.; Ahmed, Hanaa H.; Monir, Zeinab M.; Rabah, Thanaa M.; Gawad, Ayman M. Abdel
BACKGROUND: Factors predictive of growth retardation and malnutrition in patients with congenital heart disease remain unclear. OBJECTIVES: This study aimed to measure antibody response to bovine casein through assessing serum casein antibody levels in malnourished patients three year or younger with CHD, and to determine its relationship to gastrointestinal symptoms, anthropometric measures, and laboratory data. SUBJECTS AND METHODS: This cross sectional case control study was conducted in sixty patients with CHD aged 4 to 72 months. They were subdivided into thirty patients with cyanotic and thirty patients with acyanotic CHD compared with thirty apparently healthy children. RESULTS: On comparison with controls, patients showed highly significant lower anthropometric measures, calcium, iron, hemoglobin levels, and higher serum levels of casein antibody, total iron binding capacity, and alkaline phoshatase activity (P<0.000). Serum levels of casein antibody showed significantly positive correlations with serum total iron binding capacity and alkaline phosphatase activities and negatively correlated with the age at onset of symptoms, anthropometric measures, serum calcium, and iron levels. CONCLUSION: Serum casein antibody levels play a significant role in the pathogenesis of malnutrition. Encouragement of breast feeding and avoidance of early cow’s milk consumption could prevent the development of antibody response to bovine casein. PMID:27275203
Sahu, Aditi K.; Dhoot, Suyash; Singh, Amandeep; Sawant, Sharada S.; Nandakumar, Nikhila; Talathi-Desai, Sneha; Garud, Mandavi; Pagare, Sandeep; Srivastava, Sanjeeva; Nair, Sudhir; Chaturvedi, Pankaj; Murali Krishna, C.
Serum Raman spectroscopy (RS) has previously shown potential in oral cancer diagnosis and recurrence prediction. To evaluate the potential of serum RS in oral cancer screening, premalignant and cancer-specific detection was explored in the present study using 328 subjects belonging to healthy controls, premalignant, disease controls, and oral cancer groups. Spectra were acquired using a Raman microprobe. Spectral findings suggest changes in amino acids, lipids, protein, DNA, and β-carotene across the groups. A patient-wise approach was employed for data analysis using principal component linear discriminant analysis. In the first step, the classification among premalignant, disease control (nonoral cancer), oral cancer, and normal samples was evaluated in binary classification models. Thereafter, two screening-friendly classification approaches were explored to further evaluate the clinical utility of serum RS: a single four-group model and normal versus abnormal followed by determining the type of abnormality model. Results demonstrate the feasibility of premalignant and specific cancer detection. The normal versus abnormal model yields better sensitivity and specificity rates of 64 and 80% these rates are comparable to standard screening approaches. Prospectively, as the current screening procedure of visual inspection is useful mainly for high-risk populations, serum RS may serve as a useful adjunct for early and specific detection of oral precancers and cancer.
Huang, Wen-Hung; Hsu, Ching-Wei; Weng, Cheng-Hao; Yen, Tzung-Hai; Lin, Jui-Hsiang; Lee, Meng
Abstract Carpal tunnel syndrome (CTS) is the most common mononeuropathy in patients with end-stage renal disease (ESRD). The association between chronic inflammation and CTS in hemodialysis (HD) patients has rarely been investigated. HD patients with a high normalized protein catabolic rate (nPCR) and low serum albumin level likely have adequate nutrition and inflammation. In this study, we assume that a low serum albumin level and high nPCR is associated with CTS in HD patients. We recruited 866 maintenance hemodialysis (MHD) patients and divided them into 4 groups according to their nPCR and serum albumin levels: (1) nPCR <1.2 g/kg/d and serum albumin level <4 g/dL; (2) nPCR ≥1.2 g/kg/d and serum albumin level <4 g/dL; (3) nPCR <1.2 g/kg/d and serum albumin level ≥4 g/dL; and (4) nPCR ≥1.2 g/kg/d and serum albumin level ≥4 g/dL. After adjustment for related variables, HD duration and nPCR ≥1.2 g/kg/d and serum albumin level <4 g/dL were positively correlated with CTS. By calculating the area under the receiver-operating characteristic curve, we calculated that the nPCR and HD duration cut-off points for obtaining the most favorable Youden index were 1.29 g/kg/d and 7.5 years, respectively. Advance multivariate logistic regression analysis revealed that in MHD patients, nPCR ≥1.29 g/kg/d and serum albumin <4 g/dL, and also HD duration >7.5 years were associated with CTS. A high nPCR and low serum albumin level, which likely reflect adequate nutrition and inflammation, were associated with CTS in MHD patients. PMID:27368039
Yamamoto, Tatsuo; Takano, Tomomi; Iwao, Yasuhisa; Hishinuma, Akira
The New Delhi metallo-β-lactamase-1 (NDM-1) gene, bla (NDM-1), is an emerging plasmid-borne drug resistance gene, which encodes for exceptionally broad-spectrum β-lactamase, being able to hydrolyze a wide variety of β-lactams, including carbapenems, and was first reported in Klebsiella pneumoniae from a Swedish patient of Indian origin in 2009. It is widely distributed among Enterobacteriacae and has geographically exhibited extremely rapid and global spread. In this study, we characterized the bla (NDM-1)-positive ST38 Escherichia coli strain NDM-1 Dok01 (which was isolated from the blood of a 54-year-old Japanese inpatient, who had previously visited India), focusing on bacterial surface structures related to virulence. The E. coli culture contained colony variants, which developed a transparent smooth colony and a rough colony on blood agar plates. The smooth colony-forming cells (substrain M1) possessed a surface capsule and were resistant to serum killing, whereas rough colony-forming mutants (substrain B2) lacked a capsule (and a 5.3-kb plasmid) and were highly susceptible to serum killing. Reflecting the surface structural difference, substrain M1 was more flagellated and motile, whereas substrain B2 was less flagellated and apparently possessed straight pili 5 nm wide, which played a role in adherence to human intestinal cells and bacterial autoaggregation. Data suggest that the bla (NDM-1)-positive ST38 E. coli has emerged in Japan and that it is a capsulated bacterial pathogen with virulence potential in the blood stream.
Khandha, Ashutosh; Malcolmson, George; Timm, JP
and lower bounds of predictive implant debris generation modeling, where saline represents a worst-case scenario and as little as 20% serum masks all weight loss completely in highly modular articulating implants. Clinical Relevance Clinical Relevance = 5 (Oxford Centre for Evidence-based Medicine Levels of Evidence). Study findings are limited to a greater understanding of the science associated with predictive wear testing of articulating spinal implants. PMID:25802619
Minamoto, Y; Ogawa, K; Abe, H; Iochi, Y; Mitsugi, K
We tried to establish a new serum-free and heat-sterilizable medium, based on our serum-free medium in which many lymphoblastoid cells and hybridoma could grow as well as in a conventional serum-containing medium.As is well-known, L-glutamine (L-Gln) is one of the most heat-labile but essential components for cell growth. As a substitute for L-Gln, dipeptide such as Gly-L-Gln or L-Ala-L-Gln, which was quite stable even after autoclaving, was found to be utilizable for mammalian cell growth. The L-Gln dipeptide-containing serum-free medium was quite stable in a solution even after storing at 37°C for 4 months. In the serum-free medium containing L-Ala-L-Gln, mouse hybridola could grow and produce more antibody than in RPMI 1640+10% FBS.It has been proved that BSA and transferrin, which are also heat-labile but essential for the growth of various cell lines, can be substituted by heat-stable alpha-cyclodextrin and cholesterol, and Fe-gluconate, respectively. Insulin has also proved to be heat stable in a solution of Fe-gluconate. We thus established a new serum-free medium, all the components of which could be heat-sterilizable.Moreover, by adding EGF and BSA but without the adhesion factor included in FBS, the serum-free medium was found to support a long-term serial culture of a human diploid fibroblast.Finally, with this auotoclavable serum-free medium in a perfusion culture apparatus, we were able to continuously cultivate a human lymphoblastoid cell line. The production rate of IgM was found to be markedly increased by feeding the serum-free medium enriched by glucose, bicarbonate, L-Cys, and approtinin. The cell density reached as high as 2×10(8)/ml in the serum-free medium. Although the working volume in the reactor was only 1 1, the rate of IgM production reached 480 mg/day.The new heat-sterilizable serum-free medium has several advantages, because L-Gln peptide is a heat-stable and available precursor of L-Gln.
Minamoto, Y; Ogawa, K; Abe, H; Iochi, Y; Mitsugi, K
We tried to establish a new serum-free and heat-sterilizable medium, based on our serum-free medium in which many lymphoblastoid cells and hybridoma could grow as well as in a conventional serum-containing medium. As is well-known, L-glutamine (L-Gln) is one of the most heat-labile but essential components for cell growth. As a substitute for L-Gln, dipeptide such as Gly-L-Gln or L-Ala-L-Gln, which was quite stable even after autoclaving, was found to be utilizable for mammalian cell growth. The L-Gln dipeptide-containing serum-free medium was quite stable in a solution even after storing at 37 degrees C for 4 months. In the serum-free medium containing L-Ala-L-Gln, mouse hybridola could grow and produce more antibody than in RPMI 1640 + 10% FBS. It has been proved that BSA and transferrin, which are also heat-labile but essential for the growth of various cell lines, can be substituted by heat-stable alpha-cyclodextrin and cholesterol, and Fe-gluconate, respectively. Insulin has also proved to be heat stable in a solution of Fe-gluconate. We thus established a new serum-free medium, all the components of which could be heat-sterilizable. Moreover, by adding EGF and BSA but without the adhesion factor included in FBS, the serum-free medium was found to support a long-term serial culture of a human diploid fibroblast. Finally, with this auotoclavable serum-free medium in a perfusion culture apparatus, we were able to continuously cultivate a human lymphoblastoid cell line. The production rate of IgM was found to be markedly increased by feeding the serum-free medium enriched by glucose, bicarbonate, L-Cys, and approtinin. The cell density reached as high as 2 x 10(8)/ml in the serum-free medium. Although the working volume in the reactor was only 1 1, the rate of IgM production reached 480 mg/day. The new heat-sterilizable serum-free medium has several advantages, because L-Gln peptide is a heat-stable and available precursor of L-Gln.
Chen, Lingsheng; Zhai, Linhui; Li, Yanchang; Li, Ning; Zhang, Chengpu; Ping, Lingyan; Chang, Lei; Wu, Junzhu; Li, Xiangping; Shi, Deshun; Xu, Ping
The human serum proteome has been extensively screened for biomarkers. However, the large dynamic range of protein concentrations in serum and the presence of highly abundant and large molecular weight proteins, make identification and detection changes in the amount of low-molecular weight proteins (LMW, molecular weight ≤ 30kDa) difficult. Here, we developed a gel-filter method including four layers of different concentration of tricine SDS-PAGE-based gels to block high-molecular weight proteins and enrich LMW proteins. By utilizing this method, we identified 1,576 proteins (n = 2) from 10 μL serum. Among them, 559 (n = 2) proteins belonged to LMW proteins. Furthermore, this gel-filter method could identify 67.4% and 39.8% more LMW proteins than that in representative methods of glycine SDS-PAGE and optimized-DS, respectively. By utilizing SILAC-AQUA approach with labeled recombinant protein as internal standard, the recovery rate for GST spiked in serum during the treatment of gel-filter, optimized-DS, and ProteoMiner was 33.1 ± 0.01%, 18.7 ± 0.01% and 9.6 ± 0.03%, respectively. These results demonstrate that the gel-filter method offers a rapid, highly reproducible and efficient approach for screening biomarkers from serum through proteomic analyses.
Kim, Tae Jin
Objective This study aimed to examine the meaning and usefulness of sexually transmitted infection (STI) test when caring for patients who have abnormal cervical cytology and/or positive high-risk human papillomavirus (HPV) DNA test results. Methods Among patients who underwent liquid-based cervical cytology and HPV DNA tests at the Obstetrics and Gynecology outpatient clinic, 800 patients who showed abnormal cervical cytology were compared with 200 patients in the control group. Both groups were simultaneously tested via multiplex real-time polymerase chain reaction for seven types of STI-causative microorganisms. Results The positive rate of high-risk HPV infection in total STIs positive group was 1.47 times higher than that of total STIs negative group. The probability of a cytological diagnosis of a grade equal to or higher than atypical squamous cells-cannot exclude high grade squamous intraepithelial lesion (ASC-H) was significantly higher in patients testing positive for total STIs (1.46 times), Chlamydia trachomatis (3.21 times), or Mycoplasma genitalicum (3.58 times) than in those testing negative. The total STIs positive rate was significantly higher for those having a cytological diagnosis of a grade equal to or higher than atypical squamous cells of undetermined significance (ASC-US) when high-risk HPV test result was negative. Conclusion Correlations were present not only between STIs and high-risk HPV infection but also between abnormal cervical cytology and STIs. Therefore, additional evaluation of STIs will be helpful to appropriately diagnose and treat patients with abnormal cervical cytology, positive results on high-risk HPV DNA test, or a cytological diagnosis of ASC-US despite negative high-risk HPV DNA test result. PMID:27329197
Schaefer, P C; Goldsmith, R S
An HPLC method for assaying 25(OH)D3 in extracts of human serum is described. The method involves extraction of serum with methanol-dichloromethane and chromatography on a column of Sephadex LH-20 prior to HPLC with quantitation by UV absorbance. Comparison with a CBP assay for 25(OH)D3 showed no difference between the two methods.
Saucedo Marquez, Cinthia Maria; Vanaudenaerde, Bart; Troosters, Thierry; Wenderoth, Nicole
Exercise can have a positive effect on the brain by activating brain-derived neurotrophic factor (BDNF)-related processes. In healthy humans there appears to be a linear relationship between exercise intensity and the positive short-term effect of acute exercise on BDNF levels (i.e., the highest BDNF levels are reported after high-intensity exercise protocols). Here we performed two experiments to test the effectiveness of two high-intensity exercise protocols, both known to improve cardiovascular health, to determine whether they have a similar efficacy in affecting BDNF levels. Participants performed a continuous exercise (CON) protocol at 70% of maximal work rate and a high-intensity interval-training (HIT) protocol at 90% of maximal work rate for periods of 1 min alternating with 1 min of rest (both protocols lasted 20 min). We observed similar BDNF kinetics in both protocols, with maximal BDNF concentrations being reached toward the end of training (experiment 1). We then showed that both exercise protocols significantly increase BDNF levels compared with a rest condition (CON P = 0.04; HIT P < 0.001), with HIT reaching higher BDNF levels than CON (P = 0.035) (experiment 2). These results suggest that shorter bouts of high intensity exercise are slightly more effective than continuous high-intensity exercise for elevating serum BDNF. Additionally, 73% of the participants preferred the HIT protocol (P = 0.02). Therefore, we suggest that the HIT protocol might represent an effective and preferred intervention for elevating BDNF levels and potentially promoting brain health.
Zanini, Marcio; Castro, Juliana; Coelho, Fernando Morgadinho; Bittencourt, Lia; Bressan, Rodrigo A; Tufik, Sergio; Brietzke, Elisa
Sleep architecture changes, such as slow-wave sleep (SWS) percentage variations and reductions in latency and density of rapid eye movement (REM), are found in most patients with schizophrenia and are considered to be an important part of the pathophysiology of the disorder. In addition to these sleep parameters changes, disruptions in sleep homeostasis and the sleep/circadian rhythm also occur in these patients. Sleep/circadian rhythm abnormalities negatively affect neocortical plasticity and cognition and often precede the diagnosis of the illness. Thus, it has been suggested that the sleep/circadian rhythm might be involved in the pathophysiology of psychosis. Recent advances in the identification of individuals at a high risk for developing schizophrenia allow us to investigate several neurobiological processes involved in the development of psychosis. In this article, we review the current evidence of the effects of sleep parameter abnormalities, disruptions in sleep homeostasis and misalignments of sleep circadian rhythm on the early stages of schizophrenia. In addition, we discuss the preliminary evidence of sleep and circadian rhythm abnormalities during the prodromal stages of psychosis and propose that these abnormalities can be explored as potential predictors, as an adjunct to clinical diagnosis, of developing a psychotic disorder in at risk populations.
Olichney, J.M.; Taylor, J.R.; Gatherwright, J.; Salmon, D.P.; Bressler, A.J.; Kutas, M.; Iragui-Madoz, V.J.
Objective We sought cognitive event-related potential (ERP) biomarkers of disease progression and subsequent conversion to dementia in mild cognitive impairment (MCI). Background Two ERP components, the P600 and N400, are sensitive to abnormal episodic/declarative memory and semantic processing. When congruous category-exemplars are repeated, smaller P600s (relative to initial presentation) are normally elicited. Repetitions of semantically incongruous words yield smaller N400 amplitude. In mild Alzheimer disease (AD), abnormalities of both the N400 and P600 repetition effects are present, suggesting a wide-spread failure of synaptic plasticity. Methods Patients with amnestic MCI (n = 32) were longitudinally studied annually with an ERP paradigm in which semantically congruous (50%) and incongruous target words are repeated 10 to 140 seconds after initial presentation. ERP data were analyzed to contrast MCI-to-AD converters (within 3 years) vs nonconverters, using split-plot analyses of variance. Results A statistically significant P600 congruous word repetition effect was found only in the nonconverter group (F = 9.9, p = 0.005 vs MCI converters). This effect correlated with verbal memory measures. Repetition of incongruous words produced a significant N400 amplitude attenuation (across right-hemisphere sites) in nonconverters, but not in converters. Patients with MCI with abnormal/reduced N400 or P600 word repetition effects had an 87 to 88% likelihood of dementia within 3 years while those with normal/spared N400 and P600 repetition effects had only an 11 to 27% likelihood. Conclusions Abnormalities of the P600 or N400 in mild cognitive impairment are associated with an increased risk of subsequent conversion to Alzheimer disease (AD). These event-related potential components may offer useful biomarkers for the detection and staging of very early AD. PMID:18077800
Edelstein, C; Noyes, C; Keim, P; Heinrikson, R L; Fellows, R E; Scanu, A M
The covalent structure of apolipoprotein A-II, isolated from the serum high-density lipoprotein of a single male Rhesus monkey (Macaca mulatta), was determined. The amino acid sequence of this 77-residue polypeptide is: less than Glu-Ala-Glu-Glu-Pro5-Ser-Val-Glu-Ser-Leu10-Val-Ser-Gln-Tyr-Phe15-Gln-Thr-Val-Thr-Asp20-Tyr-Gly-Lys-Asp-Leu25-Met-Glu-Lys-Val-Lys30-Ser-Pro-Glu-Leu-Gln35-Ala-Gln-Ala-Lys-Ala40-Tyr-Phe-Glu-Lys-Ser45-Lys-Glu-Gln-Leu-Thr50-Pro-Leu-Val-Lys-Lys55-Ala-Gly-Thr-Asp-Leu60-Val-Asn-Phe-Leu-Ser65-Tyr-Phe-Val-Glu-Leu70-Arg-Thr-Gln-Pro-Ala75-Thr-Gln-COOH. A comparison of this structure to that of the monomeric form of human apolipoprotein A-II reveals a high degree of homology except for six conservative amino acid replacements (positions 3, 6, 40, 53, 59, and 71). Of particular structural significance is the replacement of cysteine by serine in position 6. This explaines why Rhesus A-II exists in monomeric form, contrary to the established dimeric nature of the human protein.
Aswathi, A; Rajendiren, Soundravally; Nimesh, Archana; Philip, R Ravi; Kattimani, Shivanand; Jayalakshmi, D; Ananthanarayanan, P H; Dhiman, Pooja
In view of the reported cases of mood disorders that occur in mothers following childbirth and believing that sex steroid hormones contribute to mood and behavioral changes, this study has been aimed to explore the role of sex steroid hormones as an etiological factor for postpartum depression (PPD). This study was conducted at JIPMER, Puducherry, India between January 2010 and 2011. 103 women were recruited in the study after childbirth, out of which 62 women who were believed to be suffering from PPD were categorized as cases and the remaining 41 with no mood changes as controls, using Edinburgh Postpartum Depression Scale (EPDS) (cases had EPDS score ≥10 at 24-28h, controls had score <10 at 24-48h postpartum). The hormones estimated in these two groups included estradiol, progesterone and testosterone, and their levels were compared between these two groups. A significantly high testosterone levels were observed in cases with PPD at 24-28h when compared to controls. Estradiol and progesterone levels did not show significant difference between cases and controls. ROC analysis done at 24-28h showed that testosterone levels beyond 42.71ng/mL predict the development of PPD with 79% sensitivity, 63% specificity, 68% positive predictive value, 74% negative predictive value with AUC being 0.708. This study shows that there is an association between persistent high serum testosterone level in women following childbirth and PPD.
Zhao, Liangliang; Li, Yafeng; Song, Delu; Song, Ying; Theurl, Milan; Wang, Chenguang; Cwanger, Alyssa; Su, Guanfang; Dunaief, Joshua L
The retina can be shielded by the blood-retinal barrier. Because photoreceptors are damaged by excess iron, it is important to understand whether the blood-retinal barrier protects against high serum iron levels. Bone morphogenic protein 6 (Bmp6) knockout mice have serum iron overload. Herein, we tested whether the previously documented retinal iron accumulation in Bmp6 knockout mice might result from the high serum iron levels or, alternatively, low levels of retinal hepcidin, an iron regulatory hormone whose transcription can be up-regulated by Bmp6. Furthermore, to determine whether increases in serum iron can elevate retinal iron levels, we i.v. injected iron into wild-type mice. Retinas were analyzed by real-time quantitative PCR and immunofluorescence to assess the levels of iron-regulated genes/proteins and oxidative stress. Retinal hepcidin mRNA levels in Bmp6 knockout retinas were the same as, or greater than, those in age-matched wild-type retinas, indicating that Bmp6 knockout does not cause retinal hepcidin deficiency. Changes in mRNA levels of L ferritin and transferrin receptor indicated increased retinal iron levels in i.v. iron-injected wild-type mice. Oxidative stress markers were elevated in photoreceptors of mice receiving i.v. iron. These findings suggest that elevated serum iron levels can overwhelm local retinal iron regulatory mechanisms.
Dehlink, Eleonora; Platzer, Barbara; Baker, Alexandra H.; LaRosa, Jessica; Pardo, Michael; Dwyer, Peter; Yen, Elizabeth H.; Szépfalusi, Zsolt
Soluble IgE receptors are potential in vivo modulators of IgE-mediated immune responses and are thus important for our basic understanding of allergic responses. We here characterize a novel soluble version of the IgE-binding alpha-chain of Fc-epsilon-RI (sFcεRI), the high affinity receptor for IgE. sFcεRI immunoprecipitates as a protein of ∼40 kDa and contains an intact IgE-binding site. In human serum, sFcεRI is found as a soluble free IgE receptor as well as a complex with IgE. Using a newly established ELISA, we show that serum sFcεRI levels correlate with serum IgE in patients with elevated IgE. We also show that serum of individuals with normal IgE levels can be found to contain high levels of sFcεRI. After IgE-antigen-mediated crosslinking of surface FcεRI, we detect sFcεRI in the exosome-depleted, soluble fraction of cell culture supernatants. We further show that sFcεRI can block binding of IgE to FcεRI expressed at the cell surface. In summary, we here describe the alpha-chain of FcεRI as a circulating soluble IgE receptor isoform in human serum. PMID:21544204
Ohri, V.C.; Chatterji, J.C.; Sachdev, Y.R.; Das, B.K.; Akhtar, M.; Tiwari, S.C.; Bhattacharji, P.; Behl, A.; Dutta, S.K.
Forty subjects each were rapidly inducted by road to altitudes of 3200 and 3771 meters (m). Half of subjects at each altitude were maintained on digoxin and the other half received placebos. The digoxin group showed higher serum potassium at both altitudes. Serum sodium remained unaltered. When compared to control groups, urinary volume changes were less marked in the digoxin group. Similarly, the alterations in calcium and magnesium in serum and urine at 3771 m were less pronounced. However, none of these changes in the digoxin groups were statistically significant when compared with control groups. 21 references.
Johansson, Helena; Odén, Anders; Lerner, Ulf H; Jutberger, Hans; Lorentzon, Mattias; Barrett-Connor, Elizabeth; Karlsson, Magnus K; Ljunggren, Osten; Smith, Ulf; McCloskey, Eugene; Kanis, John A; Ohlsson, Claes; Mellström, Dan
Adipocytes and osteoblasts share a common progenitor, and there is, therefore, potential for both autocrine and endocrine effects of adiponectin on skeletal metabolism. The aim of the present study was to determine whether high serum adiponectin was associated with an increased risk of fracture in elderly men. We studied the relationship between serum adiponectin and the risk of fracture in 999 elderly men drawn from the general population and recruited to the Osteoporotic Fractures in Men (MrOS) study in Gothenburg, Sweden. Baseline data included general health questionnaires, lifestyle questionnaires, body mass index (BMI), bone mineral density (BMD), serum adiponectin, osteocalcin, and leptin. Men were followed for up to 7.4 years (average, 5.2 years). Poisson regression was used to investigate the relationship between serum adiponectin, other risk variables and the time-to-event hazard function of fracture. Median levels of serum adiponectin at baseline were 10.4 µg/mL (interquartile range, 7.7-14.3). During follow-up, 150 men sustained one or more fractures. The risk of fracture increased in parallel with increasing serum adiponectin (hazard ratio [HR]/SD, 1.46; 95% confidence interval [CI], 1.23-1.72) and persisted after multivariate-adjusted analysis (HR/SD, 1.30; 95% CI, 1.09-1.55). Serum adiponectin shows graded stepwise association with a significant excess risk of fracture in elderly men that was independent of several other risk factors for fracture. Its measurement holds promise as a risk factor for fracture in men.
Dimitris, Michelle C; Perumal, Nandita; Craig-Barnes, Hayley A; Leadley, Michael; Mahmud, Abdullah A; Baqui, Abdullah H; Roth, Daniel E
Vitamin D status is conventionally defined by the serum concentration of 25-hydroxyvitamin D. However, it has been proposed that the serum cholecalciferol concentration (D3) also determines functional vitamin D sufficiency. The objective of this study was to describe the effect of weekly high-dose vitamin D3 supplementation on inter-dose serum D3 in pregnant women. We conducted a sub-study of a completed randomized double-blind placebo-controlled trial of vitamin D3 (35,000 IU/week) supplementation in late pregnancy (AViDD trial) in Dhaka, Bangladesh. This study included pregnant women enrolled at 26-29 weeks gestation who fully adhered to the prenatal supplement intervention for ≥8 consecutive weeks and for whom serum samples were available for D3 analysis (n=65). Serum D3 was uniformly low at enrolment. Mean D3 increased and was maximal at 1 day after vitamin D dose administration (152.09nmol/L, SD 25.11nmol/L) and remained significantly higher in VitD vs. Pl at 7 days (29.59nmol/L vs. 1.92nmol/L, p=0.007). Daily average of the group mean D3 during the week following dosing was 66.97nmol/L in VitD versus 2.13nmol/L in Pl. In conclusion, serum D3 remained significantly elevated throughout the week following ≥8 consecutive weekly doses of 35,000 IU D3 in pregnant women. However, the clinically significant minimum threshold of serum D3 remains to be established.
Giannetti, Luigi; Barchi, Daniela; Fiorucci, Fulvia; Gennuso, Elisa; Sanna, Patrizia; Pallagrosi, Marco; Neri, Bruno
Different extraction and purification methods are described here to determine medroxyprogesterone acetate (MPA) in pork meat and serum. Spiked samples are investigated over the concentration range of MPA 0.5-20 ng/g. Pork meat tissues are subjected to extraction using organic solvent, and pork serum is simply diluted with acetate buffer. Clean-up is performed using solid-phase extraction on a C18 cartridge, and MPA is eluted with ethanol. Aliquots are injected into a high-performance liquid chromatography-mass spectrometry system. MPA content is determined on the basis of m/z 387-327 and 387-123 transitions.
Coetzee, G A; Strachan, A F; van der Westhuyzen, D R; Hoppe, H C; Jeenah, M S; de Beer, F C
Serum amyloid A protein (apo-SAA), an acute phase reactant, is an apolipoprotein of high density lipoproteins (HDL), in particular the denser subpopulation HDL3. The structure of HDL3 isolated from humans affected by a variety of severe disease states was investigated with respect to density, size, and apolipoprotein composition, using density gradient ultracentrifugation, gradient gel electrophoresis, gel filtration, and solid phase immunoadsorption. Apo-SAA was present in HDL particles in increasing amounts as particle density increased. Apo-SAA-containing HDL3 had bigger radii than normal HDL3 of comparable density. Purified apo-SAA associated readily with normal HDL3 in vitro, giving rise to particles containing up to 80% of their apoproteins as apo-SAA. The addition of apo-SAA resulted in a displacement of apo-A-I and an increase in particle size. Acute phase HDL3 represented a mixture of particles, polydisperse with respect to apolipoprotein content; for example, some particles were isolated that contained apo-A-I, apo-A-II, and apo-SAA, whereas others contained apo-A-I and apo-SAA but no apo-A-II. We conclude that apo-SAA probably associates in the circulation of acute phase patients with existing HDL particles, causing the remodeling of the HDL shell to yield particles of bigger size and higher density that are relatively depleted of apo-A-I.
Sengupta, A; Hage, D S
This study used high-performance affinity chromatography (HPAC) and immobilized human serum albumin (HSA) columns to examine the specificity and cross-reactivity of various compounds that have been proposed as markers for the minor binding sites of HSA. These agents included acetyldigitoxin and digitoxin as probes for the digitoxin site, phenol red as a probe for the bilirubin site, and cisor trans-clomiphene as markers for the tamoxifen site. None of these probes showed any significant binding at HSA's indole-benzodiazepine site. However, phenol red did bind at the warfarin-azapropazone site of HSA, and cis/trans-clomiphene gave positive allosteric effects caused by the binding of warfarin to HSA. Digitoxin and acetyldigitoxin were found to bind to a common, unique region on HSA; cis- and trans-clomiphene also appeared to interact at a unique site, although trans-clomiphene displayed additional direct competition with phenol red. From these results it was possible to develop a model that described the general relationship between these binding regions on HSA. This information should be useful in future studies that employ HPAC for characterizing the binding of HSA to other drugs or clinical agents.
Soliman, Sherry; Aronson, William J.; Barnard, R. James
Serum from men undergoing a low-fat, high-fiber diet and exercise intervention has previously been shown to decrease growth and increase apoptosis in serum-stimulated, androgen-dependent LNCaP cells associated with a reduction in serum IGF-I. Here we sought to determine the underlying mechanisms for these anticancer effects. Again, the intervention slowed growth and increased apoptosis in LNCaP cells; responses that were eliminated when IGF-I was added back to the post-intervention samples. The p53 protein content was increased and NFκB activation reduced in the post serum-stimulated LNCaP cells. Similar results were observed when the IGF-I receptor was blocked in the pre-intervention serum. In androgen-independent PC-3 cells, growth was reduced while none of the other factors were changed by the intervention. We conclude that diet and exercise intervention might help prevent clinical PCa as well as aid in the treatment of PCa during the early stages of development. PMID:19376839
Kobtan, Abdelrahman A; El-Kalla, Ferial S; Soliman, Hanan H; Zakaria, Soha S; Goda, Mohamed A
Hepatic encephalopathy is a serious complication of liver failure. Until now, the precise pathophysiologic mechanisms are not fully determined. It has been demonstrated that manganese plays an important role in the pathogenesis of hepatic encephalopathy. Therefore, we studied manganese levels in serum of cirrhotic patients with hepatic encephalopathy in relation to grading and recurrence of hepatic encephalopathy. One hundred persons were enrolled in the study, 80 cirrhotic patients with or without encephalopathy and 20 healthy controls. Hepatic encephalopathy was diagnosed clinically and by laboratory findings. Serum manganese levels were measured in all participants. The grading of hepatic encephalopathy was significantly correlated to the severity of liver dysfunction. The mean serum manganese level was significantly higher in cirrhotic patients than in controls and in cirrhotic patients with encephalopathy than in those without encephalopathy. It was also significantly higher in patients with advanced grading of hepatic encephalopathy. Serum manganese level was positively correlated to number of recurrences of encephalopathy during a 6-month follow-up period. Serum manganese levels were able to predict recurrence of hepatic encephalopathy within 6 months following the episode. Serum manganese levels are positively correlated to the modified Child-Pugh score of cirrhosis as well as grading and number of recurrences of hepatic encephalopathy. Higher manganese levels seem to be related to worsening of the condition, and its measurement may be used as a predictor of repeated recurrences.
Mokta, Jitender; Kumar, Subash; Ganju, Neeraj; Mokta, Kiran; Panda, Prashant Kumar; Gupta, Swatantra
Background: Abnormal glucose metabolic status at admission is an important marker of future cardiovascular events and long-term mortality after acute coronary syndrome (ACS), whether or not they are known diabetics. Objective: The aims were to study the prevalence of abnormal glucose metabolism in ACS patients and to compare the different methods of diagnosing diabetes in ACS patients. Methods: We did a prospective study. About 250 consecutive nondiabetic patients (200 men and 50 women) with ACS admitted to a tertiary care institute of Himachal Pradesh in 1 year were enrolled. Admission plasma glucose, next morning fasting plasma glucose (FPG), A1C, and a standardized 75-g oral glucose tolerance test (OGTT) 72 h after admission were done. Glucose metabolism was categorized as normal glucose metabolism, impaired glucose metabolism (impaired fasting glucose or impaired glucose tolerance [IGT]), and diabetes. Diabetes was arbitrarily classified further as undiagnosed (HBA1c ≥6.5%) or possibly stress diabetes (HBA1c <6.5%). A repeat OGTT after 3 months in objects with IGT and stress hyperglycemia at a time of admission was done. Results: The mean age was 54 ± 12.46 years. The mean plasma glucose at admission was 124 ± 53.96 mg/dL, and the mean FPG was 102 ± 27.07 mg/dL. The mean 2-h postglucose load concentration was 159.5 ± 56.58 mg/dL. At baseline, 95 (38%) had normal glucose metabolism, 95 (38%) had impaired glucose metabolism (IGT and or IGT) and 60 (24%) had diabetes; 48 (19.2%) were undiagnosed diabetes and 12 (4.8%) had stress hyperglycemia. At follow up 58.66% and 55.55% of patients with impaired glucose tolerance and stress hyperglycemia continued to have impaired glucose tolerance respectively. About 75 gm OGTT has highest sensitivity and specificity to diagnose diabetes, whereas A1C most specific to rule out stress hyperglycemia. Conclusions: In this small hilly state of India, abnormal glucose metabolism (previously undiagnosed diabetes and IGT) is
Sheehan, Heidi B; Benetucci, Jorge; Muzzio, Estela; Redini, Liliana; Naveira, Jorge; Segura, Marcela; Weissenbacher, Mercedes; Tang, Alice M
Objective To describe the prevalence and correlates of low serum Se and determine whether HIV, hepatitis C virus (HCV) and/or types of drugs used are associated with serum Se in a cohort of infected and uninfected drug users. Design Independent correlates of low serum Se levels based on data collected from food recalls, physical exams, and clinical status questionnaires were identified using multivariate analysis. Setting Buenos Aires, Argentina Subjects A total of 205 (25 females and 180 males) former and current drug users Results Drug users had an average serum Se level of 69.8±32.8 μg/dl, and 82% were considered deficient (< 85μg/l). Multivariate analyses found that HIV and/or HCV infection had lower mean Se compared to healthy, uninfected drug users (HIV/HCV co-infection: −25.3 μg/l (SE =7.6, p=0.001); HIV alone: −28.9 μg/l (SE=6.9, p<0.001); HCV alone −19.4 μg/l (SE = 7.1, p=0.006). Current and previous drug use was associated with higher serum Se. Cigarette smoking and heavy alcohol consumption were not found to be associated with Se status. Conclusions Low serum Se levels are highly prevalent among drug users in Buenos Aires, Argentina. Se supplementation and/or dietary interventions may be warranted in drug users who are at high risk of HIV and/or HCV infection. PMID:21740621
Consumption of a high-fat meal containing cheese compared with a vegan alternative lowers postprandial C-reactive protein in overweight and obese individuals with metabolic abnormalities: a randomised controlled cross-over study.
Demmer, Elieke; Van Loan, Marta D; Rivera, Nancy; Rogers, Tara S; Gertz, Erik R; German, J Bruce; Zivkovic, Angela M; Smilowitz, Jennifer T
Dietary recommendations suggest decreased consumption of SFA to minimise CVD risk; however, not all foods rich in SFA are equivalent. To evaluate the effects of SFA in a dairy food matrix, as Cheddar cheese, v. SFA from a vegan-alternative test meal on postprandial inflammatory markers, a randomised controlled cross-over trial was conducted in twenty overweight or obese adults with metabolic abnormalities. Individuals consumed two isoenergetic high-fat mixed meals separated by a 1- to 2-week washout period. Serum was collected at baseline, and at 1, 3 and 6 h postprandially and analysed for inflammatory markers (IL-6, IL-8, IL-10, IL-17, IL-18, TNFα, monocyte chemotactic protein-1 (MCP-1)), acute-phase proteins C-reactive protein (CRP) and serum amyloid-A (SAA), cellular adhesion molecules and blood lipids, glucose and insulin. Following both high-fat test meals, postprandial TAG concentrations rose steadily (P < 0·05) without a decrease by 6 h. The incremental AUC (iAUC) for CRP was significantly lower (P < 0·05) in response to the cheese compared with the vegan-alternative test meal. A treatment effect was not observed for any other inflammatory markers; however, for both test meals, multiple markers significantly changed from baseline over the 6 h postprandial period (IL-6, IL-8, IL-18, TNFα, MCP-1, SAA). Saturated fat in the form of a cheese matrix reduced the iAUC for CRP compared with a vegan-alternative test meal during the postprandial 6 h period. The study is registered at clinicaltrials.gov under NCT01803633.
Li, Yuan-dong; Li, Yan; Liang, Ning-sheng; Yang, Fan; Kuang, Zhi-peng
A simple, rapid and sensitive reversed-phase high performance liquid chromatography (HPLC) method has been developed for the determination of methotrexate in human serum. After deproteinization of the serum with 40% silver nitrate solution, methotrexate and internal standard (IS) were separated on a reversed-phase column with a mobile phase consisting of 10mM sodium phosphate buffer (pH6.40)-methanol (78:22%, v/v) and ultraviolet detection at 310nm. The linearity is evaluated by a calibration curve in the concentration range of 0.05-10.0μg/mL and presented a correlation coefficient of 0.9995. The absolute recoveries were 97.52±3.9% and 96.87±3.7% for methotrexate and ferulic acid (internal standard), respectively. The intra- and inter-day precision were less 6.19 and 5.89%, respectively (n=6). The limit of quantitation was 0.02μg/mL and the limit of detection was 0.006μg/mL. The complete analysis was achieved less than 10min with no interference from endogenous components or 22 examined drugs. This method was validated by using serum samples from high-dose methotrexate treated patients with osteosarcoma, breast cancer, acute leukemia and lymphoma. The method was demonstrated to be a simple, rapid and reliable approach in quantification of methotrexate in serum samples from patients with high-dose methotrexate therapy.
Terpos, E; Christoulas, D; Kastritis, E; Bagratuni, T; Gavriatopoulou, M; Roussou, M; Papatheodorou, A; Eleutherakis-Papaiakovou, E; Kanellias, N; Liakou, C; Panagiotidis, I; Migkou, M; Kokkoris, P; Moulopoulos, L A; Dimopoulos, M A
Periostin is an extracellular matrix protein that is implicated in the biology of normal bone remodeling and in different cancer cell growth and metastasis. However, there is no information on the role of periostin in multiple myeloma (MM). Thus, we evaluated periostin in six myeloma cell lines in vitro; in the bone marrow plasma and serum of 105 newly diagnosed symptomatic MM (NDMM) patients and in the serum of 23 monoclonal gammopathy of undetermined significance (MGUS), 33 smoldering MM (SMM) patients, 30 patients at the plateau phase post-first-line therapy, 30 patients at first relapse and 30 healthy controls. We found high levels of periostin in the supernatants of myeloma cell lines compared with ovarian cancer cell lines that were not influenced by the incubation with the stromal cell line HS5. In NDMM patients the bone marrow plasma periostin was almost fourfold higher compared with the serum levels of periostin and correlated with the presence of fractures and of diffuse magnetic resonance imaging pattern of marrow infiltration. Serum periostin was elevated in NDMM patients compared with healthy controls, MGUS and SMM patients and correlated with advanced disease stage, high lactate dehydrogenase, increased activin-A, increased bone resorption and reduced bone formation. Patients at first relapse had also elevated periostin compared with healthy controls, MGUS and SMM patients, while even patients at the plateau phase had elevated serum periostin compared with healthy controls. These results support an important role of periostin in the biology of myeloma and reveal periostin as a possible target for the development of antimyeloma drugs. PMID:27716740
Moore, A B M
A total of 10 abnormal free-swimming (i.e., post-birth) elasmobranchs are reported from The (Persian-Arabian) Gulf, encompassing five species and including deformed heads, snouts, caudal fins and claspers. The complete absence of pelvic fins in a milk shark Rhizoprionodon acutus may be the first record in any elasmobranch. Possible causes, including the extreme environmental conditions and the high level of anthropogenic pollution particular to The Gulf, are briefly discussed.
Lai, Yi-Syuan; Chen, Wei-Cheng; Kuo, Tien-Chueh; Ho, Chi-Tang; Kuo, Ching-Hua; Tseng, Yufeng J; Lu, Kuan-Hung; Lin, Shih-Hang; Panyod, Suraphan; Sheen, Lee-Yan
Obesity, dyslipidemia, insulin resistance, oxidative stress, and inflammation are key clinical risk factors for the progression of non-alcoholic fatty liver disease (NAFLD). Currently, there is no comprehensive metabolic profile of a well-established animal model that effectively mimics the etiology and pathogenesis of NAFLD in humans. Here, we report the pathophysiological and metabolomic changes associated with NAFLD development in a C57BL/6J mouse model in which NAFLD was induced by feeding a high-fat diet (HFD) for 4, 8, 12, and 16 weeks. Serum metabolomic analysis was conducted using ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) and gas chromatography-mass spectrometry (GC-MS) to establish a metabolomic profile. Analysis of the metabolomic profile in combination with principal component analysis revealed marked differences in metabolites between the control and HFD group depending upon NAFLD severity. A total of 30 potential biomarkers were strongly associated with the development of NAFLD. Among these, 11 metabolites were mainly related to carbohydrate metabolism, hepatic biotransformation, collagen synthesis, and gut microbial metabolism, which are characteristics of obesity, as well as significantly increased serum glucose, total cholesterol, and hepatic triglyceride levels during the onset of NAFLD (4 weeks). At 8 weeks, 5 additional metabolites that are chiefly involved in perturbation of lipid metabolism and insulin secretion were found to be associated with hyperinsulinemia, hyperlipidemia, and hepatic steatosis in the mid-term of NAFLD progression. At the end of 12 and 16 weeks, 14 additional metabolites were predominantly correlated to abnormal bile acid synthesis, oxidative stress, and inflammation, representing hepatic inflammatory infiltration during NAFLD development. These results provide potential biomarkers for early risk assessment of NAFLD and further insights into NAFLD
Kowalczuk, Dorota; Wawrzycka, Maria Bozena; Haratym Maj, Agnieszka
Nifedipine (Nif) is widely used in treating cardiovascular disorders (especially hypertension) and for inhibiting preterm labor. A fully validated selective high-performance liquid chromatographic method with diode array detection, using solid-phase extraction, was developed for the determination of Nif in human serum. To assess specificity, Nif and its degradation products were separated on a Purospher RP-18 (5 microm, 125 x 4 mm) column plus a LiChrospher 100 RP-18 (5 microm, 4 x 4 mm) precolumn with a mobile phase of methanol-10 mM aqueous trifluoroacetic acid, pH 7.3 (57 + 43, v/v); chromatographic separation was followed by UV detection at 238 nm. For toxicological analysis, Nif in the presence of other calcium-channel antagonist drugs was identified under optimum chromatographic conditions. The calibration graph was constructed over the concentration range of 12.5-400 ng/mL in serum with good correlation (r = 0.9956). This method was not subject to interference by other plasma components and was successfully applied to the assay of Nif in spiked human serum and in serum of women in preterm labor after sublingual administration of 30 mg Nif per day divided into 3 equal doses. The mean recovery based on the ratio of the slopes of serum and mobile phase standard curves was 96.5%. The detection and quantification limits of the drug in spiked human serum were found to be 6 and 17.5 ng/mL, respectively. Validation of the method demonstrated good intraday and interday precision, which ranged from 2.18 to 6.67% and from 6.52 to 11.93%, respectively.
Geisel, Olga; Hellweg, Rainer; Müller, Christian A
The neurotrophin brain-derived neurotrophic factor (BDNF) has been suggested to be involved in the development and maintenance of addictive and other psychiatric disorders. Also, interactions of γ-aminobutyric acid (GABA)-ergic compounds and BDNF have been reported. The objective of this study was to investigate serum levels of BDNF over time in alcohol-dependent patients receiving individually titrated high-dose treatment (30-270mg/d) with the GABA-B receptor agonist baclofen or placebo for up to 20 weeks. Serum levels of BDNF were measured in patients of the baclofen/placebo group at baseline (t0), 2 weeks after reaching individual high-dose of baclofen/placebo treatment (t1) and after termination of study medication (t2) in comparison to carefully matched healthy controls. No significant differences in serum levels of BDNF between the baclofen and the placebo group or healthy controls were found at t0, t1, or at t2. Based on these findings, it seems unlikely that baclofen exerts a direct effect on serum levels of BDNF in alcohol-dependent patients. Future studies are needed to further explore the mechanism of action of baclofen and its possible relationship to BDNF in alcohol use disorders.
