Mano Arumanayagam

Antioxidant properties of carvedilol and metoprolol in heart failure: a double-blind randomized controlled trial.

Animal and human studies have shown that carvedilol has significant antioxidant properties compared with other β-blockers. The objective of this study was to determine if these antioxidant effects are detectable in patients with heart failure and to compare carvedilol with the selective β-blocker metoprolol. Twenty-four patients with chronic heart failure were randomly assigned to receive either carvedilol or metoprolol in a double-blind control trial for 12 weeks in a University teaching hospital clinic. Blood pressure, heart rate, exercise tolerance, left ventricular ejection fraction, plasma total antioxidant status, erythrocyte superoxide dismutase, and glutathione peroxidase activities were determined at baseline and every 4 weeks up to 12 weeks. The results showed that erythrocyte superoxide dismutase and glutathione peroxidase were significantly reduced in carvedilol treated patients after 12 weeks of therapy, whereas metoprolol had no significant effect, although the clinical improvement over the short-term was similar with both drugs. Thus carvedilol, in addition to improving symptoms in heart failure, also possesses significant antioxidant properties. Whether this additional action influences long-term outcome is at present unknown.

Serum Ultrafiltrable Copper, Total Copper and Caeruloplasmin Concentrations in Gynaecological Carcinomas

Serum copper and caeruloplasmin concentrations are elevated in various carcinomas, but it is not known whether the rise in serum copper is due to elevation of caeruloplasmin alone or whether it is also due to the elevation of ‘free’ copper. We therefore determined ultrafiltrable copper to answer this question. Serum ultrafiltrate was prepared using the Amicon micropartition system and ultrafiltrable (free) copper was determined by flameless atomic absorption spectrophotometry. Serum total copper was determined by flame atomic absorption spectrometry and caeruloplasmin by rate nephelometry. There was no significant difference in the ultrafiltrable copper concentration between patients with gynaecological tumours and control subjects. However, total copper and caeruloplasmin concentrations were significantly elevated in cancer patients compared with control subjects. In contrast to total copper and caeruloplasmin concentrations, ultrafiltrable copper concentrations showed no significant increase with increase in the stage of the cancer.

Influence of gene polymorphisms of the renin-angiotensin system on clinical outcome in heart failure among the Chinese

BACKGROUND An association between the DD allele of the angiotensin-converting enzyme gene and a poorer outcome in patients with heart failure has been found in whites. The DD allele frequency is lower in Chinese, but the M235T variant of the angiotensinogen gene is more common in Chinese than whites; it is not known to what extent polymorphisms of the renin-angiotensin system affect clinical status or prognosis in Chinese patients with heart failure. METHODS We assessed the relations among polymorphism of the angiotensin-converting enzyme gene, angiotensinogen M235T (AGT) gene, and angiotensin type I receptor A1166C gene with left ventricular systolic function, left and right ventricular diastolic function, serum angiotensin-converting enzyme, plasma aldosterone and atrial natriuretic peptide levels at presentation, and clinical outcome at 1 year (survival, hospital admissions) in a cohort of Chinese patients with typical systolic heart failure (n = 82). RESULTS We confirmed the low prevalence of the angiotensin-converting DD and the angiotensin type I receptor CC genotypes, and high prevalence of the AGT TT genotype in Chinese subjects compared with whites. There was no relation between the various gene polymorphisms and survival at 1 year assessed by multiple regression or Cox regression survival analysis. The AC variant of the angiotensin type I receptor gene was associated with morbidity over a 1-year period (hospital admissions) and increased baseline aldosterone levels, but none of the other polymorphisms correlated with systolic or diastolic function, aldosterone or atrial natriuretic peptide levels. By multiple regression for effects on mortality rate, only atrial natriuretic peptide and age were significant. CONCLUSIONS In Chinese patients with heart failure, polymorphisms of the renin-angiotensin system do not appear to be related to survival or severity, probably because of the different prevalence of these genotypes in the Chinese. Thus this study illustrates that large interethnic differences in the frequencies of genotype polymorphisms of the renin-angiotensin system exist and results from one ethnic group cannot be extrapolated to another.

