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Endocrine Journal Feb 2004Hyperhomocysteinemia is a risk factor for premature atherosclerotic vascular diseases. It is known that plasma homocysteine levels are higher in hypothyroid patients...
Hyperhomocysteinemia is a risk factor for premature atherosclerotic vascular diseases. It is known that plasma homocysteine levels are higher in hypothyroid patients compared to healthy subjects. The aim of our study was to assess plasma total homocysteine concentrations in hyperthyroid patients before and after treatment when euthyroid status was reached and compare them with control group. Thirteen hyperthyroid patients (age, 42.9 +/- 15.6 year) and eleven healthy subjects (age, 39.9 +/- 12.5 year) were involved in the study. Plasma levels of homocysteine and serum cholesterol, triglyceride, HDL cholesterol, urea, creatinine, vitamin B12, folate were measured before and after treatment. LDL cholesterol and creatinine clearances were calculated. Pretreatment homocycteine levels of the hyperthyroid patients were significantly lower than healthy controls (11.5 +/- 3.6 micromol/L vs. 15.1 +/- 4.5 micromol/L, respectively, p<0.05). Posttreatment homocysteine levels were significantly higher than pretreatment levels (13.9 +/- 6.3 micromol/L vs. 11.5 +/- 3.6 micromol/L, respectively, p<0.05) and posttreatment creatinine clearance were lower than pretreatment level (103.5 +/- 12.7 ml/min vs. 114.2 +/- 9.3 ml/min, respectively, p<0.01). Lower homocysteine levels in hyperthyroidism can be partially explained with the changes in creatinine clearance.
Topics: Adult; Antithyroid Agents; Case-Control Studies; Creatinine; Female; Homocysteine; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Osmolar Concentration; Propylthiouracil
PubMed: 15004418
DOI: 10.1507/endocrj.51.121 -
Blood Aug 1998Because cobalamin deficiency is routinely treated with parenteral cobalamin, we investigated the efficacy of oral therapy. We randomly assigned 38 newly diagnosed... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
Because cobalamin deficiency is routinely treated with parenteral cobalamin, we investigated the efficacy of oral therapy. We randomly assigned 38 newly diagnosed cobalamin deficient patients to receive cyanocobalamin as either 1 mg intramuscularly on days 1, 3, 7, 10, 14, 21, 30, 60, and 90 or 2 mg orally on a daily basis for 120 days. Therapeutic effectiveness was evaluated by measuring hematologic and neurologic improvement and changes in serum levels of cobalamin (normal, 200 to 900 pg/mL) methylmalonic acid (normal, 73 to 271 nmol/L), and homocysteine (normal, 5.1 to 13.9 micromol/L). Five patients were subsequently found to have folate deficiency, which left 18 evaluable patients in the oral group and 15 in the parenteral group. Correction of hematologic and neurologic abnormalities was prompt and indistinguishable between the 2 groups. The mean pretreatment values for serum cobalamin, methylmalonic acid, and homocysteine were, respectively, 93 pg/mL, 3,850 nmol/L, and 37. 2 micromol/L in the oral group and 95 pg/mL, 3,630 nmol/L, and 40.0 micromol/L in the parenteral therapy group. After 4 months of therapy, the respective mean values were 1,005 pg/mL, 169 nmol/L, and 10.6 micromol/L in the oral group and 325 pg/mL, 265 nmol/L, and 12.2 micromol/L in the parenteral group. The higher serum cobalamin and lower serum methylmalonic acid levels at 4 months posttreatment in the oral group versus the parenteral group were significant, with P < .0005 and P < .05, respectively. In cobalamin deficiency, 2 mg of cyanocobalamin administered orally on a daily basis was as effective as 1 mg administered intramuscularly on a monthly basis and may be superior.
Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Female; Folic Acid; Hematocrit; Homocysteine; Humans; Injections, Intramuscular; Male; Methylmalonic Acid; Middle Aged; Treatment Outcome; Vitamin B 12; Vitamin B 12 Deficiency
PubMed: 9694707
DOI: No ID Found -
The Journal of Nutrition Mar 2006The purpose of this study was to determine whether the plasma response to dietary cholesterol from eggs is associated with the plasma carotenoid response and whether... (Comparative Study)
Comparative Study
The purpose of this study was to determine whether the plasma response to dietary cholesterol from eggs is associated with the plasma carotenoid response and whether gender influences the carotenoid response. Using a crossover design, 40 subjects classified as either hyper- (10 men and 10 women) or hyporesponders (10 men and 10 women) to dietary cholesterol consumed an egg (EGG, 640 mg/d additional dietary cholesterol and 600 microg lutein + zeaxanthin) or placebo (SUB, 0 mg/d cholesterol, 0 microg lutein + zeaxanthin and 568 microg beta-carotene) diet for 30 d, followed by a 3-wk washout period and the alternate diet. Plasma concentrations of lutein and beta-carotene after each dietary period were then examined to determine whether the response to carotenoid intake was similar to that seen for dietary cholesterol. After the EGG period, the increase in plasma lutein in female hyperresponders (mean increase +/- SD; 0.32 +/- 0.19 micromol/L) and male hyperresponders (0.26 +/- 0.11 micromol/L) was significantly greater than that of their hyporesponsive counterparts (0.16 +/- 0.18 micromol/L for women and 0.14 +/- 0.11 micromol/L men). Gender was not a significant factor influencing lutein response. Both men and women classified as hyperresponders significantly increased plasma beta-carotene after the SUB period, whereas their hyporesponsive counterparts were not affected. The increase in plasma beta-carotene in female hyperresponders (0.29 +/- 0.48 micromol/L) was significantly greater than that in male hyperresponders (0.07 +/- 0.07 micromol/L). We conclude that plasma responses to cholesterol and carotenoids are related and that gender influences the beta-carotene response to a greater degree than the lutein response.
Topics: Analysis of Variance; Cholesterol; Cholesterol, Dietary; Cholesterol, HDL; Cholesterol, LDL; Eggs; Female; Humans; Lutein; Male; Placebos; Sex Characteristics; Triglycerides; beta Carotene
PubMed: 16484531
DOI: 10.1093/jn/136.3.601 -
HPB : the Official Journal of the... 2008In patients with malignant hilar obstruction, liver resection is associated with an increased risk of postoperative liver failure attributed to the need for major liver...
AIM
In patients with malignant hilar obstruction, liver resection is associated with an increased risk of postoperative liver failure attributed to the need for major liver resection in a context of obstructive jaundice. To overcome this issue, most authors recommend preoperative biliary drainage (PBD). However, PBD carries risks of its own, including, primarily, sepsis and, more rarely, tumor seeding, bile peritonitis, and hemobilia. We, unlike most authors, have not used routine PBD before liver resection in jaundiced patients.
MATERIAL AND METHODS
Our series includes 62 patients who underwent major liver resection for cholangiocarcinoma; 33 of these had elevated bilirubin (60-470 micromol/l) and were operated without PBD. There were 43 extended right hepatectomies and 18 extended left hepatectomies.
RESULTS
Hospital deaths occurred in 5 patients (8%) including 3 of 33 jaundiced patients (9%, ns). All deaths occurred after extended right hepatectomy (12%), including 3 patients with a serum bilirubin level above 300 micromol/l and 2 with normal bilirubin. There were no deaths after left-sided resections, whatever the level of bilirubin.
CONCLUSIONS
PBD can be omitted in the following situations: recent onset jaundice (<2-3 weeks), total bilirubin <200 micromol/l, no previous endoscopic or transhepatic cholangiography, absence of sepsis, future liver remnant >40%. These criteria include most patients requiring left-sided resections and selected patients requiring right-sided resections. In other cases, PBD is required, associated with portal vein embolization in the event of a small future liver remnant.
PubMed: 18773089
DOI: 10.1080/13651820802007472 -
Postnatal changes in maternal and neonatal plasma antioxidant vitamins and the influence of smoking.Archives of Disease in Childhood. Fetal... Jan 2002To study the postnatal changes in the plasma concentrations of fat soluble antioxidant vitamins and malondialdehyde (MDA) in mothers and their newborns and their...
OBJECTIVE
To study the postnatal changes in the plasma concentrations of fat soluble antioxidant vitamins and malondialdehyde (MDA) in mothers and their newborns and their relation to smoking.
DESIGN
Prospective cohort study.
SETTING
Tertiary perinatal centre.
SUBJECTS
Eighteen non-smoking and 14 smoking mothers and 33 infants.