Li, Hongxia; Dong, Jun; Chen, Wenxiang; Wang, Shu; Guo, Hanbang; Man, Yong; Mo, Peisheng; Li, Jianzhai
Serum levels of total glycerides and free glycerol are important indices of lipid metabolism and cardiovascular disease risk. Convenient enzymatic methods of measurement have been available, but they are susceptible to interference. Situations exist in both research and clinical laboratories in which more specific and precise methods are needed. We developed HPLC methods for the measurement of serum total glycerides and free glycerol. For total glycerides, serum was mixed with an internal standard (1,2,4-butanetriol) and treated with alcoholic sodium hydroxide to hydrolyze glycerides to glycerol. After deproteinization with tungstic acid, the glycerol was benzoylated with an optimized Schotten-Baumann reaction and analyzed by HPLC. For free glycerol, serum was equilibrated with the internal standard and deproteinized with tungstic acid to remove the glycerides. The glycerol was benzoylated and analyzed as for total glycerol. Various factors were investigated, and no significant sources of interference were detected. The total coefficients of variation ranged from 0.7% to 2.0% for total glycerides and from 1.7% to 3.2% for free glycerol. The analytical recoveries ranged from 98.5% to 101.6%. In conclusion, simple and reliable HPLC methods for serum total glycerides and free glycerol have been developed. The methods may also be used for the analyses of glycerol or glycerides in other biological samples.
Schober, Susan E; Carroll, Margaret D; Lacher, David A; Hirsch, Rosemarie
Elevated serum total cholesterol is a major and modifiable risk factor for heart disease, the lead-ing cause of death in the United States (1,2). Reducing mean total serum cholesterol levels among adults to less than 200 mg/dL and reducing the proportion who have levels of 240 mg/dL or higher to less than 17% are national Healthy People 2010 objectives (3). Age-adjusted mean serum cholesterol levels among adults aged 20-74 years declined from 222 mg/dL in 1960-1962 to 203 mg/dL in 1999-2002 (4). Among adults aged 20 years and older, the percent of the population with high serum total cholesterol levels (240 mg/dL or higher) declined from 20% during 1988-1994 to 17% during 1999-2002 (4). In individual patients, a high serum total cholesterol level indicates a potential increased risk for heart disease, but further evaluation of other risk factors and the specific components of cholesterol provide the basis for determining the need for initiating therapeutic lifestyle changes or treatment with medication (5). Low-density-lipoprotein (LDL) is the cholesterol component associated with arterial blockage, and it is the primary clinical target for cholesterol management. High-density-lipoprotein (HDL) may help to protect individuals from developing heart disease. In populations, comparisons of total cholesterol levels over time can show if population groups are experiencing improvement in cholesterol levels, and knowledge of trends in levels of total cholesterol can help identify subgroups where additional prevention efforts may be needed.
Zhang, Ling Ling; Ma, Fang Fang; Kuang, Yang Fang; Cheng, Shu; Long, Yun Fei; Xiao, Qiu Guo
A simple, fast and highly sensitive spectrophotometric method for the determination of bovine serum albumin (BSA) has been developed based on the interactions between triangular silver nanoplates (TAgNPs) and BSA in the presence of Britton-Robison buffer solution (BR). Particularly, the wavelength of absorption maximum (λ(max)) of TAgNPs is red shifted in the presence of BSA together with Britton-Robinson buffer solution (BR, pH=2.56), and the color of the solution changed from blue to light blue. This may be due to the interactions between BSA molecules on the surface of TAgNPs through electrostatic forces, hydrogen bonds, hydrophobic effects and van der Waals forces at pH2.56, which leads to the aggregation of TAgNPs. The determination of BSA was achieved by measuring the change of λ(max) corresponding to localized surface plasmon resonance (LSPR) from UV-visible spectrophotometry. It was found that the shift value in the wavelength of absorption maximum (Δλ, the difference in absorption maxima of the TAgNPs/BSA/BR mixture and the TAgNPs/BR mixture) was proportionate to the concentration of BSA in the range of 1.0 ng mL(-1) to 100.0 ng mL(-1) with the correlation coefficient of r=0.9969. The detection limit (3 σ/k) for BSA was found to be as low as 0.5 ng mL(-1).
Zhang, Ling Ling; Ma, Fang Fang; Kuang, Yang Fang; Cheng, Shu; Long, Yun Fei; Xiao, Qiu Guo
A simple, fast and highly sensitive spectrophotometric method for the determination of bovine serum albumin (BSA) has been developed based on the interactions between triangular silver nanoplates (TAgNPs) and BSA in the presence of Britton-Robison buffer solution (BR). Particularly, the wavelength of absorption maximum (λmax) of TAgNPs is red shifted in the presence of BSA together with Britton-Robinson buffer solution (BR, pH = 2.56), and the color of the solution changed from blue to light blue. This may be due to the interactions between BSA molecules on the surface of TAgNPs through electrostatic forces, hydrogen bonds, hydrophobic effects and van der Waals forces at pH 2.56, which leads to the aggregation of TAgNPs. The determination of BSA was achieved by measuring the change of λmax corresponding to localized surface plasmon resonance (LSPR) from UV-visible spectrophotometry. It was found that the shift value in the wavelength of absorption maximum (Δλ, the difference in absorption maxima of the TAgNPs/BSA/BR mixture and the TAgNPs/BR mixture) was proportionate to the concentration of BSA in the range of 1.0 ng mL- 1 to 100.0 ng mL- 1 with the correlation coefficient of r = 0.9969. The detection limit (3 σ/k) for BSA was found to be as low as 0.5 ng mL- 1.
Law, B.E.; Spencer, C.W.
Abnormal pressures, pressures above or below hydrostatic pressures, occur on all continents in a wide range of geological conditions. According to a survey of published literature on abnormal pressures, compaction disequilibrium and hydrocarbon generation are the two most commonly cited causes of abnormally high pressure in petroleum provinces. In young (Tertiary) deltaic sequences, compaction disequilibrium is the dominant cause of abnormal pressure. In older (pre-Tertiary) lithified rocks, hydrocarbon generation, aquathermal expansion, and tectonics are most often cited as the causes of abnormal pressure. The association of abnormal pressures with hydrocarbon accumulations is statistically significant. Within abnormally pressured reservoirs, empirical evidence indicates that the bulk of economically recoverable oil and gas occurs in reservoirs with pressure gradients less than 0.75 psi/ft (17.4 kPa/m) and there is very little production potential from reservoirs that exceed 0.85 psi/ft (19.6 kPa/m). Abnormally pressured rocks are also commonly associated with unconventional gas accumulations where the pressuring phase is gas of either a thermal or microbial origin. In underpressured, thermally mature rocks, the affected reservoirs have most often experienced a significant cooling history and probably evolved from an originally overpressured system.
Sujatha; Rai, Lavanya; Kumar, Pratap; Mahato, Krishna K; Kartha, Vasudevan B; Santhosh, Chidangil
High performance liquid chromatography with high sensitivity laser-induced fluorescence detection is used to study the protein profiles of serum samples from healthy volunteers and cervical cancer subjects. The protein profiles are subjected to principal component analysis (PCA). PCA shows that the large number of chromatograms of a given class of serum samples--say normal/malignant--can be expressed in terms of a small number of factors (principal components). Three parameters--scores of the factors, squared residuals, and Mahalanobis distance--are derived from PCA. The parameters are observed to have a narrow range for protein profiles of standard calibration sets formed from groups of clinically confirmed normal/malignant classes. Limit tests using match/no match of the parameters of any test sample with parameters derived for the standard calibration sets give very good discrimination between malignant and normal samples with high sensitivity (approximately 100%) aand specificity (approximately 94%).
Pramono, Adriyan; Panunggal, Binar; Rahfiludin, M. Zen; Swastawati, Fronthea
The coverage of environmental lead toxicant was quiet wide. Lead exposure recently has been expected to be associated with zinc deficiency and blood indices disturbance. Emphasizing on children, which could absorb more than 50 % of lead that enters the body. Lead became the issue on the coastal area due to it has polluted the environment and waters as the source of fisheries products. This was a cross sectional study to determined nutritional status, blood lead levels, zinc serum levels, blood indices levels, fish intake among school children in coastal region of Semarang. This study was carried out on the school children aged between 8 and 12 years old in coastal region of Semarang. Nutritional status was figured out using anthropometry measurement. Blood lead and zinc serum levels were analyzed using the Atomic Absorbent Spectrophotometry (AAS) at a wavelength of 213.9 nm for zinc serum and 283.3 nm for blood lead. Blood indices was measured using auto blood hematology analyzer. Fish intake was assessed using 3-non consecutive days 24-hours food recall. The children had high lead levels (median 34.86 μg/dl, range 11.46 - 58.86 μg/dl) compared to WHO cut off. Zinc serum levels was low (median 18.10 μg/dl, range 10.25 – 41.39 μg/dl) compared to the Joint WHO/UNICEF/IAEA/IZiNCG cut off. Approximately 26.4% of children were anemic. This study concluded that all school children had high blood lead levels, low zinc serum, and presented microcytic hypochromic anemia. This phenomenon should be considered as public health concern.
Bird, Susan S; Marur, Vasant R; Sniatynski, Matthew J; Greenberg, Heather K; Kristal, Bruce S
There is a growing need both clinically and experimentally to improve the characterization of blood lipids. A liquid chromatography-mass spectrometry (LC-MS) method, developed for the qualitative and semiquantitative detection of lipids in biological samples and previously validated in mitochondrial samples, was now evaluated for the profiling of serum lipids. Data were acquired using high-resolution, full scan MS and high-energy, collisional dissociation (HCD), all ion fragmentation. The method was designed for efficient separation and detection in both positive and negative ionization mode and evaluated using standards spanning seven lipid classes. Platform performance, related to the identification and characterization of serum triglycerides (TGs), was assessed using extracted ion chromatograms with mass tolerance windows of 5 ppm or less from full scan exact mass measurements determined using SIEVE nondifferential LC-MS analysis software. The platform showed retention time coefficients of variation (CV) of <0.3%, mass accuracy values of <2 ppm error, and peak area CV of <13%, with the majority of that error coming from sample preparation and extraction rather than the LC-MS analysis, and linearity was shown to be over 4 orders of magnitude (r(2) = 0.999) for the standard TG (15:0)(3) spiked into serum. Instrument mass accuracy and precision were critical to the identification of unknown TG species, in part because these parameters enabled us to reduce false positives. In addition to detection and relative quantitation of TGs in serum, TG structures were characterized through the use of alternating HCD scans at different energies to produce diagnostic fragmentations on all ions in the analysis. The lipidomics method was applied to serum samples from 192 rats maintained on diets differing in macronutrient composition. The analysis identified 86 TG species with 81 unique masses that varied over 3.5 orders of magnitude and showed diet-dependency, consistent with
Tanaka, Einosuke; Nakamura, Takako; Terada, Masaru; Shinozuka, Tatsuo; Hashimoto, Chikako; Kurihara, Katsuyoshi; Honda, Katsuya
A high-performance liquid chromatographic method has been developed for the simultaneous analysis of the 12 phenothiazines (chlorpromazine, fluphenazine, levomepromazine, perazine, perphenazine, prochlorperazine, profenamine, promethazine, propericiazine, thioproperazine, thioridazine and trifluoperazine) in human serum using HPLC/UV. The separation was achieved using a C(18) reversed-phase column (250 mm x 4.6 mm I.D., particle size 5 microm, Inersil ODS-SP). The mobile phase, consisting of acetonitrile-methanol-30 mM NaH(2)PO(4) (pH 5.6) (300:200:500, v/v/v), was delivered at a flow rate of 0.9 mL/min and UV detection was carried out at 250 nm. The recoveries of the 12 phenothiazines spiked into serum samples were 87.6-99.8%. Regression equations for the 12 phenothiazines showed excellent linearity, with detection limits of 3.2-5.5 ng/mL for serum. The inter-day and intra-day coefficients of variation for serum samples were commonly below 8.8%. The selectivity, accuracy and precision of this method are satisfactory for clinical and forensic purposes. This sensitive and selective method offers the opportunity for simultaneous screening and quantification of almost all phenothiazines available in Japan for the purposes of clinical and forensic applications.
Loo, LiNa; Capobianco, Joseph A.; Wu, Wei; Gao, Xiaotong; Shih, Wan Y.; Shih, Wei-Heng; Pourrezaei, Kambiz; Robinson, Matthew K.; Adams, Gregory P.
Rapid and sensitive detection of serum tumor biomarkers are needed to monitor cancer patients for disease progression. Highly sensitive piezoelectric microcantilever sensors (PEMS) offer an attractive tool for biomarker detection, however their utility in the complex environment encountered in serum has yet to be determined. As a proof of concept, we have functionalized PEMS with antibodies that specifically bind to HER2, a biomarker (antigen) that is commonly overexpressed in the blood of breast cancer patients. The function and sensitivity of these anti-HER2 PEMS biosensors was initially assessed using recombinant HER2 spiked into human serum. Their ability to detect native HER2 present in the serum of breast cancer patients was then determined. We have found that the anti-HER2 PEMS were able to accurately detect both recombinant and naturally occurring HER2 at clinically relevant levels (>2 ng/ml). This indicates that PEMS-based biosensors provide a potentially effective tool for biomarker detection. PMID:21449604
Usuki, Seigo; O’Brien, Dawn; Rivner, Michael H.; Yu, Robert K.
The enzyme-linked immunosorbent assay (ELISA) is a standard immunoassay used in measuring antibody reactivity (expressed as titers) for glycosphingolipids (GSLs) such as gangliosides and sulfoglycolipids in the sera of patients with Guillain-Barré syndrome (GBS), variants of GBS, and chronic inflammatory demyelinating polyneuropathy (CIDP). In the present study, anti-GSL antibodies were evaluated using a new formula of affinity parametric complex (APC), calculated from limiting-dilution serum assay data, followed by affinity parametric complex criterion (APCC). Using assay results based on APCC, we analyzed serum samples categorized into acute inflammatory demyelinating polyneuropathy (AIDP), acute motor-sensory axonal neuropathy (AMSAN), CIDP, CIDP with Myasthenia Gravis (MG), and Amyotrophic Lateral Sclerosis (ALS). We were able to determine the affinity strength of antibodies otherwise hidden in the non-specific background activity in highly adhesive serum samples. The thin-layer chromatography (TLC)-immuno-overlay method assured us that this new method is an accurate and reliable way for evaluating anti-GSL antibodies using ELISA serum sample data. PMID:24861939
Widera, Christian; Gottlieb, Jens; Vogel, Arndt; Schmidt, Sebastian; Brandes, Gudrun; Heuft, Hans-Gert; Lichtinghagen, Ralf; Kempf, Tibor; Wollert, Kai C.; Bauersachs, Johann; Heineke, Joerg
Background Myostatin is a muscle derived factor that functions as a negative regulator of skeletal muscle growth. Induction of myostatin expression was observed in rodent models of muscle wasting and in cachectic patients with cancer or pulmonary disease. Therefore, there is an increasing interest to use serum myostatin as a biomarker. Methods We established an immunoradiometric sandwich assay (IRMA), which uses a commercially available chicken polyclonal, affinity purified antibody directed against human myostatin prodomain. We determined the serum concentrations of myostatin prodomain in 249 healthy individuals as well as 169 patients with heart failure, 53 patients with cancer and 44 patients with chronic pulmonary disease. Results The IRMA had a detection limit of 0.7ng/ml, an intraassay imprecision of ≤14.1% and an interassay imprecision of ≤ 18.9%. The specificity of our assay was demonstrated by size exclusion chromatography, detection of myostatin by Western-blotting and a SMAD-dependent transcriptional-reporter assay in the signal-rich serum fractions, as well as lack of interference by unspecific substances like albumin, hemoglobin or lipids. Myostatin prodomain was stable at room temperature and resistant to freeze-thaw cycles. Apparently healthy individuals over the age of 55 had a median myostatin prodomain serum concentration of 3.9ng/ml (25th-75th percentiles, 2-7ng/ml) and we could not detect increased levels in patients with stable chronic heart failure or cancer related weight loss. In contrast, we found strongly elevated concentrations of myostatin prodomain (median 26.9ng/ml, 25th-75th percentiles, 7-100ng/ml) in the serum of underweight patients with chronic pulmonary disease. Conclusions We established a highly specific IRMA for the quantification of myostatin prodomain concentration in human serum. Our assay could be useful to study myostatin as a biomarker for example in patients with chronic pulmonary disease, as we detected highly
Introduction: A recent clinical trial revealed that folic acid supplementation is associated with an increased incidence of prostate cancer (1). The present study evaluates serum and prostate tissue folate levels in men with prostate cancer, compared to histologically normal prostate glands from can...
Sari, Funda; Inci, Ayca; Dolu, Suleyman; Ellidag, Hamit Yasar; Cetinkaya, Ramazan; Ersoy, Fettah Fevzi
This study aims to determine fibroblast growth factor-23 and soluble α-Klotho levels in patients with autosomal dominant polycystic kidney disease. A total of 76 patients with autosomal dominant polycystic kidney disease and 32 healthy volunteers were included in the study. Serum fibroblast growth factor-23 and soluble α-Klotho levels were measured with ELISA kits. Parathyroid hormone, phosphate, calcium, creatinine, 25-hydroxyvitamin D3 levels, urinary protein to creatinine ratio and estimated glomerular filtration rate were also measured or calculated. Patients with autosomal dominant polycystic kidney disease had significantly higher serum parathyroid hormone (p<0.001), fibroblast growth factor-23 (p<0.001), soluble α-Klotho levels (p=0.001) and lower serum 25-hydroxyvitamin D3 levels (p<0.001) as compared with healthy volunteers. Serum fibroblast growth factor-23, soluble α-Klotho and 25-hydroxyvitamin D3 levels were similar in all five chronic kidney disease stages of autosomal dominant polycystic kidney disease (p>0.05). Fibroblast growth factor-23 (r=-0.251, p=0.034) and soluble α-Klotho levels (r=-0.251, p=0.034) were found to be negatively correlated with estimated glomerular filtration rate. This study shows increased fibroblast growth factor-23 levels in patients with autosomal dominant polycystic kidney disease which is in harmony with the general trend in patients with chronic kidney disease of other aetiologies, but, unlike them, also a significant increase in serum soluble α-Klotho levels in patients with autosomal dominant polycystic kidney disease suggesting an aberrant production or a decreased clearance of α-Klotho molecule. Considering the unique increases in erythropoietin levels due to erythropoietin production in renal cysts, we assume, patients with autosomal dominant polycystic kidney disease may potentially have different soluble α-Klotho production/clearance characteristics than the patients with other parenchymal renal diseases.
Pedersen, T A L; Pedersen, E B; Munk, K; Hjortdal, V E; Emmertsen, K; Andersen, N H
We investigated the relationship between pulse pressure (PP)--a surrogate marker of arterial stiffness-and activity of the renin-angiotensin-aldosterone system (RAAS) in adult patients with repaired coarctation and normal left ventricular (LV) function. A total of 114 patients (44 (26-74) years, 13 (0.1-40) years at repair) and 20 healthy controls were examined with 24-h ambulatory blood pressure monitoring, echocardiography, vasoactive hormone levels and magnetic resonance of the thoracic aorta. Forty-one patients (36%) were taking antihypertensives (28 RAAS inhibitors). Fifty-one had mean 24-h blood pressures >130/80 mm Hg. Hypertension was not associated with age at repair (P=0.257). Patients had higher PP and LV mass compared with controls (52±11 vs. 45±5 mm Hg and 221±71 vs. 154±55 g, respectively; both P<0.05). Differences were more pronounced in the presence of recoarctation, but independently of RAA levels. Even normotensive patients had higher LV mass than controls. LV mass and recoarctation were correlated with PP levels. In conclusion, adult patients with repaired coarctation have increased PP and LV mass compared with controls. PP increased with increasing recoarctation. Hypertension was present also in the absence of recoarctation. These changes could not be explained by abnormal activation of the RAAS.
Kiefer, Hélène; Jouneau, Luc; Campion, Évelyne; Rousseau-Ralliard, Delphine; Larcher, Thibaut; Martin-Magniette, Marie-Laure; Balzergue, Sandrine; Ledevin, Mireille; Prézelin, Audrey; Chavatte-Palmer, Pascale; Heyman, Yvan; Richard, Christophe; Le Bourhis, Daniel; Renard, Jean-Paul; Jammes, Hélène
Cloning enables the generation of both clinically normal and pathological individuals from the same donor cells, and may therefore be a DNA sequence-independent driver of phenotypic variability. We took advantage of cattle clones with identical genotypes but different developmental abilities to investigate the role of epigenetic factors in perinatal mortality, a complex trait with increasing prevalence in dairy cattle. We studied livers from pathological clones dying during the perinatal period, clinically normal adult clones with the same genotypes as perinatal clones and conventional age-matched controls. The livers from deceased perinatal clones displayed histological lesions, modifications to quantitative histomorphometric and metabolic parameters such as glycogen storage and fatty acid composition, and an absence of birth-induced maturation. In a genome-wide epigenetic analysis, we identified DNA methylation patterns underlying these phenotypic alterations and targeting genes relevant to liver metabolism, including the type 2 diabetes gene TCF7L2. The adult clones were devoid of major phenotypic and epigenetic abnormalities in the liver, ruling out the effects of genotype on the phenotype observed. These results thus provide the first demonstration of a genome-wide association between DNA methylation and perinatal mortality in cattle, and highlight epigenetics as a driving force for phenotypic variability in farmed animals. PMID:27958319
Miller, Connie H.; Rice, Anne S.; Garrett, Katherine; Stein, Sidney F.
Summary To assess sources of variability in platelet function tests in normal subjects, 64 healthy young adults were tested on 2–6 occasions at 2 week intervals using 4 methods: platelet aggregation (AGG) in platelet-rich plasma (PRP) in the Bio/Data PAP-4 Aggregometer (BD) and Chrono-Log Lumi-Aggregometer (CL); and AGG in whole blood (WB) in the CL and Multiplate Platelet Function Analyzer (MP), with ATP release (REL) in CL-PRP and CL-WB. Food and medication exposures were recorded prospectively for 2 weeks prior to each blood draw. At least one AGG abnormality was seen in 21% of 81 drug-free specimens with CL-PRP, 15% with CL-WB, 13% with BD-PRP, and 6% with MP-WB, increasing with inclusion of REL to 28% for CL-PRP and 30% for CL-WB. Epinephrine AGG and REL were significantly reduced in males (P<0.0001). Ristocetin AGG and collagen and thrombin REL were significantly reduced in Blacks (P<0.0001). One-third of specimens drawn following flavonoid-rich food exposures had aberrant results, compared to 8.5% of specimens without such exposures (P=0.0035). PRP tests had less intra-individual variation than WB tests. Gender, race, diet, and test system affected results of platelet function testing in healthy subjects, suggesting caution when interpreting the results of platelet function testing in patients. PMID:24617520
Huh, Ji Hye; Ahn, Song Vogue; Choi, Jung Hye; Koh, Sang Baek; Chung, Choon Hee
Irisin, a novel exercise-induced myokine, has been suggested to regulate energy homeostasis and insulin sensitivity. However, it remains unclear whether circulating irisin plays a role in the development of DM in human. We investigated the possible association between circulating irisin levels and incident DM in a 2.6-year longitudinal study of a population-based cohort comprised of rural Korean subjects.We conducted a longitudinal study within the Korean Genome and Epidemiology Study on Atherosclerosis Risk of Rural Areas in the Korean General Population (KoGES-ARIRANG) study from November 2005 to January 2008. Cases (n=85) were patients with incident DM during the follow-up period and controls (n = 85) were matched to incident DM cases based on sex and age at baseline. The relative risk of serum irisin/adiponectin level for incident DM was analyzed using conditional logistic regression analysis.Baseline irisin_ENREF_1 levels were significantly higher in subjects who developed DM than in subjects who did not. The serum irisin level was positively associated with glycated hemoglobin (HbA1c) and postprandial glucose. Irisin was negatively associated with adiponectin (R = -0.189, P = 0.014). After adjustment for potential confounders, including body mass index, the odds ratios [95% confidence intervals] for incident DM increased in a graded manner as the serum irisin level increased (Quartile 1 vs Quartile 2 vs Quartile 3 vs Quartile 4 = 1 vs 0.80 [0.28-2.35] vs 3.33 [1.11-10.00] vs 4.10 [1.35-12.44], respectively), whereas the odds ratios for incident DM decreased in a graded manner as the serum adiponectin level increased.High serum irisin was independently associated with the development of DM, indicating that irisin may be a useful predictor of DM in Korean adults.
Nazıroğlu, Mustafa; Güler, Mustafa; Özgül, Cemil; Saydam, Gündüzalp; Küçükayaz, Mustafa; Sözbir, Ercan
The purpose of this study was to investigate the potentially beneficial effects of apple cider vinegar (ACV) supplementation on serum triglycerides, total cholesterol, liver and kidney membrane lipid peroxidation, and antioxidant levels in ovariectomized (OVX) mice fed high cholesterol. Four groups of ten female mice were treated as follows: Group I received no treatment and was used as control. Group II was OVX mice. Group III received ACV intragastrically (0.6% of feed), and group IV was OVX and was treated with ACV as described for group III. The treatment was continued for 28 days, during which the mice were fed a high-cholesterol diet. The lipid peroxidation levels in erythrocyte, liver and kidney, triglycerides, total, and VLDL cholesterol levels in serum were higher in the OVX group than in groups III and IV. The levels of vitamin E in liver, the kidney and erythrocyte glutathione peroxidase (GSH-Px), and erythrocyte-reduced glutathione (GSH) were decreased in group II. The GSH-Px, vitamin C, E, and β-carotene, and the erythrocyte GSH and GSH-Px values were higher in kidney of groups III and IV, but in liver the vitamin E and β-carotene concentrations were decreased. In conclusion, ACV induced a protective effect against erythrocyte, kidney, and liver oxidative injury, and lowered the serum lipid levels in mice fed high cholesterol, suggesting that it possesses oxidative stress scavenging effects, inhibits lipid peroxidation, and increases the levels of antioxidant enzymes and vitamin.
Fuentealba, Denis; Kato, Hanako; Nishijima, Masaki; Fukuhara, Gaku; Mori, Tadashi; Inoue, Yoshihisa; Bohne, Cornelia
The mechanism for the high enantiomeric excess (ee) (80-90%) observed in the photocyclodimerization of 2-anthracenecarboxylate (AC) in the chiral binding sites of human serum albumin (HSA) was studied using fluorescence anisotropy. A long rotational correlation time of 36 ns was observed for the excited states of the ACs bound to the HSA site responsible for the high ee, suggesting that the ACs have restricted rotational mobility in this site. The ACs in this site have the same prochiral face protected by the protein, and this protection is responsible for the high ee observed. These insights provide a strategy for the rational design of supramolecular photochirogenic systems.
Berge, Kjetil; Musa-Veloso, Kathy; Harwood, Melody; Hoem, Nils; Burri, Lena
The aim of the study was to explore the effects of 12 weeks daily krill oil supplementation on fasting serum triglyceride (TG) and lipoprotein particle levels in subjects whose habitual fish intake is low and who have borderline high or high fasting serum TG levels (150-499 mg/dL). We hypothesized that Krill oil lowers serum TG levels in subjects with borderline high or high fasting TG levels. To test our hypothesis 300 male and female subjects were included in a double-blind, randomized, multi-center, placebo-controlled study with five treatment groups: placebo (olive oil) or 0.5, 1, 2, or 4 g/day of krill oil. Serum lipids were measured after an overnight fast at baseline, 6 and 12 weeks. Due to a high intra-individual variability in TG levels, data from all subjects in the four krill oil groups were pooled to increase statistical power, and a general time- and dose-independent one-way analysis of variance was performed to assess efficacy. Relative to subjects in the placebo group, those administered krill oil had a statistically significant calculated reduction in serum TG levels of 10.2%. Moreover, LDL-C levels were not increased in the krill oil groups relative to the placebo group. The outcome of the pooled analysis suggests that krill oil is effective in reducing a cardiovascular risk factor. However, owing to the individual fluctuations of TG concentrations measured, a study with more individual measurements per treatment group is needed to increase the confidence of these findings.
Xu, Lin; Zhao, Kun; Shen, Xiao; Fan, Xin-Xin; Ding, Kai; Liu, Ren-Min; Wang, Feng
BACKGROUND As an extracellularly released mediator, high-mobility group box 1 (HMGB1) initiates sterile inflammation following severe trauma. Serum HMGB1 levels correlate well with acute traumatic coagulopathy (ATC) in trauma patients, which is independently associated with higher mortality. We investigated the involvement of HMGB1 in ATC through blocking extracellular HMGB1. MATERIAL AND METHODS The ATC model was induced by polytrauma and hemorrhage in male Sprague-Dawley rats, which were randomly assigned to sham, ATC, and ATCH (ATC with HMGB1 blockade) groups. Thrombelastography (TEG) was performed to monitor changes in coagulation function. Serum levels of HMGB1, TNF-α, and IL-6 were measured, as well as lung levels of HMGB1 and nuclear factor (NF)-κB and expression of receptor for advanced glycation end-products (RAGE). RESULTS Compared with the sham group, HMGB1 increased the serum levels of TNF-α and IL-6, whereas HMGB1 blockade inhibited the induction of TNF-α and IL-6. HMGB1 also induced elevated serum soluble P-selectin and fibrinolysis markers plasmin-antiplasmin complex, which both were reduced by HMGB1 blockade. Thrombelastography revealed the hypocoagulability status in the ATC group, which was attenuated by anti-HMGB1 antibody. Furthermore, the lung level of NF-κB and expression of RAGE were decreased by anti-HMGB1 antibody, suggesting the role of RAGE/NF-κB pathway in ATC. CONCLUSIONS HMGB1 blockade can attenuate inflammation and coagulopathy in ATC rats. Anti-HMGB1 antibody might exert protective effects partly through the RAGE/NF-κB pathway. Thus, HMGB1 has potential as a therapeutic target in ATC.
Croft, Daniel T.; Jordan, Rick M.; Patney, Heather L.; Shriver, Craig D.; Vernalis, Marina N.; Orchard, Trevor J.; Ellsworth, Darrell L.
Defining genetic variation associated with complex human diseases requires standards based on high-quality DNA from well-characterized patients. With the development of robust technologies for whole-genome amplification, sample repositories such as serum banks now represent a potentially valuable source of DNA for both genomic studies and clinical diagnostics. We assessed the performance of whole-genome amplified DNA (wgaDNA) derived from stored serum/plasma on high-density single nucleotide polymorphism arrays. Neither storage time nor usage history affected either DNA extraction or whole-genome amplification yields; however, samples that were thawed and refrozen showed significantly lower call rates (73.9 ± 7.8%) than samples that were never thawed (92.0 ± 3.3%) (P < 0.001). Genotype call rates did not differ significantly (P = 0.13) between wgaDNA from never-thawed serum/plasma (92.9 ± 2.6%) and genomic DNA (97.5 ± 0.3%) isolated from whole blood. Approximately 400,000 genotypes were consistent between wgaDNA and genomic DNA, but the overall discordance rate of 4.4 ± 3.8% reflected an average of 11,110 ± 9502 genotyping errors per sample. No distinct patterns of chromosomal clustering were observed for single nucleotide polymorphisms showing discordant genotypes or homozygote conversion. Because the effects of genotyping errors on whole-genome studies are not well defined, we recommend caution when applying wgaDNA from serum/plasma to high-density single nucleotide polymorphism arrays in addition to the use of stringent quality control requirements for the resulting genotype data. PMID:18403606
Croft, Daniel T; Jordan, Rick M; Patney, Heather L; Shriver, Craig D; Vernalis, Marina N; Orchard, Trevor J; Ellsworth, Darrell L
Defining genetic variation associated with complex human diseases requires standards based on high-quality DNA from well-characterized patients. With the development of robust technologies for whole-genome amplification, sample repositories such as serum banks now represent a potentially valuable source of DNA for both genomic studies and clinical diagnostics. We assessed the performance of whole-genome amplified DNA (wgaDNA) derived from stored serum/plasma on high-density single nucleotide polymorphism arrays. Neither storage time nor usage history affected either DNA extraction or whole-genome amplification yields; however, samples that were thawed and refrozen showed significantly lower call rates (73.9 +/- 7.8%) than samples that were never thawed (92.0 +/- 3.3%) (P < 0.001). Genotype call rates did not differ significantly (P = 0.13) between wgaDNA from never-thawed serum/plasma (92.9 +/- 2.6%) and genomic DNA (97.5 +/- 0.3%) isolated from whole blood. Approximately 400,000 genotypes were consistent between wgaDNA and genomic DNA, but the overall discordance rate of 4.4 +/- 3.8% reflected an average of 11,110 +/- 9502 genotyping errors per sample. No distinct patterns of chromosomal clustering were observed for single nucleotide polymorphisms showing discordant genotypes or homozygote conversion. Because the effects of genotyping errors on whole-genome studies are not well defined, we recommend caution when applying wgaDNA from serum/plasma to high-density single nucleotide polymorphism arrays in addition to the use of stringent quality control requirements for the resulting genotype data.
Wilkinson, Charles W.; Pagulayan, Kathleen F.; Petrie, Eric C.; Mayer, Cynthia L.; Colasurdo, Elizabeth A.; Shofer, Jane B.; Hart, Kim L.; Hoff, David; Tarabochia, Matthew A.; Peskind, Elaine R.
Studies of traumatic brain injury from all causes have found evidence of chronic hypopituitarism, defined by deficient production of one or more pituitary hormones at least 1 year after injury, in 25–50% of cases. Most studies found the occurrence of posttraumatic hypopituitarism (PTHP) to be unrelated to injury severity. Growth hormone deficiency (GHD) and hypogonadism were reported most frequently. Hypopituitarism, and in particular adult GHD, is associated with symptoms that resemble those of PTSD, including fatigue, anxiety, depression, irritability, insomnia, sexual dysfunction, cognitive deficiencies, and decreased quality of life. However, the prevalence of PTHP after blast-related mild TBI (mTBI), an extremely common injury in modern military operations, has not been characterized. We measured concentrations of 12 pituitary and target-organ hormones in two groups of male US Veterans of combat in Iraq or Afghanistan. One group consisted of participants with blast-related mTBI whose last blast exposure was at least 1 year prior to the study. The other consisted of Veterans with similar military deployment histories but without blast exposure. Eleven of 26, or 42% of participants with blast concussions were found to have abnormal hormone levels in one or more pituitary axes, a prevalence similar to that found in other forms of TBI. Five members of the mTBI group were found with markedly low age-adjusted insulin-like growth factor-I (IGF-I) levels indicative of probable GHD, and three had testosterone and gonadotropin concentrations consistent with hypogonadism. If symptoms characteristic of both PTHP and PTSD can be linked to pituitary dysfunction, they may be amenable to treatment with hormone replacement. Routine screening for chronic hypopituitarism after blast concussion shows promise for appropriately directing diagnostic and therapeutic decisions that otherwise may remain unconsidered and for markedly facilitating recovery and rehabilitation. PMID
Hayashi, Ikue; Morishita, Yukari; Imai, Kazue; Nakamura, Masakazu; Nakachi, Kei; Hayashi, Tomonori
The derivatives of reactive oxygen metabolites (D-ROM) test has been developed to determine the amount of oxygen-centered free radicals in a blood sample as a marker of oxidative stress. This study aims to improve the D-ROM test and develop an automated assay system by use of a clinical chemistry analyzer. Five microliters of serum was added to 1 well of a 96-well microtiter plate for a total 240microl of reaction solution containing alkylamine and metals. This was followed by automatic mixing, incubation and measurement of reactive oxygen species (ROS) levels as a color development at 505nm using a spectrophotometer with catalytic capability for transition metals. This assay system was used to measure serum levels of ROS in cigarette smokers and never-smokers, by way of example. The levels of serum ROS determined by this system correlate with the amounts of free radicals and peroxides, which reacted with various molecules in the body and formed stable metabolites. This test can use frozen sera as well as fresh ones. The inter- and intra-deviation of this system was within 5% and showed consistent linearity in the range between 4 and 500mg/l of hydrogen peroxides. Serum ROS levels among smokers increased with the number of cigarettes smoked per day (36.5% increment per pack per day; P<0.0001). This assay system will be a simple, inexpensive, and reliable tool for assessing oxidative stress in human populations. Our preliminary results on cigarette smoking imply that this assay system has potential for application in various epidemiological and clinical settings.
Niyi-Odumosu, F A; Bello, O A; Biliaminu, S A; Owoyele, B V; Abu, T O; Dominic, O L
There is an inverse relationship between regular physical activity and concentration of serum inflammatory markers, with variations in resting CRP in trained and untrained subjects. The effect of acute and prolonged exercises has been studied on inflammatory markers with dearth of information and controversies on the resting serum values of high sensitivity CRP (hs-CRP). Therefore, this study sought to identify and compare variations that occur in serum levels of high sensitivity CRP in groups of sportsmen (6) and physically active untrained subjects. Eighty-one healthy male participants made up of 21 untrained (control), 10 footballers, 10 athletes, 10 karates, 10 volleyballers, 10 basketballers, and 10 baseballers voluntarily participated in the study. Participants rested while in sitting position for about 30 minutes during which blood pressures and heart rates were taken. 5 mls of venous blood was withdrawn from the antecubital vein of the participants (aseptically) between 7:00 and 10:00 am into lithium heparin bottles following an overnight fast. The supernatant was decanted and centrifuged at 3000 rpm, serum was collected and stored at -20ºC prior to biochemical assay which was done with the use of enzyme linked immunosorbent assay (ELISA) kits for hs-CRP. Differences in the means within the sporting groups were analysed using one-way ANOVA while the difference between the trained sportsmen and untrained young adults was analysed using the independent T-test. Statistical significance was set at p < 0.05. The Mean ±SEM age, weight, height, and BMI of the participants were 22.0±0.8 years, 64.1±2.2 kg, 1.74±0.3 m, and 20.6±0.2 kg/m2 respectively. The resting concentration of hs-CRP (µg/ml) was 1.0±0.2 in the untrained, 2.6±0.7 in footballers, 3.6±2.1 in track athletes, 2.4±0.5 in basketballers, 2.2±0.5 in volleyballers, 2.4±1.3 in baseballers, and 1.7±0.5 in karate respectively. There was no significant difference in the resting hs-CRP amongst the
DenBesten, Lawrence; Reyna, Roberto H.; Connor, William E.; Stegink, Lewis D.
The hypothesis that diets high in carbohydrate produce hyperlipidemia in man was tested in new experiments which provided all calories either by the intravenous route or orally. After a base-line general diet, eight healthy men were fed fat-free diets consisting of 80% of the calories from glucose and 20% from an amino acid hydrolysate. The calories were adequate to maintain body weight. The solutions (1 cal/ml) were infused by constant drip over a 24 h period through either a superior vena cava catheter or a nasogastric tube. Each feeding was for 12 days in sequence but assigned in random order. The high CHO diet given orally, as expected, increased the mean base-line serum triglyceride level from 176±29 (SE) to 274±47. The identical diet given intravenously (i.v.) failed to produce hypertriglyceridemia; triglyceride levels were not significantly changed, 154±37, nor were blood glucose levels. Serum insulin levels were higher during the intravenous feeding. In contrast, both i.v. and oral feedings greatly lowered mean serum cholesterol concentration from the base-line value of 220±13 mg/100 ml to 135±11 and 151±13, respectively. However, the serum cholesterol level was significantly lower (P < 0.01) with the intravenous feeding than with the oral feeding. In addition, the fecal excretion of both neutral sterols and bile acids diminished greatly during the period of intravenous feeding. The fecal mass was likewise decreased. The bacterial conversion of cholesterol to conprostanol did not occur with either intravenous or oral feeding, but with both regimens secondary bile acids predominated, as usual, in the bile acid fraction of the stool. These results emphasize the key role of the intestinal mucosa in the etiology of carbohydrate-induced hypertriglyceridemia and as a direct or indirect contributor to plasma triglyceride and cholesterol levels in the absence of dietary lipids. When the gut mucosa was bypassed, carbohydrate-induced hypertriglyceridemia did
Guillaume, Y; Peyrin, E; Guinchard, C
A simple and rapid HPLC method for the determination of tazobactam and sulbactam, two beta-lactamase inhibitors, in serum for the therapeutic follow-up of patients is described. The effect of the pH of the aqueous mobile phase and column temperature on column efficiency and retention were examined and equations for their dependences were derived. The use of a chromatographic response function showed that methanol-buffer (5:95, v/v) (pH 6.3) as the mobile phase and a 45 degrees C column temperature were optimum values for chromatographic separation. The analytical method was linear from 10 to 200 micrograms/ml. This assay limit range is sufficient for the analysis of human serum. The limit of detection was 10 micrograms/ml for sulbactam and 5 micrograms/ml for tazobactam. The coefficient of variation was less than 5%. The speed at which this assay can be performed makes it especially useful for estimating the levels of these drugs in human serum.
Khambalia, Amina Z; Collins, Clare E; Roberts, Christine L; Morris, Jonathan M; Powell, Katie L; Tasevski, Vitomir; Nassar, Natasha
Previous studies have reported inconsistent associations between maternal serum ferritin concentrations and the risk of spontaneous preterm birth (sPTB). The aim of the present study was to examine the association between Fe biomarkers, including serum ferritin concentrations, and the risk of total ( 75th percentile ( ≥ 43 μg/l) (OR 1.49, 95% CI 1.06, 2.10) and >90th percentile ( ≥ 68 μg/l) (OR 1.92, 95% CI 1.25, 2.96). Increased odds of early and moderate-to-late sPTB were associated with ferritin levels >90th percentile (OR 2.50, 95% CI 1.32, 4.73) and >75th percentile (OR 1.56, 95% CI 1.03, 2.37), respectively. No association was found between the risk of sPTB and elevated sTfR levels or Fe deficiency. In conclusion, elevated maternal serum ferritin levels in early pregnancy are associated with an increased risk of sPTB from 34 weeks of gestation. The usefulness of early pregnancy ferritin levels in identifying women at risk of sPTB warrants further investigation.
Rybak, Michael E; Pfeiffer, Christine M
Protein precipitation followed by centrifuge filtration was tested as a simplified sample preparation procedure for quantifying pyridoxal 5'-phosphate (PLP) and 4-pyridoxic acid (4PA) in serum by high-performance liquid chromatography. Serum samples (n=160) were prepared by both centrifuge filtration and an established technique using traditional supernatant extraction with manual filtration. Bland-Altman bias analysis (95% confidence levels [CLs]) of the results showed a -1.3 (-2.2, -0.5)% difference in PLP values and a -6.2 (-7.3, -5.2)% difference in 4PA values using the simplified sample preparation. These deviations were found to be well within allowable biases on the basis of biologic variation.
Kummrow, Maya; Silvanose, Christudas; Di Somma, Antonio; Bailey, Thomas A; Vorbrüggen, Susanne
Serum protein electrophoresis has gained importance in avian medicine during the past decade. Interpretation of electrophoretic patterns should be based on species-specific reference intervals and the electrophoresis gel system. In this study, serum protein electrophoresis by using high-resolution agarose gels was performed on blood samples collected from 105 falcons, including peregrine falcons (Falco peregrinus), gyrfalcons (Falco rusticolus), saker falcons (Falco cherrug), red-naped shaheens (Falco pelegrinoides babylonicus), and hybrid falcons, that were submitted to the Dubai Falcon Hospital (Dubai, United Arab Emirates) between 2003 and 2006. Reference values were established in clinically healthy birds and compared with values from falcons infected with Aspergillus species (n = 32). Falcons with confirmed aspergillosis showed significantly lower prealbumin values, which is a novel finding. Prealbumin has been documented in many avian species, but further investigation is required to illuminate the diagnostic significance of this negative acute-phase protein.
Zheng, Jiao; Liu, Binglin; Lun, Qixing; Yao, Weijuan; Zhao, Yunfang; Xiao, Wei; Huang, Wenzhe; Wang, Yonghua; Li, Jun; Tu, Pengfei
Chinese dragon's blood, the red resin of Dracaena cochinchinensis, one of the renowned traditional medicines, has been used to facilitate blood circulation and disperse blood stasis for thousands of years. Phenolic compounds are considered to be responsible for its main biological activities. In this study, total phenolic compounds of Chinese dragon's blood were made into capsule (Longxuetongluo Capsule, LTC) and their effects on the abnormal hemorheological properties were examined by high fat diet (HFD) induced ApoE−/− mice. Compared to the model group, LTC recovered the abnormal hemorheological parameters in HFD-induced ApoE−/− mice by reducing whole blood viscosity (WBV) at high rate and improving erythrocyte function. In conclusion, LTC could ameliorate erythrocyte deformability and osmotic fragility through the reduction of lipid peroxidation on plasma and erythrocyte membranes in HFD-induced ApoE−/− mice, which supported the traditional uses of Chinese dragon's blood as an effective agent for improving blood microcirculation in hypercholesterolemia. PMID:26649134
Relationships (II) of International Classification of High-resolution Computed Tomography for Occupational and Environmental Respiratory Diseases with ventilatory functions indices for parenchymal abnormalities
TAMURA, Taro; SUGANUMA, Narufumi; HERING, Kurt G.; VEHMAS, Tapio; ITOH, Harumi; AKIRA, Masanori; TAKASHIMA, Yoshihiro; HIRANO, Harukazu; KUSAKA, Yukinori
The International Classification of High-Resolution Computed Tomography (HRCT) for Occupational and Environmental Respiratory Diseases (ICOERD) is used to screen and diagnose respiratory illnesses. Using univariate and multivariate analysis, we investigated the relationship between subject characteristics and parenchymal abnormalities according to ICOERD, and the results of ventilatory function tests (VFT). Thirty-five patients with and 27 controls without mineral-dust exposure underwent VFT and HRCT. We recorded all subjects’ occupational history for mineral dust exposure and smoking history. Experts independently assessed HRCT using the ICOERD parenchymal abnormalities (Items) grades for well-defined rounded opacities (RO), linear and/or irregular opacities (IR), and emphysema (EM). High-resolution computed tomography showed that 11 patients had RO; 15 patients, IR; and 19 patients, EM. According to the multiple regression model, age and height had significant associations with many indices ventilatory functions such as vital capacity, forced vital capacity, and forced expiratory volume in 1 s (FEV1). The EM summed grades on the upper, middle, and lower zones of the right and left lungs also had significant associations with FEV1 and the maximum mid-expiratory flow rate. The results suggest the ICOERD notation is adequate based on the good and significant multiple regression modeling of ventilatory function with the EM summed grades. PMID:25810443
Relationships (II) of International Classification of High-resolution Computed Tomography for Occupational and Environmental Respiratory Diseases with ventilatory functions indices for parenchymal abnormalities.