MAIN OUTCOME MEASURES
Plasma concentrations of vitamins E, A, and beta-carotene and MDA were measured in mothers and infants at delivery and on day 4 post partum.
RESULTS
Neonatal plasma levels of vitamins E, A, and beta-carotene were significantly lower than maternal levels both at delivery and on day 4 in both groups. There was a significant postnatal increase in plasma vitamin E levels in smoking mothers and neonates of both groups. A significant postnatal increase in maternal, but not neonatal, plasma vitamin A was noted in both groups. Cord plasma vitamin E levels were significantly lower in infants of smoking mothers (mean 4.7 v 6.5 micromol/l, p = 0.041). Plasma MDA was paradoxically lower in smoking mothers at delivery (3.19 v 4.01 micromol/l, p = 0.03) and on day 4 (1.37 v 3.29 micromol/l, p = 0.005) and in infants of the smoking group on day 4 (2.18 v 3.12 micromol/l, p = 0.014). Also, there was a significant postnatal fall in plasma MDA levels on day 4 in mothers and infants in the smoking group.
CONCLUSIONS
The postnatal changes in plasma vitamin E were more pronounced in the smoking group. The postnatal changes in plasma vitamins A and beta-carotene were similar in both groups. The rapid decline in plasma MDA in smoking mothers and their infants suggests withdrawal of oxidative stress from smoking around delivery. This coincided with the increase in plasma vitamin E.
Topics: Adolescent; Adult; Antioxidants; Diet; Female; Humans; Infant, Newborn; Male; Malondialdehyde; Maternal-Fetal Exchange; Postpartum Period; Pregnancy; Prospective Studies; Smoking; Vitamin A; Vitamin E; Vitamins; beta Carotene
PubMed: 11815546
DOI: 10.1136/fn.86.1.f36 -
Journal of Zhejiang University.... Sep 2009To investigate the effects of ursolic acid on the proliferation and apoptosis of human HT-29 colon cancer cells.
OBJECTIVE
To investigate the effects of ursolic acid on the proliferation and apoptosis of human HT-29 colon cancer cells.
METHODS
3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry assays were performed to evaluate the effects of ursolic acid on the growth and apoptosis of HT-29 cells. Western blot analysis was applied to investigate the inhibitory effects of ursolic acid on the phosphorylation of the epidermal growth factor receptor (EGFR), extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (p38 MAPK), and the activity of B cell leukemia-2 (Bcl-2), B cell leukemia-xL (Bcl-xL), caspase-3, and caspase-9.
RESULTS
Ursolic acid inhibited the growth of HT-29 cells in dose- and time-dependent manners. The median inhibition concentration (IC50) values for 24, 48, and 72 h treatment were 26, 20, and 18 micromol/L, respectively. The apoptotic rates of 10, 20, and 40 micromol/L ursolic acid treatments for 24 h were 5.74%, 14.49%, and 33.05%, and for 48 h were 9%, 21.39%, and 40.49%, respectively. Ursolic acid suppressed the phosphorylation of EGFR, ERK1/2, p38 MAPK, and JNK, which is well correlated with its growth inhibitory effect. 10, 20, and 40 micromol/L ursolic acid significantly inhibited the proliferation of EGF-stimulated HT-29 cells (P<0.05). Cell proliferation was most significantly inhibited when treated with 10 and 20 micromol/L ursolic acid combined with 200 nmol/L AG 1478 or 10 micromol/L U0126 (P<0.01). Besides, it also down-regulated the expression of Bcl-2 and Bcl-xL and activated caspase-3 and caspase-9.
CONCLUSION
Ursolic acid induces apoptosis in HT-29 cells by suppressing the EGFR/MAPK pathway, suggesting that it may be a potent agent for the treatment of colorectal cancer.
Topics: Apoptosis; Dose-Response Relationship, Drug; ErbB Receptors; HT29 Cells; Humans; MAP Kinase Signaling System; Triterpenes; Ursolic Acid
PubMed: 19735099
DOI: 10.1631/jzus.B0920149 -
Plant Physiology Jan 1987Seven day old wheat and maize seedlings were exposed to 1300 or 2000 microeinsteins per square meter per second photosynthetically active radiation in CO(2)-free air for...