Tamura, Taro; Suganuma, Narufumi; Hering, Kurt G; Vehmas, Tapio; Itoh, Harumi; Akira, Masanori; Takashima, Yoshihiro; Hirano, Harukazu; Kusaka, Yukinori
The International Classification of High-Resolution Computed Tomography (HRCT) for Occupational and Environmental Respiratory Diseases (ICOERD) is used to screen and diagnose respiratory illnesses. Using univariate and multivariate analysis, we investigated the relationship between subject characteristics and parenchymal abnormalities according to ICOERD, and the results of ventilatory function tests (VFT). Thirty-five patients with and 27 controls without mineral-dust exposure underwent VFT and HRCT. We recorded all subjects' occupational history for mineral dust exposure and smoking history. Experts independently assessed HRCT using the ICOERD parenchymal abnormalities (Items) grades for well-defined rounded opacities (RO), linear and/or irregular opacities (IR), and emphysema (EM). High-resolution computed tomography showed that 11 patients had RO; 15 patients, IR; and 19 patients, EM. According to the multiple regression model, age and height had significant associations with many indices ventilatory functions such as vital capacity, forced vital capacity, and forced expiratory volume in 1 s (FEV1). The EM summed grades on the upper, middle, and lower zones of the right and left lungs also had significant associations with FEV1 and the maximum mid-expiratory flow rate. The results suggest the ICOERD notation is adequate based on the good and significant multiple regression modeling of ventilatory function with the EM summed grades.
Alfonsi, Grace A.; Datta, S. Deblina; Mickiewicz, Theresa; Koutsky, Laura A.; Ghanem, Khalil; Hagensee, Michael; Kerndt, Peter; Hsu, Katherine; Weinstock, Hillard; Shlay, Judith C.
Objectives We described prevalence estimates of high-risk human papillomavirus (HR-HPV), HPV types 16 and 18, and abnormal Papanicolaou (Pap) smear tests among American Indian/Alaska Native (AI/AN) women compared with women of other races/ethnicities. Methods A total of 9,706 women presenting for cervical screening in a sentinel network of 26 clinics (sexually transmitted disease, family planning, and primary care) received Pap smears and HR-HPV type-specific testing. We compared characteristics of 291 women self-identified as AI/AN with other racial/ethnic minority groups. Results In our population, AI/AN and non-Hispanic white (NHW) women had similar age- and clinic-adjusted prevalences of HR-HPV (29.1%, 95% confidence interval [CI] 23.9, 34.3 for AI/AN women vs. 25.8%, 95% CI 24.4, 27.2 for NHW women), HPV 16 and 18 (6.7%, 95% CI 3.9, 9.6 for AI/AN women vs. 8.8%, 95% CI 7.9, 9.7 for NHW women), and abnormal Pap smear test results (16%, 95% CI 11.7, 20.3 for AI/AN women vs. 14.9%, 95% CI 13.7, 16.0 for NHW women). AI/AN women had a higher prevalence of HR-HPV than Hispanic women, and a similar prevalence of HPV 16 and 18 as compared with Hispanic and African American women. Conclusions We could not demonstrate differences in the prevalence of HR-HPV, HPV 16 and 18, or abnormal Pap smear test results between AI/AN and NHW women. This finding should improve confidence in the benefit of HPV vaccine and Pap smear screening in the AI/AN population as an effective strategy to reduce rates of cervical cancer. PMID:21553660
... cause. Can a longstanding head turn lead to any permanent problems? Yes, a significant abnormal head posture could cause permanent ... occipitocervical synostosis and unilateral hearing loss. Are there any ... postures? Yes. Abnormal head postures can usually be improved depending ...
Fornari, M. C.; Bava, A. J.; Guereño, M. T.; Berardi, V. E.; Silaf, M. R.; Negroni, R.; Diez, R. A.
In patients with chronic paracoccidioidomycosis (n = 10), levels of tumor necrosis factor alpha, interleukin-10, and interleukin-2 in serum, measured by enzyme-linked immunosorbent assay (in picograms per milliliter, as mean ± standard error of the mean), were higher than in normal controls (n = 8): 186 ± 40 versus 40 ± 7 (P < 0.05), 203 ± 95 versus 20 ± 8 (P = 0.001), and 96.3 ± 78.57 versus 1.19 ± 1.19 (P = 0.045), respectively. Gamma interferon and interleukin-4 levels were similar in patients and controls. PMID:11527826
Karl, J Philip; Fu, Xueyan; Dolnikowski, Gregory G; Saltzman, Edward; Booth, Sarah L
Vitamin K, comprising phylloquinone (PK) and menaquinones (MKn), is a family of vitamers found in multiple biological and environmental matrices. Advancing emerging evidence for novel and distinct physiologic roles of these vitamers in human health and disease necessitates sensitive and selective methods for quantifying PK and MKn in these matrices. We developed a novel method employing high-performance liquid chromatography-mass spectrometry with atmospheric pressure chemical ionization (LC-APCI-MS) for simultaneous quantification of 11 vitamin K vitamers that can be applied in feces, serum and food. Minimal detectable concentrations of vitamin K vitamers ranged from 1 pmol/g to 30 pmol/g. Limits of quantification ranged from 5 pmol/g to 90 pmol/g. Inter-assay and intra-assay variations were <17% and <8%, respectively, in food, and <12% and <8%, respectively, in feces. Recovery exceeded 80% for all vitamers in both food and feces. The method successfully quantified PK and MKn concentrations in rat chow, feces and serum. In summary, this LC-APCI-MS method provides a sensitive and selective tool for quantifying vitamin K vitamers in feces, serum and food. This method can be applied in human and animal studies examining the role of vitamin K vitamers derived from the diet and gut bacteria synthesis in health and disease.
Miyake, Teruki; Hiasa, Yoichi; Hirooka, Masashi; Tokumoto, Yoshio; Watanabe, Takao; Furukawa, Shinya; Ueda, Teruhisa; Yamamoto, Shin; Kumagi, Teru; Miyaoka, Hiroaki; Abe, Masanori; Matsuura, Bunzo; Onji, Morikazu
Hepatitis C virus (HCV) infection alters fatty acid synthesis and metabolism in association with HCV replication. The present study examined the effect of serum fatty acid composition on interferon (IFN)-based therapy. Fifty-five patients with HCV were enrolled and received IFN-based therapy. Patient characteristics, laboratory data (including fatty acids), and viral factors that could be associated with the anti-HCV effects of IFN-based therapy were evaluated. The effects of individual fatty acids on viral replication and IFN-based therapy were also examined in an in-vitro system. Multivariate logistic regression analysis showed that the level of serum palmitic acid before treatment and HCV genotype were significant predictors for rapid virological response (RVR), early virological response (EVR), and sustained virological response (SVR). High levels of palmitic acid inhibited the anti-HCV effects of IFN-based therapy. HCV replication assays confirmed the inhibitory effects of palmitic acid on anti-HCV therapy. The concentration of serum palmitic acid is an independent predictive factor for RVR, EVR, and SVR in IFN-based antiviral therapy. These results suggest that the effect of IFN-based antiviral therapy in patients with HCV infection might be enhanced by treatment that modulates palmitic acid levels.
Yuan, Yang; Qiu, Xi; Nikolic, Dejan; Dahl, Jeffrey H; van Breemen, Richard B
Hops (Humulus lupulus L.) are used in the brewing of beer, and hop extracts containing prenylated compounds, such as xanthohumol (XN) and 8-prenylnaringenin (8-PN), are under investigation as dietary supplements for cancer chemoprevention and the management of hot flashes in menopausal women. To facilitate clinical studies of hop safety and efficacy, a selective, sensitive, and fast ultra-high-pressure LC (UHPLC) tandem MS method was developed and validated for the simultaneous determination of the hop prenylflavonoids XN, isoxanthohumol (IX), 6-prenylnaringenin (6-PN), and 8-PN in human serum. The analytical method requires 300 microL of human serum, which is processed using liquid-liquid extraction. UHPLC separation was carried out in 2.5 min with gradient elution using an RP C18 column containing 1.6 pm particle size packing material. Prenylflavonoids were measured using negative ion electrospray MS with collision-induced dissociation and selected reaction monitoring. The method was validated and showed good accuracy and precision with an LOQ of 0.50 ng/mL for XN (1.4 nM) and 1.0 ng/mL for 6-PN, 8-PN (2.94 nM), and IX (2.82 nM) in serum.
... PROBLEMS Abnormal Uterine Bleeding • What is a normal menstrual cycle? • When is bleeding abnormal? • At what ages is ... treat abnormal bleeding? •Glossary What is a normal menstrual cycle? The normal length of the menstrual cycle is ...
Sugiura, Minoru; Nakamura, Mieko; Ogawa, Kazunori; Ikoma, Yoshinori; Yano, Masamichi
Recent epidemiological studies show the association of carotenoids with the metabolic syndrome (MetS), but thorough longitudinal cohort studies regarding this association have not been well conducted. The objective of this study was to investigate longitudinally whether serum carotenoids are associated with the risk of developing the MetS and its components in Japanese subjects. We conducted a follow-up study on 1073 men and women aged 30-79 years at the baseline from the Mikkabi prospective cohort study. Those who participated in the baseline and completed follow-up surveys were examined longitudinally. Over the 10-year period, 910 subjects (295 men and 615 women) took part in the follow-up survey at least once. Over a mean follow-up period of 7·8 (sd 2·9) years, thirty-six men and thirty-one women developed new MetS. After adjustments for confounders, the hazard ratio (HR) for the MetS in the highest tertile of serum β-carotene against the lowest tertile was 0·47 (95 % CI 0·23, 0·95). On the other hand, significantly lower risks for dyslipidaemia were observed in the highest tertiles of serum α- and β-carotene and β-cryptoxanthin (HR 0·66; 95 % CI 0·46, 0·96; HR, 0·54; 95 % CI 0·37, 0·79; and HR 0·66; 95 % CI 0·44, 0·99, respectively). Other significant associations between the risks for obesity, high blood pressure and hyperglycaemia with serum carotenoids were not observed. Our results further support the hypothesis that eating a diet rich in carotenoids might help prevent the development of the MetS and its complications in Japanese subjects.
Kohno, Takashi; Anzai, Toshihisa; Shimizu, Hideyuki; Kaneko, Hidehiro; Sugano, Yasuo; Yamada, Shingo; Yoshikawa, Tsutomu; Ishizaka, Akitoshi; Yozu, Ryohei; Ogawa, Satoshi
High-mobility group box 1 protein (HMGB1) is a late mediator of inflammatory responses that can cause acute lung injury. We examined the significance of serum HMGB1 elevation in the development of systemic inflammatory response syndrome (SIRS) and lung oxygenation impairment (LOI) after thoracic aortic aneurysm (TAA) repair. Serial measurements of the serum HMGB1 level and SIRS score for 7 days after surgery were determined in 20 patients with TAA who underwent surgical repair. Arterial oxygen tension was measured serially for at least 4 days after surgery, and LOI was defined as the lowest PaO(2)/FiO(2) ratio ≤ 200 mmHg. The serum HMGB1 level was markedly increased after surgery, peaking on day 2, and remained significantly elevated on day 7. Peak HMGB1 level positively correlated with SIRS duration and the cumulative SIRS score during postoperative days 1-7 (P = 0.0013 and P = 0.0004, respectively). Peak HMGB1 level and cumulative SIRS score were higher in patients with LOI than in those without (P = 0.01 and P = 0.044, respectively). Peak HMGB1 level was negatively correlated with the lowest PaO(2)/FiO(2) ratio (P = 0.0077) and positively correlated with postoperative length of hospitalization (P = 0.042). A greater serum HMGB1 elevation after TAA repair was associated with more severe SIRS and a higher incidence of LOI. HMGB1 might play a key role in the pathogenesis of SIRS and LOI after surgical TAA repair.
Determination of the serum or plasma levels of retinol (vitamin A), 25-hydroxyvitamin D, and alpha-tocopherol (vitamin E) are the most frequently used parameters to evaluate status of vitamin A, D, and E, and also to assess the gastrointestinal absorption of the vitamins. We present a simple and sensitive method for simultaneous determination of these vitamins in 0.5 ml human serum or plasma. The vitamins were extracted from serum by methanol/iso-propanol (80/20, v/v) and n-hexane. The n-hexane phase was evaporated and injected to a reversed-phase (C-18) high-performance liquid chromatography system. Elution was performed with methanol/water (85:15, v/v) for 25-hydroxyvitamin D and retinol, and after that by methanol/water (98:2, v/v) for alpha-tocopherol. The eluate was monitored by a UV detector at 265 nm for detection of the vitamins. Baseline separation was obtained for all vitamins, and the system also permitted separate determinations of the D2 and D3 forms of 25-hydroxyvitamin D. The limit of detection and interassay variation for determination in 0.5 ml serum were 6.0 nmol/L and 6.2% for 25-hydroxyvitamin D2, 6 nmol/l and 6.1% for 25-hydroxyvitamin D3, 0.035 mumol/L and 5.0% for retinol, and 1.2 mumol/l and 5.5% for alpha-tocopherol.
Liu, Tzu-Wen; Heden, Timothy D.; Morris, E. Matthew; Fritsche, Kevin L.; Vieira-Potter, Victoria J.; Thyfault, John P.
High-fat diets (HFD) are commonly used in rodents to induce obesity, increase serum fatty acids, and induce lipotoxicity in various organs. In-vitro studies commonly utilize individual free fatty acids (FFA) to study lipid exposure in an effort to model what is occurring in-vivo, however, these approaches are not physiological as tissues are exposed to multiple fatty acids in-vivo. Here we characterize circulating lipids in obese-prone rats fed a HFD in both fasted and fed states with the goal of developing physiologically relevant fatty acid mixtures for subsequent in-vitro studies. Rats were fed a HFD (60% kcal fat) or a control diet (10% kcal fat) for 3 weeks; liver tissue, and both portal and systemic blood was collected. Fatty acid profiles and absolute concentrations of triglycerides (TAG) and FFA in the serum and TAG, diacylglycerol (DAG), and phospholipids (PL) in the liver were measured. Surprisingly, both systemic and portal serum TAG were ~40% lower in HFD-fed compared to controls. Overall, compared to the control diet, HFD feeding consistently induced an increase in the proportion of circulating polyunsaturated fatty acids (PUFA) with a concomitant decline in monounsaturated fatty acids (MUFA), and saturated fatty acids (SFA) in both serum TAG and FFA. The elevations of PUFA were mostly attributed to increases in n-6 PUFA, linoleic acid and arachidonic acid. In conclusion, fatty acid mixtures enriched with linoleic and arachidonic acid in addition to SFA and MUFA should be utilized for in-vitro studies attempting to model lipid exposures that occur during in-vivo HFD condition. PMID:26318121
Poptani, Harish; Kumar, Manoj; Nasrallah, Ilya M; Kim, Sungheon; Ittyerah, Ranjit; Pickup, Stephen; Li, Joel; Parente, Michael K; Wolfe, John H.
High-resolution microscopic magnetic resonance imaging (μMRI) and diffusion tensor imaging (DTI) were performed to characterize brain structural abnormalities in a mouse model of mucopolysaccharidosis type VII (MPS VII). μMRI demonstrated a decrease in the volume of anterior commissure and corpus callosum and a slight increase in the volume of the hippocampus in MPS VII vs. wild-type mice. DTI indices were analyzed in gray and white matter. In vivo and ex vivo DTI demonstrated significantly reduced fractional anisotropy in the anterior commissure, corpus callosum, external capsule and hippocampus in MPS VII vs. control brains. Significantly increased mean diffusivity was also found in the anterior commissure and corpus callosum from ex-vivo DTI. Significantly reduced linear anisotropy was observed from the hippocampus from in-vivo DTI, whereas significantly decreased planar anisotropy and spherical anisotropy were observed in the external capsule from only ex-vivo DTI. There were corresponding morphological differences in the brains of MPS VII mice by hematoxylin and eosin staining. Luxol fast blue staining demonstrated less intense staining of the corpus callosum and external capsule; myelin abnormalities in the corpus callosum were also demonstrated quantitatively in toluidine blue-stained sections and confirmed by electron microscopy. These results demonstrate the potential for μMRI and DTI for quantitative assessment of brain pathology in murine models of brain diseases. PMID:24335527
Stabile, Achille; Compagnone, Adele; Napodano, Salvatore; Raffaele, Carmela Gerarda Luana; Patti, Maria; Rigante, Donato
In selected cases, childhood's recurrent fevers of unknown origin can be referred to systemic autoinflammatory diseases as mevalonate kinase deficiency (MKD), caused by mutations in the mevalonate kinase gene (MVK), previously named "hyper-IgD syndrome" due to its characteristic increase in serum IgD level. There is no clear evidence for studying MVK genotype in these patients. From a cohort of 305 children evaluated for recurrent fevers in our outpatient clinic during the decade 2001-2011, we have retrospectively selected 10 unrelated Italian children displaying febrile episodes, associated with recurrent inflammatory signs (variably involving gastrointestinal tube, joints, lymph nodes, and skin) and persistently increased serum IgD levels. All these patients were examined for MVK genotype: only 2 presented bonafide MVK mutations, 5 showed the same S52N MVK polymorphism, while the remaining 3 had a wild-type MVK sequence. Clinical details of these patients have been reviewed through the critical analysis of their medical charts. Our report underscores the pitfalls of MKD diagnosis based on clinical grounds and IgD levels, emphasizing the uncertain contribution of MVK polymorphisms in the diagnostic assessment of the syndrome.
Hasbal, Baris; Aydin, Kubra; Bozkurt, Mustafa; Namal, Esat; Oz, Buge; Kaynak, Kamil; Demir, Gokhan
Although gynecomastia is a well-defined paraneoplastic syndrome in patients with non-small cell lung cancer, the association with pleomorphic carcinoma has not been reported. A 50-yr-old man presented with bilateral gynecomastia and elevated serum beta-human chorionic gonadotropin (βhCG) level. Chest tomography showed a mass in the right middle lobe. Right middle lobectomy and mediastinal lymph node dissection were performed. βhCG levels decreased rapidly after surgery. Histological examination revealed pleomorphic carcinoma with positive immunostaining for βhCG. Serum βhCG levels began to increase gradually on postoperatively 4th month. Computed tomography detected recurrence and chemotherapy was started. After second cycle of chemotherapy, βhCG levels decreased dramatically again and tomography showed regression in mass. Patient died 6 months later due to brain metastasis. βhCG expression may be associated with aggressive clinical course and increased risk of recurrence, also βhCG levels may be used to evaluate therapy response in patients with pleomorphic carcinoma. PMID:21165299
Demyda-Peyrás, Sebastian; Dorado, Jesus; Hidalgo, Manuel; Anter, Jaouad; De Luca, Leonardo; Genero, Enrique; Moreno-Millán, Miguel
Chromosomal aberrations are one of the major causes of embryo developmental failures in mammals. The occurrence of these types of abnormalities is higher in in vitro-produced (IVP) embryos. The aim of the present study was to investigate the effect of oocyte morphology and maturation conditions on the rate of chromosomal abnormalities in bovine preimplantational embryos. To this end, 790 early cattle embryos derived from oocytes with different morphologies and matured under different conditions, including maturation period (24 v. 36h) and maturation media (five different serum supplements in TCM-199), were evaluated cytogenetically in three sequential experiments. The rates of normal diploidy and abnormal haploidy, polyploidy and aneuploidy were determined in each embryo. Throughout all the experiments, the rate of chromosomal abnormalities was significantly (P<0.05) affected by oocyte morphology and maturation conditions (maturation time and culture medium). Lower morphological quality was associated with a high rate of chromosome abnormalities (P<0.05). Moreover, polyploidy was associated with increased maturation time (P<0.01), whereas the maturation medium significantly (P<0.05) affected the rates of haploidy and polyploidy. In general, supplementing the maturation medium with oestrous cow serum or fetal calf serum resulted in higher rates of chromosomal aberrations (P<0.05) compared with the other serum supplements tested (bovine steer serum, anoestroues cow serum, bovine amniotic fluid and bovine serum albumin). On the basis of the results of the present study, we conclude that the morphological quality of oocytes and the maturation conditions affect the rate of chromosomal abnormalities in IVP bovine embryos.
Tagawa, A; Ono, S; Shibata, M; Imai, T; Suzuki, M; Shimizu, N
A few patients with an affected CNS involving abnormalities in copper metabolism have been described that do not fit any known nosological entities such as Wilson's disease or Menkes' disease. Three sporadic patients (two men and one woman) were examined with involuntary movements and dysarthria associated with abnormal concentrations of serum copper, serum ceruloplasmin, and urinary copper excretion. The onset of neurological symptoms occurred at the age of 15 to 17 years. The common clinical symptoms were involuntary movements and dysarthria. The involuntary movements included dystonia in the neck, myoclonus in the shoulder, athetosis in the neck, and rapid orobuccal movements. The dysarthria consisted of unclear, slow, and stuttering speech. Two of the three patients did not have dementia. A cousin of the female patient had been diagnosed as having Wilson's disease and had died of liver cirrhosis. Laboratory findings showed a mild reduction in serum copper and ceruloplasmin concentrations, whereas urinary copper excretion was significantly reduced in all three patients. Two of the three patients showed a high signal intensity in the basal ganglia on T2 weighted brain MRI. In conclusion, the unique findings of involuntary movements, dysarthria, and abnormal serum copper and urinary copper concentrations suggest that the three patients may constitute a new clinical entity that is distinct from either Wilson's or Menkes disease. PMID:11723201
This action plan describes the criteria and the organizational responsibilities required for ensuring that waste storage tanks with high organic contents are maintained in a safe condition at the Hanford Site. In addition, response actions are outlined for (1) prevention or mitigation of excessive temperatures; or (2) a material release from any waste tank with high organic content. Other response actions may be defined by Westinghouse Hanford Company Systems Engineering if a waste tank parameter goes out of specification. Trend analysis indicates the waste tank parameters have seasonal variations, but are otherwise stable.
Adachi, Y; Inufusa, H; Yamashita, M; Ozaki, K; Kanbe, A; Nanno, T; Ohba, Y; Nakamura, H; Yamamoto, T
The Ektachem multilayer film method (Ektachem) and high performance liquid chromatography (HPLC) were employed to fractionate and evaluate serum bilirubin species in 45 serum samples. The false-positive or false-high levels of bilirubin close-bonded with albumin (i.e. the delta bilirubin fraction (B delta] was obtained by Ektachem in sera of cases with normal bilirubin concentration and cases with unconjugated hyperbilirubinemia when compared with the results of HPLC. In the sera of cases with conjugated hyperbilirubinemia, Ektachem gave comparable levels of total bilirubin (TB), and unconjugated bilirubin (Bu) to those of HPLC, but underestimated conjugated bilirubin (Bc) and slightly overestimated B delta. To investigate the clinical significance of B delta in 113 cases of various hepatobiliary diseases with conjugated hyperbilirubinemia, the ratios of B delta to TB (B delta/TB) and to directly-reacting bilirubin fractions (B delta/(Bc + B delta] and that of Bc to B delta (Bc/B delta) were calculated based on the results of Ektachem and compared with each other during the course of jaundice. The mean B delta/TB was below 40% in various hepatobiliary diseases but became as high as approximately 60% in the convalescence stage. The mean B delta/(Bc + B delta) was below 50% in acute hepatitis (the serum bilirubin-elevating stage) and obstructive jaundice, and it increased to above 80% in the recovery stage. In decompensated liver cirrhosis and intrahepatic cholestasis the mean B delta/(Bc + B delta) was about 60%, indicating continuous backflow of Bc from liver cells. The changes in B delta/(Bc + B delta) were much greater than in B delta/TB.(ABSTRACT TRUNCATED AT 250 WORDS)
Deluca, Gerardo Daniel; Lucero, Raúl Horacio; Martin de Civetta, María T; Vicente, Lilian; de Gorodner, Ofelia L Z; Schelover, Eduardo; Alonso, José Mario
It has been well demonstrated the relationship between the infection with high-risk human papillomavirus (HPVs) genotypes and cervical cancer. In Northeastern Argentina a high incidence of this pathology has been described and therefore a high prevalence of HPV infection is expected. In order to identify HPV genotypes associated with malignant and pre-malignant cervical lesions present in the area, 53 ecto-endo cervical cell specimens obtained from women with cytohistological alterations were studied by a PCR-RFLP technique. Out of 53 patients, 34 (64.2%) were positive for HPV infection, being HPV-16 (32.3%) the most frequently found genotype, followed by HPV-58 (14.7%), -6, -18 and -45 (5.9%), -33, -52, -53, -54, -56, -66, -MM4 and -LVX100 (2.9%). Also 5 cases of infection caused by multiple genotypes were found, which corresponded to 14.7% of the positive cases. Results indicate that besides HPV-16 and -18, the most prevalent high-risk HPV genotypes worldwide, others like -45 and -58 as well as co-infection cases are frequent between women of Northeastern Argentina, and a particular attention should be paid to this circumstance because it could be an epidemiological feature of regional importance and a useful information for a future vaccination program.
Gilbert, Sam J.; Meuwese, Julia D. I.; Towgood, Karren J.; Frith, Christopher D.; Burgess, Paul W.
Multi-voxel pattern analyses have proved successful in "decoding" mental states from fMRI data, but have not been used to examine brain differences associated with atypical populations. We investigated a group of 16 (14 males) high-functioning participants with autism spectrum disorder (ASD) and 16 non-autistic control participants (12 males)…
Gökçora, I H; Yagmurlu, A
The popular incision for surgical approach to pediatric inguinal pathologies has been the suprapubic transverse inguinal incision. Yet alternative incisions may be considered. A prospectively randomized study of a consecutive series of 256 male infants and children with various inguinal pathologies (mainly indirect inguinal hernias) were treated surgically using the "high trans-scrotal skin-crease incision," over a period of 84 months (7 years) and were compared and found to be clinically better than age- and sex-matched 278 controls with suprapubic transverse inguinal incisions for wound healing/infection, edema, seroma, hematoma, malpositioning or atrophy of testes and recurrence of the primary pathology. The results in the study group were cosmetically and clinically more favorable, and better than the control group. Nosocomial infections, complications of incarceration, and emergency surgery have resulted in an acceptable morbidity rate of approximately 5%. Popularized use of the high trans-scrotal incision and further clinical experience is recommended to facilitate even better results.
Reddy, S Sreenivasa; Ramatholisamma, P; Ramesh, B; Baskar, R; Saralakumari, D
High intake of dietary fructose has been shown to exert a number of adverse metabolic eff ects in humans and experimental animals. The present study was designed to investigate the eff ect of the aqueous extract of Tinospora cordifolia stem (TCAE) on the adverse eff ects of fructose loading toward carbohydrate and lipid metabolism in rats. Adult male Wistar rats of body weight around 200 g were divided into four groups, two of which were fed with starch diet and the other two with high fructose (66 %) diet. Plant extract of TC (400 mg/kg/day) was administered orally to each group of the starch fed rats and the highfructose fed rats. At the end of 60 days of experimental period, biochemical parameters related to carbohydrate and lipid metabolism were assayed. Hyperglycemia, hyperinsulinemia, hypertriglyceridemia, insulin resistance, and elevated levels of hepatic total lipids, cholesterol, triglycerides, and free fatty acids (p < 0.05) observed in fructose-fed rats were completely prevented with TCAE treatment. Alterations in the activities of enzymes of glucose metabolism (hexokinase, phosphofructokinase, pyruvate kinase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, and glucose-6-phosphate dehydrogenase) and lipid metabolism (fatty acid synthetase, lipoprotein lipase, and malic enzyme) as observed in the high fructose-fed rats were prevented with TCAE administration. In conclusion, our fi ndings indicate improvement of glucose and lipid metabolism in high-fructose fed rats by treatment with Tinospora cordifolia, and suggest that the plant can be used as an adjuvant for the prevention and/or management of insulin resistance and disorders related to it.
Du, Jingyun; Jiang, Jianjun; Jia, Xuesong; Chen, Chuangfu; Wang, Yuanzhi
Multiple human papillomavirus (HPV) genotypes often coexist within the cervical epithelia and are frequently detected together in various grades of the cervical neoplasia. To date, only a few reports exist on multiple HPV infections of HPV in Xinjiang Uygur Autonomous Region (XUAR). In the present study, we investigated the prevalence of High-Risk HPV (HR-HPV) genotypes and multiple infections. Cervical cytology samples were collected from 428 women who presented cervical abnormalities. Genotyping of HPV was performed by polymerase chain reaction–sequencing based typing (PCR-SBT) using consensus primers and specific primers. Of them, 166 samples were positive for HPV according to PCR results using the consensus primers. These samples contained cervical abnormalities enriched with inflammation (n = 107), cervical intraepithelial neoplasia (CIN) I (n = 19), CINII-III (n = 9) and cervical cancer (n = 31). Of the 166 HPV positive samples as determined by PCR analysis, 151 were further typed by PCR-SBT using 19 pairs of genotype-specific primers. Using this method, 17 different HR-HPV genotypes were identified. The most frequently observed HPV genotypes were HPV16 (44.0%, 73/166), 53 (28.9%, 48/166), 52 (25.3%, 42/166), 58 (22.3%, 37/166) and 35 (17.5%, 29/166). The proportions of single and multiple infections in the HPV-positive specimens were 34.9% and 65.1%, respectively. Multiple HPV types were most prevalent in the inflammatory state (63.0%), followed by cervical cancer (24.1%), CINI (11.1%), and CINII-III (1.9%). The results of our data analyses suggested that i) multiple HPV infection is not necessarily correlated with the severity of cervical abnormalities; and ii) among the multiple HPV infections, double infections combined with HPV16 is the most common. In addition, L1 full-length sequences of the top five high-risk HPV genotypes were amplified and sequenced. According to the L1 sequence of the epidemic genotypes that were amplified, we found that these
Wang, Lina; Wang, Pengyan; Ren, Yan; Du, Jingyun; Jiang, Jianjun; Jia, Xuesong; Chen, Chuangfu; Wang, Yuanzhi
Multiple human papillomavirus (HPV) genotypes often coexist within the cervical epithelia and are frequently detected together in various grades of the cervical neoplasia. To date, only a few reports exist on multiple HPV infections of HPV in Xinjiang Uygur Autonomous Region (XUAR). In the present study, we investigated the prevalence of High-Risk HPV (HR-HPV) genotypes and multiple infections. Cervical cytology samples were collected from 428 women who presented cervical abnormalities. Genotyping of HPV was performed by polymerase chain reaction-sequencing based typing (PCR-SBT) using consensus primers and specific primers. Of them, 166 samples were positive for HPV according to PCR results using the consensus primers. These samples contained cervical abnormalities enriched with inflammation (n = 107), cervical intraepithelial neoplasia (CIN) I (n = 19), CINII-III (n = 9) and cervical cancer (n = 31). Of the 166 HPV positive samples as determined by PCR analysis, 151 were further typed by PCR-SBT using 19 pairs of genotype-specific primers. Using this method, 17 different HR-HPV genotypes were identified. The most frequently observed HPV genotypes were HPV16 (44.0%, 73/166), 53 (28.9%, 48/166), 52 (25.3%, 42/166), 58 (22.3%, 37/166) and 35 (17.5%, 29/166). The proportions of single and multiple infections in the HPV-positive specimens were 34.9% and 65.1%, respectively. Multiple HPV types were most prevalent in the inflammatory state (63.0%), followed by cervical cancer (24.1%), CINI (11.1%), and CINII-III (1.9%). The results of our data analyses suggested that i) multiple HPV infection is not necessarily correlated with the severity of cervical abnormalities; and ii) among the multiple HPV infections, double infections combined with HPV16 is the most common. In addition, L1 full-length sequences of the top five high-risk HPV genotypes were amplified and sequenced. According to the L1 sequence of the epidemic genotypes that were amplified, we found that these
Lamy, Pierre-Jean; Sault, Corinne; Renard, Eric
Insulin-antibodies are a cause of misleading results in insulin immunoassays. They may also mediate deleterious blood glucose variations. A patient presented with overtiredness, recurrent episodes of sweating, dizziness and fainting fits. A fasting serum insulin assay performed on a Modular platform (Modular analytic E170, Roche Diagnostic, Meylan, France) showed a highly elevated value of 194.7 mIU/L, whereas on the same sample glucose and C-peptide levels were normal. Other immunometric insulin assays were performed, as well as antibodies anti-insulin radiobinding assay (RBA) and gel filtration chromatography (GFC). While complementary insulin assays yielded closer to normal fasting levels, the free insulin concentration assessed after PEG precipitation was 14.0 mIU/L and the RBA was positive. GFC revealed that most of the insulin was complexed with a 150 kDa molecule, corresponding to an immunoglobulin G (IgG). A high fasting serum insulin level in a patient with neuroglucopenic symptoms was related to a high insulin-antibody level, suggesting an insulin autoimmune syndrome.
Puhlmann, A; Dülffer, T; Kobold, U
A two-dimensional high-performance liquid chromatographic method for the determination of creatinine with direct serum injection without sample pretreatment has been developed. The column-switching technique allowed a switch from columns packed with internal surface reversed-phase (ISRP) material to columns of almost any other material, even if the eluents necessary in a particular case do not appear to be directly compatible. A Pinkerton ISRP column, which stands out because of its very good stability when loaded with undiluted serum samples, was used as precolumn. The creatinine-containing fraction was switched to a reversed-phase Shandon RP18 column and was focused there by alteration of the eluent from pH 6.5 to phosphoric acid-ion-pair reagent. The separation occurs via a pH gradient, with ultraviolet detection at 234 nm. This method stands out particularly for its good long-term stability, simple sample handling without pretreatment, high selectivity, a broad linearity (0.3-30 mg/dl creatinine), good reproducibility (inter-assay coefficient of variation less than 3%) and high recovery (97-100%) relative to values obtained with gas chromatography-mass spectrometry.
Hormann, Annette M.; vom Saal, Frederick S.; Nagel, Susan C.; Stahlhut, Richard W.; Moyer, Carol L.; Ellersieck, Mark R.; Welshons, Wade V.; Toutain, Pierre-Louis; Taylor, Julia A.
Bisphenol A (BPA) is an endocrine disrupting environmental contaminant used in a wide variety of products, and BPA metabolites are found in almost everyone’s urine, suggesting widespread exposure from multiple sources. Regulatory agencies estimate that virtually all BPA exposure is from food and beverage packaging. However, free BPA is applied to the outer layer of thermal receipt paper present in very high (∼20 mg BPA/g paper) quantities as a print developer. Not taken into account when considering thermal paper as a source of BPA exposure is that some commonly used hand sanitizers, as well as other skin care products, contain mixtures of dermal penetration enhancing chemicals that can increase by up to 100 fold the dermal absorption of lipophilic compounds such as BPA. We found that when men and women held thermal receipt paper immediately after using a hand sanitizer with penetration enhancing chemicals, significant free BPA was transferred to their hands and then to French fries that were eaten, and the combination of dermal and oral BPA absorption led to a rapid and dramatic average maximum increase (Cmax) in unconjugated (bioactive) BPA of ∼7 ng/mL in serum and ∼20 µg total BPA/g creatinine in urine within 90 min. The default method used by regulatory agencies to test for hazards posed by chemicals is intra-gastric gavage. For BPA this approach results in less than 1% of the administered dose being bioavailable in blood. It also ignores dermal absorption as well as sublingual absorption in the mouth that both bypass first-pass liver metabolism. The elevated levels of BPA that we observed due to holding thermal paper after using a product containing dermal penetration enhancing chemicals have been related to an increased risk for a wide range of developmental abnormalities as well as diseases in adults. PMID:25337790
Hormann, Annette M; Vom Saal, Frederick S; Nagel, Susan C; Stahlhut, Richard W; Moyer, Carol L; Ellersieck, Mark R; Welshons, Wade V; Toutain, Pierre-Louis; Taylor, Julia A
Bisphenol A (BPA) is an endocrine disrupting environmental contaminant used in a wide variety of products, and BPA metabolites are found in almost everyone's urine, suggesting widespread exposure from multiple sources. Regulatory agencies estimate that virtually all BPA exposure is from food and beverage packaging. However, free BPA is applied to the outer layer of thermal receipt paper present in very high (∼20 mg BPA/g paper) quantities as a print developer. Not taken into account when considering thermal paper as a source of BPA exposure is that some commonly used hand sanitizers, as well as other skin care products, contain mixtures of dermal penetration enhancing chemicals that can increase by up to 100 fold the dermal absorption of lipophilic compounds such as BPA. We found that when men and women held thermal receipt paper immediately after using a hand sanitizer with penetration enhancing chemicals, significant free BPA was transferred to their hands and then to French fries that were eaten, and the combination of dermal and oral BPA absorption led to a rapid and dramatic average maximum increase (Cmax) in unconjugated (bioactive) BPA of ∼7 ng/mL in serum and ∼20 µg total BPA/g creatinine in urine within 90 min. The default method used by regulatory agencies to test for hazards posed by chemicals is intra-gastric gavage. For BPA this approach results in less than 1% of the administered dose being bioavailable in blood. It also ignores dermal absorption as well as sublingual absorption in the mouth that both bypass first-pass liver metabolism. The elevated levels of BPA that we observed due to holding thermal paper after using a product containing dermal penetration enhancing chemicals have been related to an increased risk for a wide range of developmental abnormalities as well as diseases in adults.
Nelson, Randin; Cañate, Raul; Pascale, Juan Miguel; Dragoo, Jerry W.; Armien, Blas; Armien, Anibal G.; Koster, Frederick
Choclo virus (CHOV) was described in sigmodontine rodents, Oligoryzomys fulvescens, and humans during an outbreak of hantavirus cardiopulmonary syndrome (HCPS) in 1999 to 2000 in western Panama. Although HCPS is rare, hantavirus-specific serum antibody prevalence among the general population is high suggesting that CHOV may cause many mild or asymptomatic infections. The goals of this study were to confirm the role of CHOV in HCPS and in the frequently detected serum antibody and to established the phylogenetic relationship with other New World hantaviruses. CHOV was cultured to facilitate the sequencing of the small (S) and medium (M) segments and to perform CHOV-specific serum neutralization antibody assays. Sequences of the S and M segments found a close relationship to other Oligoryzomys-borne hantaviruses in the Americas, highly conserved terminal nucleotides, and no evidence for recombination events. The maximum likelihood and maximum parsimony analyses of complete M segment nucleotide sequences indicate a close relationship to Maporal and Laguna Negra viruses, found at the base of the South American clade. In a focus neutralization assay acute and convalescent sera from 6 Panamanian HCPS patients neutralized CHOV in dilutions from 1:200 to 1:6400. In a sample of antibody-positive adults without a history of HCPS, 9 of 10 sera neutralized CHOV in dilutions ranging from 1:100 to 1:6400. Although cross-neutralization with other sympatric hantaviruses not yet associated with human disease is possible, CHOV appears to be the causal agent for most of the mild or asymptomatic hantavirus infections, as well as HCPS, in Panama. PMID:20648614
Kang, Dae Ryong; Yadav, Dhananjay; Koh, Sang-Baek; Kim, Jang-Young
Purpose The ratio of serum leptin to adiponectin (L/A ratio) could be used as a marker for insulin resistance. However, few prospective studies have investigated the impact of L/A ratio on improvement of metabolic components in high-risk individuals with metabolic syndrome. We examined the association between L/A ratio and the regression of metabolic syndrome in a population-based longitudinal study. Materials and Methods A total of 1017 subjects (431 men and 586 women) with metabolic syndrome at baseline (2005–2008) were examined and followed (2008–2011). Baseline serum levels of leptin and adiponectin were analyzed by radioimmunoassay. Area under the receiver operating characteristics curve (AUROC) analyses were used to assess the predictive ability of L/A ratio for the regression of metabolic syndrome. Results During an average of 2.8 years of follow-up, metabolic syndrome disappeared in 142 men (32.9%) and 196 women (33.4%). After multivariable adjustment, the odds ratios (95% confidence interval) for regression of metabolic syndrome in comparisons of the lowest to the highest tertiles of L/A ratio were 1.84 (1.02–3.31) in men and 2.32 (1.37–3.91) in women. In AUROC analyses, L/A ratio had a greater predictive power than serum adiponectin for the regression of metabolic syndrome in both men (p=0.024) and women (p=0.019). Conclusion Low L/A ratio is a predictor for the regression of metabolic syndrome. The L/A ratio could be a useful clinical marker for management of high-risk individuals with metabolic syndrome. PMID:28120564
Ramraj, Satish Kumar; Aravindan, Sheeja; Somasundaram, Dinesh Babu; Herman, Terence S.; Natarajan, Mohan; Aravindan, Natarajan
Background Circulating miRNAs have momentous clinical relevance as prognostic biomarkers and in the progression of solid tumors. Recognizing novel candidates of neuroblastoma-specific circulating miRNAs would allow us to identify potential prognostic biomarkers that could predict the switch from favorable to high-risk metastatic neuroblastoma (HR-NB). Results Utilizing mouse models of favorable and HR-NB and whole miRnome profiling, we identified high serum levels of 34 and low levels of 46 miRNAs in animals with HR-NB. Preferential sequence homology exclusion of mouse miRNAs identified 25 (11 increased; 14 decreased) human-specific prognostic marker candidates, of which, 21 were unique to HR-NB. miRNA QPCR validated miRnome profile. Target analysis defined the candidate miRNAs' signal transduction flow-through and demonstrated their converged roles in tumor progression. miRNA silencing studies verified the function of select miRNAs on the translation of at least 14 target proteins. Expressions of critical targets that correlate tumor progression in tissue of multifarious organs identify the orchestration of HR-NB. Significant (>10 fold) increase in serum levels of miR-381, miR-548h, and miR-580 identify them as potential prognostic markers for neuroblastoma progression. Conclusion For the first time, we identified serum-circulating miRNAs that predict the switch from favorable to HR-NB and, further imply that these miRNAs could play a functional role in tumor progression. PMID:26921195
Saul, Allan; Rondini, Simona
Serum Bactericidal Activity (SBA) assay is the method of choice to evaluate the complement-mediated functional activity of both infection- and vaccine-induced antibodies. To perform a typical SBA assay, serial dilutions of sera are incubated with target bacterial strains and complement. The conventional SBA assay is based on plating on agar the SBA reaction mix and counting the surviving bacterial colony forming units (CFU) at each serum dilution. Even with automated colony counting, it is labor-intensive, time-consuming and not amenable for large-scale studies. Here, we have developed a luminescence-based SBA (L-SBA) method able to detect surviving bacteria by measuring their ATP. At the end of the SBA reaction, a single commercially available reagent is added to each well of the SBA plate, and the resulting luminescence signal is measured in a microplate reader. The signal obtained is proportional to the ATP present, which is directly proportional to the number of viable bacteria. Bactericidal activity is subsequently calculated. We demonstrated the applicability of L-SBA with multiple bacterial serovars, from 5 species: Citrobacter freundii, Salmonella enterica serovars Typhimurium and Enteritidis, Shigella flexneri serovars 2a and 3a, Shigella sonnei and Neisseria meningitidis. Serum bactericidal titers obtained by the luminescence readout method strongly correlate with the data obtained by the conventional agar plate-based assay, and the new assay is highly reproducible. L-SBA considerably shortens assay time, facilitates data acquisition and analysis and reduces the operator dependency, avoiding the plating and counting of CFUs. Our results demonstrate that L-SBA is a useful high-throughput bactericidal assay. PMID:28192483
Kiviniemi, Aida; Gardberg, Maria; Frantzén, Janek; Parkkola, Riitta; Vuorinen, Ville; Pesola, Marko; Minn, Heikki
Our aim was to study the association of two potential serum biomarkers glial fibrillary acidic protein (GFAP) and epidermal growth factor receptor (EGFR) with prognostic markers such as IDH1 mutation, tumor burden, and survival in patients with high-grade gliomas (HGG). Additionally, our objective was to evaluate the potential of serum EGFR as a surrogate marker for EGFR status in the tumor. Pre-operative serum samples were prospectively collected from patients with primary (n = 17) or recurrent (n = 10) HGG. Serum GFAP and EGFR levels were determined by ELISA and studied for correlation with molecular markers including EGFR amplification, tumor volume in contrast-enhanced T1-weighted MRI, and progression-free survival (PFS). Pre-operative serum GFAP level of ≥0.014 ng/ml was 86 % sensitive and 85 % specific for the diagnosis of glioblastoma. High GFAP was related to the lack of IDH1 mutation (P = 0.016), high Ki67 proliferation index (P < 0.001), and poor PFS (HR 5.9, CI 1.2-29.9, P = 0.032). Serum GFAP correlated with enhancing tumor volume in primary (r = 0.64 P = 0.005), but also in recurrent HGGs (r = 0.76 P = 0.011). In contrast, serum EGFR levels did not differ between HGG patients and 13 healthy controls, and were not related to EGFR status in the tumor. We conclude that high serum GFAP associates with IDH1 mutation-negative HGG, and poor PFS. Correlation with tumor burden in recurrent HGG implicates the potential of serum GFAP for detection of tumor recurrence. Our results suggest that circulating EGFR is not derived from glioma cells and cannot be used as a marker for EGFR status in the tumor.
Vihinen, Pia; Tervahartiala, Taina; Sorsa, Timo; Hansson, Johan; Bastholt, Lars; Aamdal, Steinar; Stierner, Ulrika; Pyrhönen, Seppo; Syrjänen, Kari; Lundin, Johan; Hernberg, Micaela
Matrix metalloproteinases (MMPs) are important enzymes in tissue turnover and various inflammatory processes. In this study, it was evaluated whether serum MMP-8 can predict the response to adjuvant interferon alfa-2b (IFN-α) therapy in patients with operated high-risk cutaneous melanoma. Pre-treatment sera from 460 patients with stage IIB-IIIC melanoma were analyzed for MMP-8. The patients were randomized after surgery to adjuvant IFN-α for 12 or 24 months (n = 313) or observation only (n = 147). The median serum MMP-8 level was used to classify the patients into a low MMP-8 (n = 232) and a high MMP-8 (n = 228) group. In the high MMP-8 subgroup, IFN-α therapy significantly improved relapse-free survival (RFS). RFS was 36.8 months in patients with high MMP-8 levels receiving IFN-α therapy, whereas RFS for those with high MMP-8 levels with observation only was 10.6 months (P = 0.027). Median overall survival for patients with high MMP-8 and observation only was 36.7 versus 71.7 months in those receiving IFN-α (P = 0.13). In a multivariate model, IFN-α therapy was a significant predictor of favorable RFS (HR 0.74; 95 % CI 0.55-0.99; P = 0.048), after adjustment for pre-treatment MMP-8 (HR 1.17; 95 % CI 0.88-1.55; P = 0.28), gender (HR 1.16; 95 % CI 0.86-1.56; P = 0.32), age (HR 1.00; 95 % CI 1.00-1.02; P = 0.12), ulceration (HR 1.09; 95 % CI 0.81-1.46; P = 0.58), and the presence of node metastases (HR 1.36; 95 % CI 1.17-1.58; P < 0.0001). In conclusion, patients with high serum MMP-8 levels may benefit from adjuvant IFN-α therapy, but this observation should be further investigated.
Baroni, Argelinda; Castellanos, F. Xavier
The ongoing release of the Human Connectome Project (HCP) data is a watershed event in clinical neuroscience. By attaining a quantum leap in spatial and temporal resolution within the framework of a twin/sibling design, this open science resource provides the basis for delineating brain-behavior relationships across the neuropsychiatric landscape. Here we focus on attention-deficit/hyperactivity disorder (ADHD), which is at least partly continuous across the population, highlighting constructs that have been proposed for ADHD and which are included in the HCP phenotypic battery. We review constructs implicated in ADHD (reward-related processing, inhibition, vigilant attention, reaction time variability, timing and emotional lability) which can be examined in the HCP data and in future “high definition” clinical datasets. PMID:25212469
Baroni, Argelinda; Castellanos, F Xavier
The ongoing release of the Human Connectome Project (HCP) data is a watershed event in clinical neuroscience. By attaining a quantum leap in spatial and temporal resolution within the framework of a twin/sibling design, this open science resource provides the basis for delineating brain-behavior relationships across the neuropsychiatric landscape. Here we focus on attention-deficit/hyperactivity disorder (ADHD), which is at least partly continuous across the population, highlighting constructs that have been proposed for ADHD and which are included in the HCP phenotypic battery. We review constructs implicated in ADHD (reward-related processing, inhibition, vigilant attention, reaction time variability, timing and emotional lability) which can be examined in the HCP data and in future 'high definition' clinical datasets.
Heparan sulfate (HS) polysaccharides are ubiquitous in animal tissues as components of proteoglycans, and they participate in many important biological processes. HS carbohydrate chains are complex and can contain rare structural components such as N-unsubstituted glucosamine (GlcN). Commercially available HS preparations have been invaluable in many types of research activities. In the course of preparing microarrays to include probes derived from HS oligosaccharides, we found an unusually high content of GlcN residue in a recently purchased batch of porcine intestinal mucosal HS. Composition and sequence analysis by mass spectrometry of the oligosaccharides obtained after heparin lyase III digestion of the polysaccharide indicated two and three GlcN in the tetrasaccharide and hexasaccharide fractions, respectively. 1H NMR of the intact polysaccharide showed that this unusual batch differed strikingly from other HS preparations obtained from bovine kidney and porcine intestine. The very high content of GlcN (30%) and low content of GlcNAc (4.2%) determined by disaccharide composition analysis indicated that N-deacetylation and/or N-desulfation may have taken place. HS is widely used by the scientific community to investigate HS structures and activities. Great care has to be taken in drawing conclusions from investigations of structural features of HS and specificities of HS interaction with proteins when commercial HS is used without further analysis. Pending the availability of a validated commercial HS reference preparation, our data may be useful to members of the scientific community who have used the present preparation in their studies. PMID:27295282
Cheng, De-lei; Xu, Hao; Lv, Wei-fu; Hua, Rong; Du, Hongtao; Zhang, Qing-qiao
Objective. To investigate the serum level of CA-125 and its corresponding clinical significance in Chinese patients with primary BCS. Methods. Serum CA-125 was measured in 243 patients with primary BCS receiving interventional treatment in the participating hospitals and in 120 healthy volunteers. The correlation between serum CA-125 levels and ascites volume, liver function, and prognosis was analyzed. Results. Serum CA-125 was significantly elevated in BCS patients compared to healthy volunteers (P < 0.001). Higher levels of CA-125 were found in BCS patients with abnormal hepatic function and low serum albumin levels and in patients with high volume of ascites compared to patients without these abnormalities. Serum CA-125 levels significantly correlated with ascites volume, serum level of alanine aminotransferase, aspartate aminotransferase, albumin, and Rotterdam BCS scores. The follow-up study indicated that the survival rate and asymptomatic survival rate after interventional treatment were lower in BCS patients with serum CA-125 > 175 U/mL (P < 0.05). Conclusion. Serum CA-125 was significantly higher in patients with primary BCS and had a positive correlation with the volume of ascites, severity of liver damage, and poor prognosis. Thus the serum CA-125 levels may be used to estimate the severity and prognosis of BCS in Chinese patients. PMID:26451141
Caslavska, Jitka; Joneli, Jeannine; Wanzenried, Ursula; Schiess, Jeannette; Lanz, Christian; Thormann, Wolfgang
High-resolution capillary zone electrophoresis in the routine arena with stringent quality assurance is employed for the determination of carbohydrate-deficient transferrin in human serum. The assay comprises mixing of human serum with a Fe(III) -containing solution prior to analysis of the iron-saturated mixture in a dynamically double-coated capillary using a commercial buffer at alkaline pH. In contrast to other assays, it provides sufficient resolution for proper recognition of genetic transferrin variants. Analysis of 7290 patient sera revealed 166 isoform patterns that could be assigned to genetic variants, namely, 109 BC, 53 CD, one BD and three CC variants. Several subtypes of transferrin D can be distinguished as they have large enough differences in pI values. Subtypes of transferrin C and B cannot be resolved. However, analysis of the detection time ratios of tetrasialo isoforms of transferrin BC and transferrin CD variants revealed multimodal frequency histograms, indicating the presence of subtypes of transferrin C, B and D. The data gathered over 11 years demonstrate the robustness of the high-resolution capillary zone electrophoresis assay. This is the first account of a capillary zone electrophoresis based carbohydrate-deficient transferrin assay with a broad overview on transferrin isoform patterns associated with genetic transferrin variants.
Leutgeb, V; Leitner, M; Wabnegger, A; Klug, D; Scharmüller, W; Zussner, T; Schienle, A
Measures of psychopathy have been proved to be valuable for risk assessment in violent criminals. However, the neuronal basis of psychopathy and its contribution to the prediction of criminal recidivism is still poorly understood. We compared structural imaging data from 40 male high-risk violent offenders and 37 non-delinquent healthy controls via voxel-based morphometry. Psychopathic traits and risk of violence recidivism were correlated with gray matter volume (GMV) of regions of interest previously shown relevant for criminal behavior. Relative to controls, criminals showed less GMV in the prefrontal cortex (PFC) and more GMV in cerebellar regions and basal ganglia structures. Within criminals, we found a negative correlation between prefrontal GMV and psychopathy. Additionally, there was a positive correlation between cerebellar GMV and psychopathy as well as risk of recidivism for violence. Moreover, GMVs of the basal ganglia and supplementary motor area (SMA) were positively correlated with anti-sociality. GMV of the amygdala was negatively correlated with dynamic risk for violence recidivism. In contrast, GMV of (para)limbic areas (orbitofrontal cortex, insula) was positively correlated with anti-sociality and risk of violence recidivism. The current investigation revealed that in violent offenders deviations in GMV of the PFC as well as areas involved in the motor component of impulse control (cerebellum, basal ganglia, SMA) are differentially related to psychopathic traits and the risk of violence recidivism. The results might be valuable for improving existing risk assessment tools.
Rezaei, Mohammad; Nahrani, Morteza Hamidi; Bolandi, Masoud
Background and Objectives This paper aimed at evaluating the characteristics of high-frequency (1,000 Hz) acoustic admittance (ya) for the neonates with transient evoked otoacoustic emissions (TEOAE) as either pass or refer group. Subjects and Methods Using a 1,000 Hz probe tone, 297neonates (152 male, 145 female aged 0–104 days old) were evaluated. Tympanometric parameters admittance value at +200 dapa, middle ear admittance, and tympanometric peak pressure were calculated for each tympanogram. Results The mean of ya was 0.9678 mmho in the TEOAE for the pass group and 0.7229 mmho in the refer group. The mean of acoustic admittance at +200 (y200) was 2.0657 in the TEOAE for the pass group and 1.7191 for the refer group. The mean of Tpp was 23/8591 in the TEOAE for the pass group and 59/7619 for the refer group. Conclusions There were significant differences in the distribution of different types of tympanograms, the mean of ya, tympanic peak pressure, and y200 between the TEOAEs for the pass and the refer groups. PMID:27942601
Nagaraj, Niranjan; Berwal, Pramod Kumar; Srinivas, Anusha; Sehra, Ramnarayan; Swami, Sarika; Jeevaji, Prathyusha; Swami, Gotam; Choudary, Lokesh; Berwal, Ayush
Background: Neonatal sonography of the brain is now an essential part of newborn care, particularly in high risk and unstable premature infants. Cranial ultrasound is the most available and easily repeatable imaging technique for the neonatal brain showing brain development and the most frequently occurring forms of cerebral injury in the preterm and terms. This study aims to assess the importance of cranial ultrasound as an investigatory modality for high-risk neonates and to find out the morphology of various cerebral lesions and correlate clinically. Methodology: An observational correlation clinical study was conducted at Sardar Patel Medical College, Bikaner involving 100 high-risk neonates admitted to Neonatal Intensive Care Unit (NICU) who was subjected to neurosonography on selected days as per protocol. Perinatal details were recorded, and clinical examination with appropriate investigations was done. The cranial ultrasound was done, and morphology of various findings was studied and recorded. Clinical correlation with cranial ultrasound findings and follow-up was done. Results: On cranial ultrasound, 38% of neonates had abnormal findings. Twelve percent of these had evidence of intracranial bleed, 13% periventricular echogenicity, 7% had ventriculomegaly, 2% had cerebral edema, and 1% had leukomalacia. Three neonates had findings suggestive of simple cyst in middle cranial fossa, agenesis of corpus callosum, and choroid plexus cyst. Conclusions: Cranial ultrasonography is the best point of care neuroimaging method available for high-risk neonates. It is critical as an investigatory modality in NICU and effectively documents morphology of cerebral damage. PMID:27857787
Moncayo, Jorge; Bogousslavsky, Julien
Generation and control of eye movements requires the participation of the cortex, basal ganglia, cerebellum and brainstem. The signals of this complex neural network finally converge on the ocular motoneurons of the brainstem. Infarct or hemorrhage at any level of the oculomotor system (though more frequent in the brain-stem) may give rise to a broad spectrum of eye movement abnormalities (EMAs). Consequently, neurologists and particularly stroke neurologists are routinely confronted with EMAs, some of which may be overlooked in the acute stroke setting and others that, when recognized, may have a high localizing value. The most complex EMAs are due to midbrain stroke. Horizontal gaze disorders, some of them manifesting unusual patterns, may occur in pontine stroke. Distinct varieties of nystagmus occur in cerebellar and medullary stroke. This review summarizes the most representative EMAs from the supratentorial level to the brainstem.
Mifune, Hiroharu; Tajiri, Yuji; Nishi, Yoshihiro; Hara, Kento; Iwata, Shimpei; Tokubuchi, Ichiro; Mitsuzono, Ryouichi; Yamada, Kentaro; Kojima, Masayasu
In the present study, effects of voluntary exercise in an obese animal model were investigated in relation to the rhythm of daily activity and ghrelin production. Male Sprague-Dawley rats were fed either a high fat diet (HFD) or a chow diet (CD) from four to 16 weeks old. They were further subdivided into either an exercise group (HFD-Ex, CD-Ex) with a running wheel for three days of every other week or sedentary group (HFD-Se, CD-Se). At 16 weeks old, marked increases in body weight and visceral fat were observed in the HFD-Se group, together with disrupted rhythms of feeding and locomotor activity. The induction of voluntary exercise brought about an effective reduction of weight and fat, and ameliorated abnormal rhythms of activity and feeding in the HFD-Ex rats. Wheel counts as voluntary exercise was greater in HFD-Ex rats than those in CD-Ex rats. The HFD-obese had exhibited a deterioration of ghrelin production, which was restored by the induction of voluntary exercise. These findings demonstrated that abnormal rhythms of feeding and locomotor activity in HFD-obese rats were restored by infrequent voluntary exercise with a concomitant amelioration of the ghrelin production and weight reduction. Because ghrelin is related to food anticipatory activity, it is plausible that ghrelin participates in the circadian rhythm of daily activity including eating behavior. A beneficial effect of voluntary exercise has now been confirmed in terms of the amelioration of the daily rhythms in eating behavior and physical activity in an animal model of obesity.
Millán, Mónica; Sobrino, Tomás; Arenillas, Juan Francisco; Rodríguez-Yáñez, Manuel; García, María; Nombela, Florentino; Castellanos, Mar; de la Ossa, Natalia Pérez; Cuadras, Patricia; Serena, Joaquín; Castillo, José; Dávalos, Antoni
Background and purpose: Increased body iron stores have been related to greater oxidative stress and brain injury in clinical and experimental cerebral ischemia and reperfusion. We aimed to investigate the biological signatures of excitotoxicity, inflammation and blood brain barrier disruption potentially associated with high serum ferritin levels-related damage in acute stroke patients treated with i.v. t-PA. Methods: Serum levels of ferritin (as index of increased cellular iron stores), glutamate, interleukin-6, matrix metalloproteinase-9 and cellular fibronectin were determined in 134 patients treated with i.v. t-PA within 3 hours from stroke onset in blood samples obtained before t-PA treatment, at 24 and 72 hours. Results: Serum ferritin levels before t-PA infusion correlated to glutamate (r = 0.59, p < 0.001) and interleukin-6 (r = 0.55, p <0.001) levels at baseline, and with glutamate (r = 0.57,p <0.001), interleukin-6 (r = 0.49,p <0.001), metalloproteinase-9 (r = 0.23, p = 0.007) and cellular fibronectin (r = 0.27, p = 0.002) levels measured at 24 hours and glutamate (r = 0.415, p < 0.001), interleukin-6 (r = 0.359, p < 0.001) and metalloproteinase-9 (r = 0.261, p = 0.004) at 72 hours. The association between ferritin and glutamate levels remained after adjustment for confounding factors in generalized linear models. Conclusions: Brain damage associated with increased iron stores in acute ischemic stroke patients treated with iv. tPA may be mediated by mechanisms linked to excitotoxic damage. The role of inflammation, blood brain barrier disruption and oxidative stress in this condition needs further research. PMID:19096131
The present article describes the quantification of mirtazapine, O-desmethylvenlafaxine, quetiapine, venlafaxine, and ziprasidone (group 1), and amitriptyline, citalopram, clomipramine, clozapine, desmethylclomipramine, desipramine, imipramine, and nortriptyline (group 2) in human serum for therapeutic drug monitoring. The method was developed to replace old techniques which applied solid phase extraction and ultra-violet detection. The old methods had reached their limit of capacity regarding the number of samples and co-medicated drugs interfering with the detection. Serum samples were precipitated with zinc sulphate and methanol containing a stable isotope labelled analog for each analyte. Quantitative analysis was performed by ultra high pressure liquid chromatography combined with a tandem mass spectrometer using a Zorbax SB-C8 column (2.0 × 50 mm; 1.8 μm) with a mobile phase consisting of 0.1% formic acid in water and methanol, respectively. The total run time of the chromatography was 4 min. Precision and trueness varied from 2.6% to 14.9% and 87.6% to 103.5%, respectively. At the lower limit of quantification, precision was up to 17.9% and trueness varied from 89.5% to 111.5%. A five point standard curve covering the clinically relevant ranges with a power function fit was applied for calibration. Ion suppression from matrix effects and internal standards were thoroughly investigated and are discussed. Process efficiency rates varied from 42% to 99%. The method has shortened the response time, reduced interference from other drugs, avoided acetonitrile usage, and reduced the amount of serum needed for analysis 50-fold.
Lan, Bing; Chen, Peng; Jiri, Mutu; He, Na; Feng, Tian; Liu, Kai; Jin, Tianbo; Kang, Longli
Current evidence suggests heredity and metabolic syndrome contributes to gout progression. Specifically, the WDR1 and CLNK genes may play a role in gout progression in European ancestry populations. However, no studies have focused on Chinese populations, especially Tibetan individuals. This study aims to determine whether variations in these two genes correlate with gout-related indices in Chinese-Tibetan gout patients. Eleven single-nucleotide polymorphisms in the WDR1 and CLNK genes were detected in 319 Chinese-Tibetan gout patients and 318 controls. We used one-way analysis of variance to evaluate the polymorphisms' effects on gout based on mean serum levels of metabolism indicators, such as albumin, glucose (GLU), triglycerides, cholesterol, high-density lipoproteins (HDL-C), creatinine, and uric acid, from fasting venous blood samples. All p values were Bonferroni corrected. Polymorphisms of the WDR1 and CLNK genes affected multiple risk factors for gout development. Significant differences in serum GLU levels were detected between different genotypic groups with WDRI polymorphisms rs4604059 (p = 0.005) and rs12498927 (p = 0.005). In addition, significant differences in serum HDL-C levels were detected between different genotypic groups with the CLNK polymorphism rs2041215 (p = 0.001). Polymorphisms of CLNK also affected levels of albumin, triglycerides, and creatinine. This study is the first to investigate and identify positive correlations between WDR1 and CLNK gene polymorphisms in Chinese-Tibetan populations. Our findings provide significant evidence for the effect of genetic polymorphisms on gout-related factors in Chinese-Tibetan populations.
Osaki, Aimi; Okazaki, Yukako; Kimoto, Akiko; Izu, Hanae; Kato, Norihisa
This study investigated the effects of the consumption of 1% or 2% (v/v) ethanol in drinking water for 12 wk on rats fed a high-fat diet. Body weight gain, food intake, and fluid intake were unaffected by ethanol intake. Adipose tissue weight, and serum glucose and lipids were unaffected. Compared to the control (no ethanol), 1% ethanol intake significantly reduced serum levels of alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and ammonia (p<0.05), whereas 2% ethanol intake did so to a lesser extent. Serum urate was significantly lower in both the 1% and 2% ethanol groups than that in the control group (p<0.05). The results suggest a low dose of ethanol has beneficial effects on liver function and serum urate in rats fed a high-fat diet.
Mikheeva, E V; Zhigal'skiĭ, O A; Mamina, V P; Baĭtimirova, E A
Morphophysiological characteristics and peculiarities of adrenal gland of bank vole (Clethrionomys glareolus) were studied in the area of natural biogeochemical province with abnormally high content of nickel, cobalt and chromium. The control population inhabited area with usual content of these elements. We used 4-factor analysis of variance to estimate the influence of geochemical conditions, phase of population cycle, sex and reproductive state on the morphophysiological characteristics of animals and functional activity of adrenal gland. Animals from area with high concentration of Ni, Co and Cr show an increase in relative mass of adrenal glands, fascicular zone of adrenal cortex, size of cells and their nuclei. All these changes can be considered as an evidence of increased secretion of glucocorticoids. It is shown that phase of population cycle influences fatness of animals, size of nuclei, cells and adrenal cortex. Females in comparison with males are characterized with higher indexes of liver and adrenal gland, as well as morphometric indexes of adrenal cortex. The maturation of animals is accompanied with increase in body mass, fatness and relative mass of adrenal glands, the size of cortex zone, nuclei and cells themselves. It is supposed that the effect of "geochemical factor" results in intensification of glucocorticoid secretion of adrenal costex, thus increasing non-specific resistance of animals inhabiting area with high concentration of heavy metals. Such factors as "phase of population cycle", "sex" and "reproductive state", influence mineralocorticoid activity, glucocorticoid and androgenic functions of adrenal cortex. Some factors show synergetic effect.
Alexandrescu, Doru T; Wiernik, Peter H
An important biological alteration in chronic lymphocytic leukemia (CLL) is the dysregulation of immunoglobulin production, as a consequence of complex and yet incompletely understood interactions between plasma cells and the neoplastic B-cell clone. As a result, most patients develop severe hypogammaglobulinemia during the course of the disease. Fourteen patients were analyzed retrospectively for changes in globulins produced by antineoplastic treatments. During maximum response to fludarabine, chlorambucil, and overall rituximab, the mean levels of globulins were 2.500, 2.752, and 3.018 g/dl. The mean increase in globulins during clinical response to individual treatments compared to pre-treatment values were 0.050 g/dl for fludarabine, 0.302 g/dl for chlorambucil, 0.267 g/dl for low-dose rituximab, and 0.346 g/dl for high-dose rituximab. Overall, treatment with rituximab produced an average increase in globulins at clinical response of 11.6%, which increased further to 17.3% at maximum clinical response. Serum globulins increased significantly compared with pre-treatment values at maximum clinical response to rituximab overall (P=0.001) and high-dose rituximab (P=0.001), but no statistical significance occurred in the cases of fludarabine (P=0.5), chlorambucil/prednisone (P=0.14), and low-dose rituximab (P=0.07). Serum globulins levels correlate with disease status (complete responders versus partial responders and stable disease groups), but not with peripheral neoplastic load. Therefore, although rituximab is efficient in decreasing the tumor burden, additional mechanisms may be involved in relieving suppressive effects on immunoglobulin-producing cells, which especially manifest at high doses of the agent. Use of high doses of rituximab in CLL can avoid T-cell dysfunction and neutropenia, and is associated with humoral immunorestorative effects.
Hutchison, Colin A; Harding, Stephen; Mead, Graham; Goehl, Hermann; Storr, Markus; Bradwell, Arthur; Cockwell, Paul
In multiple myeloma the predominant cause of irreversible renal failure is cast nephropathy, secondary to excess kappa or lambda serum free light chains (FLCs). These molecules are efficiently cleared by hemodialysis (HD) using the Gambro HCO 1100 dialyzer. To optimize the removal of FLCs by this dialyzer we have studied the effect of dialyzers in series, dialyzer change, and hemodiafiltration in 14 patients with multiple myeloma and renal failure. The clearance rates of both kappa FLCs and lambda FLCs were significantly increased on two dialyzers from 19 (7.3-34)-15.3 (9-28) mL/min to 47 (17-79)-35.5 (20-57) mL/min, respectively. Clearance rates of both FLCs decreased over the course of the dialysis sessions (both P < 0.001). Changing the dialyzer during a HD session increased lambda FLC clearance rates (22.5 [6-41] to 37.6 [9-52] mL/min; P < 0.001) and decreased kappa FLC clearance rates (39.6 [9-72] to 19 [8-59] mL/min; P < 0.003). Ultrafiltration during HD increased the clearance rates of kappa FLCs (R 0.52, P < 0.01) but not lambda FLCs (R -0.25; P < 0.076). Hemodiafiltration increased the clearance rates of both kappa (19 [SD 6.8] to 32 [SD 9.8] mL/min) and lambda FLCs (15 [SD 7.8] to 20 [SD 7.7] mL/min). Albumin replacement requirements for 8 h of HD increased from 12 g for a single dialyzer to 45 g for two dialyzers in series (P < 0.001). Different protocols are required to optimize the removal of kappa and lambda FLCs in patients with myeloma and renal failure.
Ishima, Yu; Shinagawa, Takuya; Yoneshige, Shinji; Kragh-Hansen, Ulrich; Ohya, Yuki; Inomata, Yukihiro; Kai, Toshiya; Otagiri, Masaki; Maruyama, Toru
S-Nitrosated human serum albumin (SNO-HSA) is useful in preventing liver ischemia/reperfusion injury, and SNO-HSA should thus be able to prevent cell injury during liver transplantation. However, the potential protective effect of SNO-HSA on a combination of cold and warm ischemia, which is obligatory when performing liver transplantation, has not been examined. Therefore, we evaluated the protective effect of SNO-HSA added to University of Wisconsin (UW) solution during cold or/and warm ischemia in situ and in vitro. First, we observed that apoptotic and necrotic cell death were increased during cold and warm ischemia, respectively. SNO-HSA, which possesses anti-apoptosis activity at low NO concentrations, can inhibit cold ischemia injury both in situ and in vitro. In contrast, SNO-HSA had no significant effect on warm liver ischemia injury which, however, can be reduced by UW solution. We also demonstrated that the cellular uptake of NO from SNO-HSA can occur during cold ischemia resulting in induction of heme oxygenase-1 within 3h of cold ischemia. Our results indicate that treatment with SNO-HSA or UW solution alone is not sufficient to inhibit liver injury during a period of both cold and warm ischemia. However, a combination of SNO-HSA and UW solution can be used to prevent the two types of ischemia. SNO-HSA-added UW solution could be very useful in transplantation, because the previously imposed constraints on preservation time can be removed. This is a great advantage in a situation as the present one with increased utilization of scarce donor organs for more recipients.
Arnold, Edith; Rivera, José C.; Thebault, Stéphanie; Moreno-Páramo, Daniel; Quiroz-Mercado, Hugo; Quintanar-Stéphano, Andrés; Binart, Nadine; Martínez de la Escalera, Gonzalo; Clapp, Carmen
OBJECTIVE Increased retinal vasopermeability (RVP) occurs early in diabetes and is crucial for the development of sight-threatening proliferative diabetic retinopathy (DR). The hormone prolactin (PRL) is proteolytically processed to vasoinhibins, a family of peptides that inhibit the excessive RVP related to DR. Here, we investigate the circulating levels of PRL in association with DR in men and test whether increased circulating PRL, by serving as a source of ocular vasoinhibins, can reduce the pathological RVP in diabetes. RESEARCH DESIGN AND METHODS Serum PRL was evaluated in 40 nondiabetic and 181 diabetic men at various stages of DR. Retinal vasoinhibins were measured in rats rendered hyperprolactinemic by placing two anterior pituitary grafts under the kidney capsule and in PRL receptor–null mice. RVP was determined in hyperprolactinemic rats subjected to the intraocular injection of vascular endothelial growth factor (VEGF) or made diabetic with streptozotocin. RESULTS The circulating levels of PRL increased in diabetes and were higher in diabetic patients without retinopathy than in those with proliferative DR. In rodents, hyperprolactinemia led to vasoinhibin accumulation within the retina; genetic deletion of the PRL receptor prevented this effect, indicating receptor-mediated incorporation of systemic PRL into the eye. Hyperprolactinemia reduced both VEGF-induced and diabetes-induced increase of RVP. This reduction was blocked by bromocriptine, an inhibitor of pituitary PRL secretion, which lowers the levels of circulating PRL and retinal vasoinhibins. CONCLUSIONS Circulating PRL influences the progression of DR after its intraocular conversion to vasoinhibins. Inducing hyperprolactinemia may represent a novel therapy against DR. PMID:20823101
Baltz, M L; Rowe, I F; Caspi, D; Turnell, W G; Pepys, M B
Serum amyloid A protein (SAA), an apolipoprotein of high density lipoprotein (HDL), is generally considered to be the precursor of AA protein, which forms the fibrils in reactive systemic amyloidosis in man and animals. This view is based on amino acid sequence identity between AA and the amino-terminal portion of SAA. However, in extensive and well-controlled studies of experimentally induced murine AA amyloidosis, we were unable to demonstrate a direct precursor-product relationship between SAA, in SAA-rich HDL preparations from acute phase or amyloidotic mouse or human serum, and AA protein in the amyloid deposits. This raises the possibility that SAA in its usual form, as an apolipoprotein of HDL synthesized during the acute phase response, may not be the major precursor of AA fibrils. The amyloidogenic forms of circulating SAA molecules may not be isolated during the preparation of HDL. Alternatively, particularly in the light of recent evidence that SAA mRNA is expressed in many different tissues throughout the body of appropriately stimulated animals, amyloidogenic SAA may be derived from sources other than the liver cells in which SAA-rich HDL is synthesized. PMID:3105937
Li, Jer-Chuan; Wu, Du-An; Hou, Jia-Sian; Subeq, Yi-Maun; Chen, Hsin-Dean
Adipocyte fatty acid binding protein (A-FABP) is a key mediator of obesity-related metabolic syndrome (MetS). The aim of this study was to evaluate the relationship between A-FABP concentration and MetS in type 2 diabetes mellitus (DM) patients. Fasting blood samples were obtained from 165 type 2 DM volunteers. MetS and its components were defined using diagnostic criteria from the International Diabetes Federation. Among 165 DM patients, 113 patients (68.5%) had MetS. Diabetic persons who had MetS had significantly higher A-FABP levels (P < 0.001) than those without MetS. Female DM persons had higher A-FABP level than man (P < 0.001). No statistically significant differences in A-FABP levels were found in use of statin, fibrate, or antidiabetic drugs. Multivariate forward stepwise linear regression analysis revealed that body fat mass (P < 0.001), logarithmically transformed creatinine (log-creatinine; P < 0.001), female DM patients (P < 0.001), and logarithmically transformed high sensitive C-reactive protein (log-hs-CRP; P = 0.013) were positively correlated, while albumin (P = 0.004) and glomerular filtration rate (GFR; P = 0.043) were negatively correlated with serum A-FABP levels in type 2 DM patients. In this study, higher serum A-FABP level was positively associated with MetS in type 2 DM patients. PMID:28042581
Barre, Douglas E; Mizier-Barre, Kazimiera A; Griscti, Odette; Hafez, Kevin
Type 2 diabetes is characterized partially by elevated fasting blood serum glucose and insulin concentrations and the percentage of hemoglobin as HbA1c. It was hypothesized that each of blood glucose and its co-factors insulin and HbA1c and would show a more favorable profile as the result of flaxseed oil supplementation. Patients were recruited at random from a population pool responding to a recruitment advertisement in the local newspaper and 2 area physicians. Completing the trial were 10 flaxseed oil males, 8 flaxseed oil females, 8 safflower (placebo) oil males and 6 safflower oil females. Patients visited on two pre-treatment occasions each three months apart (visits 1 and 2). At visit 2 subjects were randomly assigned in double blind fashion and in equal gender numbers to take flaxseed oil or safflower oil for three further months until visit 3. Oil consumption in both groups was approximately 10 g/d. ALA intake in the intervention group was approximately 5.5 g/d. Power was 0.80 to see a difference of 1 mmol of glucose /L using 12 subjects per group with a p < 0.05. Flaxseed oil had no impact on fasting blood serum glucose, insulin or HbA1c levels. It is concluded that high doses of flaxseed oil have no effect on glycemic control in type 2 diabetics.
Origuchi, Tomoki; Arima, Kazuhiko; Kawashiri, Shin-Ya; Tamai, Mami; Yamasaki, Satoshi; Nakamura, Hideki; Tsukada, Toshiaki; Aramaki, Toshiyuki; Furuyama, Masako; Miyashita, Taiichiro; Kawabe, Yojiro; Iwanaga, Nozomi; Terada, Kaoru; Ueki, Yukitaka; Fukuda, Takaaki; Eguchi, Katsumi; Kawakami, Atsushi
Recently, it was reported that remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome could be complicated with solid tumors. In a retrospective, multicenter study between October, 2003 and September, 2010, we investigated the characteristics of patients with paraneoplastic RS3PE syndrome who fulfilled following criteria: (1) bilateral pitting edema of hands or feet or both, (2) sudden onset of polyarthritis, and (3) age >50 years, (4) seronegativity for rheumatoid factor (RF). A total of 33 cases fulfilled the above criteria. Eight patients (seven men and one woman) developed cancer within 2 years of RS3PE syndrome onset. There was no significant difference between the neoplastic and nonneoplastic groups in the proportions of patients with fever, symmetrical polyarthritis, pitting edema, and good response to corticosteroids. Serum matrix metalloproteinase 3 (MMP-3) level (median 437.3 ng/ml) in the paraneoplastic RS3PE patients was significantly higher than that in patients without neoplasia (median 114.7 ng/ml) (p < 0.05). We found that high serum MMP-3 is characteristic of patients with paraneoplastic RS3PE syndrome.
Shimonov, M; Pinchuk, I; Bor, A; Beigel, I; Fainaru, M; Rubin, M; Lichtenberg, D
As a first step in evaluating the significance of our recently developed method of monitoring the kinetics of copper-induced oxidation in unfractionated serum, we recorded the kinetics of lipid oxidation in the sera of 62 hyperlipidemic patients and analyzed the correlation between oxidation and lipid composition of the sera [high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, and triglycerides]. We used six factors to characterize the kinetics of oxidation, namely, the maximal absorbance of oxidation products (ODmax), the maximal rate of their production (Vmax), and the time at which the rate was maximal (t(max)) at two wavelengths (245 nm, where 7-ketocholesterol and conjugated dienic hydroperoxides absorb intensely, and 268 nm, where the absorbance is mostly due to dienals). The major conclusions of our analyses are that: (i) Both ODmax and Vmax correlate positively with the sum of concentrations of the major oxidizable lipids, cholesterol, and cholesteryl esters. (ii). The value of t(max), which is a measure of the lag preceding oxidation and therefore reflects the resistance of the serum lipids to copper-induced oxidation, exhibits a negative correlation with HDL cholesterol. Although this finding accords with the observation of shorter lags for HDL than for LDL, it is apparently inconsistent with the role of HDL as an antirisk factor in coronary heart diseases.
McCarthy, P T; Hughes, S; Paton, C
A simple method for the measurement of clozapine and its N-desmethyl metabolite in human plasma or serum by high performance liquid chromatography is described. An internal standard (aqueous nortriptyline, 4 mg/L) (50 microL) and Tris buffer (2 mol/L, pH 10.6) (100 microL) are added to plasma/serum (200 microL) and the analytes and internal standard extracted into methyl tert-butyl ether (200 microL). The extracts are analysed on a 150 mm column containing Spherisorb S5SCX using methanol containing ammonium perchlorate (35 mmol/L, pH 6.7) as eluent at a flow rate of 1.5 mL/min. Detection is by ultraviolet absorption (215 nm). The limit of detection is better than 0.05 mg/L for both analytes and the intra-assay precision (CV) for clozapine and norclozapine was 5.3 and 7.3% at 0.5 mg/L and 2.6 and 2.8% at 1.5 mg/L, respectively. The method can be applied to the measurement of these compounds in plasma after acute overdosage, for the assessment of compliance in patients apparently refractory to therapy and to identify interactions between clozapine and other neuroleptic and antidepressant drugs which may effect toxicity.
Vicente, Faye B; Vespa, Gina; Miller, Alan; Haymond, Shannon
Iohexol is a nonradioactive contrast medium, and its clearance from serum or urine is used to measure glomerular filtration rate (GFR). GFR is the most useful indicator of kidney function and progression of kidney disease. GFR determination using iohexol clearance is increasingly being applied in clinical practice, given its advantages over and correlation with inulin. We describe a high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS) method for iohexol clearance, requiring only 50 μL of serum. The sample preparation involves protein precipitation with LC/MS-grade methanol, containing ioversol as the internal standard. Samples are centrifuged and supernatant is dried under nitrogen gas at room temperature. Samples are reconstituted with mobile phase (ammonium acetate-formic acid-water). Iohexol is separated using an HPLC gradient method on a C-8 analytical column. MS/MS detection is in the multiple-reaction monitoring (MRM) mode and the transitions monitored are m/z 822.0 to m/z 804.0 and m/z 807.0 to m/z 588.0 for iohexol and ioversol, respectively.
Zlosnik, James E. A.; Gunaratnam, L. Cynthia; Speert, David P.
Burkholderia cepacia complex (BCC) bacteria can cause devastating chronic infections in people with cystic fibrosis. Of particular concern is “cepacia syndrome,” a rapidly progressive and usually fatal decline in health, characterized by a necrotizing bacteremic pneumonia. An important component of defense against bloodstream infections is the bactericidal action of serum. Traditional methods to determine the capacity of bacterial isolates to resist the bactericidal effects of serum are relatively low-throughput viability assays. In this study, we developed a novel growth-based assay for serum susceptibility, which allows for high throughput analysis. We applied this assay to a range of clinical isolates of BCC as well as isolates comprising the BCC experimental strain panel. Our data demonstrate that isolates from all species of BCC examined can possess serum resistant or serum sensitive/intermediate phenotypes. Of particular clinical significance, we also found no direct link between the last saved pulmonary isolate from patients who subsequently developed “cepacia syndrome” and their capacity to resist the inhibitory effects of human serum, suggesting serum resistance cannot be used as a marker of an isolate’s capacity to escape from the lung and cause bacteremia. PMID:22919658
Rosenthal, M B; Barnard, R J; Rose, D P; Inkeles, S; Hall, J; Pritikin, N
Recent studies have implicated elevated levels of serum estradiol in males as the major predisposing factor for myocardial infarction, with serum cholesterol playing a secondary role. The purpose of the present study was to investigate the effects of a high-complex-carbohydrate, low-fat, low-cholesterol diet and daily exercise on levels of serum estradiol, testosterone, and lipids in males. Twenty-one males participating in the Pritikin Longevity Center 26-day residential program volunteered for the study. During the program, serum estradiol levels were significantly reduced from 47.2 +/- 4.6 to 23.8 +/- 2.5 pg/ml (mean +/- SE) whereas serum testosterone levels were unchanged (5.1 +/- 0.3 versus 5.1 +/- 0.2 ng/ml). Total serum cholesterol levels were reduced from 229 +/- 9 to 181 +/- 7 mg/dl whereas triglyceride levels were reduced from 301 +/- 66 to 151 +/- 13 mg/dl. High-density lipoprotein-cholesterol levels fell from 41 +/- 3 to 35 +/- 1 mg/dl whereas the ratio of total cholesterol to high-density lipoprotein-cholesterol was unchanged (5.5 +/- 0.4 versus 5.1 +/- 0.3).
Montoya, Carlos J; Toro, Maria F; Aguirre, Carlos; Bustamante, Alberto; Hernandez, Mariluz; Arango, Liliana P; Echeverry, Marta; Arango, Ana E; Prada, Maria C; Alarcon, Herminia del P; Rojas, Mauricio
Given that highly active antiretroviral therapy (HAART) has been demonstrated useful to restore immune competence in type-1 human immunodeficiency virus (HIV-1)-infected subjects, we evaluated the specific antibody response to influenza vaccine in a cohort of HIV-1-infected children on HAART so as to analyze the quality of this immune response in patients under antiretroviral therapy. Sixteen HIV-1-infected children and 10 HIV-1 seronegative controls were immunized with a commercially available trivalent inactivated influenza vaccine containing the strains A/H1N1, A/H3N2, and B. Serum hemagglutinin inhibition (HI) antibody titers were determined for the three viral strains at the time of vaccination and 1 month later. Immunization induced a significantly increased humoral response against the three influenza virus strains in controls, and only against A/H3N2 in HIV-1-infected children. The comparison of post-vaccination HI titers between HIV-1+ patients and HIV-1 negative controls showed significantly higher HI titers against the three strains in controls. In addition, post vaccination protective HI titers (defined as equal to or higher than 1:40) against the strains A/H3N2 and B were observed in a lower proportion of HIV-1+ children than in controls, while a similar proportion of individuals from each group achieved protective HI titers against the A/H1N1 strain. The CD4+ T cell count, CD4/CD8 T cells ratio, and serum viral load were not affected by influenza virus vaccination when pre- vs post-vaccination values were compared. These findings suggest that despite the fact that HAART is efficient in controlling HIV-1 replication and in increasing CD4+ T cell count in HIV-1-infected children, restoration of immune competence and response to cognate antigens remain incomplete, indicating that additional therapeutic strategies are required to achieve a full reconstitution of immune functions.
Chapter 25, discusses structurally abnormal human autosomes. This discussion includes: structurally abnormal chromosomes, chromosomal polymorphisms, pericentric inversions, paracentric inversions, deletions or partial monosomies, cri du chat (cat cry) syndrome, ring chromosomes, insertions, duplication or pure partial trisomy and mosaicism. 71 refs., 8 figs.
Holsen, Laura M.; Lawson, Elizabeth A.; Christensen, Kara; Klibanski, Anne; Goldstein, Jill M.
Evidence contributing to the understanding of neurobiological mechanisms underlying appetite dysregulation in anorexia nervosa draws heavily on separate lines of research into neuroendocrine and neural circuitry functioning. In particular, studies consistently cite elevated ghrelin and abnormal activation patterns in homeostatic (hypothalamus) and hedonic (striatum, amygdala, insula) regions governing appetite. The current preliminary study examined the interaction of these systems, based on research demonstrating associations between circulating ghrelin levels and activity in these regions in healthy individuals. In a cross-sectional design, we studied 13 women with active anorexia nervosa (AN), 9 women weight-recovered from AN (AN-WR), and 12 healthy-weight control women using a food cue functional magnetic resonance imaging paradigm, with assessment of fasting levels of acylated ghrelin. Healthy-weight control women exhibited significant positive associations between fasting acylated ghrelin and activity in the right amygdala, hippocampus, insula, and orbitofrontal cortex in response to high-calorie foods, associations which were absent in the AN and AN-WR groups. Women with AN-WR demonstrated a negative relationship between ghrelin and activity in the left hippocampus in response to high-calorie foods, while women with AN showed a positive association between ghrelin and activity in the right orbitofrontal cortex in response to low-calorie foods. Findings suggest a breakdown in the interaction between ghrelin signaling and neural activity in relation to reward responsivity in AN, a phenomenon that may be further characterized using pharmacogenetic studies. PMID:24862390
Hänggi, Pascal; Makhro, Asya; Gassmann, Max; Schmugge, Markus; Goede, Jeroen S; Speer, Oliver; Bogdanova, Anna
Recently we showed that N-methyl D-aspartate receptors (NMDARs) are expressed in erythroid precursors (EPCs) and present in the circulating red blood cells (RBCs) of healthy humans, regulating intracellular Ca(2+) in these cells. This study focuses on investigating the possible role of NMDARs in abnormally high Ca(2+) permeability in the RBCs of patients with sickle cell disease (SCD). Protein levels of the NMDAR subunits in the EPCs of SCD patients did not differ from those in EPCs of healthy humans. However, the number and activity of the NMDARs in circulating SCD-RBCs was substantially up-regulated, being particularly high during haemolytic crises. The number of active NMDARs correlated negatively with haematocrit and haemoglobin levels in the blood of SCD patients. Calcium uptake via these non-selective cation channels was induced by RBC treatment with glycine, glutamate and homocysteine and was facilitated by de-oxygenation of SCD-RBCs. Oxidative stress and RBC dehydration followed receptor stimulation and Ca(2+) uptake. Inhibition of the NMDARs with an antagonist memantine caused re-hydration and largely prevented hypoxia-induced sickling. The EPCs of SCD patients showed higher tolerance to memantine than those of healthy subjects. Consequently, NMDARs in the RBCs of SCD patients appear to be an attractive target for pharmacological intervention.
Manion, Patrick J.
The experimental control of the sea lamprey (Petromyzon marinus) in the Great Lakes has required the collection of thousands of lampreys. Representatives of each life stage of the four species of the Lake Superior basin were examined for structural abnormalities. The most common aberration was the presence of additional tails. The accessory tails were always postanal and smaller than the normal tail. The point of origin varied; the extra tails occurred on dorsal, ventral, or lateral surfaces. Some of the extra tails were misshaped and curled, but others were normal in shape and pigment pattern. Other abnormalities in larval sea lampreys were malformed or twisted tails and bodies. The cause of the structural abnormalities is unknown. The presence of extra caudal fins could be genetically controlled, or be due to partial amputation or injury followed by abnormal regeneration. Few if any lampreys with structural abnormalities live to sexual maturity.
Guzelmeric, K; Seker, N; Unal, O; Turan, C
Using an ultrasensitive assay, prostate-specific antigen (PSA) has been detected in female serum and has been proposed as a potential marker of androgen excess in hirsute women. Measurement of PSA levels in serum may play a role in monitoring hirsutism during antiandrogen therapy. We investigated the role of PSA as a marker of androgen activity in hirsute patients taking spironolactone together with oral contraceptive pills containing ethinyl estradiol and gestodene. Twenty-eight hirsute patients were included in the study. Clinical and biochemical variables including serum levels of PSA (using an ultrasensitive chemiluminscent immunoassay), dehydroepiandrosterone sulfate, total testosterone, free testosterone and 17-hydroxyprogesterone concentrations were recorded at baseline and after six cycles of treatment. Fifteen healthy women were included in the study as controls. Serum PSA levels in hirsute women were clearly higher than in the control group (0.023 +/- 0.004 vs. 0.006 +/- 0.003 ng/ml, p < 0.001) and correlated with baseline serum free testosterone concentrations (r = 0.518, p = 0.005). After 6 months, serum PSA concentrations as compared with baseline values did not change significantly in patients who were given spironolactone plus contraceptive pills (p = 0.4) despite a marked decrease in total testosterone, free testosterone, 17-hydroxyprogesterone, dehydroepiandrosterone sulfate and hirsutism score (p < 0.05). Thus, serum PSA levels in hirsute women were higher than in non-hirsute healthy controls. A 6-month course of treatment with spironolactone combined with contraceptive pills containing ethinylestradiol and gestodene did not reduce high serum PSA levels in these subjects. In conclusion, the serum PSA level is not a convenient biochemical marker with the available assays for the management of hirsute women treated with the combination of spironolactone and oral contraceptives.
Kaga, Akimune; Saito-Hakoda, Akiko; Uematsu, Mitsugu; Kamimura, Miki; Kanno, Junko; Kure, Shigeo; Fujiwara, Ikuma
Several studies have described brain white matter abnormalities on magnetic resonance imaging (MRI) in children and adults with congenital adrenal hyperplasia (CAH), while the brain MRI findings of newborn infants with CAH have not been clarified. We report a newborn boy with CAH who presented brain white matter abnormality on MRI. He was diagnosed as having salt-wasting CAH with a high 17-OHP level at neonatal screening and was initially treated with hydrocortisone at 8 days of age. On day 11 after birth, he had a generalized tonic seizure. No evidence of serum electrolyte abnormalities was observed. Brain MRI revealed white matter abnormalities that consisted of bilateral small diffuse hyperintensities on T1-weighted images with slightly low intensity on T2-weighted images in the watershed area. Several factors associated with brain white matter abnormalities in adults with CAH, such as increasing age, hypertension, diabetes and corticosteroid replacement, were not applicable. Although the cause of the phenomenon in this case is unclear, brain white matter abnormality could be observed in newborn infants with CAH as well as in adult patients.