Seven day old wheat and maize seedlings were exposed to 1300 or 2000 microeinsteins per square meter per second photosynthetically active radiation in CO(2)-free air for 3 hours with either 1% O(2) in N(2) or N(2)-only and then returned to normal air of 340 microliters per liter CO(2), 21% O(2) in N(2). Activity of the ribulose bisphosphate carboxylase and amount of the substrate, ribulose 1,5-bisphosphate, were measured during and following the CO(2)-free treatments as was photosynthetic CO(2) fixation. Photoinhibition of photosynthesis was observed only with wheat seedlings following the N(2) only treatment. During the CO(2)-free treatments, the levels of RuBP rose during all experiments except when wheat was photoinhibited. The activity of the ribulose bisphophate carboxylase, measured directly upon grinding the leaves, declined during the CO(2)-free conditions. The carboxylase total activity increased in minutes in the leaf during and following the CO(2)-free treatments. The specific activities of the wheat carboxylase went from 0.16 to 1.06 micromoles CO(2) fixed per milligram protein per minute while the maize carboxylase varied from 0.05 to 0.36 micromole CO(2) fixed per millogram protein per minute. This suggests that in these seedlings considerable inactive carboxylase must be stored in a form not activatable in extracts by CO(2) and Mg(2+). Possible mechanisms of regulation of photosynthesis by the ribulose bisphosphate carboxylase must consider not only the amount of active enzyme, but the amount of enzyme which the plant can make activatable upon demand.
PubMed: 16665196
DOI: 10.1104/pp.83.1.170 -
Cureus Jun 2023Background Placenta-mediated complications, such as preeclampsia, placental abruption, and fetal growth restriction, can indeed lead to significant maternal and...
Background Placenta-mediated complications, such as preeclampsia, placental abruption, and fetal growth restriction, can indeed lead to significant maternal and perinatal morbidity and mortality. Early detection and management of these conditions are crucial to ensuring optimal outcomes for both the mother and baby. However, there have been inconsistent correlations found between maternal homocysteine levels and placenta-related problems in various studies. Therefore, prospective research based on data pointing to a role for hyperhomocysteinemia in placenta-mediated complications will open doors for early detection and management of these complications. Thus, this study aims to determine if a higher risk of placenta-mediated problems is connected with a higher maternal plasma homocysteine content between 10 and 14 weeks of gestation. Methodology An observational prospective cohort study was conducted in the Department of Obstetrics and Gynecology, consisting of all the antenatal women between 10 and 14 weeks of gestation attending outpatient departments or inpatients admitted in labor rooms or wards having singleton pregnancies. Along with socio-demographic information and detailed history, a clinical examination was performed, and blood samples were collected to determine plasma homocysteine levels. Results As per the receiver operating characteristic curve (ROC curve), the cut-off value taken was <5 for the low level of serum homocysteine, 5 to 15 micromol/L for the normal value, and >15 micromol/L for a raised serum homocysteine level. The cutoff value for our study was 45 micromol/L with a sensitivity of 78.33%, a specificity of 91.67%, a positive predictive value of 90.38%, and a negative predictive value of 80.88% with a diagnostic accuracy of 85%. This means that, for most of the women included in the present study, those who developed placenta-mediated complications had serum blood homocysteine levels of 45 micromol/L or more at 10-14 weeks of gestation. Conclusion Women with high homocysteine levels in the late first trimester had more placenta-mediated complications, such as abruption, pre-eclampsia, restricted fetal growth, and recurrent pregnancy losses, compared to women with a normal level of homocysteine in the late first trimester. Therefore, measuring blood homocysteine levels in pregnancy may be helpful as a diagnostic test for the early detection of high-risk individuals for placenta-mediated complications.
PubMed: 37456448
DOI: 10.7759/cureus.40423 -
PeerJ 2017Chronic inflammation is a characteristic of sickle cell disease (SCD), and is invariably associated with vascular endothelial injury. Hydroxyurea (HU), a naturally...
BACKGROUND
Chronic inflammation is a characteristic of sickle cell disease (SCD), and is invariably associated with vascular endothelial injury. Hydroxyurea (HU), a naturally cytotoxic chemotherapeutic agent, is the only FDA drug approved for SCD, and is therefore naturally cytotoxic. Quercetin (QCT) is a dietary flavonoid found ubiquitously in plants and foods that have anti-oxidative and anti-inflammatory characteristics. Our hypothesis is that dietary QCT will decrease cytotoxic effects of lipopolysaccharide (LPS) and HU induced vascular cell damage.