... test to look for signs of the disease phenylketonuria (PKU). The test detects abnormally high levels of ... MO: Elsevier Saunders; 2013:chap P. Read More Phenylketonuria Review Date 4/21/2015 Updated by: Neil ...
Peynet, J.; Legrand, A.; Messing, B.; Thuillier, F.; Rousselet, F.
An alpha slow-moving high-density-lipoprotein (HDL) subfraction was seen in a patient presenting with radiation enteritis and peritoneal carcinosis, who was given long-term cyclic parenteral nutrition. This subfraction, observed in addition to normal HDL, was precipitated with low-density lipoproteins (LDL) and very-low-density lipoproteins (VLDL) by sodium phosphotungstate-magnesium chloride. The patient's serum lipoproteins were analyzed after fractionation by density gradient ultracentrifugation. The alpha slow-moving HDL floated in the ultracentrifugation subfractions with densities ranging from 1.028 to 1.084 kg/L, and their main apolipoproteins included apolipoprotein E in addition to apolipoprotein A-I. These HDL were larger than HDL2. The pathogenesis of this unusual HDL subfraction is hypothesized.
Wang, Xing-He; Li, Chun-Yan; Muhammad, Ishfaq; Zhang, Xiu-Ying
In this study, we investigated the correlation between the serum fatty acid composition and hepatic steatosis, inflammation, hepatocellular ballooning scores, and liver fatty acids composition in mice fed a high-fat diet. Livers were collected for non-alcoholic fatty liver disease score analysis. Fatty acid compositions were analysed by gas chromatography. Correlations were determined by Pearson correlation coefficient. Exposed to a high-fat diet, mice developed fatty liver disease with varying severity without fibrosis. The serum fatty acid variation became more severe with prolonged exposure to a high-fat diet. This variation also correlated significantly with the variation in livers, with the types of fatty acids corresponding to liver steatosis, inflammation, and hepatocellular ballooning scores. Results of this study lead to the following hypothesis: the extent of serum fatty acid variation may be a preliminary biomarker of fatty liver disease caused by high-fat intake.
Jenkinson, Carl; Adams, John S.; Stewart, Paul M.; Hewison, Martin; Keevil, Brian G.
Recent studies suggest that vitamin D-deficiency is linked to increased risk of common human health problems. To define vitamin D ‘status’ most routine analytical methods quantify one particular vitamin D metabolite, 25-hydroxyvitamin D3 (25OHD3). However, vitamin D is characterized by complex metabolic pathways, and simultaneous measurement of multiple vitamin D metabolites may provide a more accurate interpretation of vitamin D status. To address this we developed a high-throughput liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to analyse multiple vitamin D analytes, with particular emphasis on the separation of epimer metabolites. A supportive liquid-liquid extraction (SLE) and LC-MS/MS method was developed to quantify 10 vitamin D metabolites as well as separation of an interfering 7α-hydroxy-4-cholesten-3-one (7αC4) isobar (precursor of bile acid), and validated by analysis of human serum samples. In a cohort of 116 healthy subjects, circulating concentrations of 25-hydroxyvitamin D3 (25OHD3), 3-epi-25-hydroxyvitamin D3 (3-epi-25OHD3), 24,25-dihydroxyvitamin D3 (24R,25(OH)2D3), 1,25-dihydroxyvitamin D3 (1α,25(OH)2D3), and 25-hydroxyvitamin D2 (25OHD2) were quantifiable using 220 μl of serum, with 25OHD3 and 24R,25(OH)2D3 showing significant seasonal variations. This high-throughput LC-MS/MS method provides a novel strategy for assessing the impact of vitamin D on human health and disease. PMID:26874878
Jenkinson, Carl; Taylor, Angela E; Hassan-Smith, Zaki K; Adams, John S; Stewart, Paul M; Hewison, Martin; Keevil, Brian G
Recent studies suggest that vitamin D-deficiency is linked to increased risk of common human health problems. To define vitamin D 'status' most routine analytical methods quantify one particular vitamin D metabolite, 25-hydroxyvitamin D3 (25OHD3). However, vitamin D is characterized by complex metabolic pathways, and simultaneous measurement of multiple vitamin D metabolites may provide a more accurate interpretation of vitamin D status. To address this we developed a high-throughput liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to analyse multiple vitamin D analytes, with particular emphasis on the separation of epimer metabolites. A supportive liquid-liquid extraction (SLE) and LC-MS/MS method was developed to quantify 10 vitamin D metabolites as well as separation of an interfering 7α-hydroxy-4-cholesten-3-one (7αC4) isobar (precursor of bile acid), and validated by analysis of human serum samples. In a cohort of 116 healthy subjects, circulating concentrations of 25-hydroxyvitamin D3 (25OHD3), 3-epi-25-hydroxyvitamin D3 (3-epi-25OHD3), 24,25-dihydroxyvitamin D3 (24R,25(OH)2D3), 1,25-dihydroxyvitamin D3 (1α,25(OH)2D3), and 25-hydroxyvitamin D2 (25OHD2) were quantifiable using 220μL of serum, with 25OHD3 and 24R,25(OH)2D3 showing significant seasonal variations. This high-throughput LC-MS/MS method provides a novel strategy for assessing the impact of vitamin D on human health and disease.
Ability of Serum Glial Fibrillary Acidic Protein, Ubiquitin C-Terminal Hydrolase-L1, and S100B To Differentiate Normal and Abnormal Head Computed Tomography Findings in Patients with Suspected Mild or Moderate Traumatic Brain Injury.
Welch, Robert D; Ayaz, Syed I; Lewis, Lawrence M; Unden, Johan; Chen, James Y; Mika, Valerie H; Saville, Ben; Tyndall, Joseph A; Nash, Marshall; Buki, Andras; Barzo, Pal; Hack, Dallas; Tortella, Frank C; Schmid, Kara; Hayes, Ronald L; Vossough, Arastoo; Sweriduk, Stephen T; Bazarian, Jeffrey J
Head computed tomography (CT) imaging is still a commonly obtained diagnostic test for patients with minor head injury despite availability of clinical decision rules to guide imaging use and recommendations to reduce radiation exposure resulting from unnecessary imaging. This prospective multicenter observational study of 251 patients with suspected mild to moderate traumatic brain injury (TBI) evaluated three serum biomarkers' (glial fibrillary acidic protein [GFAP], ubiquitin C-terminal hydrolase-L1 [UCH-L1] and S100B measured within 6 h of injury) ability to differentiate CT negative and CT positive findings. Of the 251 patients, 60.2% were male and 225 (89.6%) had a presenting Glasgow Coma Scale score of 15. A positive head CT (intracranial injury) was found in 36 (14.3%). UCH-L1 was 100% sensitive and 39% specific at a cutoff value >40 pg/mL. To retain 100% sensitivity, GFAP was 0% specific (cutoff value 0 pg/mL) and S100B had a specificity of only 2% (cutoff value 30 pg/mL). All three biomarkers had similar values for areas under the receiver operator characteristic curve: 0.79 (95% confidence interval; 0.70-0.88) for GFAP, 0.80 (0.71-0.89) for UCH-L1, and 0.75 (0.65-0.85) for S100B. Neither GFAP nor UCH-L1 curve values differed significantly from S100B (p = 0.21 and p = 0.77, respectively). In our patient cohort, UCH-L1 outperformed GFAP and S100B when the goal was to reduce CT use without sacrificing sensitivity. UCH-L1 values <40 pg/mL could potentially have aided in eliminating 83 of the 215 negative CT scans. These results require replication in other studies before the test is used in actual clinical practice.
Effects of partial and total colectomy on mineral and acid-base homoeostasis in the rat: magnesium deficiency, hyperphosphaturia and osteopathy, in the presence of high serum 1,25-dihydroxyvitamin D but normal parathyroid hormone.
Croner, R; Schwille, P O; Erben, R G; Gepp, H; Stahr, K; Rümenapf, G; Parth, R; Scheuerlein, H
The effects of colectomy on acid-base status, extra-osseous and bone minerals, calciotropic hormones and bone morphology have not yet been studied. To rectify this, groups of normally fed male rats were subjected to distal (n=11), proximal (n=12) or total (n=12) colectomy. Sham-operated rats (n=12) served as controls. At 112 (+/-2) days after colectomy the following changes were noted: (1) weight gain was delayed; (2) faecal excretion of calcium and phosphorus was normal, whereas that of magnesium was increased; (3) intestinal calcium secretion and absorption of calcium and phosphorus were normal, but magnesium absorption was decreased; (4) urinary excretion of magnesium was also decreased, that of phosphorus was increased, and that of pyridinium and deoxypyridinium tended to be high; (5) the serum levels of ionized magnesium, total calcium, 25-hydroxyvitamin D and parathyroid hormone were normal, while that of 1,25-dihydroxyvitamin D was markedly elevated; and (6) bone magnesium and phosphorus content were decreased, but bone calcium was normal, and thus the bone calcium/phosphorus ratio was high. These abnormalities were associated with moderate metabolic acidosis, as reflected by high urinary ammonium, low citrate and low total CO(2), but normal blood gases. Significant structural abnormalities of bone were not detectable, but trabecular bone tended to show rarefication. Distal colectomy had the least effect, whereas proximal and total colectomies had a distinct effect, on these parameters. It is concluded that colectomy in the rat causes: (1) a syndrome of magnesium deficiency of intestinal origin, compensated metabolic acidosis, urinary phosphorus loss, and high circulating 1,25-dihydroxyvitamin D levels, with the degree depending on the extent of surgical resection; and (2) brittle bones, a feature characteristic of low bone magnesium and more generalized magnesium deficiency. The mechanisms leading to this syndrome are unknown, but altered tissue levels of
Thuy, Le Thi Thanh; Van Thuy, Tuong Thi; Matsumoto, Yoshinari; Hai, Hoang; Ikura, Yoshihiro; Yoshizato, Katsutoshi; Kawada, Norifumi
Cytoglobin (Cygb) was identified in hepatic stellate cells (HSCs) and pericytes of all organs; however, the effects of Cygb on cellular functions remain unclear. Here, we report spontaneous and age-dependent malformations in multiple organs of Cygb−/− mice. Twenty-six percent of young Cygb−/− mice (<1 year old) showed heart hypertrophy, cystic disease in the kidney or ovary, loss of balance, liver fibrosis and lymphoma. Furthermore, 71.3% (82/115) of aged Cygb−/− mice (1–2 years old) exhibited abnormalities, such as heart hypertrophy and cancer development in multiple organs; by contrast, 5.8% (4/68) of aged wild-type (WT) mice had abnormalities (p < 0.0001). Interestingly, serum and urine analysis demonstrated that the concentration of nitric oxide metabolites increased significantly in Cygb−/− mice, resulting in an imbalance in the oxidative stress and antioxidant defence system that was reversed by NG-monomethyl-L-arginine treatment. A senescent phenotype and evidence of DNA damage were found in primary HSCs and the liver of aged Cygb−/− mice. Moreover, compared with HSC+/+, HSC−/− showed high expression of Il-6 and chemokine mRNA when cocultured with mouse Hepa 1–6 cells. Thus, the absence of Cygb in pericytes provokes organ abnormalities, possibly via derangement of the nitric oxide and antioxidant defence system and through accelerated cellular senescence. PMID:27146058
Salsano, Ettore; Fancellu, Roberto; Di Fede, Giuseppe; Ciano, Claudia; Scaioli, Vidmer; Nanetti, Lorenzo; Politi, Letterio Salvatore; Tagliavini, Fabrizio; Mariotti, Caterina; Pareyson, Davide
Gerstmann-Sträussler-Scheinker disease Pro102Leu (GSS102) is a rare autosomal dominant inherited prion disease due to a substitution of proline for leucine at codon 102 in the Prion Protein gene, and characterized by early walking difficulties and much later occurring dementia. We report clinical, electrophysiological and neuroradiological features of seven novel Italian cases of GSS102. The findings in our series support the thesis that early signs of GSS102 (including areflexia, ataxia, lower limb weakness, and painful dysesthesias) are likely due to a caudal myelopathic process, and suggest that GSS102 should be included among the causes of ataxia with areflexia. Moreover, our observations show that in patients with GSS102, as opposed to Friedreich's ataxia and other forms of ataxia with areflexia, nerve conduction studies and somato-sensory evoked potentials are normal, despite the presence of lower limb areflexia. Hence, in subjects with walking difficulties, the presence of lower limb areflexia without central and peripheral conduction abnormalities is highly suggestive or possibly pathognomonic of GSS102, and can easily guide the clinicians to make the diagnosis of this rare neurodegenerative disease.
Neshatdoust, Sara; Saunders, Caroline; Castle, Sophie M.; Vauzour, David; Williams, Claire; Butler, Laurie; Lovegrove, Julie A.; Spencer, Jeremy P. E.
BACKGROUND: Recent clinical studies have indicated the beneficial impact of dietary flavonoid intake on human cognitive performance. Although the mechanisms that mediate such improvements are currently unclear, animal and human trial data suggest that changes in neurotrophin expression, and related signalling apparatus, may be involved. OBJECTIVE: To investigate the link between changes in serum brain-derived neurotrophic factor (BDNF) and changes in human cognitive performance following flavonoid intake. METHODS: The relationship between serum levels of BDNF and age, gender, BMI, waist circumference, blood pressure and cognition at baseline, and following flavonoid intake, was investigated in two distinct randomised, controlled clinical trials. Trial 1 was conducted in men and women (aged 26–70 y; consuming an average of 3 portions of fruit and vegetables per day) and delivered high-flavonoid (>15 mg/100 g) or low-flavonoid (<5 mg/100 g) fruit and vegetables and increased intake by 2 portions every 6 weeks. The control arm was habitual diet over the same time frame. Trial 2 was conducted in an older males and female cohort (aged 62–75 y) intervening with a high-flavanol cocoa drink (494 mg total flavanols) and a low-flavanol cocoa drink (23 mg total flavanols) for 12 weeks. RESULTS: Serum BDNF levels increased linearly to the age of 65, after which BDNF levels were found to decrease markedly. All other physiological and anthropometric measurements proved to not be significantly associated with serum BDNF levels (p > 0.05), although higher levels in males compared to females almost achieved significance (p = 0.056). At baseline, higher serum BDNF levels were associated with significantly better global cognition scores, relative to individuals with lower serum levels. In addition, following intervention for 18 weeks, high-flavonoid, but not low-flavonoid, fruit and vegetable intake induced significant improvements in cognitive
Tian, Shuge; Liu, Wenxian; Liu, Feng; Zhang, Xuejia; Upur, Halmuart
Aims: Given the high-effectiveness and low-toxicity of abnormal savda munziq (ASMQ), its herbal formulation has long been used in traditional Uyghur medicine to treat complex diseases, such as cancer, diabetes, and cardiovascular diseases. Settings and Design: ASMQ decoction by reversed-phase high-performance liquid chromatography coupled with a diode array detector was successfully developed for the simultaneous quality assessment of gallic acid, protocatechuic acid, caffeic acid, rutin, rosmarinic acid, and luteolin. The six phenolic compounds were separated on an Agilent TC-C18 reversed-phase analytical column (4.6 × 250 mm, 5 μm) by gradient elution using 0.3% aqueous formic acid (v/v) and 0.3% methanol formic acid (v/v) at 1.0 mL/min. Materials and Methods: The plant material was separately ground and mixed at the following ratios (10): Cordia dichotoma (10.6), Anchusa italic (10.6), Euphorbia humifusa (4.9), Adiantum capillus-veneris (4.9), Ziziphus jujube (4.9), Glycyrrhiza uralensis (7.1), Foeniculum vulgare (4.9), Lavandula angustifolia (4.9), Dracocephalum moldavica L. (4.9), and Alhagi pseudoalhagi (42.3). Statistical Analysis Used: The precisions of all six compounds were <0.60%, and the average recoveries ranged from 99.39% to 104.85%. Highly significant linear correlations were found between component concentrations and specific chromatographic peak areas (R2 > 0.999). Results: The proposed method was successfully applied to determine the levels of six active components in ASMQ. Conclusions: Given the simplicity, precision, specificity, and sensitivity of the method, it can be utilized as a quality control approach to simultaneously determining the six phenolic compounds in AMSQ. PMID:25709227
Gordeuk, Victor R.; Diaz, Sharmin F.; Onojobi, Gladys O.; Kasvosve, Ishmael; Debebe, Zufan; Edossa, Amanuel; Pantin, Jeremy M.; Xiong, Shigang; Nekhai, Sergei; Nouraie, Mehdi; Tsukamoto, Hidekazu; Taylor, Robert E.
Background Alcohol consumption is associated with increased iron stores. In sub-Saharan Africa, high dietary ionic iron and the ferroportin Q248H allele have also been implicated in iron accumulation. We examined the associations of ferroportin Q248H, alcohol and dietary iron with serum ferritin, aspartate aminotransaminase (AST) and alanine aminotransaminase (ALT) concentrations in African Americans. Methods Inner-city African Americans (103 men, 40 women) were recruited from the community according to reported ingestion of >4 alcoholic drinks per day or <2 per week. Typical daily heme iron, non-heme iron and alcohol were estimated using University of Hawaii’s multiethnic dietary questionnaire. Based on dietary questionnaire estimates we established categories of < versus ≥56 g alcohol per day, equivalent to 4 alcoholic drinks per day assuming 14 g alcohol per drink. Results Among 143 participants, 77% drank <56 g alcohol/day and 23% ≥56 g/d as estimated by the questionnaire. The prevalence of ferroportin Q248H was 23.3% with alcohol >56 g/d versus 7.5% with lower amounts (P=0.012). Among subjects with no history of HIV disease, serum ferritin concentration had positive relationships with male gender (P=0.041), alcohol consumption (P=0.021) and ALT concentration (P=0.0001) but not with dietary iron intake or ferroportin Q248H. Serum AST and ALT concentrations had significant positive associations with male gender and hepatitis C seropositivity but not with alcohol or dietary iron intake or ferroportin Q248H. Conclusions Our findings suggest a higher prevalence of ferroportin Q248H with greater alcohol consumption, and this higher prevalence raises the possibility that the allele might ameliorate the toxicity of alcohol. Our results suggest that alcohol but not dietary iron contributes to higher body iron stores in African Americans. Studies with larger numbers of participants are needed to further clarify the relationship of ferroportin Q248H with the
Mistretta, V; Dubois, N; Denooz, R; Charlier, C
Azole antifungals are a group of fungistatic agents that can be administered orally or parenterally. The determination of the concentrations of these antifungals (miconazole, fluconazole, ketoconazole, posaconazole, voriconazole, itraconazole, and its major active metabolite, hydroxy-itraconazole) in serum can be useful to adapt the doses to pharmacological ranges because of large variability in the absorption and metabolism of the drugs, multiple drug interactions, but also potential resistance or toxicity. A method was developed and validated for the simultaneous determination of these drugs in serum utilizing ultra-high pressure liquid chromatography and diode array detection (UHPLC-DAD). After a simple and rapid liquid-liquid extraction, the pre-treated sample was analysed on an UHPLC-DAD system (Waters Corporation(®)). The chromatographic separation was carried out on an Acquity BEH C18 column (Waters Corporation) with a gradient mode of mobile phase composed of acetonitrile and aqueous ammonium bicarbonate 10·0 M pH10. The flow rate was 0·4 ml/min and the injection volume was 5 μl. The identification wavelength varied according to the drug from 210 to 260 nm. The method was validated by the total error method approach by using an analytical validation software (e•noval V3·0 Arlenda(®)). The seven azole antifungals were identified by retention time and specific UV spectra, over a 13-minute run time. All calibration curves showed good linearity (r(2)>0·99) in ranges considered clinically adequate. The assay was linear from 0·05 to 10 mg/l for voriconazole, posaconazole, itraconazole, hydroxy-itraconazole, and ketoconazole, from 0·3 to 10 mg/l for fluconazole, and from 0·1 to 10 mg/l for miconazole. The bias and imprecision values for intra- and inter-assays were lower than 10% and than 15%, respectively. In conclusion, a simple, sensitive, and selective UHPLC-DAD method was developed and validated to determine seven azole antifungal drugs in human
Ability of Serum Glial Fibrillary Acidic Protein, Ubiquitin C-Terminal Hydrolase-L1, and S100B To Differentiate Normal and Abnormal Head Computed Tomography Findings in Patients with Suspected Mild or Moderate Traumatic Brain Injury
Ayaz, Syed I.; Lewis, Lawrence M.; Unden, Johan; Chen, James Y.; Mika, Valerie H.; Saville, Ben; Tyndall, Joseph A.; Nash, Marshall; Buki, Andras; Barzo, Pal; Hack, Dallas; Tortella, Frank C.; Schmid, Kara; Hayes, Ronald L.; Vossough, Arastoo; Sweriduk, Stephen T.; Bazarian, Jeffrey J.
Abstract Head computed tomography (CT) imaging is still a commonly obtained diagnostic test for patients with minor head injury despite availability of clinical decision rules to guide imaging use and recommendations to reduce radiation exposure resulting from unnecessary imaging. This prospective multicenter observational study of 251 patients with suspected mild to moderate traumatic brain injury (TBI) evaluated three serum biomarkers' (glial fibrillary acidic protein [GFAP], ubiquitin C-terminal hydrolase-L1 [UCH-L1] and S100B measured within 6 h of injury) ability to differentiate CT negative and CT positive findings. Of the 251 patients, 60.2% were male and 225 (89.6%) had a presenting Glasgow Coma Scale score of 15. A positive head CT (intracranial injury) was found in 36 (14.3%). UCH-L1 was 100% sensitive and 39% specific at a cutoff value >40 pg/mL. To retain 100% sensitivity, GFAP was 0% specific (cutoff value 0 pg/mL) and S100B had a specificity of only 2% (cutoff value 30 pg/mL). All three biomarkers had similar values for areas under the receiver operator characteristic curve: 0.79 (95% confidence interval; 0.70–0.88) for GFAP, 0.80 (0.71–0.89) for UCH-L1, and 0.75 (0.65–0.85) for S100B. Neither GFAP nor UCH-L1 curve values differed significantly from S100B (p = 0.21 and p = 0.77, respectively). In our patient cohort, UCH-L1 outperformed GFAP and S100B when the goal was to reduce CT use without sacrificing sensitivity. UCH-L1 values <40 pg/mL could potentially have aided in eliminating 83 of the 215 negative CT scans. These results require replication in other studies before the test is used in actual clinical practice. PMID:26467555
Background Serum free light chain assay (SFLCA) and κ/λ ratio, and protein electrophoretic methods are used in the diagnosis and monitoring of monoclonal gammopathies. Methods Results for serum free light chains, serum and urine protein electrophoreses and immunofixation electrophoreses in 468 patients with a diagnosis of monoclonal gammopathy were compared. The results of the two methods were graded as concordant, non-concordant or discordant with the established diagnoses to assess the relative performance of the methods. Results of κ/λ ratio in samples with monoclonal protein detectable by electrophoretic methods were also analyzed. Results Protein electrophoreses results were concordant with the established diagnoses significantly more often than κ/λ ratio. The false negative rate for κ/λ ratio was higher than that for electrophoretic methods. κ/λ ratio was falsely negative in about 27% of the 1,860 samples with detectable monoclonal immunoglobulin. The false negative rate was higher in lesions with lambda chains (32%) than those with kappa chains (24%). The false negative rate for κ/λ ratio was over 55% in samples with monoclonal gammopathy of undetermined significance. Even at first encounter, the false negative rates for κ/λ ratios for monoclonal gammopathy of undetermined significance, smoldering myeloma and multiple myeloma were 66.98%, 23.08%, and 30.15%, respectively, with false negative rate for lambda chain lesions being higher. Conclusions Electrophoretic studies of serum and urine are superior to SFLCA and κ/λ ratio. Abnormal κ/λ ratio, per se, is not diagnostic of monoclonal gammopathy. A normal κ/λ ratio does not exclude monoclonal gammopathy. False negative rates for lesions with lambda chain are higher than those for lesions with kappa chains. Electrophoretic studies of urine are underutilized. Clinical usefulness and medical necessity of SFLCA and κ/λ ratio is of questionable value in routine clinical testing. PMID:27924175
Ma, Ying; Liu, Bei; Yuan, Bin; Wang, Jiuping; Yu, Haitao; Zhang, Yun; Xu, Zhuwei; Zhang, Yusi; Yi, Jing; Zhang, Chunmei; Zhou, Xingchun; Yang, Angang; Zhuang, Ran; Jin, Boquan
To investigate the role of vascular endothelial growth factor (VEGF) in the increased permeability of vascular endothelial cells after Hantaan virus (HTNV) infection in humans, the concentration of VEGF in serum from HTNV infected patients was quantified with sandwich ELISA. Generally, the level of serum VEGF in patients was elevated to 607.0 (542.2-671.9) pg/mL, which was dramatically higher compared with healthy controls (P < 0.001). There was a rapid increase of the serum VEGF level in all patients from the fever onset to oliguric stage, at which the serum creatinine reached the peak level of the disease, indicating that VEGF may be involved in the pathogenesis of renal hyper-permeability. Moreover, the serum VEGF level at convalescent stage was positively correlated with the degree of the disease severity. The sustained high level of serum VEGF at convalescence was observed in critical HFRS patients, suggesting that VEGF would probably contribute to the renal recovery after the virus clearance. Taken together, our results suggested that the VEGF would be involved in the pathogenesis of renal dysfunction at the oliguric stage after HTNV infection, but may function as a recovery factor during the convalescence to help the body self-repair of the renal injury.
Qu, Xiao; Pang, Zhaofei; Yi, Weiwei; Wang, Ying; Wang, Kai; Liu, Qi; Du, Jiajun
The association of the percentage composition of serum protein in patients undergoing lung resections for non-small cell lung cancer (NSCLC) with overall survival and recurrence-free survival has never been investigated. Patients were selected consecutively from the database of the Bio-Bank of Shandong Provincial Hospital. We retrospectively examined the impact of preoperative percentage composition of serum protein detected by serum protein electrophoresis on survival. Furthermore, we investigated the relationships between the potential prognostic biomarkers and clinicopathological factors. A total of 390 patients were evaluated. The higher percentage of α1-globulin in serum protein was significantly associated with histology type (p<0.001), worse tumor status (p<0.001) and higher pathological stage (p=0.004). The α1-globulin percentage composition was an independent prognostic factor for overall survival (hazard ratio 1.52, 95% CI 1.04-2.23, p=0.03). High percentage of α1-globulin in serum protein was also related to short recurrence survival (hazard ratio 1.56, 95% CI 1.14-2.13, p=0.005). Our results showed that the percentage of α1-globulin in serum protein may be an independent prognostic factor in NSCLC.
Pan, Shujuan; Tan, Yunlong; Yao, Shangwu; Zhao, Xiaoyan; Xiong, Jing
Increased levels of high-sensitivity C reactive protein (hsCRP) have been reported in schizophrenia, but to date, no study is designed to examine serum hsCRP in acutely agitated patients with schizophrenia, an extreme state that requires immediate diagnosis and medical treatment. Serum hsCRP levels were assessed in 32 clinically acutely agitated patients and 42 healthy control subjects matched for demographic properties. Further, serum hsCRP levels in acutely agitated patients were compared with control subjects and with the levels after the patients were treated with anti-psychiatric medications. Meanwhile, the influence of clinical subtypes, family history, and gender, as well as the levels of white blood cell (WBC) counts were also considered. In results, serum hsCRP levels were significantly higher in acutely agitated patients with schizophrenia than in healthy subjects. The elevation of serum hsCRP in patients was not affected by gender, family history (P>0.05), and clinical classification of schizophrenia (P>0.05). However, the elevation of hsCRP was suppressed by the medical treatment for schizophrenia with acute agitation (P<0.05). In addition, WBC counts, another inflammation-related indicator, were also increased significantly in acutely agitated patients compared with healthy subjects, consistent with the elevation of serum hsCRP. In conclusion, hsCRP is an important indicator of immune alterations in the pathogenesis of schizophrenia and has potential to be developed into a sensitive marker for the acute agitation in schizophrenia.
the whole study. 6. Once a week on Saturday nights, subjects had the choice to take foods prepared by the study personnel or eat out with restrictions...substituted for high saturated fat food items and therefore be a potential element in a healthy diet, it was felt to be valuable to investigate the...personnel required, and are more expensive. Two types of test meals reported in studies of these factors: 1) primarily single food meals containing a
Seckin, Berna; Ozaksit, Gulnur; Batioglu, Sertac; Ozel, Murat; Aydoğan, Munube; Senturk, Bahar
The aim of this study was to assess whether the extent of the change in high sensitivity C-reactive protein (hs-CRP) levels is related with in vitro fertilization (IVF) success. A total of 69 IVF cycles using long luteal GnRH agonist protocol at the IVF unit, were prospectively studied. The serum levels of hs-CRP were measured on the day of initiation of gonadotrophin stimulation and 7 days after embryo transfer. CRP ratio was defined as the levels of CRP on day 7 of transfer/day of initiation of ovarian stimulation. Clinical pregnancy rates were examined. The mean concentrations of hs-CRP were not significantly different on the first day of ovarian stimulation and on day 7 after embryo transfer among pregnant and non-pregnant women. There was a significant rise in hs-CRP levels at 7th day after embryo transfer as compared with the first day of gonadotrophin treatment in both groups (10.58 ± 11.35 versus 3.61 ± 2.86 mg/L for pregnant women and 9.14 ± 11.36 versus 3.24 ± 2.68 mg/L for non-pregnant women, p = 0.001). In addition, the mean CRP ratio was not different between the pregnant and non-pregnant groups. Our data show that serum hs-CRP levels increase during IVF treatment, but the extent of the rise in CRP levels is not a predictive marker of IVF success.
Kaler, Maryann; Cuento, Rosemarie A.; Gordon, Elizabeth M.; Weir, Nargues A.; Sampson, Maureen; Fontana, Joseph R.; MacDonald, Sandra; Moss, Joel; Manganiello, Vincent; Remaley, Alan T.; Levine, Stewart J.
Rationale: Although lipids, apolipoproteins, and lipoprotein particles are important modulators of inflammation, varying relationships exist between these parameters and asthma. Objectives: To determine whether serum lipids and apolipoproteins correlate with the severity of airflow obstruction in subjects with atopy and asthma. Methods: Serum samples were obtained from 154 atopic and nonatopic subjects without asthma, and 159 subjects with atopy and asthma. Serum lipid and lipoprotein levels were quantified using standard diagnostic assays and nuclear magnetic resonance (NMR) spectroscopy. Airflow obstruction was assessed by FEV1% predicted. Measurements and Main Results: Serum lipid levels correlated with FEV1 only in the subjects with atopy and asthma. Serum levels of high-density lipoprotein (HDL) cholesterol and apolipoprotein A-I (apoA-I) were positively correlated with FEV1 in subjects with atopy and asthma, whereas a negative correlation existed between FEV1 and serum levels of triglycerides, low-density lipoprotein (LDL) cholesterol, apolipoprotein B (apoB), and the apoB/apoA-I ratio. NMR spectroscopy identified a positive correlation between FEV1 and HDLNMR particle size, as well as the concentrations of large HDLNMR particles and total IDLNMR (intermediate-density lipoprotein) particles in subjects with atopy and asthma. In contrast, LDLNMR particle size and concentrations of LDLNMR and VLDLNMR (very-low-density lipoprotein) particles were negatively correlated with FEV1 in subjects with atopy and asthma. Conclusions: In subjects with atopy and asthma, serum levels of apoA-I and large HDLNMR particles are positively correlated with FEV1, whereas serum triglycerides, LDL cholesterol, and apoB are associated with more severe airflow obstruction. These results may facilitate future studies to assess whether apoA-I and large HDLNMR particles can reduce airflow obstruction and disease severity in asthma. PMID:25692941
Background Dipeptidyl peptidase 4/CD26 (DPP-4) is a widely expressed cell surface serine protease. DPP-4 inhibitors, one of common anti-diabetic agents play a protective role in bone metabolism in recent studies. A soluble form of DPP-4 is found in serum, and exhibits DPP-4 enzymatic activity. However, the physiological role of serum or soluble DPP-4 and its relationship with DPP-4 enzymatic function remain poorly understood. The aims of current study were to determine the association between serum DPP-4 activity and bone mineral density (BMD) in postmenopausal women. Methods We recruited data and serum samples from 124 consecutive healthy postmenopausal women aged >50 years. We divided study subjects into obese (body mass index [BMI] ≥25 kg/m2) and non-obese (BMI <25 kg/m2) postmenopausal women and examined the correlation between serum DPP-4 activity and clinical variables in each groups. Results A total of 124 postmenopausal women was enrolled, with a mean age of 59.9±7.1 years. The mean BMI of the study patients was 24.4±2.8 kg/m2. Regarding bone turnover markers, serum DPP-4 activity was positively correlated with serum calcium concentrations, intact parathyroid hormone, and serum C-telopeptide levels in all of the study subjects. However, there was no association between serum DPP-4 activity and BMD in the spine or femoral neck in all of the study subjects. Serum DPP-4 activity was negatively correlated (R=−0.288, P=0.038) with BMD of the spine in obese postmenopausal women. Conclusion This study demonstrated for the first time that serum soluble DPP-4 activity was negatively correlated with BMD in obese postmenopausal women. PMID:26676330
Keutzer, Carolin S.
Describes the use of the board game, Jeopardy, in a college level abnormal psychology course. Finds increased student interaction and improved application of information. Reports generally favorable student evaluation of the technique. (CFR)
MacKelvie, K; Taunton, J; McKay, H; Khan, K
Objectives—To identify physical activity that is beneficial for the maintenance of bone strength with increasing age by examining the relation between bone mineral density (BMD) and chronic endurance training in men. BMD at the proximal femur, its subregions, and the lumbar spine, and serum testosterone were compared between two groups of long distance runners with more than 20 years of training experience and non-athletic controls. Methods—Runners (n = 12) were divided into (a) high volume runners (n = 7), running 64–80 km a week, and (b) very high volume runners (n = 5), running more than 95 km a week, and compared with non-athletic male controls, exercising in non-endurance oriented activities two to four times a week. BMD (g/cm2) at the total proximal femur, femoral neck, trochanteric region, and lumbar spine was measured by dual energy x ray absorptiometry. Total testosterone (nmol/l) and free testosterone (pmol/l) in serum were measured by radioimmunoassay from single fasting blood samples. Results—Height, weight, and age (range = 40–55 years) were not significantly different between groups. The high volume runners had significantly higher BMD at the total proximal femur (1.09 (0.17) v 0.94 (0.056)), femoral neck (0.91 (0.16) v 0.78 (0.071)), and trochanteric region (0.85 (0.14) v 0.73 (0.053)) than controls (p<0.05). The differences in BMD for the proximal femur between the very high volume runners and the other two groups were not significant. There was no difference in lumbar spine BMD, total testosterone, or free testosterone between groups. However, there was a significant negative correlation between total testosterone (r = -0.73, p<0.01) and free testosterone (r = -0.79, p<0.005) and running volume in the distance runners. Conclusions—Long term distance running with training volumes less than 80 km a week had a positive effect on BMD of the proximal femur. With running volumes greater than 64 km a week, training was inversely related to
Christiansen, Anders; Kringelum, Jens V.; Hansen, Christian S.; Bøgh, Katrine L.; Sullivan, Eric; Patel, Jigar; Rigby, Neil M.; Eiwegger, Thomas; Szépfalusi, Zsolt; Masi, Federico de; Nielsen, Morten; Lund, Ole; Dufva, Martin
Phage display is a prominent screening technique with a multitude of applications including therapeutic antibody development and mapping of antigen epitopes. In this study, phages were selected based on their interaction with patient serum and exhaustively characterised by high-throughput sequencing. A bioinformatics approach was developed in order to identify peptide motifs of interest based on clustering and contrasting to control samples. Comparison of patient and control samples confirmed a major issue in phage display, namely the selection of unspecific peptides. The potential of the bioinformatic approach was demonstrated by identifying epitopes of a prominent peanut allergen, Ara h 1, in sera from patients with severe peanut allergy. The identified epitopes were confirmed by high-density peptide micro-arrays. The present study demonstrates that high-throughput sequencing can empower phage display by (i) enabling the analysis of complex biological samples, (ii) circumventing the traditional laborious picking and functional testing of individual phage clones and (iii) reducing the number of selection rounds. PMID:26246327
Salinas Carmona, M C; Flores de Castañeda, M S; Garza Elizondo, M A; Pérez Rivera, L I
One hundred forty human sera distributed in 2 groups were analyzed. In group I, 50 serum samples from healthy individuals that did not belong to the high-risk acquired immune deficiency syndrome (AIDS) population were included. In group II, there were 90 individuals, most of whom were apparently healthy but were at high risk of getting AIDS through their life styles or by transfusion. Of the 90 persons, 5 had a clinical picture of AIDS. All sera were analyzed by the enzyme - linked immunosorbent assay (ELISA) for the anti VIH antibodies. The positive cases were confirmed by the Western blot assay. In all samples the presence of the human immune deficiency virus antigens was sought. The results showed that the 50 healthy individuals (control group) were negative for both HIV antigens and antibodies. Of the 90 sera for the high-risk group, 50 were negative for antibodies, and 2 of them (4%) were positive for HIV antigens. Forty sera were positive for anti HIV antibody and among them, 5 patients were diagnosed as AIDS, and showed positive for antigen and antibody. The other 35 patients were all positive for HIV antibody and in 8 of them HIV antigen was also present.
Binding of L-tryptophan, diazepam, salicylate and Phenol Red to defatted human serum albumin was studied by ultrafiltration at pH 7.0. All ligands bind to one high-affinity binding site with association constants of the order of 10(4)-10(5)M-1. The number of secondary binding sites was found to vary from zero to five, with association constants about 10(3)M-1. Competitive binding studies with different pairs of the ligands were performed. Binding of both ligands was determined simultaneously. L-Tryptophan and diazepam were found to compete for a common high-affinity binding site on albumin. The following combinations of ligands do not bind competitively to albumin: L-tryptophan-Phenol Red, L-tryptophan-salicylate and Phenol Red-salicylate. On the other hand, high-affinity bindings of the three ligands do not take place independently but in such a way that binding of one of the ligands results in a decrease in binding of the other ligands. The decreases in binding are reciprocal and can be accounted for by introducing a coupling constant. The magnitude of the constant is dependent on the ligands being bound. In the present study, the mutual decrease in binding was more pronounced with L-tryptophan-salicylate and Phenol Red-salicylate than with L-tryptophan-Phenol Red. PMID:6847607
Background Resistin, secreted from adipocytes, causes insulin resistance in mice. The relationship between resistin and coronary artery disease is highly controversial, and the information regarding resistin and ischemic stroke is limited. In the present study, the association between serum resistin concentration and cardiovascular disease (CVD) was investigated in a general Japanese population. Methods A total of 3,201 community-dwelling individuals aged 40 years or older (1,382 men and 1,819 women) were divided into quintiles of serum resistin, and the association between resistin and CVD was examined cross-sectionally. The combined effect of either diabetes or hypertension and high serum resistin was also assessed. Serum resistin was measured using ELISA. Results Compared to those without CVD, age- and sex-adjusted mean serum resistin concentrations were greater in subjects with CVD (p = 0.002) or ischemic stroke (p < 0.001), especially in those with lacunar and atherothrombotic infarction, but not elevated in subjects with hemorrhagic stroke or coronary heart disease. When analyzed by quintile of serum resistin concentration, the age- and sex-adjusted odds ratio (OR) for having CVD and ischemic stroke increased with quintile of serum resistin (p for trends, 0.02 for CVD, < 0.001 for ischemic stroke), while such associations were not observed for hemorrhagic stroke or coronary heart disease. Compared to the first quintile, the age- and sex-adjusted OR of ischemic stroke was greater in the third (OR = 3.54; 95% confidence interval [CI], 1.17-10.67; p = 0.02), fourth (OR = 4.48; 95% CI, 1.53-13.09; p = 0.006), and fifth quintiles (OR = 4.70; 95% CI, 1.62-13.61; p = 0.004). These associations remained substantially unchanged even after adjustment for other confounding factors including high-sensitivity C-reactive protein. In the stratified analysis, the combination of high serum resistin and either diabetes or hypertension markedly increased the risk of ischemic
da Rocha, Guilherme L; Crisp, Alex H; de Oliveira, Maria R M; da Silva, Carlos A; Silva, Jadson O; Duarte, Ana C G O; Sene-Fiorese, Marcela; Verlengia, Rozangela
This study aimed to investigate the effects of interval and continuous training on the body mass gain and adiposity levels of rats fed a high-fat diet. Forty-eight male Sprague-Dawley rats were randomly divided into two groups, standard diet and high-fat diet, and received their respective diets for a period of four weeks without exercise stimuli. After this period, the animals were randomly divided into six groups (n = 8): control standard diet (CS), control high-fat diet (CH), continuous training standard diet (CTS), continuous training high-fat diet (CTH), interval training standard diet (ITS), and interval training high-fat diet (ITH). The interval and continuous training consisted of a swimming exercise performed over eight weeks. CH rats had greater body mass gain, sum of adipose tissues mass, and lower serum high density lipoprotein values than CS. The trained groups showed lower values of feed intake, caloric intake, body mass gain, and adiposity levels compared with the CH group. No significant differences were observed between the trained groups (CTS versus ITS and CTH versus ITH) on body mass gains and adiposity levels. In conclusion, both training methodologies were shown to be effective in controlling body mass gain and adiposity levels in high-fat diet fed rats.
da Rocha, Guilherme L.; Crisp, Alex H.; de Oliveira, Maria R. M.; da Silva, Carlos A.; Silva, Jadson O.; Duarte, Ana C. G. O.; Sene-Fiorese, Marcela; Verlengia, Rozangela
This study aimed to investigate the effects of interval and continuous training on the body mass gain and adiposity levels of rats fed a high-fat diet. Forty-eight male Sprague-Dawley rats were randomly divided into two groups, standard diet and high-fat diet, and received their respective diets for a period of four weeks without exercise stimuli. After this period, the animals were randomly divided into six groups (n = 8): control standard diet (CS), control high-fat diet (CH), continuous training standard diet (CTS), continuous training high-fat diet (CTH), interval training standard diet (ITS), and interval training high-fat diet (ITH). The interval and continuous training consisted of a swimming exercise performed over eight weeks. CH rats had greater body mass gain, sum of adipose tissues mass, and lower serum high density lipoprotein values than CS. The trained groups showed lower values of feed intake, caloric intake, body mass gain, and adiposity levels compared with the CH group. No significant differences were observed between the trained groups (CTS versus ITS and CTH versus ITH) on body mass gains and adiposity levels. In conclusion, both training methodologies were shown to be effective in controlling body mass gain and adiposity levels in high-fat diet fed rats. PMID:26904718
Steckling, F M; Farinha, J B; Santos, D L D; Bresciani, G; Mortari, J A; Stefanello, S T; Courtes, A A; Duarte, T; Duarte, M M M F; Moresco, R N; Cardoso, M S; Soares, F A A
Objectives: This study investigate the effects of a high intensity interval training (HIIT) and 2 weeks of detraining in functional and body composition parameters, lipoproteins, glucose metabolismand inflammation markers in postmenopausal women with metabolic syndrome (MS). Design: 17 untrained women with MS underwent a HIIT program for 12 weeks. Methods: The training was performed in treadmills, 3 days per week, with intensity ranging from 70-90% of the maximum heart rate (HRmax) and 2 weeks untrained (inactive). Functional and body composition parameters were evaluated before and after the training, while maximal oxygen uptake, lipoprotein and inflammation markers were analyzed before, after training and also in detraining. Results: The HITT program resulted in changesparameters as glucose, HbA1cand NOx after training. In addition, a reduction in pro-inflammatory interleukins and an increase in IL-10 after the HIIT program were found. However, an increase in plasma levels of lipoprotein was found and body composition parameters remain unaltered.Besides, only 2 weeks of detraining are able to revert the effects on inflammatory parameters afforded by the HIIT program. Conclusions: The HIIT program used here positively affected inflammatory profile and other parameters, as glucose, HbA1cand NOx, on postmenopausal women with MS. Moreover, 2 weeks of detraining can reverse the beneficial effects of HIIT program. Our results point out the necessity to aply acontinuous HITT program, in order maintain the benefits detected, to post menopausal women with MS.
Battles, August H.; Knapka, Joseph T.; Stevens, Bruce R.; Lewis, Laura; Lang, Marie T.; Gruendel, Douglas J.
Rats were fed an irradiated high-moisture diet (KSC-25) with or without access to a water bottle. Physiologic values were compared between these two groups and a group of rats fed a purified diet. Hematologic and serum biochemical values, urine specific gravity, and intestinal enzyme activities were determined from samples collected from the three groups of rats. Sprague Dawley rats (n=32) fed the irradiated high-moisture diet with or without a water bottle were the test animals. Rats (n=16) fed an irradiated purified diet and water provided via a water bottle were the control group. The purified diet formulation, modified AIN-76A, is a commonly used purified diet for laboratory rodents. All rats remained alert and healthy throughout the study. A comparison of the physiologic values of rats in this study with reported normal values indicated that all of the rats in the study were in good health. Significant differences (P less than 0.05) of the physiologic values from each rat group are reported.
Ajaxon, Ingrid; Öhman, Caroline; Persson, Cecilia
Bone loss and fractures may call for the use of bone substituting materials, such as calcium phosphate cements (CPCs). CPCs can be degradable, and, to determine their limitations in terms of applications, their mechanical as well as chemical properties need to be evaluated over longer periods of time, under physiological conditions. However, there is lack of data on how the in vitro degradation affects high-strength brushite CPCs over longer periods of time, that is, longer than it takes for a bone fracture to heal. This study aimed at evaluating the long-term in vitro degradation properties of a high-strength brushite CPC in three different solutions: water, phosphate buffered saline, and a serum solution. Microcomputed tomography was used to evaluate the degradation nondestructively, complemented with gravimetric analysis. The compressive strength, chemical composition, and microstructure were also evaluated. Major changes from 10 weeks onwards were seen, in terms of formation of a porous outer layer of octacalcium phosphate on the specimens with a concomitant change in phase composition, increased porosity, decrease in object volume, and mechanical properties. This study illustrates the importance of long-term evaluation of similar cement compositions to be able to predict the material's physical changes over a relevant time frame. PMID:26587540
Ajaxon, Ingrid; Öhman, Caroline; Persson, Cecilia
Bone loss and fractures may call for the use of bone substituting materials, such as calcium phosphate cements (CPCs). CPCs can be degradable, and, to determine their limitations in terms of applications, their mechanical as well as chemical properties need to be evaluated over longer periods of time, under physiological conditions. However, there is lack of data on how the in vitro degradation affects high-strength brushite CPCs over longer periods of time, that is, longer than it takes for a bone fracture to heal. This study aimed at evaluating the long-term in vitro degradation properties of a high-strength brushite CPC in three different solutions: water, phosphate buffered saline, and a serum solution. Microcomputed tomography was used to evaluate the degradation nondestructively, complemented with gravimetric analysis. The compressive strength, chemical composition, and microstructure were also evaluated. Major changes from 10 weeks onwards were seen, in terms of formation of a porous outer layer of octacalcium phosphate on the specimens with a concomitant change in phase composition, increased porosity, decrease in object volume, and mechanical properties. This study illustrates the importance of long-term evaluation of similar cement compositions to be able to predict the material's physical changes over a relevant time frame.
Yatsuyanagi, Eiji; Sato, Kazuhiro; Sato, Keisuke
We investigated sialylated carbohydrate antigen( Krebs von den Lungen-6:KL-6) expression in lung tissue and correlation between the expression and serum KL-6 level in the patients with primary lung cancer. Thirty-four primary lung cancer patients with high serum KL-6 levels( >500 U/ml) were evaluated. A coexistence of interstitial pneumonia (IP) was histopathologically evaluated and an immunohistochemical staining using a mouse anti-human KL-6 antibody (mKL-6) was performed. A multiple regression analysis was also caluculated using a serum KL-6 level as a target variable and the histopathological and immunohistochemical factors (KL-6 expression in cancer tissue and IP tissue, coexistence of IP, tumor size, pathological staging) as descriptive variables. Twenty-two patients (64.7%) were histopathologically concomitant with IP. Cancer tissues were positively stained by mKL-6 in 32 patients (94.1%). Among them, 20 patients were concomitant with IP and all of their cancer tissues were more strongly stained by mKL-6 than IP tissues. Although considerable high rate of lung cancer patients might express the KL-6 in the cancer tissue, we could not reveal the relationship between the expression and serum KL-6 level by a multiple regression analysis. For revealing the mechanism of elevating serum KL-6 level in the patients with lung cancer, more detailed and powerful study is thought to be needed.
Sala-Llonch, Roser; Bosch, Beatriz; Arenaza-Urquijo, Eider M; Rami, Lorena; Bargalló, Núria; Junqué, Carme; Molinuevo, José-Luis; Bartrés-Faz, David
We conducted an integrated multi-modal magnetic resonance imaging (MRI) study based on functional MRI (fMRI) data during a complex but cognitively preserved visual task in 15 amnestic mild cognitive impairment (a-MCI) patients and 15 Healthy Elders (HE). Independent Component Analysis of fMRI data identified a functional network containing an Activation Task Related Pattern (ATRP), including regions of the dorsal and ventral visual stream, and a Deactivation Task Related Pattern network (DTRP), with high spatial correspondence with the default-mode network (DMN). Gray matter (GM) volumes of the underlying ATRP and DTRP cortical areas were measured, and probabilistic tractography (based on diffusion MRI) identified fiber pathways within each functional network. For the ATRP network, a-MCI patients exhibited increased fMRI responses in inferior-ventral visual areas, possibly reflecting compensatory activations for more compromised dorsal regions. However, no significant GM or white matter group differences were observed within the ATRP network. For the DTRP/DMN, a-MCI showed deactivation deficits and reduced GM volumes in the posterior cingulate/precuneus, excessive deactivations in the inferior parietal lobe, and less fiber tract integrity in the cingulate bundles. Task performance correlated with DTRP-functionality in the HE group. Besides allowing the identification of functional reorganizations in the cortical network directly processing the task-stimuli, these findings highlight the importance of conducting integrated multi-modal MRI studies in MCI based on spared cognitive domains in order to identify functional abnormalities in critical areas of the DMN and their precise anatomical substrates. These latter findings may reflect early neuroimaging biomarkers in dementia.
(1) Brief introduction to iron metabolism and the biochemistry of ferritin. (2) Early studies of circulating ferritin. (3) Methods for measuring serum ferritin concentrations -- immunoradiometric, radioimmuno- and enzyme-linked immuno assays based on liver or spleen ferritin -- an evaluation of these techniques. (4) Serum ferritin concentrations in normal subjects -- definition of normality -- relationship between storage iron and serum ferritin concentrations -- changes during development from birth to old age -- iron deficiency -- variability of serum ferritin concentration -- evaluation of use of ferritin assay for assessment of storage iron levels. (5) Serum ferritin concentrations in disease -- hemochromatosis -- secondary iron overload -- liver damage -- infection and chronic disease -- cancer. (6) Assay of serum ferritin with antibodies to ferritins other than liver or spleen -- ferritinemia and cancer. (7) Properties of serum ferritin -- molecular weight -- iron content -- isoelectric focusing patterns -- carbohydrate content -- immunological properties. (8) Physiology of circulating ferritin -- release of ferritin from tissues -- origin of circulating ferritin -- clearance from the plasma -- iron and protein turnover. (9) Summary -- factors influencing serum ferritin concentrations and clinical use of ferritin estimations.
Li, Peng; Yang, Cong-Qiao; Jin, Jun; Wang, Ying; Liu, Wei-Zhi; Ding, Wen-Wei
The levels of hexabromocyclododecane (HBCD) in human serum from the HBCD production source region were detected by UPLC-ESI-MS/MS. The concentrations (lipid weight) of ∑ HBCD in 80 serum samples ranged from not detectable to 2702.5 ng · g(-1). The mean and median values were 104.9 ng · g(-1) and 5.9 ng · g(-1), respectively. The most abundant HBCD isomer in 42 samples was γ-HBCD, while α-HBCD was the most abundant isomer in the other 26 serum samples. There was no significant difference in ∑ HBCD concentration among different age and gender. In this study, the thyroid hormone abnormality rate in the 80 residents was up to 33%. The thyroid hormone abnormality rate of the residents whose serum HBCD was detected was significantly higher than those without HBCD in serum. Since the local residents were highly exposed to HBCD, the probability of thyroid abnormality might be significantly increased.
Ardawi, Mohammed-Salleh M; Rouzi, Abdulrahim A; Al-Sibiani, Sharifa A; Al-Senani, Nawal S; Qari, Mohammed H; Mousa, Shaker A
Sclerostin regulates bone formation by inhibiting Wnt pathway signaling. Low circulating sclerostin levels cause high bone mass. We hypothesized that postmenopausal women with increased sclerostin levels have a greater risk for osteoporosis-related fractures. We examined the association between circulating sclerostin together with bone turnover markers and osteoporosis-related fracture risk in 707 postmenopausal women, in a population-based study with a mean follow-up period of 5.2 ± 1.3 years. Multivariate Cox proportional hazards regression models were used to analyze fracture risk, adjusted for age, body mass index, and other confounding risk factors. High sclerostin levels were strongly associated with increased fracture risk. After adjustment for age and other confounders, the relative fracture risk was more than sevenfold among postmenopausal women for each 1-SD increment increase in sclerostin level. Women in the highest quartile of sclerostin levels had about a 15-fold increase in fracture risk. Results were similar when we compared sclerostin at the 1-year visit to an average of two to three annual measurements. Fracture risk attributable to sclerostin levels was 56.6% in the highest quartile. Only high levels of bone resorption markers (plasma cross-linked C-terminal telopeptide of type 1 collagen [p-CTx], urinary CTx [u-CTx], and urinary N-telopeptide of type 1 collagen [u-NTx]) were predictive of osteoporosis-related fractures but at much lower hazard ratio (HR) values than that of serum sclerostin. Associations between sclerostin levels and fracture risk were independent of bone mineral density and other confounding risk factors. High sclerostin levels are a strong and independent risk factor for osteoporosis-related fractures among postmenopausal women. © 2012 American Society for Bone and Mineral Research.
Gürsel, Feraye Esen; Ateş, Atila; Bilal, Tanay; Altiner, Ayşen
The aim of the study was to investigate the effect of Garcinia cambogia extract on serum calcium (Ca), phosphorus (P), magnesium (Mg), iron (Fe), zinc (Zn) and copper (Cu) concentrations in rats fed with the normal or the high-lipid and -cholesterol diet. Thirty 1-year-old female Sprague-Dawley rats (pathogen-free), weighing an average of 229 g, were randomly assigned to three experimental groups of ten animals each. Diets and tap water were given ad libitum for 75 days. Group 1 (control group) was fed with basal diet (2 % liquid vegetable oil, 0 % cholesterol), while the diets of groups 2 and 3 contained vegetable oil (2 % liquid vegetable oil and 5 % hydrogenated vegetable oil) and cholesterol (3 %) in high levels. 4,5 % G. cambogia extract containing 65 % HCA was added to the diet of group 3 as from day 45. Blood samples were withdrawn on days 0, 45 and 75. Serum mineral levels were analyzed using standard enzymatic colorimetric methods with a spectrophotometer. All significant differences were p<0.05. Serum Ca levels were not significantly different between all groups on days 45 and 75. Serum P level was significantly higher in the group fed with high-lipid diet and G. cambogia extract than in the control group on day 45. Serum Mg level was significantly higher in group 2 than in the control group on day 45. Serum Fe levels were significantly lower in the control group than in the other groups on days 45 and 75. Serum Zn level of the group fed with high-lipid diet and G. cambogia extract was significantly higher than in the control group on day 75. Serum Cu levels were significantly higher in group 2 than in the control group, and in group 3 than in group 2 on day 75. In conclusion, a diet containing the high fat amounts may lead to the increase in circular levels of some minerals due to the short-chain fatty acid production lowering the luminal pH which increases mineral solubility, or serving as a fuel for mucosal cells and stimulating cell proliferation in
Reimer, Raylene A; Grover, Gary J; Koetzner, Lee; Gahler, Roland J; Lyon, Michael R; Wood, Simon
Viscous soluble fibers have been shown to reduce risk factors associated with type 2 diabetes and cardiovascular disease. The novel functional fiber, PolyGlycopleX (PGX) (InovoBiologic Inc, Calgary, Alberta, Canada) displays greater viscosity than other currently identified soluble fibers. The objective of this study was to determine if PGX lowers serum and hepatic triglycerides (TGs) in a high-sucrose-fed rat model. In this rodent model, feeding a high-sucrose diet consistently increases serum TGs. We hypothesized that consumption of PGX would attenuate hypertriglyceridemia and reduce hepatic steatosis compared with cellulose in rats fed a high-sucrose background diet. Male Sprague-Dawley rats were fed diets containing 65% sucrose and supplemented with either 5% cellulose (control) or 5% PGX (wt/wt) for 43 weeks. At study termination, serum insulin and TGs, hepatic steatosis, and hepatocellular injury were assessed. Body weight increased over time in both groups, but weight gain was attenuated in rats fed PGX vs cellulose in weeks 2 through 22 (P < .05). Serum TGs did not differ from baseline for the first half of the study but consistently increased in the cellulose group thereafter. PolyGlycopleX significantly reduced serum TG to near-baseline levels. At study termination, rats fed PGX had significantly lower hepatic steatosis scores (measured by Sudan black staining) compared with rats fed cellulose. Hepatocellular injury scores did not differ between the groups. In conclusion, PGX reduced serum TG and lipid accumulation in the liver of sucrose-fed rats. Further examination of its potential as a fiber supplement aimed at lessening the burden of hepatic steatosis is warranted.
He, Jiang; Cui, Jianhua; Wang, Rui; Gao, Liang; Gao, Xiaokang; Yang, Liu; Zhang, Qiong; Cao, Jinjun; Yu, Wuzhong
This study investigated the effect of hypoxia at high altitude on the semen quality and the serum reproductive hormone levels in male adults. A total of 52 male soldiers were enrolled in this cohort study. They were exposed to hypoxia at high altitude (5380 m) for 12 months when undergoing a service. After exposure, they were followed up for 6 months. The samples of semen and peripheral blood were collected at 1 month before exposure (M0), 6 months of exposure (M6), 12 months of exposure (M12), and 6 months after exposure (M18). The semen quality was assessed with computer-assisted analysis system, and the serum levels of reproductive hormones, including prolactin (PRL), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone were analyzed by ELISA. Compared with those at M0, total sperm count, sperm density, motility, survival rate, and serum levels of LH, PRL and testosterone were significantly decreased, whereas the liquefaction time was significantly prolonged and serum FSH level was significantly increased at M6 (p<0.05). At M12, total sperm count and sperm density increased, whereas sperm motility, survival rate, and the liquefaction time further decreased. Sperm velocities, progression ratios, and lateral head displacements were also decreased. Serum FSH level decreased while serum LH, PRL, and testosterone levels increased. Compared with those at M6, the changes in these detected parameters of semen and hormone at M12 were significant (p<0.05). At M18, all these detected parameters except testosterone level returned to levels comparable to those before exposure. In conclusion, hypoxia at high altitude causes adverse effects on semen quality and reproductive hormones, and these effects are reversible.
Weinmann, A R; Oliveira, M S; Jorge, S M; Martins, A R
The simultaneous determination of retinol and tocopherol by isocratic HPLC in 100 microl serum from preterm newborns is described. Retinol (tR 2.02+/-0.04 min) and retinyl acetate were detected fluorometrically, and were baseline-resolved in 4 min. Tocopherol (tR 8.4+/-0.16 min) and tocopheryl acetate were detected by UV absorbance. Intra- and inter-assay RSD were: retinol, 5.6 and 8.1, and tocopherol, 3.6 and 6.7, respectively. This method is fast, selective and highly sensitive for retinol. It permits the measurement of serum concentrations of retinol and tocopherol with good accuracy and precision.
Gouveia, Telma Luciana Furtado; Vieira de Sousa, Paula Viviane; de Almeida, Sandro Soares; Nejm, Mariana Bocca; Vieira de Brito, Joíse Marques; Cysneiros, Roberta Monterazzo; de Brito, Marlon Vilela; Salu, Bruno Ramos; Oliva, Maria Luiza Vilela; Scorza, Fúlvio Alexandre; Naffah-Mazzacoratti, Maria da Graça
During the epileptogenic process, several events may occur, such as an important activation of the immune system in the central nervous system. The response to seizure activity results in an inflammation in the brain as well as in the periphery. Moreover, CRP and cytokines may be able to interact with numerous ligands in response to cardiac injury caused by sympathetic stimulation in ictal and postictal states. Based on this, we measured the serum levels of C-reactive protein (CRP) and cytokines during acute, silent, and chronic phases of rats submitted to the pilocarpine model of epilepsy. We have also analyzed the effect of a chronic treatment of these rats with omega-3 fatty acid in CRP and cytokine levels, during an epileptic focus generation. C-reactive protein and cytokines such as IL-1β, IL-6, and TNF-α presented high concentration in the blood of rats, even well after the occurrence of SE. We found reduced levels of CRP and all proinflammatory cytokines in the blood of animals with chronic seizures, treated with omega-3, when compared with those treated with vehicle solution. Taken together, our results strongly suggest that the omega-3 is an effective treatment to prevent SUDEP occurrence due to its capability to act as an anti-inflammatory compound, reducing the systemic inflammatory parameters altered by seizures.
Yang, Junwen; Chen, Shuijiao; Chen, Linlin; Ouyang, Miao; Li, Fujun
Abstract Rationale: Chronic diarrhea in adult patients due to various causes is very common in clinic, but patient suffering with mal-absorption due to immunoproliferative small intestinal disease was rarely reported in China. Patient concerns and Diagnoses: A 35-year-old female presented with more than three years history of chronic diarrhea, rickets, high serum value of immunoglobulin A protein, and anemia. Bone marrow aspiration suggested that the patient was in a sideropenic and megalobastic anemia stage. Duodenal and ileac biopsies revealed atrophy and blunting villi. The bowel lamina propria was infiltrated with slightly increased intraepithelial lymphocytes and mainly with diffuse plasma cells. The following enzyme labeling immunohistochemistry results were strongly positive to alpha-heavy-chain. Computed tomography manifested she had diffuse thickening of small intestine wall. At last a diagnosis of immunoproliferative small intestinal disease was made. Interventions and Outcomes: On the first month, the patient was treated with vitamin D supplements, calcium, magnesium, potassium, iron, folic acid, mecobalamin replacements and microflora probiotics. The patient frequency of water diarrhea alleviated slightly, but her weight loss, anxiety neurosis and other disorders were still severe. After taking with prednisone (40 mg per day, and gradually reduced to the lowest dose) for another month, the symptoms was gradually subsided. Lessons: The study shows that immunohistochemical staining for alpha-heavy chain proteins should be completed on small intestine biopsy specimens if the patient is suspected a diagnosis of immunoproliferative small intestinal disease. PMID:28151917
Schoknecht, P A; Ebner, S; Pond, W G; Zhang, S; McWhinney, V; Wong, W W; Klein, P D; Dudley, M; Goddard-Finegold, J; Mersmann, H J
We hypothesized that, in pigs selected for low (L) or high (H) serum cholesterol for four generations, neonatal endogenous cholesterol synthesis would be sufficient to meet requirements for brain and body growth. In Experiment 1, eight 16-wk-old L pigs received a diet with or without 200 mg cholesterol/100 g diet for 35 d. Supplemented pigs grew approximately 25% faster and had a significantly greater concentration of free cholesterol in the cerebrum. In Experiment 2, 16 H and 16 L newborn pigs were fed a milk replacer with or without 200 mg cholesterol/100 g diet for 28 d. Pigs fed cholesterol had greater average daily gain (P < or = 0.09), significantly reduced liver 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity, and significantly increased cerebral cholesterol content than pigs not fed cholesterol. One of three indices of exploratory behavior was significantly greater in the L pigs that received cholesterol compared with L pigs that did not receive cholesterol. These data suggest that these neonatal pigs are unable to produce sufficient cholesterol to meet requirements for normal growth and brain development and are dependent on dietary cholesterol in milk.
Desiderio, C; Rudaz, S; Raggi, M A; Fanali, S
A capillary electrophoresis method was optimized for the stereoselective analysis of the antidepressant drug fluoxetine and its main demethylated metabolite norfluoxetine using a cyclodextrin-modified sodium phosphate buffer at pH 2.5. The combination of a neutral and a negatively charged cyclodextrin, dimethylated-beta- and phosphated-gamma-respectively, provided the baseline enantiomeric separation of the two compounds. The very low concentrations of chiral selectors employed together with the use of a high sensitivity detection cell of special design (zeta-shaped) in a diode array UV detector allowed us to reach a limit of detection of 0.005 and 0.01 microg/mL for fluoxetine and norfluoxetine, respectively. Analysis of fluoxetine and norfluoxetine standard mixtures showed a reproducibility of migration times and peak area and linearity in the concentration range of 0.1-2.0 microg/mL. The optimized method was applied to the analysis of clinical serum and plasma samples of patients under depression therapy. In all the analyzed samples the enantiomeric forms of fluoxetine and norfluoxetine were easily identified. The fluoxetine and metabolite enantiomeric ratio confirmed the stereoselectivity of the metabolic process of the fluoxetine drug in accordance with the literature data.
Liu, Pengpeng; Zhang, Changchang; Liu, Xiang; Cui, Ping
An economic and green approach of manufacturing carbon quantum dots (CQDs) with a high quantum yield (denoted with HQY-CQDs) and the application in labeling bovine serum albumin (BSA) were described in detail in this work. Firstly, the cheap resources of citric acid and glycine were pyrolysed in drying oven for preparing the CQDs. Then the product was immersed in tetrahydrofuran for 8 h. HQY-CQDs were obtained by removing tetrahydrofuran from the supernate and were evaluated that they possessed a much higher quantum yield compared with that without dealing with tetrahydrofuran and a wonderful photo-bleaching resistance. Such HQY-CQDs could be functionalized by N-hydroxysuccinimide and successively combined with BSA covalently. Thus fluorescent labeling on BSA was realized. The HQY-CQDs were demonstrated with transmission electron microscopy and the chemical modification with N-hydroxysuccinimide was proved by infrared and X-ray photoelectron spectra. Labeling BSA with the HQY-CQDs was confirmed by gel electrophoresis and fluorescence imaging.
Stokes, Peter; O'Connor, Gavin
An LC-MS method for the high-accuracy determination of creatinine in serum has been developed and used to provide results for an international measurement evaluation programme (IMEP) and the Comité Consultatif pour la Quantité de Matière (CCQM) international inter-laboratory studies. An assessment of different sample preparation methods, including ion-exchange chromatography, solid-phase extraction, plasma ultrafiltration and ethanol protein precipitation, revealed that no bias or reduced precision was associated with the quicker less extensive clean-up methods, when using liquid chromatography-isotope dilution mass spectrometry (LC-IDMS) for quantitation. A number of different calibration regimes were also investigated. External calibration was shown to provide adequate calibration for most routine analysis with a relative associated expanded uncertainty (k=2) of 6% at the 95% confidence level. The use of a non-isotopically labelled internal standard was shown to improve the relative expanded uncertainty (k=2) to 4%. However, the difference in retention time between the internal standard and the creatinine was such that a matrix interferent produced an observed bias of over 16%. The use of an isotopically labelled internal standard was shown to reduce any bias to less than 0.2% with an expanded uncertainty (k=2) of less than 0.3%. The developed method was then used, in a blind trial organised jointly by IMEP and CCQM, to determine the amount of creatinine in human serum. The method performed well against the established reference method of ion-exchange chromatography followed by derivatisation gas chromatography (GC)-IDMS. The observed difference between the values determined by LC-IDMS and the key comparison reference value (average of all the submitted results) was less than 0.3%. The biggest advantage of the described method is in the speed of analysis. With a chromatographic run time of less than 10 min and sample preparation consisting of a simple protein
Cass, R T; Villa, J S; Karr, D E; Schmidt, D E
A novel high-performance liquid chromatography tandem mass spectrometry (LC/MS/MS) method is described for the determination of vancomycin in serum and urine. After the addition of internal standard (teicoplanin), serum and urine samples were directly injected onto an HPLC system consisting of an extraction column and dual analytical columns. The columns are plumbed through two switching valves. A six-port valve directs extraction column effluent either to waste or to an analytical column. A ten-port valve simultaneously permits equilibration of one analytical column while the other is used for sample analysis. Thus, off-line analytical column equilibration time does not require mass spectrometer time, freeing the detector for increased sample throughput. The on-line sample extraction step takes 15 seconds followed by gradient chromatography taking another 90 seconds. Having minimal sample pretreatment the method is both simple and fast. This system has been used to successfully develop a validated positive-ion electrospray bioanalytical method for the quantitation of vancomycin. Detection of vancomycin was accurate and precise, with a limit of detection of 1 ng/mL in serum and urine. The calibration curves for vancomycin in rat, dog and primate were linear in a concentration range of 0.001-10 microg/mL for serum and urine. This method has been successfully applied to determine the concentration of vancomycin in rat, dog and primate serum and urine samples from pharmacokinetic and urinary excretion studies.
Hill, Jonathan R
In animals produced by assisted reproductive technologies, two abnormal phenotypes have been characterized. Large offspring syndrome (LOS) occurs in offspring derived from in vitro cultured embryos, and the abnormal clone phenotype includes placental and fetal changes. LOS is readily apparent in ruminants, where a large calf or lamb derived from in vitro embryo production or cloning may weigh up to twice the expected body weight. The incidence of LOS varies widely between species. When similar embryo culture conditions are applied to nonruminant species, LOS either is not as dramatic or may even be unapparent. Coculture with serum and somatic cells was identified in the 1990s as a risk factor for abnormal development of ruminant pregnancies. Animals cloned from somatic cells may display a combination of fetal and placental abnormalities that are manifested at different stages of pregnancy and postnatally. In highly interventional technologies, such as nuclear transfer (cloning), the incidence of abnormal offspring continues to be a limiting factor to broader application of the technique. This review details the breadth of phenotypes found in nonviable pregnancies, together with the phenotypes of animals that survive the transition to extrauterine life. The focus is on animals produced using in vitro embryo culture and nuclear transfer in comparison to naturally occurring phenotypes.
Yasuda, Makoto; Ota, Tatsuhiro; Morikawa, Atsushi; Mawatari, Ken-ichi; Fukuuchi, Tomoko; Yamaoka, Noriko; Kaneko, Kiyoko; Nakagomi, Kazuya
A simple and rapid method for the simultaneous determination of serum nicotine and cotinine using high-performance liquid chromatography (HPLC)-fluorometric detection with a postcolumn ultraviolet-photoirradiation system was developed. Analytes were extracted from alkalinized human serum via liquid-liquid extraction using chloroform. The organic phase was back-extracted with the acidified aqueous phase, and the analytes were directly injected into an ion-pair reversed-phase HPLC system. 6-Aminoquinoline was used as an internal standard. Nicotine, cotinine, and 6-aminoquinoline were separated within 14min. The extraction efficiency of nicotine and cotinine was greater than 91%. The linear range was 0.30-1000ng for nicotine and 0.06-1000ng for cotinine. In serum samples from smokers, the concentrations of nicotine and cotinine were 8-15ng/mL and 156-372ng/mL, respectively.
Sobolesky, Philip; Parry, Celeste; Boxall, Baylye; Wells, Randall; Venn-Watson, Stephanie; Janech, Michael G
Targeted approaches have been widely used to help explain physiological adaptations, but few studies have used non-targeted omics approaches to explore differences between diving marine mammals and terrestrial mammals. A rank comparison of undepleted serum proteins from common bottlenose dolphins (Tursiops truncatus) and pooled normal human serum led to the discovery of 11 proteins that appeared exclusive to dolphin serum. Compared to the comprehensive human plasma proteome, 5 of 11 serum proteins had a differential rank greater than 200. One of these proteins, Vanin-1, was quantified using parallel reaction monitoring in dolphins under human care and free-ranging dolphins. Dolphin serum Vanin-1 ranged between 31-106 μg/ml, which is 20-1000 times higher than concentrations reported for healthy humans. Serum Vanin-1 was also higher in dolphins under human care compared to free-ranging dolphins (64 ± 16 vs. 47 ± 12 μg/ml P < 0.05). Vanin-1 levels positively correlated with liver enzymes AST and ALT, and negatively correlated with white blood cell counts and fibrinogen in free-ranging dolphins. Major differences exist in the circulating blood proteome of the bottlenose dolphin compared to terrestrial mammals and exploration of these differences in bottlenose dolphins and other marine mammals may identify veiled protective strategies to counter physiological stress.
Sobolesky, Philip; Parry, Celeste; Boxall, Baylye; Wells, Randall; Venn-Watson, Stephanie; Janech, Michael G.
Targeted approaches have been widely used to help explain physiological adaptations, but few studies have used non-targeted omics approaches to explore differences between diving marine mammals and terrestrial mammals. A rank comparison of undepleted serum proteins from common bottlenose dolphins (Tursiops truncatus) and pooled normal human serum led to the discovery of 11 proteins that appeared exclusive to dolphin serum. Compared to the comprehensive human plasma proteome, 5 of 11 serum proteins had a differential rank greater than 200. One of these proteins, Vanin-1, was quantified using parallel reaction monitoring in dolphins under human care and free-ranging dolphins. Dolphin serum Vanin-1 ranged between 31–106 μg/ml, which is 20–1000 times higher than concentrations reported for healthy humans. Serum Vanin-1 was also higher in dolphins under human care compared to free-ranging dolphins (64 ± 16 vs. 47 ± 12 μg/ml P < 0.05). Vanin-1 levels positively correlated with liver enzymes AST and ALT, and negatively correlated with white blood cell counts and fibrinogen in free-ranging dolphins. Major differences exist in the circulating blood proteome of the bottlenose dolphin compared to terrestrial mammals and exploration of these differences in bottlenose dolphins and other marine mammals may identify veiled protective strategies to counter physiological stress. PMID:27667588
Birnbaum, Julius; Duncan, Trisha; Owoyemi, Kristie; Wang, Kenneth C.; Carrino, John; Chhabra, Avneesh
Abstract The diagnosis and treatment of patients with Sjögren syndrome (SS) with neuropathic pain pose several challenges. Patients with SS may experience unorthodox patterns of burning pain not conforming to a traditional “stocking-and-glove” distribution, which can affect the face, torso, and proximal extremities. This distribution of neuropathic pain may reflect mechanisms targeting the proximal-most element of the peripheral nervous system—the dorsal root ganglia (DRG). Skin biopsy can diagnose such a small-fiber neuropathy and is a surrogate marker of DRG neuronal cell loss. However, SS patients have been reported who have similar patterns of proximal neuropathic pain, despite having normal skin biopsy studies. In such cases, DRGs may be targeted by mechanisms not associated with neuronal cell loss. Therefore, alternative approaches are warranted to help characterize abnormal DRGs in SS patients with proximal neuropathic pain. We performed a systematic review of the literature to define the frequency and spectrum of SS peripheral neuropathies, and to better understand the attribution of SS neuropathic pain to peripheral neuropathies. We found that the frequency of SS neuropathic pain exceeded the prevalence of peripheral neuropathies, and that painful peripheral neuropathies occurred less frequently than neuropathies not always associated with pain. We developed a novel magnetic resonance neurography (MRN) protocol to evaluate DRG abnormalities. Ten SS patients with proximal neuropathic pain were evaluated by this MRN protocol, as well as by punch skin biopsies evaluating for intraepidermal nerve fiber density (IENFD) of unmyelinated nerves. Five patients had radiographic evidence of DRG abnormalities. Patients with MRN DRG abnormalities had increased IENFD of unmyelinated nerves compared to patients without MRN DRG abnormalities (30.2 [interquartile range, 4.4] fibers/mm vs. 11.0 [4.1] fibers/mm, respectively; p = 0.03). Two of these 5 SS patients
Hasegawa, Ayumi; Mochida, Keiji; Inoue, Hiroki; Noda, Yoshihiro; Endo, Tamao; Watanabe, Gen; Ogura, Atsuo
Producing many mature oocytes is of great importance for assisted reproductive technologies. In mice, superovulation by consecutive injections of equine chorionic gonadotropin (eCG) and human chorionic gonadotropin (hCG) has been the gold standard for oocyte collection. However, the yield of mature oocytes by this regimen can fluctuate according to the stage of the estrous cycle, strain, and age. Therefore, our objective was to develop a high-yield superovulation protocol to collect higher numbers of oocytes from adult female mice of different strains and ages. First, we aimed to synchronize the estrous cycle using C57BL/6 (B6) female mice. Most (93%) were synchronized to metestrus after two daily injections of progesterone. Second, we found that with the injection of anti-inhibin serum (AIS) instead of eCG, the mean number of ovulated oocytes almost doubled (21 vs. 41 per mouse). Third, by combining estrous cycle synchronization with two AIS injections, we obtained 62 oocytes per mouse, about three times that with the eCG-hCG protocol. Importantly, this approach increased the proportion of mice that ovulated >25 oocytes from about 40% (eCG-hCG) to 90%. The same protocol was also effective in other inbred (BALB/cA), outbred (ICR), and hybrid (B6D2F1) strains. In addition, B6 female mice aged over 1 yr ovulated 1.8-fold more oocytes by this protocol. Thus, estrous cycle synchronization followed by AIS-hCG yielded a broadly applicable, highly efficient superovulation. This protocol should promote the effective use of invaluable female mouse strains and decrease the numbers of animals euthanized.
Nemecek, Julie; Nag, Nabanita; Carlson, Christina M.; Schneider, Jay R.; Heisey, Dennis M.; Johnson, Christopher J.; Asher, David M.; Gregori, Luisa
Rapid antemortem tests to detect individuals with transmissible spongiform encephalopathies (TSE) would contribute to public health. We investigated a technique known as protein misfolding cyclic amplification (PMCA) to amplify abnormal prion protein (PrPTSE) from highly diluted variant Creutzfeldt-Jakob disease (vCJD)-infected human and macaque brain homogenates, seeking to improve the rapid detection of PrPTSE in tissues and blood. Macaque vCJD PrPTSE did not amplify using normal macaque brain homogenate as substrate (intraspecies PMCA). Next, we tested interspecies PMCA with normal brain homogenate of the southern red-backed vole (RBV), a close relative of the bank vole, seeded with macaque vCJD PrPTSE. The RBV has a natural polymorphism at residue 170 of the PrP-encoding gene (N/N, S/S, and S/N). We investigated the effect of this polymorphism on amplification of human and macaque vCJD PrPTSE. Meadow vole brain (170N/N PrP genotype) was also included in the panel of substrates tested. Both humans and macaques have the same 170S/S PrP genotype. Macaque PrPTSE was best amplified with RBV 170S/S brain, although 170N/N and 170S/N were also competent substrates, while meadow vole brain was a poor substrate. In contrast, human PrPTSE demonstrated a striking narrow selectivity for PMCA substrate and was successfully amplified only with RBV 170S/S brain. These observations suggest that macaque PrPTSE was more permissive than human PrPTSE in selecting the competent RBV substrate. RBV 170S/S brain was used to assess the sensitivity of PMCA with PrPTSE from brains of humans and macaques with vCJD. PrPTSE signals were reproducibly detected by Western blot in dilutions through 10-12 of vCJD-infected 10% brain homogenates. This is the first report showing PrPTSE from vCJD-infected human and macaque brains efficiently amplified with RBV brain as the substrate. Based on our estimates, PMCA showed a sensitivity that might be sufficient to detect PrPTSE in v
Nemecek, Julie; Nag, Nabanita; Carlson, Christina M.; Schneider, Jay R.; Heisey, Dennis M.; Johnson, Christopher J.; Asher, David M.; Gregori, Luisa
Rapid antemortem tests to detect individuals with transmissible spongiform encephalopathies (TSE) would contribute to public health. We investigated a technique known as protein misfolding cyclic amplification (PMCA) to amplify abnormal prion protein (PrPTSE) from highly diluted variant Creutzfeldt-Jakob disease (vCJD)-infected human and macaque brain homogenates, seeking to improve the rapid detection of PrPTSE in tissues and blood. Macaque vCJD PrPTSE did not amplify using normal macaque brain homogenate as substrate (intraspecies PMCA). Next, we tested interspecies PMCA with normal brain homogenate of the southern red-backed vole (RBV), a close relative of the bank vole, seeded with macaque vCJD PrPTSE. The RBV has a natural polymorphism at residue 170 of the PrP-encoding gene (N/N, S/S, and S/N). We investigated the effect of this polymorphism on amplification of human and macaque vCJD PrPTSE. Meadow vole brain (170N/N PrP genotype) was also included in the panel of substrates tested. Both humans and macaques have the same 170S/S PrP genotype. Macaque PrPTSE was best amplified with RBV 170S/S brain, although 170N/N and 170S/N were also competent substrates, while meadow vole brain was a poor substrate. In contrast, human PrPTSE demonstrated a striking narrow selectivity for PMCA substrate and was successfully amplified only with RBV 170S/S brain. These observations suggest that macaque PrPTSE was more permissive than human PrPTSE in selecting the competent RBV substrate. RBV 170S/S brain was used to assess the sensitivity of PMCA with PrPTSE from brains of humans and macaques with vCJD. PrPTSE signals were reproducibly detected by Western blot in dilutions through 10-12 of vCJD-infected 10% brain homogenates. This is the first report showing PrPTSE from vCJD-infected human and macaque brains efficiently amplified with RBV brain as the substrate. Based on our estimates, PMCA showed a sensitivity that might be sufficient to detect PrPTSE in vCJD-infected human
Painschab, Matthew S.; Malpartida, Gary E.; Dávila-Roman, Victor G.; Gilman, Robert H.; Kolb, Todd M.; León-Velarde, Fabiola; Miranda, J. Jaime
Abstract Painschab, Matthew S., Gary E. Malpartida, Victor G. Davila-Roman, Robert H. Gilman, Todd M. Kolb, Fabiola Leon-Velarde, J. Jaime Miranda, and William Checkley. Association between serum concentrations of hypoxia inducible factor responsive proteins and excessive erythrocytosis in high altitude Peru. High Alt Med Biol 16:26–33, 2015.—Long-term residence at high altitude is associated with the development of chronic mountain sickness (CMS), which is characterized by excessive erythrocytosis (EE). EE occurs under chronic hypoxia, and a strongly selected mutation in hypoxia-inducible factor 2α (HIF2A) has been found in native Tibetans that correlates with having a normal hemoglobin at high altitude. We sought to evaluate differences in plasma levels of four HIF-responsive proteins in 20 participants with EE (hemoglobin >21 g/dL in men and >19 in women) and in 20 healthy, age- and sex-matched participants without EE living at high altitude in Puno, Peru. We performed ELISA to measure plasma levels of the four HIF-responsive proteins: vascular endothelial growth factor (VEGF), soluble VEGF receptor 1 (sVEGF-R1), endothelin-1, and erythropoietin. As a secondary aim, we evaluated the association between HIF-responsive proteins and echocardiography-estimated pulmonary artery systolic pressure (PASP) in a subset of 26 participants. sVEGF-R1 was higher in participants with vs. without EE (mean 107 pg/mL vs. 90 pg/mL; p=0.007). Although plasma concentrations of endothelin-1, VEGF, and erythropoietin were higher in participants with vs. without EE, they did not achieve statistical significance (all p>0.25). Both sVEGF-R1 (p=0.04) and erythropoietin (p=0.04) were positively associated with PASP after adjustment for age, sex, and BMI. HIF-responsive proteins may play a pathophysiological role in altitude-related, chronic diseases but our results did not show consistent changes in all measured HIF-responsive proteins. Larger studies are needed to evaluate for
In the late 19th century and in the beginning of the 20th century, mental diseases and abnormal behavior was considered to be a great danger to culture and society. "Degeneration" was the buzzword of the time, used and misused by artists and scientists alike. At the same time, some scientists saw abnormity as the key to unlock the mysteries of the ordinary mind. Naturalistic curiosity left Pandoras box open when religion declined in Darwins wake. Two swedish scientists, the physician Bror Gadelius (1862-1938) and his friend the philosopher Axel Herrlin (1870-1937), inspired by the French psychologist Theodule Ribots (1839-1916) "psychology without a soul", denied all fixed demarcation lines between abnormity and normality. All humans are natures creatures ruled by physiological laws, not ruled by God or convention. Even ordinary morality was considered to be an utterly backward explanation and guideline for complex human behavior. Different forms of therapy, not various kinds of penalties for wicked and disturbing behavior, are the now the solution for lots of people, "normal" as well as "abnormal". Psychiatry is expanding.
Berkovitz, G D; Seeherunvong, T
Gonadal differentiation involves a complex interplay of developmental pathways. The sex determining region Y (SRY) gene plays a key role in testis determination, but its interaction with other genes is less well understood. Abnormalities of gonadal differentiation result in a range of clinical problems. 46,XY complete gonadal dysgenesis is defined by an absence of testis determination. Subjects have female external genitalia and come to clinical attention because of delayed puberty. Individuals with 46,XY partial gonadal dysgenesis usually present in the newborn period for the valuation of ambiguous genitalia. Gonadal histology always shows an abnormality of seminiferous tubule formation. A diagnosis of 46,XY true hermaphroditism is made if the gonads contain well-formed testicular and ovarian elements. Despite the pivotal role of the SRY gene in testis development, mutations of SRY are unusual in subjects with a 46,XY karyotype and abnormal gonadal development. 46,XX maleness is defined by testis determination in an individual with a 46,XX karyotype. Most affected individuals have a phenotype similar to that of Klinefelter syndrome. In contrast, subjects with 46,XX true hermaphroditism usually present with ambiguous genitalia. The majority of subjects with 46,XX maleness have Y sequences including SRY in genomic DNA. However, only rare subjects with 46,XX true hermaphroditism have translocated sequences encoding SRY. Mosaicism and chimaerism involving the Y chromosome can also be associated with abnormal gonadal development. However, the vast majority of subjects with 45,X/46,XY mosaicism have normal testes and normal male external genitalia.
Chen, Qingquan; Xue, Heng; Chen, Min; Gao, Feng; Xu, Jianping; Liu, Qicai; Yang, Xiulin; Zheng, Lie; Chen, Hong
Neonatal sepsis remains an important and common cause of morbidity and mortality among newborn infants, especially in developing countries. The aim of the present study was to determine whether serum trypsin levels and genotypes of cationic trypsinogen (PRSS1) gene could be served as markers for predicting neonatal sepsis. The serum trypsin levels and genotypes of PRSS1 were examined in both 50 infants with infection during neonatal period and 56 healthy neonates as controls. The infected infants were further subdivided into infants with sepsis group (n=18) and infected infants without sepsis (n=32). The genotype of PRSS1 was analyzed by direct sequencing, and the serum trypsin level was measured by immunoassay. It showed that the median value of serum trypsin was significantly higher in infected infants (31.90 ng/mL) than in controls (12.85 ng/mL; P=0.030). More importantly, sepsis subgroup (50.95 ng/mL) had significantly higher median serum trypsin than infected infants without sepsis subgroup (19.10 ng/mL) and controls (12.85 ng/mL) (P=0.015 and P=0.002, respectively). Additionally, the median serum trypsin levels were found significantly higher in infants who had T/T (37.90 ng/mL) genotype of PRSS1 compared with those who had C/T genotype (12.80 ng/mL; P=0.005). This study suggested that serum trypsin and rs10273639 C/T of PRSS1 were revealed to be novel markers for predicting neonatal sepsis.
Pownall, H J; Brauchi, D; Kilinç, C; Osmundsen, K; Pao, Q; Payton-Ross, C; Gotto, A M; Ballantyne, C M
Serum triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) concentrations are inversely correlated and mechanistically linked by means of lipid transfer activities. Phospholipid transfer activity (PLTA) moves phospholipids among serum lipoproteins; cholesteryl ester transfer activity (CETA), which exchanges cholesteryl esters (CE) and TG among lipoproteins, is stimulated by nonesterified fatty acids (NEFA). The aims of this study were (a) to develop a quantitative model that correlates the neutral lipid (NL = CE + TG) compositions of HDL and LDL with serum TG concentration; (b) identify the serum lipid determinants of CETA and PLTA, and; (c) identify the effects of serum TG reductions on the neutral lipid compositions of HDL and LDL, serum NEFA concentrations, and on PLTA and CETA. These aims were addressed in 40 hypertriglyceridemic subjects before and after treatment with an 85% concentrate of omega-3 fatty acids (Omacor) and in 16 untreated normolipidemic subjects. In vivo, the NL compositions of LDL and HDL were described by a mathematical model having the form of adsorption isotherms: HDL - (TG/NL) = (0.90 +/- 0.07) serum TG/(7.0 +/- 1.2 mmol/l + serum TG) and LDL - (TG/NL) = (0.65 +/- 0.08) serum TG/(4.9 +/- 1.5 mmol/l + serum TG). Reduction of serum TG was associated with reductions in HDL - (TG/NL), serum NEFA concentration, and serum CETA but not PLTA. These data suggest that both hypertriglyceridemia and the attendant elevated serum CETA but not PLTA are determinants of HDL and LDL composition and structure and that serum TG concentrations are good predictors of the NL compositions of HDL and LDL.
Ponda, Manish P.; Breslow, Jan L.
Chemokines and their receptors play a critical role in immune function by directing cell-specific movement. C-C chemokine receptor 7 (CCR7) facilitates entry of T cells into lymph nodes. CCR7-dependent chemotaxis requires either of the cognate ligands C-C chemokine ligand 19 (CCL19) or CCL21. Although CCR7-dependent chemotaxis can be augmented through receptor up-regulation or by increased chemokine concentrations, we found that chemotaxis is also markedly enhanced by serum in vitro. Upon purification, the serum cofactor activity was ascribed to domain 5 of high-molecular-weight kininogen. This peptide was necessary and sufficient for accelerated chemotaxis. The cofactor activity in serum was dependent on coagulation factor XIIa, a serine protease known to induce cleavage of high-molecular-weight kininogen (HK) at sites of inflammation. Within domain 5, we synthesized a 24-amino acid peptide that could recapitulate the activity of intact serum through a mechanism distinct from up-regulating CCR7 expression or promoting chemokine binding to CCR7. This peptide interacts with the extracellular matrix protein thrombospondin 4 (TSP4), and antibodies to TSP4 neutralize its activity. In vivo, an HK domain 5 peptide stimulated homing of both T and B cells to lymph nodes. A circulating cofactor that is activated at inflammatory foci to enhance lymphocyte chemotaxis represents a powerful mechanism coupling inflammation to adaptive immunity. PMID:27791187
Ponda, Manish P; Breslow, Jan L
Chemokines and their receptors play a critical role in immune function by directing cell-specific movement. C-C chemokine receptor 7 (CCR7) facilitates entry of T cells into lymph nodes. CCR7-dependent chemotaxis requires either of the cognate ligands C-C chemokine ligand 19 (CCL19) or CCL21. Although CCR7-dependent chemotaxis can be augmented through receptor up-regulation or by increased chemokine concentrations, we found that chemotaxis is also markedly enhanced by serum in vitro. Upon purification, the serum cofactor activity was ascribed to domain 5 of high-molecular-weight kininogen. This peptide was necessary and sufficient for accelerated chemotaxis. The cofactor activity in serum was dependent on coagulation factor XIIa, a serine protease known to induce cleavage of high-molecular-weight kininogen (HK) at sites of inflammation. Within domain 5, we synthesized a 24-amino acid peptide that could recapitulate the activity of intact serum through a mechanism distinct from up-regulating CCR7 expression or promoting chemokine binding to CCR7. This peptide interacts with the extracellular matrix protein thrombospondin 4 (TSP4), and antibodies to TSP4 neutralize its activity. In vivo, an HK domain 5 peptide stimulated homing of both T and B cells to lymph nodes. A circulating cofactor that is activated at inflammatory foci to enhance lymphocyte chemotaxis represents a powerful mechanism coupling inflammation to adaptive immunity.