METHODS
Lipopolysaccharide (LPS) was used to induce inflammation in immortalized mouse aortic endothelial cells (iMAECs), providing an in vitro model of inflamed endothelial cells. The cells were exposed to LPS throughout the entire experiment. Interventions included treating the LPS exposed cells with QCT, HU, or QCT + HU over 50 hours. The 50-hour period included 24 hours of varying treatments, followed by two hours of hypoxic exposure and then 24 hours under normal aerobic exposure.
RESULTS
LDH level was significantly higher for LPS treated versus untreated cells ( = 0.0004). LPS plus 30 micromole QCT reduced the LDH ( = 0.1, trend), whereas LPS plus 100 micromoles HU, significantly increased LDH ( = 0.0004). However, LPS plus treatment with 30 micromoles QCT/100 micromoles HU, significantly reduced LDH, compared with HU alone ( = 0.0002).
DISCUSSION
These results suggest that quercetin may be effective against vascular endothelial cell damage for iMAECs . In particular, it shows promise in preventing HU-induced cytotoxicity, surprisingly found from these results. This latter finding is important, and should be given more consideration, since HU is the only FDA-approved drug for treating sickle cell patients, and its use is rapidly increasing.
PubMed: 28584711
DOI: 10.7717/peerj.3376 -
Kidney International May 2003Serum cystatin C (CysC) is a novel marker for kidney function that has been claimed to be superior to serum creatinine. Thyroid dysfunction may alter creatinine, which...
BACKGROUND
Serum cystatin C (CysC) is a novel marker for kidney function that has been claimed to be superior to serum creatinine. Thyroid dysfunction may alter creatinine, which has been found to be increased in hypothyroidism and decreased in hyperthyroidism. This study was performed to evaluate whether changes in CysC and creatinine are parallel during the treatment of hypo- and hyperthyroidism, respectively.
METHODS
Prospective case series of 22 consecutively referred patients with thyroid dysfunction. Creatinine and CysC were determined at the time of diagnosis of hypo- and hyperthyroidism, and when free thyroxine (fT4) returned into the normal range. Hypothyroid patients were treated with levothyroxine. Hyperthyroid patients were treated with antithyroid drugs, surgery, or radioiodine.
RESULTS
Nine patients with hypothyroidism and 13 patients with hyperthyroidism were included. In patients with hypothyroidism mean fT4 (+/-SD) was 4.9 +/- 2.5 pmol/L (reference, 12 to 22) at diagnosis and increased to 16.6 +/- 3.6 pmol/L when patients were treated with levothyroxine. Creatinine decreased from 86 +/- 13 micromol/L (reference, 70 to 105) in the hypothyroid state to 76 +/- 16 micromol/L when fT4 normalized (P = 0.062), whereas CysC increased from 0.84 +/- 0.17 mg/L (reference, 0.63 to 1.33) to 1.1 +/- 0.28 mg/L (P < 0.001). In patients with hyperthyroidism, mean fT4 was 54.6 +/- 22.7 pmol/L (reference, 12 to 22) at diagnosis and decreased to 15.8 +/- 3.6 pmol/L following treatment with antithyroid drugs, thyroid surgery, or radioiodine. Creatinine increased from 67 +/- 15 micromol/L at diagnosis of hyperthyroidism to 75 +/- 9 micromol/L when fT4 normalized (P = 0.004), whereas CysC declined from 1.32 +/- 0.17 mg/L to 0.95 +/- 0.19 mg/L (P < 0.001).
CONCLUSION
Thyroid dysfunction has a major impact on CysC levels. Therefore, thyroid function has to be considered when CysC is used as a marker of kidney function. In contrast to creatinine concentrations, CysC levels are lower in the hypothyroid and higher in the hyperthyroid state as compared with the euthyroid state.
Topics: Adolescent; Adult; Creatinine; Cystatin C; Cystatins; Female; Humans; Hyperthyroidism; Hypothyroidism; Kidney; Kidney Diseases; Male; Middle Aged
PubMed: 12675875
DOI: 10.1046/j.1523-1755.2003.00925.x