Makoveichuk, Elena; Ruge, Toralph; Nilsson, Solveig; Södergren, Anna
Angiopoietin-like protein 4 (ANGPTL4) is suggested to be a master regulator of plasma triglyceride metabolism. Our aim was to study whether the previously reported high levels of ANGPTL4 detected in serum from patients with rheumatoid arthritis (RA) by ELISA was due to any specific molecular form of this protein (oligomers, monomers or fragments). ANGPTL4 levels were first determined in serum from 68 RA patients and 43 age and sex matched control subjects and the mean values differed by a factor of 5.0. Then, ANGPTL4 was analyzed after size exclusion chromatography (SEC) of serum samples. With serum from one of the RA patients with high levels of ANGPTL4, the dominant reactivity was found in fractions corresponding to high-molecular weight proteins. In addition, a minor peak of reactivity eluting late from the column was found both in the patient and in controls. By the use of HeteroBlock®, and by careful selection of antibodies, we documented non-specific reactions for ANGPTL4 in 39% of samples from the RA patients, most likely due to cross-reactivity of the antibodies with rheumatoid factor (RF). The corresponding figure for control subjects was 6.3%. After corrections for non-specific reactions, the mean level of ANGPTL4 in serum from RA patients was still significantly higher than in control individuals (mean levels were 101±62 and 67±39 ng/ml respectively, P = 0.02). We re-analyzed samples from our previously published studies on ANGPL4 levels in patients on hemodialysis and patients with diabetes type 2. These samples did not show false positive reactions. The levels of ANGPTL4 were comparable to those detected previously. PMID:28107351
Saxena, Ashima; Hastings, Nicholas B; Sun, Wei; Dabisch, Paul A; Hulet, Stanley W; Jakubowski, Edward M; Mioduszewski, Robert J; Doctor, Bhupendra P
Serum-derived human butyrylcholinesterase (Hu BChE) is a stoichiometric bioscavenger that is being developed as a potential prophylactic nerve agent countermeasure. Previously, we reported the prophylactic efficacy of Hu BChE in Göttingen minipigs against a whole-body exposure to 4.1mg/m(3) of sarin (GB) vapor, which produced lethality over 60min. Since the toxicity of nerve agent is concentration-dependent, in the present study, we investigated the toxic effects of an almost 3-fold higher rate of GB vapor exposure and the ability of Hu BChE to protect minipigs against this exposure. Male minipigs were subjected to: (1) air exposure; (2) GB vapor exposure; or (3) pretreatment with 7.5mg/kg of Hu BChE by i.m. injection, 24h prior to whole-body exposure to 11.4mg/m(3) of GB vapor for 10min. Electrocardiogram, electroencephalogram, and pupil size were monitored throughout exposure. Blood drawn before and throughout exposure was analyzed for blood gases, electrolytes, metabolites, acetylcholinesterase and BChE activities, and amount of GB bound to red blood cells and plasma. A novel finding was that saline-treated animals exposed to GB vapor did not develop any seizures, but manifested a variety of cardiac and whole blood toxic signs and rapidly died due to respiratory failure. Strikingly, pre-treatment with 7.5mg/kg of Hu BChE not only prevented lethality, but also avoided all cardiac toxic signs manifested in the non-treated cohort. Thus, Hu BChE alone can serve as an effective prophylactic countermeasure versus a lethal high-dose exposure to GB vapor.
Gaskins, Audrey J; Mumford, Sunni L; Rovner, Alisha J; Zhang, Cuilin; Chen, Liwei; Wactawski-Wende, Jean; Perkins, Neil J; Schisterman, Enrique F
In premenopausal women, elevated C-reactive protein (CRP) concentrations have been associated with an increased risk of negative reproductive outcomes. Whole grain consumption has been associated with lower CRP concentrations in older women; however, less is known about this relationship in younger women. We investigated whether whole grain intake was associated with serum high sensitivity CRP (hs-CRP) concentrations in young women. BioCycle was a prospective cohort study conducted at the University of Buffalo from 2005 to 2007, which followed 259 healthy women aged 18-44 y for
Xia, Xuejuan; Li, Guannan; Ding, Yongbo; Ren, Tingyuan; Zheng, Jiong; Kan, Jianquan
This study investigated the hypolipidemic effect of whole grain Qingke (WGQ) and its influence on intestinal microbiota. Changes in the serum lipid, intestinal environment, and microbiota of Sprague-Dawley rats fed high-fat diets supplemented with different doses of WGQ were determined. Results showed that high doses of WGQ significantly decreased (P < 0.05) the Lee's index, serum total cholesterol, low-density lipoprotein cholesterol, and non-high-density lipoprotein cholesterol levels whereas they increased the body weight of the rats. Cecal weight and short-chain fatty acid (SCFA) concentration increased with increasing WGQ dose. An Illumina-based sequencing approach showed that the relative abundance of putative SCFA-producing bacteria Prevotella and Anaerovibrio increased in the rats fed the WGQ diet. Principal component analysis revealed a significant difference in intestinal microbiota composition after the administration of the WGQ diet. These findings provide insights into the contribution of the intestinal microbiota to the hypolipidemic effect of WGQ.
Miranda, K A; Vasconcelos, L R S; Coelho, L C B B; Lima Filho, J L; Cavalcanti, M S M; Moura, P
The clinical heterogeneity observed in leptospirosis may be associated with host factors or bacteria virulence. Human serum mannose-binding lectin (MBL) recognizes many pathogens, and low levels of this lectin are associated with susceptibility to infection. MBL is also implicated in the modulation of the inflammatory process. We determined the levels of serum MBL during leptospirosis infection. A double-antibody sandwich ELISA was used to detect the immunoreactive serum MBL. The ELISA plates were coated with monoclonal antibody to MBL and bound MBL or recombinant human MBL were detected by rabbit anti-human MBL serum. HRPO-conjugated goat anti-rabbit antibody was used for detection of the reaction. Two groups of patients seen at referral hospitals in Recife, PE, Brazil, were divided according to the year of infection, 2001 (N = 61) or 2002 (N = 57) and compared in terms of disease severity and levels of serum MBL. A group of healthy volunteers (N = 97) matched by age, gender, and ethnic background was used as control. Patients infected in 2001 had more severe outcomes than those infected in 2002, including jaundice, hemorrhage, respiratory alteration, and renal complication (P = 0.0009; chi-square test). The frequency of patients producing serum MBL >1000 ng/mL was higher in the 2001 group than in the 2002 and control groups (P < 0.01), suggesting an association of MBL level with disease severity. The involvement of MBL and genetic variation of the MBL2 gene should be further evaluated to establish the role of this lectin in the pathogenesis of leptospirosis.
Whitlock, B K; Kaiser, L; Maxwell, H S
The etiologies for congenital bovine fetal anomalies can be divided into heritable, toxic, nutritional, and infectious categories. Although uncommon in most herds, inherited congenital anomalies are probably present in all breeds of cattle and propagated as a result of specific trait selection that inadvertently results in propagation of the defect. In some herds, the occurrence of inherited anomalies has become frequent, and economically important. Anomalous traits can affect animals in a range of ways, some being lethal or requiring euthanasia on humane grounds, others altering structure, function, or performance of affected animals. Veterinary practitioners should be aware of the potential for inherited defects, and be prepared to investigate and report animals exhibiting abnormal characteristics. This review will discuss the morphologic characteristics, mode of inheritance, breeding lines affected, and the availability of genetic testing for selected heritable bovine fetal abnormalities.
Meyers-Wallen, V N
Preovulatory serum progesterone concentrations are used to estimate the day of LH peak (day 0), not only to accurately time insemination and predict parturition, but to identify abnormal or unusual estrous cycles due to ovarian dysfunction. Early identification of these disorders is of therapeutic and economic importance. This review discusses anovulation, slow preovulatory progesterone rise, "split heat", insufficient luteal phase, and persistent estrus in the bitch. Some of these were temporary dysfunctions; with appropriate breeding management, pregnancy can be achieved. However, in other cases, these were signs of severe, permanent ovarian dysfunction associated with infertility, with potentially lethal sequelae.
El-Hady, D Abd; Albishri, H M
Retinol and retinoic acid are Vitamin A components that are critical for many biological processes. Both of them are strongly complexing with serum albumins giving constants of the order of 10(5)Lmol(-1) or higher. With respect to this fact, affinity capillary electrophoresis (ACE) is not applicable in its commonly used form. Therefore, for the first time, the hyphenated ACE with a high-sensitivity cell was developed and employed to investigate the binding of retinol and retinoic acid in nanomolars with human serum albumin (HSA) and bovine serum albumin (BSA) under physiological conditions. ACE/high-sensitivity coupled cell had contributed to fast the association and dissociation rates of the complexes in nanomolar scale of analytes ensuring the establishment of a dynamic equilibrium within a short electrophoresis time. In addition, this hyphenation led to reduce the concentrations of serum albumins as additives in background electrolyte making a sense beside the proper rinsing protocol for the negligible possibility of their adsorption. The mobility ratio based on nonlinear regression analysis was used to deduce precise binding constants of analytes with serum albumins. The binding constants (K, Lmol(-1)) of retinol were 1.28×10(5) and 5.25×10(6) and retinoic acid were 3.29×10(5) and 2.27×10(6) with HSA and BSA, respectively. The displacement and reciprocal competitive binding of analytes were investigated and indicated that retinoic acid was able to replace retinol from HSA and vice versa in the case of BSA.
Gustafson, R; Gardulf, A; Hansen, S; Leibl, H; Engl, W; Lindén, M; Müller, A; Hammarström, L
Subcutaneous immunoglobulin G (SCIG) infusions as life-long replacement therapy in patients with primary antibody deficiences (PAD) is being applied increasingly. However, only a few published pharmacokinetic studies are available for this route of administration. Therefore, the pharmacokinetics of a 16% immunoglobulin G (IgG) preparation intended for subcutaneous use were investigated in patients with common variable immunodeficiency and X-linked agammaglobulinaemia. SCIG infusions (200 mg/kg body weight) were administered to 12 adult patients every 14 days for 24 weeks (total of 144 infusions). Pharmacokinetic parameters were determined based on serum IgG trough levels and antibody levels against tetanus. The median half-life of the total serum IgG and for the tetanus antibodies was 40·6 and 23·3 days respectively. Median in vivo recovery of serum IgG and tetanus immunoglobulins were 36% and 46% respectively. Median, preinfusion serum IgG trough levels per patient were high without major variations between infusions and ranged from 7·24 to 7·86 g/l. Safety, in terms of adverse events including systemic adverse reactions and local tissue reactions at infusions sites, was monitored throughout the study. Six mild, local tissue reactions were observed during the study in one patient. No systemic adverse reactions related to the study drug were observed and no serious other adverse event occurred during the study. It is concluded that the bi-weekly SCIG therapy was well tolerated in the study and that it results in high and stable serum IgG levels, offering an alternative therapy regimen to patients suffering from PAD. PMID:18341618
Haar, Shlomi; Berman, Sigal; Behrmann, Marlene; Dinstein, Ilan
Substantial controversy exists regarding the presence and significance of anatomical abnormalities in autism spectrum disorders (ASD). The release of the Autism Brain Imaging Data Exchange (∼1000 participants, age 6-65 years) offers an unprecedented opportunity to conduct large-scale comparisons of anatomical MRI scans across groups and to resolve many of the outstanding questions. Comprehensive univariate analyses using volumetric, thickness, and surface area measures of over 180 anatomically defined brain areas, revealed significantly larger ventricular volumes, smaller corpus callosum volume (central segment only), and several cortical areas with increased thickness in the ASD group. Previously reported anatomical abnormalities in ASD including larger intracranial volumes, smaller cerebellar volumes, and larger amygdala volumes were not substantiated by the current study. In addition, multivariate classification analyses yielded modest decoding accuracies of individuals' group identity (<60%), suggesting that the examined anatomical measures are of limited diagnostic utility for ASD. While anatomical abnormalities may be present in distinct subgroups of ASD individuals, the current findings show that many previously reported anatomical measures are likely to be of low clinical and scientific significance for understanding ASD neuropathology as a whole in individuals 6-35 years old.
Lee, Bum Ju; Kim, Jong Yeol
Serum high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol levels are associated with risk factors for various diseases and are related to anthropometric measures. However, controversy remains regarding the best anthropometric indicators of the HDL and LDL cholesterol levels. The objectives of this study were to identify the best predictors of HDL and LDL cholesterol using statistical analyses and two machine learning algorithms and to compare the predictive power of combined anthropometric measures in Korean adults. A total of 13,014 subjects participated in this study. The anthropometric measures were assessed with binary logistic regression (LR) to evaluate statistically significant differences between the subjects with normal and high LDL cholesterol levels and between the subjects with normal and low HDL cholesterol levels. LR and the naive Bayes algorithm (NB), which provides more reasonable and reliable results, were used in the analyses of the predictive power of individual and combined measures. The best predictor of HDL was the rib to hip ratio (p =< 0.0001; odds ratio (OR) = 1.895; area under curve (AUC) = 0.681) in women and the waist to hip ratio (WHR) (p =< 0.0001; OR = 1.624; AUC = 0.633) in men. In women, the strongest indicator of LDL was age (p =< 0.0001; OR = 1.662; AUC by NB = 0.653 ; AUC by LR = 0.636). Among the anthropometric measures, the body mass index (BMI), WHR, forehead to waist ratio, forehead to rib ratio, and forehead to chest ratio were the strongest predictors of LDL; these measures had similar predictive powers. The strongest predictor in men was BMI (p =< 0.0001; OR = 1.369; AUC by NB = 0.594; AUC by LR = 0.595 ). The predictive power of almost all individual anthropometric measures was higher for HDL than for LDL, and the predictive power for both HDL and LDL in women was higher than for men. A combination of anthropometric measures slightly improved the predictive power for both HDL and LDL cholesterol
Measurement of serum estrogen and estrogen metabolites in pre- and postmenopausal women with osteoarthritis using high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry.
Gao, W L; Wu, L S; Zi, J H; Wu, B; Li, Y Z; Song, Y C; Cai, D Z
Although 17β-estradiol (E2) deficiency has been linked to the development of osteoarthritis (OA) in middle-aged women, there are few studies relating other estrogens and estrogen metabolites (EMs) to this condition. We developed a high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) method to measure the levels of six EMs (i.e., estrone, E2, estriol, 2-hydroxyestrone, 2-hydroxyestradiol, and 16a-hydroxyestrone) in healthy pre- and postmenopausal women and women with OA. This method had a precision ranging from 1.1 to 3.1% and a detection limit ranging from 10 to 15 pg. Compared to healthy women, serum-free E2 was lower in the luteal and postmenopausal phases in women with OA, and total serum E2 was lower in postmenopausal women with OA. Moreover, compared to healthy women, total serum 2-hydroxyestradiol was higher in postmenopausal women with OA and total serum 2-hydroxyestrone was lower in both the luteal and follicular phases in women with OA. In conclusion, our HPLC-ESI-MS/MS method allowed the measurement of multiple biochemical targets in a single assay, and, given its increased cost-effectiveness, simplicity, and speed relative to previous methods, this method is suitable for clinical studies.
Jozan, S.; Faye, J.C.; Tournier, J.F.; Tauber, J.P.; David, J.F.; Bayard, F.
The responsiveness of the human mammary carcinoma cell line MCF-7 to estradiol and tamoxifen treatment has been studied in different culture conditions. Cells from exponentially growing cultures were compared with cells in their initial cycles after replating from confluent cultures (''confluent-log'' cells). It has been observed that estradiol stimulation of tritiated thymidine incorporation decreases with cell density and that ''confluent-log'' cells are estrogen unresponsive for a period of four cell cycles in serum-free medium conditions. On the other hand, growth of cells replated from exponentially growing, as well as from confluent cultures, can be inhibited by tamoxifen or a combined treatment with tamoxifen and the progestin levonorgestrel. This growth inhibitory effect can be rescued by estradiol when cells are replated from exponentially growing cultures. The growth inhibitory effect cannot be rescued by estradiol alone (10(-10) to 10(-8) M) when cells are replated from confluent cultures. In this condition, the addition of steroid depleted serum is necessary to reverse the state of estradiol unresponsiveness. Serum can be replaced by high density lipoproteins but not by low density lipoproteins or lipoprotein deficient serum. The present data show that estradiol and HDL interact in the control of MCF-7 cell proliferation.
Rehan, Ibrahim F; Ueda, Koichiro; Mitani, Tomohiro; Amano, Maho; Hinou, Hiroshi; Ohashi, Tetsu; Kondo, Seiji; Nishimura, Shin-Ichiro
Because various stresses strongly influence the food productivity of livestock, biomarkers to indicate unmeasurable environmental stress in domestic animals are of increasing importance. Thermal comfort is one of the basic principles of dairy cow welfare that enhances productivity. To discover sensitive biomarkers that monitor such environmental stresses in dairy cows, we herein performed, for the first time, large-scale glycomics on 336 lactating Holstein cow serum samples over 9 months between February and October. Glycoblotting combined with MALDI-TOF/MS and DMB/HPLC allowed for comprehensive glycomics of whole serum glycoproteins. The results obtained revealed seasonal alterations in serum N-glycan levels and their structural characteristics, such as an increase in high-mannose type N-glycans in spring, the occurrence of di/triantennary complex type N-glycans terminating with two or three Neu5Gc residues in summer and autumn, and N-glycans in winter dominantly displaying Neu5Ac. A multivariate analysis revealed a correlation between the serum expression levels of these season-specific glycoforms and productivity.
Bahrami, Gholamreza; Kiani, Amir
Most of the published methods for analysis of gabapentin, an antiepileptic agent, in human serum are based on the same approach, involving o-phthaldialdehyde derivatization of deproteinized serum samples. The present paper however, describes a new, simple and sensitive high-performance liquid chromatographic method for determination of gabapentin in human serum using liquid-liquid extraction and 9-fluorenylmethyl chloroformate (FMOC-Cl) as pre-column labeling agent. The drug and an internal standard (azithromycin) were extracted from serum by salting-out approach using a mixture of dichloromethane-2 propanol (1:1, v/v) as the extracting solvent. The extracted analytes were subjected to derivatization with FMOC-Cl in the presence of phosphate buffer (pH 7). A mobile phase consisting of methanol-0.05 M sodium phosphate buffer (73/27, v/v; pH of 3.9) containing 1 ml/l triethylamine was eluted and chromatographic separation was performed on a Shimpack CLC-C18 (150 mm x 4.6 mm) column. The standard curve was linear over the range of 0.03-20 microg/ml and limit of quantification was 0.03 microg/ml. The performance of analysis was studied and the validated method showed excellent performance in terms of selectivity, specificity, sensitivity, precision and accuracy. No interferences were found from commonly co-administered antiepileptic agents.
Quantification of gadodiamide as Gd in serum, peritoneal dialysate and faeces by inductively coupled plasma atomic emission spectroscopy and comparative analysis by high-performance liquid chromatography.
Normann PT-; Joffe, P; Martinsen, I; Thomsen, H S
An inductively coupled plasma atomic emission spectroscopy (ICP-AES) method for determination of gadodiamide as Gd in serum, peritoneal dialysate and faeces was developed. The within-day and between-day precision for determination of Gd in serum and peritoneal dialysate were 0.60-2.9 and 1.8-4.4%, respectively, and the accuracy was 98.0-99.3%. The quantification limits in serum and peritoneal dialysate were 6.5 and 1.6 microM Gd, respectively. The within-day and between-day precision determination of gadolinium in faeces were 1.0-5.3 and 2.2-7.9%, respectively, and the accuracy was 104-116%. The quantification limit was 11 nmol Gd/g dry weight. For the high-performance liquid chromatography (HPLC) method, the within-day precision in determination of gadodiamide in peritoneal dialysate was 1.2% and the accuracy was 103%. The quantification limit was 0.9 microM Gd. Comparative analysis of gadodiamide in serum and peritoneal dialysate from severely impaired renal patients by ICP-AES and HPLC revealed no metabolism of chelator or transmetallation of gadolinium, even in samples obtained as long as 7 days after dosing. Furthermore, the ICP-AES determination of Gd in faeces allows for the determination of faeces content of Gd corresponding to less than 0.1% of a clinical dosage of a Gd-based contrast medium.
Vester, Brittany M; Belsito, Katherine R; Swanson, Kelly S
The objective of this study was to evaluate the effects of in utero and postnatal exposure of a high-protein (HP; n=9) or moderate-protein (MP; n=16) diet on growth, and serum metabolite, ghrelin and leptin concentrations during the first 4 months of life in kittens. It was hypothesized that blood indices would be modified due to diet. Blood samples were collected from kittens at 4, 8, 12 and 16 weeks of age. Kittens were weaned at 8 weeks of age onto the same diet as the dam. Body weight was measured weekly from birth and daily food intake for each litter was recorded post-weaning. Serum concentrations of urea nitrogen, total protein and triglycerides were greater (P<0.05) in kittens fed the HP diet. Serum cholesterol concentrations were greater (P <0.05) in MP-fed kittens at 4 weeks of age. Moderate-protein fed kittens tended to have greater (P < 0.10) serum ghrelin concentrations. Leptin concentrations were not affected by diet, but changed over time (P<0.05). Our data indicate that diet and age of kittens affect circulating concentrations of peptides important in appetite regulation. Further research testing the effects of in utero and early postnatal nutrient exposure on feline obesity risk in adulthood is needed.
Honda, Akira; Yamashita, Kouwa; Ikegami, Tadashi; Hara, Takashi; Miyazaki, Teruo; Hirayama, Takeshi; Numazawa, Mitsuteru; Matsuzaki, Yasushi
We describe a new sensitive and specific method for the quantification of serum malonate (malonic acid, MA), which could be a new biomarker for de novo lipogenesis (fatty acid synthesis). This method is based upon a stable isotope-dilution technique using LC-MS/MS. MA from 50 microl of serum was derivatized into di-(1-methyl-3-piperidinyl)malonate (DMP-MA) and quantified by LC-MS/MS using the positive electrospray ionization mode. The detection limit of the DMP-MA was approximately 4.8 fmol (500 fg) (signal-to-noise ratio = 10), which was more than 100 times more sensitive compared with that of MA by LC-MS/MS using the negative electrospray ionization mode. The relative standard deviations between sample preparations and measurements made using the present method were 4.4% and 3.2%, respectively, by one-way ANOVA. Recovery experiments were performed using 50 microl aliquots of normal human serum spiked with 9.6 pmol (1 ng) to 28.8 pmol (3 ng) of MA and were validated by orthogonal regression analysis. The results showed that the estimated amount within a 95% confidence limit was 14.1 +/- 1.1 pmol, which was in complete agreement with the observed X(0) = 15.0 +/- 0.6 pmol, with a mean recovery of 96.0%. This method provides reliable and reproducible results for the quantification of MA in human serum.
Kim, Young-Eun; Roh, Yong-Kyun; Ju, Sang-Yhun; Yoon, Yeo-Joon; Nam, Ga-Eun; Nam, Hyo-Yun; Choi, Jun-Seok; Lee, Jong-Eun; Sang, Jung-Eun; Han, Kyungdo
Background Ferritin is associated with various cardiometabolic risk factors such as dyslipidemia, hypertension, obesity, and insulin resistance in adults. We aimed to study the association between serum ferritin levels and dyslipidemia in adolescents, because dyslipidemia is considered an important modifiable cardiovascular risk factor in the young. Methods We analyzed 1,879 subjects (1,026 boys and 853 girls) from the 2009–2010 Korean National Health and Nutrition Examination Survey IV. Subjects were categorized into quartiles according to their lipid parameters, which were classified according to age and gender. Those in the highest quartile groups for total cholesterol, low-density lipoprotein cholesterol (LDL-C), and triglyceride concentrations were diagnosed as having dyslipidemia. Those in the lowest quartile for high-density lipoprotein cholesterol (HDL-C) values were diagnosed with abnormal levels. Results In boys, total cholesterol, LDL-C, and triglyceride concentrations were significantly correlated with serum ferritin levels. In both boys and girls, serum ferritin levels were negatively associated with HDL-C values, even after adjusting for all covariates. Furthermore, there was no significant correlation between serum ferritin levels and total cholesterol, LDL, and triglyceride concentrations in girls. Conclusion Serum ferritin levels were significantly associated with major dyslipidemia parameters, more prominently in boys than in girls, and this association represents a cardiometabolic risk factor. PMID:27070153
Van Wijk, R.; Wiegant, F. A. C.; Popp, Fritz A.; Storms, G. E. M. G.
The concept that free radicals mediate vascular abnormalities in diabetes has been debated. This study examines the relationship between serum free radical activity and glycaemic regulation. A cross-sectional assessment is presented of the chemiluminescence of blood serum, long term glycaemic control (HbAlc, fructosamine) and blood glucose concentrations in patients with type-1 (n equals 114) and patients with type-2 (n equals 112) diabetes. The average value of serum chemiluminescence of type-1 patients is higher than that of type-2 patients (p equals 0.014). Spectral analysis suggests that different sources of free radical activity are responsible in different ratios for chemiluminescence in type-1 and type-2 sera. Serum chemiluminescence values of type-1 patients strongly correspond with blood glucose levels (p < 0.001). Chemiluminescence values were higher, although not significant (p equals 0.082) in the 'poorly' controlled group characterized by high values of HbAlc and/or fructosamine in comparision with the group of 'good' glycaemic control with lower values of HbAlc and/or fructosamine. Serum chemeluminescence values of type-2 patients neither correspond to their long tern glycaemic status nor to their blood glucose levels. It is concluded that changes in glucose metabolism and changes in chemiluminescence are coordinated for type-1 but not for type-2 patients. This strongly indicates the relevance of ther free radical connection to diabetes type-1 complications.
So-called abnormal pressures, subsurface fluid pressures significantly higher or lower than hydrostatic, have excited speculation about their origin since subsurface exploration first encountered them. Two distinct conceptual models for abnormal pressures have gained currency among earth scientists. The static model sees abnormal pressures generally as relict features preserved by a virtual absence of fluid flow over geologic time. The hydrodynamic model instead envisions abnormal pressures as phenomena in which flow usually plays an important role. This paper develops the theoretical framework for abnormal pressures as hydrodynamic phenomena, shows that it explains the manifold occurrences of abnormal pressures, and examines the implications of this approach. -from Author
Numerous molecular abnormalities have been described in lymphomas. They are of diagnostic and prognostic value and are taken into account for the WHO classification of these tumors. They also shed some light on the underlying molecular mechanisms involved in lymphomas. Overall, four types of molecular abnormalities are involved: mutations, translocations, amplifications and deletions of tumor suppressor genes. Several techniques are available to detect these molecular anomalies: conventional cytogenetic analysis, multicolor FISH, CGH array or gene expression profiling using DNA microarrays. In some lymphomas, genetic abnormalities are responsible for the expression of an abnormal protein (e.g. tyrosine-kinase, transcription factor) detectable by immunohistochemistry. In the present review, molecular abnormalities observed in the most frequent B, T or NK cell lymphomas are discussed. In the broad spectrum of diffuse large B-cell lymphomas microarray analysis shows mostly two subgroups of tumors, one with gene expression signature corresponding to germinal center B-cell-like (GCB: CD10+, BCL6 [B-Cell Lymphoma 6]+, centerine+, MUM1-) and a subgroup expressing an activated B-cell-like signature (ABC: CD10-, BCL6-, centerine-, MUM1+). Among other B-cell lymphomas with well characterized molecular abnormalies are follicular lymphoma (BCL2 deregulation), MALT lymphoma (Mucosa Associated Lymphoid Tissue) [API2-MALT1 (mucosa-associated-lymphoid-tissue-lymphoma-translocation-gene1) fusion protein or deregulation BCL10, MALT1, FOXP1. MALT1 transcription factors], mantle cell lymphoma (cycline D1 [CCND1] overexpression) and Burkitt lymphoma (c-Myc expression). Except for ALK (anaplastic lymphoma kinase)-positive anaplastic large cell lymphoma, well characterized molecular anomalies are rare in lymphomas developed from T or NK cells. Peripheral T cell lymphomas not otherwise specified are a heterogeneous group of tumors with frequent but not recurrent molecular abnormalities
Scambia, G.; Benedetti Panici, P.; Perrone, L.; Sonsini, C.; Giannelli, S.; Gallo, A.; Natali, P. G.; Mancuso, S.
Serum levels of TAG 72 were measured in 726 serum samples from patients with benign and malignant gynaecological conditions in order to evaluate the clinical usefulness of TAG 72 alone or in combination with other tumour markers. Sixty-six per cent of patients with ovarian cancer showed abnormal concentrations of TAG 72 antigen. A good correlation was also found between serial TAG 72 values and the clinical course of disease during chemotherapy and follow-up. In cervical and endometrial cancer abnormal TAG 72 values occurred in 23% and 14% of cases, while none of the patients with breast cancer had abnormal TAG 72 levels. Among patients with benign disease only one out of 12 patients (8%) with benign ovarian tumours and one of 15 patients with uterine fibromyomatosis (7%) showed high TAG 72 serum levels. However, the determination of TAG 72 did not increase the sensitivity of CA 125 and squamous cell carcinoma antigen (SCC), in ovarian and cervical cancer, respectively. The systemic administration of recombinant interferon alpha-2b to 15 patients with ovarian cancer and different basal levels of TAG 72 did not increase serum levels of the antigen. PMID:2167724
Fernald, Charles D.
Describes activity in which student in abnormal psychology and psychology of exceptional children classes personally experience being judged abnormal. The experience allows the students to remember relevant research, become sensitized to the feelings of individuals classified as deviant, and use caution in classifying individuals as abnormal.…
Trascasa, M L; Egido, J; Sancho, J; Hernando, L
High levels of polymeric IgA were found in the serum of patients with IgA glomerulonephritis. In four of the patients the IgA percentage distribution was established by ultracentrifugation in sucrose density gradients before and after six months of phenytoin treatment. A decrease in polymeric IgA, adopting a pattern similar to the controls, was observed. These findings may have both pathogenic and therapeutic implications.
Yates, D T; Löest, C A; Ross, T T; Hallford, D M; Carter, B H; Limesand, S W
Bacterial lipopolysaccharide endotoxins (LPS) elicit inflammatory responses reflective of acute bacterial infection. We determined if feeding ewes high-CP (15.5%) or low-CP (8.5%) diets for 10 d altered inflammatory responses to an intravenous bolus of 0 (control), 0.75 (L75), or 1.50 (L150) μg of LPS/kg of BW in a 2 × 3 factorial arrangement of treatments (n = 5/treatment). Rectal temperatures, heart and respiratory rates, blood leukocyte concentrations, and serum cortisol, insulin, and glucose concentrations were measured for 24 h after an LPS bolus (bolus = 0 h). In general, rectal temperatures were greater (P ≤ 0.05) in control ewes fed high CP, but LPS increased (P ≤ 0.05) rectal temperatures in a dose-dependent manner at most times between 2 and 24 h after the bolus. Peak rectal temperatures in L75 and L150 occurred 4 h after the bolus. A monophasic, dose-independent increase (P ≤ 0.023) in serum cortisol occurred from 0.5 to 24 h after the bolus, with peak cortisol at 4 h. Serum insulin was increased (P ≤ 0.016) by LPS in a dose-dependent manner from 4 to 24 h after the bolus. Insulin did not differ between control ewes fed high- and low-CP diets but was greater (P < 0.001) in L75 ewes fed low CP compared with high CP and in L150 ewes fed high CP compared with low CP. Increased insulin was not preceded by increased serum glucose. Total white blood cell concentrations were not affected (P ≥ 0.135) by LPS, but the neutrophil and monocyte fractions of white blood cells were increased (P ≤ 0.047) by LPS at 12 and 24 h and at 24 h after the bolus, respectively, and the lymphocyte fraction was increased (P = 0.037) at 2 h and decreased (P ≤ 0.006) at 12 and 24 h after the bolus. Red blood cell and hemoglobin concentrations and hematocrit (%) were increased (P ≤ 0.022) by LPS at 2 and 4 h after the bolus. Rectal temperatures and serum glucose were greater (P ≤ 0.033) in ewes fed a high-CP diet before LPS injection, but these effects were lost at
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Chapter 22, discusses abnormal human sex chromosome constitution. Aneuploidy of X chromosomes with a female phenotype, sex chromosome aneuploidy with a male phenotype, and various abnormalities in X chromosome behavior are described. 31 refs., 2 figs.
Nakamura, Toshihiko; Nakamura, Mari; Takahashi, Naoto
A newborn male with pulmonary edema was delivered at term by elective Caesarian section. Cytokine profiles of 17 cytokines and KL-6 in cord blood and serial serum values were investigated. The cord blood values of all 17 cytokines and KL-6 were within normal limits. Subsequently, IL-6, IL-8, IL-10, IL-13, IL-17, and IFNγ rapidly elevated during the first several hours after birth and dramatically decreased thereafter, whereas KL-6 rose to 611 U/ml on the 3(rd) day of life and then gradually decreased. These cytokines may induce pulmonary permeability, and KL-6 secreted in lining fluid could result in influx into the bloodstream. This is the first report that we have differentiated neonatal pulmonary edema from TTN by the measurement of serial cytokine profiles and KL-6 in serum.
Chruszcz, Maksymilian; Mikolajczak, Katarzyna; Mank, Nicholas; Majorek, Karolina A.; Porebski, Przemyslaw J.; Minor, Wladek
Background Albumins are multifunctional proteins present in the blood serum of animals. They can bind and transport a wide variety of ligands which they accommodate due to their conformational flexibility. Serum albumins are highly conserved both in amino acid sequence and three-dimensional structure. Several mammalian and avian serum albumins (SAs) are also allergens. Sensitization to one of the SAs coupled with the high degree of conservation between SAs may result in cross-reactive antibodies in allergic individuals. Sensitivity to SA generally begins with exposure to an aeroallergen, which can then lead to cross-sensitization to serum albumins present in food. Scope of Review This review focuses on the allergenicity of SAs presented in a structural context. Major Conclusions SA allergenicity is unusual taking into account the high sequence identity and similarity between SA from different species and human serum albumin. Cross-reactivity of human antibodies towards different SAs is one of the most important characteristics of these allergens. General Significance Establishing a relationship between sequence and structure of different SAs and their interactions with antibodies is crucial for understanding the mechanisms of cross-sensitization of atopic individuals. Structural information can also lead to better design and production of recombinant SAs to replace natural proteins in allergy testing and desensitization. Therefore, structural analyses are important for diagnostic and treatment purposes. PMID:23811341
Choi, Ju Young; Park, Joon Min; Kim, Kyung Hwan; Park, Jun Seok; Shin, Dong Wun; Kim, Hoon; Jeon, Woo Chan; Kim, Hyun Jong
A 77-year-old woman was admitted to a local clinic for altered consciousness and presented with a suspected basal ganglion hemorrhage detected on brain computed tomography. The patient was stuporous, but her vital signs were stable. Her initial blood glucose was 607 mg/dL, and a hyperdense lesion was found in the right basal ganglion on brain computed tomography. T1-weighted magnetic resonance imaging revealed high signal intensity in the right basal ganglion. Electroencephalography showed no seizure activity. The patient was treated with a fluid infusion, and serum glucose level was controlled with insulin. The patient gradually recovered consciousness and was alert within 24 hours as serum glucose level normalized. The basal ganglion lesion caused by hyperglycemia was not accompanied by involuntary limb movement. This is the first report of a patient presenting with decreased consciousness and typical neural radiographic changes associated with nonketotic hyperglycemia but without movement abnormalities. PMID:28168232
Peterson, Michael G; Peterson, Sarah H; Debier, Cathy; Covaci, Adrian; Dirtu, Alin C; Malarvannan, Govindan; Crocker, Daniel E; Costa, Daniel P
Long-lived, upper trophic level marine mammals are vulnerable to bioaccumulation of persistent organic pollutants (POPs). Internal tissues may accumulate and mobilize POP compounds at different rates related to the body condition of the animal and the chemical characteristics of individual POP compounds; however, collection of samples from multiple tissues is a major challenge to ecotoxicology studies of free-ranging marine mammals and the ability to predict POP concentrations in one tissue from another tissue remains rare. Northern elephant seals (Mirounga angustirostris) forage on mesopelagic fish and squid for months at a time in the northeastern Pacific Ocean, interspersed with two periods of fasting on land, which results in dramatic seasonal fluctuations in body condition. Using northern elephant seals, we examined commonly studied tissues in mammalian toxicology to describe relationships and determine predictive equations among tissues for a suite of POP compounds, including ΣDDTs, ΣPCBs, Σchlordanes, and ΣPBDEs. We collected paired blubber (inner and outer) and blood serum samples from adult female and male seals in 2012 and 2013 at Año Nuevo State Reserve (California, USA). For females (N = 24), we sampled the same seals before (late in molting fast) and after (early in breeding fast) their approximately seven month foraging trip. For males, we sampled different seals before (N = 14) and after (N = 15) their approximately four month foraging trip. We observed strong relationships among tissues for many, but not all compounds. Serum POP concentrations were strong predictors of inner blubber POP concentrations for both females and males, while serum was a more consistent predictor of outer blubber for males than females. The ability to estimate POP blubber concentrations from serum, or vice versa, has the potential to enhance toxicological assessment and physiological modeling. Furthermore, predictive equations may illuminate commonalities or
Background Many chromosomal abnormalities are associated with Central Nervous System (CNS) malformations and other neurological alterations, among which seizures and epilepsy. Some of these show a peculiar epileptic and EEG pattern. We describe some epileptic syndromes frequently reported in chromosomal disorders. Methods Detailed clinical assessment, electrophysiological studies, survey of the literature. Results In some of these congenital syndromes the clinical presentation and EEG anomalies seems to be quite typical, in others the manifestations appear aspecific and no strictly linked with the chromosomal imbalance. The onset of seizures is often during the neonatal period of the infancy. Conclusions A better characterization of the electro clinical patterns associated with specific chromosomal aberrations could give us a valuable key in the identification of epilepsy susceptibility of some chromosomal loci, using the new advances in molecular cytogenetics techniques - such as fluorescent in situ hybridization (FISH), subtelomeric analysis and CGH (comparative genomic hybridization) microarray. However further studies are needed to understand the mechanism of epilepsy associated with chromosomal abnormalities. PMID:20438626
Mendoza, C E; Rosado, M F; Bernal, L
We performed this prospective study to evaluate the correlation of interleukin-6 serum levels with preoperative constitutional symptoms and immunologic abnormalities, and the possible role played by this cytokine in tumor recurrence. Eight patients with atrial myxoma were evaluated at our institution from July 1993 to November 1998. We measured their interleukin-6 serum levels by enzyme-linked immunosorbent assay method preoperatively and 1 and 6 months after surgery. Two of the cases involved recurrent tumor, 1 patient had undergone his 1st surgery at a different institution and died during the 2nd procedure, so his data were incomplete. Preoperatively the whole group of patients had elevated interleukin-6 serum levels. Although patients with a 1st occurrence of tumor demonstrated a positive correlation between interleukin-6 serum level and tumor size, the 2 patients with recurrent tumors appeared to have higher interleukin-6 levels regardless of tumor size. Once the tumor was surgically removed, interleukin-6 levels returned to normal values, and this was associated with regression of clinical manifestations and immunologic features. According to our study, the overproduction of interleukin-6 by cardiac myxomas is responsible for the constitutional symptoms and immunologic abnormalities observed in patients with such tumors and might also play a role as a marker of recurrence. This study also suggests that recurrent cardiac myxomas form a subgroup of cardiac myxomas with a highly intrinsic aggressiveness, as implied by their greater interleukin-6 production despite their smaller size. Further studies are needed to confirm these results.
Mendoza, Cesar Emilio; Rosado, Manuel Francisco; Bernal, Leon
We performed this prospective study to evaluate the correlation of interleukin-6 serum levels with preoperative constitutional symptoms and immunologic abnormalities, and the possible role played by this cytokine in tumor recurrence. Eight patients with atrial myxoma were evaluated at our institution from July 1993 to November 1998. We measured their interleukin-6 serum levels by enzyme-linked immunosorbent assay method preoperatively and 1 and 6 months after surgery. Two of the cases involved recurrent tumor; 1 patient had undergone his 1st surgery at a different institution and died during the 2nd procedure, so his data were incomplete. Preoperatively, the whole group of patients had elevated interleukin-6 serum levels. Although patients with a 1st occurrence of tumor demonstrated a positive correlation between interleukin-6 serum level and tumor size, the 2 patients with recurrent tumors appeared to have higher interleukin-6 levels regardless of tumor size. Once the tumor was surgically removed, interleukin-6 levels returned to normal values, and this was associated with regression of clinical manifestations and immunologic features. According to our study, the overproduction of interleukin-6 by cardiac myxomas is responsible for the constitutional symptoms and immunologic abnormalities observed in patients with such tumors and might also play a role as a marker of recurrence. This study also suggests that recurrent cardiac myxomas form a subgroup of cardiac myxomas with a highly intrinsic aggressiveness, as implied by their greater interleukin-6 production despite their smaller size. Further studies are needed to confirm these results. PMID:11330738
Scarpi, Emanuela; Maltoni, Paolo; Dorizzi, Romolo M.; Passardi, Alessandro; Frassineti, Giovanni Luca; Cortesi, Pietro; Giannini, Maria Benedetta; Marisi, Giorgia; Amadori, Dino; Lucchesi, Alessandro
Serum levels of C-reactive protein are (CRP) higher in patients with neoplastic conditions and numerous studies have been performed to clarify the etiologic and prognostic role of the high-sensitivity CRP (hs-CRP) in cancer. Our study was conducted on patients enrolled in the prospective randomized “Italian Trial in Advanced Colorectal Cancer (ITACa)” to assess hs-CRP levels and their impact on overall survival (OS) and progression-free survival (PFS). Serum samples from 132 ITACa patients were collected at baseline and 2 months after starting first-line chemotherapy. The supernatant was immediately transferred to cryovials and stored at −80°C. After thawing, hs-CRP was measured with the Cobas c501 analyzer. High levels of hs-CRP (≥ 13.1 mg/L) were associated with poorer median PFS (p < 0.0001) and OS (p < 0.0001) than low hs-CRP levels (< 13.1 mg/L). hs-CRP values in 107 patients were evaluated again after 2 months of therapy, revealing that patients with low hs-CRP levels in both baseline and second serum samples had the best median PFS and OS. Our study confirms the prognostic value of hs-CRP in patients with metastatic colorectal carcinoma. PMID:26848624
Grootveld, M; Bell, J D; Halliwell, B; Aruoma, O I; Bomford, A; Sadler, P J
The nature of non-transferrin-bound iron in the plasma or serum of iron-overloaded hemochromatosis patients was studied by high performance liquid chromatography (HPLC) and high resolution nuclear magnetic resonance (NMR). 500-MHz proton Hahn spin-echo NMR spectra of plasma or serum, combined with the use of the iron chelator desferrioxamine, suggests complexation of iron ions with citrate and a possible involvement of acetate. Addition of FeCl3 to hemochromatosis samples broadened the NMR signals from citrate. HPLC analysis rigorously confirmed the presence of an iron-citrate complex in ultrafiltrates of plasma or serum studies with added FeCl3 or desferrioxamine supported this conclusion. It is proposed that non-transferrin-bound iron in the plasma of iron-overloaded patients exists largely as complexes with citrate and possibly also as ternary iron-citrate-acetate complexes. The presence of such complexes would account for the ability of non-transferrin-bound iron to be measurable by the bleomycin assay and for its rapid clearance from the circulation by the liver.
Fan, Shengjie; Zhang, Yu; Sun, Qinhu; Yu, Lijing; Li, Mingxia; Zheng, Bin; Wu, Ximin; Yang, Baican; Li, Yiming; Huang, Cheng
Okra is an important tropical vegetable and source of dietary medicine. Here, we assayed the effects of an ethanol extract of okra (EO) and its major flavonoids isoquercitrin and quercetin 3-O-gentiobioside on metabolic disorders in high-fat diet-induced obese mouse. We found that treatment with EO, isoquercitrin and quercetin 3-O-gentiobioside reduced blood glucose and serum insulin levels and improved glucose tolerance in obese mice. Meanwhile, serum triglyceride levels and liver morphology in the mice were significantly ameliorated by EO and isoquercitrin treatment. Total cholesterol levels in isoquercitrin and quercetin 3-O-gentiobioside treated mice were also reduced. We also found that EO inhibited the expression of nuclear receptor transcription factor PPARγ, which is an important regulator of lipid and glucose homeostasis. Furthermore, we determined that EO and quercetin 3-O-gentiobioside have antioxidant activity in vitro. Our results indicate that okra may serve as a dietary therapy for hyperglycemia and hypertriglyceridemia.
Xia, Hai-Feng; Don, Bin-Bin; Zheng, Meng-Jie
A type of mixed-mode chromatography was integrated with high-performance liquid chromatography for protein analysis and separation. The chromatographic behavior was tested using bovine serum albumin and lysozyme as model proteins. For the mixed-mode column, the silica beads were activated with γ-(2,3-epoxypropoxy)-propytrimethoxysilane and coupled with 4-mercaptopyridine as the functional ligand. The effects of pH, salt, and the organic solvent conditions of the mobile phase on the retention behavior were studied, which provided valuable clues for separation strategy. When eluted with a suitable pH gradient, salt concentration gradient, and acetonitrile content gradient, the separation behavior of bovine serum albumin and lysozyme could be controlled by altering the conditions of the mobile phase. The results indicated this type of chromatography might be a useful method for protein analysis and separation.
Hecker, Michael; Fitzner, Brit; Wendt, Matthias; Lorenz, Peter; Flechtner, Kristin; Steinbeck, Felix; Schröder, Ina; Thiesen, Hans-Jürgen; Zettl, Uwe Klaus
Intrathecal immunoglobulin G (IgG) synthesis and oligoclonal IgG bands in cerebrospinal fluid (CSF) are hallmarks of multiple sclerosis (MS), but the antigen specificities remain enigmatic. Our study is the first investigating the autoantibody repertoire in paired serum and CSF samples from patients with relapsing-remitting MS (RRMS), primary progressive MS (PPMS), and other neurological diseases by the use of high-density peptide microarrays. Protein sequences of 45 presumed MS autoantigens (e.g. MOG, MBP, and MAG) were represented on the microarrays by overlapping 15mer peptides. IgG reactivities were screened against a total of 3991 peptides, including also selected viral epitopes. The measured antibody reactivities were highly individual but correlated for matched serum and CSF samples. We found 54 peptides to be recognized significantly more often by serum or CSF antibodies from MS patients compared with controls (p values <0.05). The results for RRMS and PPMS clearly overlapped. However, PPMS patients presented a broader peptide-antibody signature. The highest signals were detected for a peptide mapping to a region of the Epstein-Barr virus protein EBNA1 (amino acids 392–411), which is homologous to the N-terminal part of human crystallin alpha-B. Our data confirmed several known MS-associated antigens and epitopes, and they delivered additional potential linear epitopes, which await further validation. The peripheral and intrathecal humoral immune response in MS is polyspecific and includes antibodies that are also found in serum of patients with other diseases. Further studies are required to assess the pathogenic relevance of autoreactive and anti-EBNA1 antibodies as well as their combinatorial value as biomarkers for MS. PMID:26831522
Simultaneous quantification of acylcarnitine isomers containing dicarboxylic acylcarnitines in human serum and urine by high-performance liquid chromatography/electrospray ionization tandem mass spectrometry.
Maeda, Yasuhiro; Ito, Tetsuya; Suzuki, Atsuko; Kurono, Yukihisa; Ueta, Akihito; Yokoi, Kyoko; Sumi, Satoshi; Togari, Hajime; Sugiyama, Naruji
Tandem mass spectrometry (MS/MS) has become a prominent method for screening newborns for diseases such as organic acidemia and fatty acid oxidation defects, although current methods cannot separate acylcarnitine isomers. Accurate determination of dicarboxylic acylcarnitines such as methylmalonylcarnitine and glutarylcarnitine has not been carried out, because obtaining standards of these acylcarnitines is difficult. We attempted the individual determinations of acylcarnitines with isomers and dicarboxylic acylcarnitines by applying high-performance liquid chromatography (HPLC). Chromatographic separation was performed by gradient elution using a mixture of 0.08% aqueous ion-pairing agent and acetonitrile as the mobile phase. Mass transitions of m/z 161.8-->84.8 for carnitine and m/z 164.8-->84.8 for deuterated carnitine were monitored in positive ion electrospray ionization mode. One carnitine and 16 acylcarnitines were quantified. The limit of quantitation (LOQ) was 0.1 micromol/L for methylmalonylcarnitine and 0.05 micromol/L for the other acylcarnitines. Intra-day and inter-day coefficients of variance (CVs) were <8.3% and <8.8%, respectively, for all acylcarnitines in serum, and both were <9.2% in urine. Mean recoveries were >90% for all acylcarnitines. Human samples were quantified by this method. After addition of deuterated acylcarnitines as internal standards, acylcarnitines in serum or urine were extracted using a solid-phase extraction cartridge. In healthy adult individuals, isobutyryl-, 2-methylbutyryl- and isovalerylcarnitine were detected in serum and urine. Dicarboxylic acylcarnitines were detected in urine. High concentrations of methylmalonylcarnitine and propionylcarnitine were found in both the serum and the urine of a patient with methylmalonic acidemia. The described HPLC/MS/MS method could separate most acylcarnitine isomers and quantify them, potentially allowing detailed diagnoses and follow-up treatment for those diseases.
Song, Qi-Ying; Luo, Wei-Ping; Zhang, Cai-Xia
The exact cause of hypertensive disorders in pregnancy (HDP) has not been clearly elucidated. Some researchers have recently investigated the relationship between the serum iron level and the incidence of HDP. However, the results are inconsistent, and these data have not been systematically evaluated. Therefore, we conducted a meta-analysis to evaluate the real association between the serum iron level and the incidence of HDP. We searched for published and ongoing trials in PubMed, EMBASE, Scopus, Web of Science, the Chinese Biomedical Database, CNKI, and the WANFANG database from January 1990 to May 2015 to identify studies that met our predefined criteria. Finally, 26 studies, including 1 cross-sectional study, 23 case-control studies, and 2 prospective nested case-control studies, including 1349 patients and 1119 control participants, were selected for this meta-analysis. The pooled results show that a high serum iron level increased the incidence of HDP (standard mean deviation [SMD], 1.50; 95% confidence interval [CI], 0.94-2.06; P < .0001), especially gestational hypertension (SMD, 3.65; 95% CI, 1.50-5.81; P = .0009) and preeclampsia (SMD, 1.27; 95% CI, 0.76-1.78; P < .0001). No significant difference was seen between the eclampsia groups and the control participants (SMD, 3.34; 95% CI, -0.02 to 6.69; P = .05). The results of this meta-analysis indicate that a high serum iron level is associated with an increased risk of HDP, especially gestational hypertension and preeclampsia.
Marcus, J C; Altura, B T; Altura, B M
The objective of this study was to determine the values of serum ionized magnesium, total magnesium, and ionized calcium/ionized magnesium ratios in children with headaches. One hundred thirty-five children with primary complaints of headaches were classified according to the criteria of the International Headache Society. Blood samples were obtained and tested for ionized magnesium (IMg(2+)), total magnesium, ionized calcium (ICa(2+)), and pH. The ICa(2+)/IMg(2+) ratio was calculated. Nine children were given a diagnosis of post-traumatic headache. Six of them had statistically significant (P <.05) lowered IMg(2+) levels and high ICa(2+)/IMg(2+) ratios. Abnormalities in serum IMg(2+) concentrations and ICa(2+)/IMg(2+) ratios were found in children with post-traumatic headaches, but total magnesium levels were normal.
Yoon, Joon; Chu, Jae Ryang; Bae, Yun Jung; Lee, Seungyeoun; Park, Taesung; Sung, Mi-Kyung
Obesity-induced chronic inflammation is known to increase the risk of ulcerative colitis, Crohn’s disease, and colorectal cancer. Accumulating evidence suggests that leptin and insulin are key molecules linking obesity with diseases of the lower intestine. Here, we identified serum phenotype-associated genes in the colon of diet-induced obese mice as early biomarkers of obesity-associated colonic diseases. C57BL/6J mice were fed with either normal diet (ND, 15% of fat calories) or high-fat diet (HFD, 45% of fat calories) for 8 weeks. Serum concentrations of insulin, insulin-like growth factor-1 (IGF-1), leptin, and adiponectin were measured as obesity-related phenotypic markers. Genome-wide gene expression profiles of colon tissue were determined, followed by statistical analyses to detect differentially expressed and serum phenotype-associated genes. HFD-fed mice showed higher serum concentrations of leptin (P < 0.001) and insulin (P < 0.01) than those in the ND group, whereas serum IGF-1 and adiponectin concentrations did not differ between the two dietary groups. Among differentially expressed genes affected by HFD, 135, 128, 110, and 341 genes were associated with serum levels of leptin, insulin, IGF-1, and adiponectin, respectively. We identified 17 leptin-associated genes and 4 insulin-associated genes that inversely responded to HFD and ND. Among these, leptin-associated Peli3 (Pellino E3 ubiquitin protein ligase family member 3), Creb1 (cAMP responsive element binding protein 1), and Enpp2 (ectonucleotide pyrophosphatase/phosphodiesterase 2, autotaxin) and insulin-associated Centg1 (AGAP2, ArfGAP with GTPase domain) are reported to play a role either in obesity or colonic diseases. mRNA expression of these genes was validated by RT-qPCR. Our data suggest Peli3, Creb1, Enpp2, and Centg1 as potential early biomarker candidates for obesity-induced pathophysiological changes in the colon. Future studies verifying the function of these candidates are needed
Hagen, Ingrid V; Helland, Anita; Bratlie, Marianne; Brokstad, Karl A; Rosenlund, Grethe; Sveier, Harald; Mellgren, Gunnar; Gudbrandsen, Oddrun A
The aim of the present study was to examine whether high intake of lean or fatty fish (cod and farmed salmon, respectively) by healthy, normal-weight adults would affect risk factors of type 2 diabetes and CVD when compared with lean meat (chicken). More knowledge is needed concerning the potential health effects of high fish intake (>300 g/week) in normal-weight adults. In this randomised clinical trial, thirty-eight young, healthy, normal-weight participants consumed 750 g/week of lean or fatty fish or lean meat (as control) for 4 weeks at dinner according to provided recipes to ensure similar ways of preparations and choices of side dishes between the groups. Energy and macronutrient intakes at baseline and end point were similar in all groups, and there were no changes in energy and macronutrient intakes within any of the groups during the course of the study. High intake of fatty fish, but not lean fish, significantly reduced TAG and increased HDL-cholesterol concentrations in fasting serum when compared with lean meat intake. When compared with lean fish intake, fatty fish intake increased serum HDL-cholesterol. No differences were observed between lean fish, fatty fish and lean meat groups regarding fasting and postprandial glucose regulation. These findings suggest that high intake of fatty fish, but not of lean fish, could beneficially affect serum concentrations of TAG and HDL-cholesterol, which are CVD risk factors, in healthy, normal-weight adults, when compared with high intake of lean meat.
Brenton, D. P.
The skeletal changes of thirty-four patients with the biochemical and clinical features of cystathionine synthase deficiency are described. It is emphasized that there is clinical evidence of excessive bone growth and the formation for bone which is structurally weaker than normal. The similarities and differences between this condition and Marfan's syndrome are stressed and the possible nature of the connective tissue defect leading to the skeletal changes discussed. The most characteristic skeletal changes in homocystinuria are the skeletal disproportion (pubis-heel length greater than crown-pubis length), the abnormal vertebrae, sternal deformities, genu valgum and large metaphyses and epiphyses. Images Fig. 2 Fig. 3 Fig. 4 Fig. 8 Fig. 9 Fig. 10 PMID:917963
Nien, Hsiao-Ching; Hsu, Shih-Jer; Su, Tung-Hung; Yang, Po-Jen; Sheu, Jin-Chuan; Wang, Jin-Town; Chow, Lu-Ping; Chen, Chi-Ling
Background Lipopolysaccharide-binding protein (LBP) has been reported to associate with metabolic diseases, such as obesity, diabetes, and non-alcoholic fatty liver disease. Since chronic hepatitis C virus (HCV) infection is associated with metabolic derangements, the relationship between LBP and HCV deserves additional studies. This study aimed to determine the serum LBP level in subjects with or without HCV infection and investigate the change of its level after anti-viral treatments with or without interferon. Methods and Findings We recruited 120 non-HCV subjects, 42 and 17 HCV-infected subjects respectively treated with peginterferon α-2a/ribavirin and direct-acting antiviral drugs. Basic information, clinical data, serum LBP level and abdominal ultrasonography were collected. All the subjects provided written informed consent before being enrolled approved by the Research Ethics Committee of the National Taiwan University Hospital. Serum LBP level was significantly higher in HCV-infected subjects than non-HCV subjects (31.0 ± 8.8 versus 20.0 ± 6.4 μg/mL; p-value < 0.001). After multivariate analyses, LBP at baseline was independently associated with body mass index, hemoglobin A1c, alanine aminotransferase (ALT) and HCV infection. Moreover, the baseline LBP was only significantly positively associated with ALT and inversely with fatty liver in HCV-infected subjects. The LBP level significantly decreased at sustained virologic response (27.4 ± 6.6 versus 34.6 ± 7.3 μg/mL, p-value < 0.001; 15.9 ± 4.4 versus 22.2 ± 5.7 μg/mL, p-value = 0.001), regardless of interferon-based or -free therapy. Conclusions LBP, an endotoxemia associated protein might be used as an inflammatory biomarker of both infectious and non-infectious origins in HCV-infected subjects. PMID:28107471
Telesco, Shannon E.; Brodmerkel, Carrie; Argmann, Carmen; Dudley, Joel; Cho, Judy; Schadt, Eric E.; Kasarskis, Andrew; Hao, Ke
To date, no large scale, systematic description of the blood serum proteome has been performed in inflammatory bowel disease (IBD) patients. By using microarray technology, a more complete description of the blood proteome of IBD patients is feasible. It may help to achieve a better understanding of the disease. We analyzed blood serum profiles of 1128 proteins in IBD patients of European descent (84 Crohn’s Disease (CD) subjects and 88 Ulcerative Colitis (UC) subjects) as well as 15 healthy control subjects, and linked protein variability to patient age (all cohorts) and genetic components (genotype data generated from CD patients). We discovered new, previously unreported aging-associated proteomic traits (such as serum Albumin level), confirmed previously reported results from different tissues (i.e., upregulation of APOE with aging), and found loss of regulation of MMP7 in CD patients. In carrying out a genome wide genotype-protein association study (proteomic Quantitative Trait Loci, pQTL) within the CD patients, we identified 41 distinct proteomic traits influenced by cis pQTLs (underlying SNPs are referred to as pSNPs). Significant overlaps between pQTLs and cis eQTLs corresponding to the same gene were observed and in some cases the QTL were related to inflammatory disease susceptibility. Importantly, we discovered that serum protein levels of MST1 (Macrophage Stimulating 1) were regulated by SNP rs3197999 (p = 5.96E-10, FDR<5%), an accepted GWAS locus for IBD. Filling the knowledge gap of molecular mechanisms between GWAS hits and disease susceptibility requires systematically dissecting the impact of the locus at the cell, mRNA expression, and protein levels. The technology and analysis tools that are now available for large-scale molecular studies can elucidate how alterations in the proteome driven by genetic polymorphisms cause or provide protection against disease. Herein, we demonstrated this directly by integrating proteomic and pQTLs with
Di Narzo, Antonio F; Telesco, Shannon E; Brodmerkel, Carrie; Argmann, Carmen; Peters, Lauren A; Li, Katherine; Kidd, Brian; Dudley, Joel; Cho, Judy; Schadt, Eric E; Kasarskis, Andrew; Dobrin, Radu; Hao, Ke
To date, no large scale, systematic description of the blood serum proteome has been performed in inflammatory bowel disease (IBD) patients. By using microarray technology, a more complete description of the blood proteome of IBD patients is feasible. It may help to achieve a better understanding of the disease. We analyzed blood serum profiles of 1128 proteins in IBD patients of European descent (84 Crohn's Disease (CD) subjects and 88 Ulcerative Colitis (UC) subjects) as well as 15 healthy control subjects, and linked protein variability to patient age (all cohorts) and genetic components (genotype data generated from CD patients). We discovered new, previously unreported aging-associated proteomic traits (such as serum Albumin level), confirmed previously reported results from different tissues (i.e., upregulation of APOE with aging), and found loss of regulation of MMP7 in CD patients. In carrying out a genome wide genotype-protein association study (proteomic Quantitative Trait Loci, pQTL) within the CD patients, we identified 41 distinct proteomic traits influenced by cis pQTLs (underlying SNPs are referred to as pSNPs). Significant overlaps between pQTLs and cis eQTLs corresponding to the same gene were observed and in some cases the QTL were related to inflammatory disease susceptibility. Importantly, we discovered that serum protein levels of MST1 (Macrophage Stimulating 1) were regulated by SNP rs3197999 (p = 5.96E-10, FDR<5%), an accepted GWAS locus for IBD. Filling the knowledge gap of molecular mechanisms between GWAS hits and disease susceptibility requires systematically dissecting the impact of the locus at the cell, mRNA expression, and protein levels. The technology and analysis tools that are now available for large-scale molecular studies can elucidate how alterations in the proteome driven by genetic polymorphisms cause or provide protection against disease. Herein, we demonstrated this directly by integrating proteomic and pQTLs with existing
Barr, John R; Woolfitt, Adrian R; Maggio, Vincent L; Patterson, Donald G
Because human toxaphene exposure data are largely lacking, we surveyed human serum pools collected from U.S. residents to determine the feasibility of measuring toxaphene in human samples and to determine whether additional analytical requirements were needed for routine measurement of toxaphene. We report a method for quantification of toxaphene congeners in human serum using a mixed-bed gradient solid-phase extraction and analysis using gas chromatography-high-resolution mass spectrometry with electron-impact ionization. In this method, we monitored low-mass fragment ions that were common to all 22 congeners. To verify the specific congeners detected, we further analyzed the extract using negative methane chemical ionization. We used this method to measure two specific congeners, Parlar 26 and 50, at concentrations ranging from about 3 to 30 pg/ml (0.7-7 ng/g lipid) in pooled human serum collected in Atlanta, Chicago, and Cincinnati. We identified several analytical parameters that must be strengthened to routinely measure toxaphene congeners in human samples.
Patil, Ajeetkumar; Prabhu, Vijendra; Choudhari, K. S.; Unnikrishnan, V. K.; George, Sajan D.; Ongole, Ravikiran; Pai, Keerthilatha M.; Shetty, Jayarama K.; Bhat, Sujatha; Kartha, Vasudevan Bhaskaran; Chidangil, Santhosh
The present work deals with the evaluation of a high-performance liquid chromatography laser-induced fluorescence (HPLC-LIF) technique developed in our laboratory for early detection of oral cancer from protein profiles of body fluids. The results show that protein profiles of serum samples from a given class of samples, say, normal, premalignant, or malignant, are statistically very close to each other, while profiles of members of any class are significantly different from other classes. The performance of the technique is evaluated by the use of sensitivity and specificity pairs, receiver operating characteristic (ROC) analysis, and Youden's Index. The technique uses protein profile differences in serum samples, registered by the HPLC-LIF technique. The study is carried out using serum samples from volunteers diagnosed as normal or premalignant clinically, and as malignant by histopathology. The specificities and sensitivities of the HPLC-LIF method at an ideal threshold (M-distance = 2) for normal, malignant, and premalignant classes are 100, 69.5, and 61.5%, and 86.5, 87.5, and 87.5% respectively.
Khayat Nouri, Mir Hadi; Namvaran Abbas Abad, Ali
Background Hypercholesterolemia is one of the risk factors of cardiovascular diseases. Increased blood cholesterol affects general health and increases mortality due to cardiovascular disease. Poor nutrition increases LDL cholesterol and decreases LDL receptor activities in the liver. Scientists have shown that consumption of antioxidants can reduce hypercholesterolemia and proved benefits of fruit and vegetables. Tomato reduces oxidative stress by increasing serum total antioxidant level. Objectives This study compared the tomato and tomato paste supplementation on the level of serum lipids and lipoproteins in rats fed with high cholesterol. Materials and Methods In this study, four male rat groups (10 rats per group) were used. Control group received basal diet, second group received basal diet and 2% cholesterol (Chol), third and fourth groups received basal diet, 2% cholesterol tomato and tomato paste respectively (20 percent of the diet) for a month. Then serum TC, LDL, HDL and TG were measured. Results Results showed that in Chol group, all lipids increased significantly (P < 0.05) except HDL compared to the control group. Tomato and tomato paste supplementation decreased TC, LDL and TG concentration significantly (P < 0.05) compared to Chol group. Tomato paste had the higher effect on lipids decreasing than tomato. Conclusions Decreases of TC, LDL and TG may be related to tomato antioxidant effect. This course in human required more investigations. PMID:24082999
Jin, Micong; Yang, Yiwen; Su, Baogen; Ren, Qilong
A rapid, sensitive and selective high-performance liquid chromatography-tandem mass spectrometric method (HPLC-MS-MS) has been developed and validated for the determination of soyasaponins Ba and Bb in human serum using glycyrrhizin as internal standard (I.S.). Soyasaponins Ba and Bb were extracted from human serum by liquid-liquid extraction and cleaned up by C(18) solid-phase extraction (SPE), followed by separation on a C(18) reversed-phase column using acetonitrile/water containing 0.025% acetic acid as a mobile phase for gradient elution. Soyasaponins Ba and Bb, and I.S. were ionized by negative ion pneumatically assisted electrospray and detected by HPLC-MS-MS in the multiple-reaction monitoring (MRM) mode using precursor-->product ion combinations at m/z 958-->940, 942-->924 and 822-->351, respectively. The calibration curves were linear (r(2)>0.991) in the concentration range of 0.5-100.0 ng/mL, with lower limits of quantification of 0.5 and 0.3 ng/mL for soyasaponins Ba and Bb, respectively, in human serum. Intra-day and inter-day relative standard deviations (R.S.D.) were less than 7.9 and 11.3%, respectively. The mean recoveries of soyasaponins Ba and Bb ranged from 92 to 101% and from 85 to 94%, respectively.
Hovden, A-O; Cox, R J; Madhun, A; Haaheim, L R
We have previously found that whole influenza virus vaccine induced a more rapid and stronger humoral response, particularly after the first dose of vaccine, than split virus vaccine in mice. In this study, we have evaluated the protective efficacy of whole and split influenza virus vaccines in mice using a nonlethal upper respiratory tract challenge model. We have also investigated the immunological correlates associated with no or very little viral shedding after viral challenge. Vaccination resulted in reduced viral shedding and shortened the duration of infection by at least 2 days. After one dose of vaccine, whole virus vaccine generally resulted in less viral shedding than split virus vaccine. In contrast, two doses of split virus vaccine, particularly the highest vaccine strengths of 15 and 30 microg HA, most effectively limited viral replication and these mice had high concentrations of prechallenge influenza-specific serum IgG. The vaccine formulation influenced the IgG2a/IgG1 ratio, and this IgG subclass profile was maintained upon challenge to some extent, although it did not influence the level of viral shedding. The concentration of postvaccination serum IgG showed an inverse relationship with the level of viral shedding after viral challenge. Therefore, serum IgG is an important factor in limiting viral replication in the upper respiratory tract upon challenge of an antigenically similar virus.
Liu, Xiaodan; Yu, Yingjia; Li, Yan; Zhang, Haiying; Ling, Jin; Sun, Xueni; Feng, Jianan; Duan, Gengli
We report herein an extraction method for the analysis of perfluorinated compounds in human serum based on magnetic core-mesoporous shell microspheres with decyl-perfluorinated interior pore-walls (Fe3O4@mSiO2-F17). Thanks to the unique properties of the Fe3O4@mSiO2-F17 microspheres, macromolecules like proteins could be easily excluded from the mesoporous channels due to size exclusion effect, and perfluorinated compounds (PFCs) in protein-rich biosamples such as serum could thus be directly extracted with the fluorocarbon modified on the channel wall without any other pretreatment procedure. The PFCs adsorbed Fe3O4@mSiO2-F17 microspheres could then be simply and rapidly isolated by using a magnet, followed by being identified and quantified by LC-MS/MS (high-performance liquid chromatography coupled to tandem mass spectrometry). Five perfluorinatedcarboxylic acids (C6, C8-C11) and perfluorooctane sulfonate (PFOS) were selected as model analytes. In order to achieve the best extraction efficiency, some important factors including the amount of Fe3O4@mSiO2-F17 microspheres added, adsorption time, type of elution solvent, eluting solvent volume and elution time were investigated. The ranges of the LOD were 0.02-0.05 ng mL(-1) for the six PFCs. The recovery of the optimized method varies from 83.13% to 92.42% for human serum samples.
Wu, Feng-Bo; Han, Shi-Quan; Zhang, Chao; He, You-Feng
A new highly fluorescent beta-diketone-europium chelate was synthesized and employed as a tracer to develop a time-resolved fluoroimmunoassay (TRFIA) for detection of serum total thyroxine (T4). The tetradentate beta-diketone chelator, 1,10-bis(thiophene-2'-yl)-4,4,5,5,6,6,7,7-octafluorodecane-1,3,8,10-tetraone (BTOT), was structurally composed of two units of thenoyltrifluoroacetone (TTA) derivatives but expressed fluorescence that was greatly enhanced, as compared to the original TTA molecules, in the presence of excess amount of Eu3+. The luminescence properties of the europium chelate of BTOT werestudied in aqueous solution. Chlorosulfonylation of BTOT afforded 1, 10-bis(5'-chlorosulfo-thiophene-2'-yl)-4,4,5,5,6,6,7,7-octafluorodecane-1,3,8,10-tetraone (BCTOT), which could be coupled to proteins (i.e., streptavidin or the BSA-T4 conjugate) and used as a tracer for TRFIA. Although the BCTOT-Eu complex could be detected at a very low level (approximately 1.07 x 10(-12) mol/L) in buffered aqueous solution (50 mmoVLTris-HCl; pH, 8.0), the application of the chelate label in direct serum T4 TRFIA experienced a problem of matrix interference, which was probably caused by some unknown chelating components in the samples as a result of the fact that the fluorescence of the BCTOT-Eu chelate was prone to quenching or enhancement by some chelating reagents. To remove this problem, an indirect serum T4 TRFIA was proposed with the use of BCTOT-Eu-labeled streptavidin (SA) as signal generation reagent. The concentrations of T4 in 27 human serums were determined by indirect T4 TRFIA, and the assay results correlated well with those obtained by commercial Coming-CLIA (r = 0.955) and Wallac-DELFIA (r 0.965).
Titov, V N; Sazhina, N N
Total antioxidant activity of the serum in patients with liver pathology was assessed by two chemiluminescent methods based on different models of free radical oxidation: Hb-H2O2-luminol and ABAP-luminol. Comparative analysis showed a significant, but not high correlation of the results (r=0.798), which can be explained by different mechanisms of induction of free radicals and effects of various serum components (proteins and bilirubin) on the initiation process. The influence of aphysiological concentration of analyzed values manifested in the Hb-H2O2 model. Disagreement between the results of measurements was more pronounced in patients with abnormally high serum bilirubin content. The results suggested that ABAP-luminol chemiluminescent model is more preferable for evaluation of antioxidant activity in clinical practice.
Babel, Ingrid; Barderas, Rodrigo; Díaz-Uriarte, Ramón; Martínez-Torrecuadrada, Jorge Luis; Sánchez-Carbayo, Marta; Casal, J Ignacio
There is a mounting evidence of the existence of autoantibodies associated to cancer progression. Antibodies are the target of choice for serum screening because of their stability and suitability for sensitive immunoassays. By using commercial protein microarrays containing 8000 human proteins, we examined 20 sera from colorectal cancer (CRC) patients and healthy subjects to identify autoantibody patterns and associated antigens. Forty-three proteins were differentially recognized by tumoral and reference sera (p value <0.04) in the protein microarrays. Five immunoreactive antigens, PIM1, MAPKAPK3, STK4, SRC, and FGFR4, showed the highest prevalence in cancer samples, whereas ACVR2B was more abundant in normal sera. Three of them, PIM1, MAPKAPK3, and ACVR2B, were used for further validation. A significant increase in the expression level of these antigens on CRC cell lines and colonic mucosa was confirmed by immunoblotting and immunohistochemistry on tissue microarrays. A diagnostic ELISA based on the combination of MAPKAPK3 and ACVR2B proteins yielded specificity and sensitivity values of 73.9 and 83.3% (area under the curve, 0.85), respectively, for CRC discrimination after using an independent sample set containing 94 sera representative of different stages of progression and control subjects. In summary, these studies confirmed the presence of specific autoantibodies for CRC and revealed new individual markers of disease (PIM1, MAPKAPK3, and ACVR2B) with the potential to diagnose CRC with higher specificity and sensitivity than previously reported serum biomarkers.
Cai, Mei-Qiang; Chen, Xiao-Hong; Ouyang, Xiao-Kun; Jin, Mi-Cong
Valone is a chronic anticoagulant rodenticide that has come into wide use in China. Current literature lacks analytical methods for the determination of valone. In this paper, a sensitive and selective assay was established for the identification and quantification of valone in serum by liquid chromatography-tandem mass spectrometry. After addition of the internal standard, warfarin, serum samples were extracted with 10% methanol in acetonitrile and cleaned using Oasis HLB solid-phase extraction (SPE) cartridges. The compounds were separated on an Agilent SB C18 column with a mobile phase of methanol/acetic acid-ammonium acetate (5 mmol/L, pH 6.3) (75:25, v/v). Detection was performed by electrospray ionization ion trap mass spectrometry in the negative multiple reaction monitoring mode. The transition ions of m/z 229 --> 145 and m/z 307 --> 161 were selected for quantification of valone and the internal standard, respectively. The overall extraction efficiency was between 81.1% and 91.1%. The limit of quantification was 0.5 ng/mL. Regression analysis of the calibration data revealed good correlation (r(2) > 0.99) for valone. Intra- and interday precisions for quality-control samples were less than 7.8% and 12.8%, respectively. This method combines a rapid SPE procedure with an extremely fast chromatographic analysis, which is especially advantageous or clinical laboratories.
Torchio, L; Lombardi, F; Visconti, M; Doyle, E
A sensitive and fully automated column-switching HPLC method was developed for the determination of a novel cognition enhancer, dimiracetam, in human plasma and serum. A sample of plasma was ultrafiltered and then directly injected onto a first mu Bondapak C18 column. The sample was eluted with water. The portion of the eluate (heart-cut) from this column containing the drug was selected and loaded on a second mu Bondapak C18 column and eluted with water. During the elution of the second column, the first column was automatically rinsed with water-acetonitrile (50:50, v/v) and then equilibrated for a new injection. The total analysis time for each sample was 35 min. This corresponded to a 30% decrease in analysis time compared with the time that would have been needed with a simple run with two mu Bondapak C18 columns assembled in series. Ultraviolet detection at 200 nm was used to monitor the eluate. The method was fully validated over the quantitation range 27 ng/ml-15 micrograms/ml. The applicability of the method was demonstrated by analysis of serum samples from a study performed in human healthy volunteers.
Kim, Beom-Jun; Koh, Jung-Min; Ahn, Seong Hee; Lee, Seung Hun; Kim, Eun Hee; Bae, Sung Jin; Kim, Hong-Kyu; Choe, Jae Won; Kim, Ghi Su
Bilirubin is known to have a physiologic role as an antioxidant that efficiently scavenges peroxyl radicals and suppresses oxidation, and oxidative stress has detrimental effects on bone metabolism. In the present study, we performed a 3-year longitudinal study of healthy middle-aged men, investigating the association between serum total bilirubin concentrations and annualized changes in bone mineral density (BMD). The study enrolled a total of 917 Korean men aged 40 years or older who had undergone comprehensive routine health examinations with an average follow-up interval of 3 years. BMD at proximal femur sites was measured with dual-energy X-ray absorptiometry using the same equipment at baseline and follow-up. The overall mean annualized rates of bone loss at the total femur, femoral neck, and trochanter were -0.25 %/year, -0.34 %/year, and -0.44 %/year, respectively. After adjustment for potential confounders, the rates of bone loss at all proximal femur sites were significantly attenuated in a dose-response fashion across increasing bilirubin concentrations (P = 0.006-0.046). Moreover, compared to subjects in the lowest bilirubin quartile category, those in the highest bilirubin quartile category showed significantly less bone loss at all proximal femur sites after adjustment for confounding factors (P = 0.010-0.048). This study provides the first clinical evidence that serum total bilirubin could be a protective marker against future bone loss, especially in subjects without liver diseases.
Holm, P; Booth, P J; Schmidt, M H; Greve, T; Callesen, H
We describe a bovine embryo culture system that supports repeatable high development in the presence of serum or BSA as well as under defined conditions in the absence of those components. In the first experiment, embryo development in SOF with amino acids (SOFaa), sodium citrate (SOFaac) and myo-inositol (SOFaaci) and with BSA or polyvinyl alcohol (PVA) was compared with that in a M199 granulosa cell co-culture (M199 co-culture). Subsequently, development and cell numbers of blastocysts cultured under defined conditions in SOFaaci with PVA (SOFaaci-PVA), or under undefined conditions in SOFaaci with 5% cow serum (SOFaaci-CS) or M199 co-culture were compared. The repeatability of culture results in SOFaaci-CS was checked by weekly replicates (n = 30) spread over 11 months. The viability of embryos developed in SOFaaci-PVA was estimated by transfer of morphologically good blastocysts (n = 10) to synchronized recipients. In the second experiment, the effect of omitting CS or BSA from IVM and IVM-IVF on subsequent embryo development in SOFaaci-PVA or in SOFaaci-CS was investigated. Blastocyst development in SOFaa-PVA, SOFaac-PVA, SOFaa-BSA and M199 was 16 +/- 3b, 23 +/- 2ab, 30 +/- 8a and 36 +/- 7a%, respectively (Pab < 0.05). Additional inclusion of myoinositol resulted in 42 +/- 1a% blastocysts in SOFaaci-PVA vs 19 +/- 3b% in SOFaac-PVA, 47 +/- 7a% in SOFaac-BSA, and 36 +/- 7a% in M199 co-culture, respectively (Pab < 0.01). In 30 replicates, the average cleavage and blastocyst rates of oocytes in SOFaaci-CS were 87 +/- 4 and 49 +/- 5%, respectively. Five normal calves were produced after transfer of 10 blastocysts developed in defined culture medium (i.e., SOFaaci-PVA). Defined IVM or IVM-IVF (i.e., in absence of CS and BSA) reduced cleavage rates (83 +/- 3 and 55 +/- 3% vs 90 +/- 1% in presence of CS; P < 0.01). Subsequent embryo development in SOFaaci-CS was not affected in either of these defined conditions. However, cleavage and blastocyst rates under completely
Pang, Xiaowen; Lin, Kai; Liu, Wen; Zhang, Ping; Zhu, Sainan
Psoriasis is a chronic inflammatory skin disease that has been associated with abnormal lipid metabolism. To characterize the lipid profile in Chinese, 86 patients with psoriasis and 84 healthy control subjects were assessed. Compared with healthy controls, the fasting serum values of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (ApoA-I) were lower in the patient group. Compared with vulgaris psoriasis, special types of psoriasis had even lower levels of HDL-C and ApoA-I. Considering the severity of psoriasis, the level of ApoA-I and HDL-C were also the only two serum lipid parameters decreased in the mild group compared to those in controls. In the moderate and the severe group, the values of TC, LDL-C, HDL-C and ApoA-I were all decreased compared to healthy control group. Further analysis indicated that the values of HDL-C and ApoA-I were significantly lower in the severe group compared to the moderate group. Correlation analysis indicated that the levels of HDL-C but not ApoA-I was negatively associated with the severity of the disease. Interestingly, when psoriasis was improved by treatment, the serum levels of TG, TC, HDL-C and ApoA-I were increased from the pre-treatment values. We conclude that abnormalities in serum lipid metabolism may play an important role in the pathogenesis of Chinese patients with psoriasis. PMID:26823881
Vendrell, J M; García, F; Veiga, A; Calderón, G; Egozcue, S; Egozcue, J; Barri, P N
The incidence of meiotic abnormalities and their relationship with different spermatogenic parameters was assessed in 103 male patients with presumably idiopathic severe oligoasthenozoospermia (motile sperm concentration < or = 1.5 x 10(6)/ml). Meiosis on testicular biopsies was independently evaluated by two observers. Meiotic patterns included normal meiosis and two meiotic abnormalities, i.e. severe arrest and synaptic anomalies. A normal pattern was found in 64 (62.1%), severe arrest in 21 (20.4%) and synaptic anomalies in 18 (17.5%). The overall rate of meiotic abnormalities was 37.9%. Most (66.7%) meiotic abnormalities occurred in patients with a sperm concentration < or = 1 x 10(6)/ml. In this group, total meiotic abnormalities were found in 57.8% of the patients; of these, 26.7% had synaptic anomalies. When the sperm concentration was < or = 0.5 x 10(6)/ml, synaptic anomalies were detected in 40% of the patients. In patients with increased follicle stimulating hormone (FSH) concentrations, total meiotic abnormalities occurred in 54.8% (synaptic anomalies in 22.6%). There were statistically significant differences among the three meiotic patterns in relation to sperm concentration (P < 0.001) and serum FSH concentration (P < 0.05). In the multivariate analysis, sperm concentration < or = 1 x 10(6)/ml and/or FSH concentration > 10 IU/l were the only predictors of meiotic abnormalities.
Setianto, Budi Y.; Mubarika, Sofia; Irawan, Bambang; Astuti, Indwiani
Background Matrix metalloproteinase (MMP)-9 is excessively expressed in frail region of atherosclerotic plaque and released in circulation following plaque rupture. High MMP-9 level associated with severity of occluded thrombus and subsequent myocardial infarction. MMP-9 (-1562C>T) polymorphism associated with acute myocardial infarction, however conflicting data present regarding impact of MMP-9 (-1562C>T) polymorphism on circulating MMP-9 level in acute myocardial infarction with ST-elevation (STEMI), clinical entity represents totally occluded coronary thrombus. Methods We enrolled consecutively subjects with acute coronary syndrome treated in intensive coronary care unit. Acute coronary syndrome diagnosis were classified into STEMI and non-ST-elevation acute coronary syndrome (NSTEACS). Seventy consecutive subjects were enrolled for this study, 31 subjects with STEMI and 39 subjects with NSTEACS. Results On admission serum MMP-9 level, measured with sandwich enzyme immunoassay, were higher in STEMI as compared with NSTEACS (1,574.2 ± 604.1 ng/mL vs. 1,104.4 ± 591.5 ng/mL, P < 0.01). Proportion of subjects with MMP-9 (-1562C>T) polymorphism, analyzed with PCR-RFLP, were higher in STEMI as compared with NSTEACS (66.7% vs. 33.3%, P = 0.15). T allele frequency was almost twice in STEMI as compared to in NSTEACS. Almost all (83%) subjects with MMP-9 (-1562C>T) polymorphism had high serum MMP-9 level (> 1,334.5 ng/mL) during STEMI, whereas in NSTEACS all subjects had low level. Conclusion MMP-9 (-1562C>T) polymorphism associated with high serum MMP-9 level in patients with STEMI.
Xue, Y-J; Turner, Kenneth C; Meeker, Jeff B; Pursley, Janice; Arnold, Mark; Unger, Steve
A simple, high throughput, direct-injection high-performance liquid chromatography tandem mass spectrometry method (LC/MS/MS) has been developed and validated for the quantitation of pioglitazone in human serum. After mixing the internal standard with a sample, a 10 microl portion of the mixture was directly injected into a high-flow LC/MS/MS system, which included an extraction column, an analytical column and a six-port switching valve. The on-line extraction was achieved on an Oasis HLB column (1 mm x 50 mm, 30 microm) with a 100% aqueous loading mobile phase containing 5 mM ammonium acetate (pH 4.0) at a flow rate of 4 ml/min. The extracted analyte was eluted by a mobile phase which contained 5 mM ammonium acetate and acetonitrile. The analytical column was a Luna C18 column (4.6 mm x 50 mm, 5 microm). Detection was achieved by positive ion electrospray tandem mass spectrometry. The lower limit of quantitation of the method was 9 ng/ml. The standard curve, which ranged from 9 to 1350 ng/ml, was fitted by a weighted (1/x2) quadratic regression model. The validation results demonstrated that this method had satisfactory precision and accuracy across the calibration range. There was no evidence of instability of the analyte in human serum following three freeze-thaw cycles, and samples could be stored for at least 2 weeks at -30 degrees C. This method was used to analyze pioglitazone concentrations in human serum samples from a bioequivalence study of a blinded Actos formulation (encapsulated 15 mg tablet) and an Actos 15 mg tablet. The blinded formulation was shown to be bioequivalent to an Actos 15 mg tablet.
Kochenderfer, James N; Somerville, Robert P T; Lu, Tangying; Shi, Victoria; Bot, Adrian; Rossi, John; Xue, Allen; Goff, Stephanie L; Yang, James C; Sherry, Richard M; Klebanoff, Christopher A; Kammula, Udai S; Sherman, Marika; Perez, Arianne; Yuan, Constance M; Feldman, Tatyana; Friedberg, Jonathan W; Roschewski, Mark J; Feldman, Steven A; McIntyre, Lori; Toomey, Mary Ann; Rosenberg, Steven A
Purpose T cells genetically modified to express chimeric antigen receptors (CARs) targeting CD19 (CAR-19) have potent activity against acute lymphoblastic leukemia, but fewer results supporting treatment of lymphoma with CAR-19 T cells have been published. Patients with lymphoma that is chemotherapy refractory or relapsed after autologous stem-cell transplantation have a grim prognosis, and new treatments for these patients are clearly needed. Chemotherapy administered before adoptive T-cell transfer has been shown to enhance the antimalignancy activity of adoptively transferred T cells. Patients and Methods We treated 22 patients with advanced-stage lymphoma in a clinical trial of CAR-19 T cells preceded by low-dose chemotherapy. Nineteen patients had diffuse large B-cell lymphoma, two patients had follicular lymphoma, and one patient had mantle cell lymphoma. Patients received a single dose of CAR-19 T cells 2 days after a low-dose chemotherapy conditioning regimen of cyclophosphamide plus fludarabine. Results The overall remission rate was 73% with 55% complete remissions and 18% partial remissions. Eleven of 12 complete remissions are ongoing. Fifty-five percent of patients had grade 3 or 4 neurologic toxicities that completely resolved. The low-dose chemotherapy conditioning regimen depleted blood lymphocytes and increased serum interleukin-15 (IL-15). Patients who achieved a remission had a median peak blood CAR(+) cell level of 98/μL and those who did not achieve a remission had a median peak blood CAR(+) cell level of 15/μL ( P = .027). High serum IL-15 levels were associated with high peak blood CAR(+) cell levels ( P = .001) and remissions of lymphoma ( P < .001). Conclusion CAR-19 T cells preceded by low-dose chemotherapy induced remission of advanced-stage lymphoma, and high serum IL-15 levels were associated with the effectiveness of this treatment regimen. CAR-19 T cells will likely become an important treatment for patients with relapsed lymphoma.
Goddard, Marcia N; Swaab, Hanna; Rombouts, Serge A R B; van Rijn, Sophie
Klinefelter syndrome (47, XXY) is associated with several physical, cognitive, and behavioral consequences. In terms of social development, there is an increased risk of autism symptomatology. However, it remains unclear how social deficits are related to abnormal brain development and to what degree underlying mechanisms of social dysfunction in 47, XXY are similar to, or different from, those in idiopathic autism (ASD). This study was aimed at investigating the neural architecture of brain structures related to social information processing in boys with 47, XXY, also in comparison with boys with idiopathic ASD. MRI scans of 16 boys with 47, XXY, 16 with ASD, and 16 nonclinical, male controls were analyzed using voxel-based morphometry (VBM). A region of interest mask containing the superior temporal cortex, amygdala, orbitofrontal cortex (OFC), insular cortex, and medial frontal cortex was used. The Social Responsiveness Scale (SRS) was used to assess degree of autism spectrum symptoms. The 47, XXY group could not be distinguished from the ASD group on mean SRS scores, and their scores were significantly higher than in controls. VBM showed that boys with 47, XXY have significant gray matter volume reductions in the left and right insula, and the left OFC, compared with controls and boys with ASD. Additionally, boys with 47, XXY had significantly less gray matter in the right superior temporal gyrus than controls. These results imply social challenges associated with 47, XXY may be rooted in neural anatomy, and autism symptoms in boys with 47, XXY and boys with ASD might have, at least partially, different underlying etiologies.
Rapid and Highly Sensitive Detection of Variant Creutzfeldt - Jakob Disease Abnormal Prion Protein on Steel Surfaces by Protein Misfolding Cyclic Amplification: Application to Prion Decontamination Studies
Belondrade, Maxime; Nicot, Simon; Béringue, Vincent; Coste, Joliette; Lehmann, Sylvain; Bougard, Daisy
The prevalence of variant Creutzfeldt-Jakob disease (vCJD) in the population remains uncertain, although it has been estimated that 1 in 2000 people in the United Kingdom are positive for abnormal prion protein (PrPTSE) by a recent survey of archived appendix tissues. The prominent lymphotropism of vCJD prions raises the possibility that some surgical procedures may be at risk of iatrogenic vCJD transmission in healthcare facilities. It is therefore vital that decontamination procedures applied to medical devices before their reprocessing are thoroughly validated. A current limitation is the lack of a rapid model permissive to human prions. Here, we developed a prion detection assay based on protein misfolding cyclic amplification (PMCA) technology combined with stainless-steel wire surfaces as carriers of prions (Surf-PMCA). This assay allowed the specific detection of minute quantities (10−8 brain dilution) of either human vCJD or ovine scrapie PrPTSE adsorbed onto a single steel wire, within a two week timeframe. Using Surf-PMCA we evaluated the performance of several reference and commercially available prion-specific decontamination procedures. Surprisingly, we found the efficiency of several marketed reagents to remove human vCJD PrPTSE was lower than expected. Overall, our results demonstrate that Surf-PMCA can be used as a rapid and ultrasensitive assay for the detection of human vCJD PrPTSE adsorbed onto a metallic surface, therefore facilitating the development and validation of decontamination procedures against human prions. PMID:26800081
Mathur, Vani A.; Moayedi, Massieh; Keaser, Michael L.; Khan, Shariq A.; Hubbard, Catherine S.; Goyal, Madhav; Seminowicz, David A.
Migraine is a pain disorder associated with abnormal brain structure and function, yet the effect of migraine on acute pain processing remains unclear. It also remains unclear whether altered pain-related brain responses and related structural changes are associated with clinical migraine characteristics. Using fMRI and three levels of thermal stimuli (non-painful, mildly painful, and moderately painful), we compared whole-brain activity between 14 migraine patients and 14 matched controls. Although, there were no significant differences in pain thresholds nor in pre-scan pain ratings to mildly painful thermal stimuli, patients did have aberrant suprathreshold nociceptive processing. Brain imaging showed that, compared to controls, patients had reduced activity in pain modulatory regions including left dorsolateral prefrontal, posterior parietal, and middle temporal cortices and, at a lower-threshold, greater activation in the right mid-insula to moderate pain vs. mild pain. We also found that pain-related activity in the insula was associated with clinical variables in patients, including associations between: bilateral anterior insula and pain catastrophizing (PCS); bilateral anterior insula and contralateral posterior insula and migraine pain intensity; and bilateral posterior insula and migraine frequency at a lower-threshold. PCS and migraine pain intensity were also negatively associated with activity in midline regions including posterior cingulate and medial prefrontal cortices. Diffusion tensor imaging revealed a negative correlation between fractional anisotropy (a measure of white matter integrity; FA) and migraine duration in the right mid-insula and a positive correlation between left mid-insula FA and PCS. In sum, while patients showed lower sensitivity to acute noxious stimuli, the neuroimaging findings suggest enhanced nociceptive processing and significantly disrupted modulatory networks, particularly involving the insula, associated with indices