Serum ceruloplasmin, plasma copper concentration and copper to ceruloplasmin ratio in cervical carcinoma.

Several studies have shown that plasma/serum copper and ceruloplasmin concentrations are increased in various carcinomas. We determined serum concentrations of ceruloplasmin and plasma copper concentration to evaluate the clinical usefulness of these tests in patients with cervical carcinomas. There was a significantly higher ceruloplasmin concentration in patients with cervical carcinoma compared to healthy controls. Plasma concentrations of copper were not significantly different in the two groups of subjects. The copper to ceruloplasmin ratio was lower in cancer patients than in control subjects. There was a significant increase in the serum concentrations of ceruloplasmin with increasing FIGO stage of cancer. Copper concentration in advanced tumours (FIGO stage 3) were significantly higher compared to control subjects or FIGO 1 and 2. Copper to ceruloplasmin ratio was lower in FIGO stage 2 and 3 patients compared to stage 1 or control subjects. Ceruloplasmin can also discriminate between large tumours which are inoperable and early cervical carcinomas better than copper or copper to ceruloplasmin ratio.

Hematological indices and the prevalence of anemia in an elderly chinese population

&NA; Hematological indices were determined in a group of 427 elderly Chinese subjects over 60 years old; reference ranges were established after excluding subjects with hemoglobinopathies8 or diseases giving rise to anemia19 and those with values less or greater than 3 SD from the mean.20 The values were similar to those for elderly Caucasians. All the red cell indices were significantly higher in men than women, possibly reflecting the influence of androgens on bone marrow function. Previously reported age‐related decline in hemoglobin, red cell count and hematocrit from studies of all age groups was not seen in men or women above age 60 years, but a fall in platelet count with age, which had not been previously reported, was observed. There were no age‐related changes in any other indices. Reference ranges were lower for Hb, MCV, and MCH in men and women, compared to those derived from a study of Chinese of all age groups. The prevalence of anemia due to disease and hemoglobinpathies in this population was 6.4% in men and 6.3% in women.

Differences in Erythrocyte Cation (Sodium) Transport Between Chinese and Non Chinese Males

Erythrocyte sodium content, sodium pump activity (ouabain sensitive efflux rate, efflux rate constant, ouabain binding sites and Na+, K+-ATPase activity), sodium-lithium countertransport and sodium-potassium cotransport activities were measured in 10 European males, 11 non Chinese Asian males and 12 Chinese males. There were no differences between the 3 groups in any of the measurements of active transport. The sodium-lithium countertransport was higher and sodium-potassium cotransport (measured as lithium-potassium cotransport) was lower in Chinese compared to either the Europeans or non Chinese Asians. There were no differences in counter and cotransport activities between the Europeans and non Chinese Asians. Multiple regression analysis showed that the co and countertransport pathways contribute little to the maintenance of erythrocyte sodium content in healthy subjects.

The predictive value of serum 1,5-anhydro-D-glucitol in pregnancies at increased risk of gestational diabetes mellitus and gestational impaired glucose tolerance

The objective of the study was to determine the efficacy of 1,5‐anhydro‐D‐glucitol (1,5 AG) for the prediction of gestational diabetes and gestational impaired glucose tolerance (GIGT). One hundred and eighty‐five pregnant women with epidemiological risk factors of gestational diabetes or GIGT underwent 75 g oral glucose tolerance test and plasma 1,5 AG assay at 26 to 28 weeks of gestation. There was no significant difference in plasma 1,5 AG either before or after an oral glucose load. The area under the receiver operator characteristic curve for 1,5 AG was only 0.485 which implies that 1,5 AG is a poor predictor of GIGT or gestational diabetes.

Diurnal Variation in Excretion of N-Acetyl-β-Glucosaminidase during Pregnancy: Implications for the Prediction of Pre-Eclampsia

Significant differences in urinary excretion of N-acetyl-β-glycosaminidase (NAG) were observed between nulliparous and multiparous patients and between fasted and nonfasted individuals. No significant difference was observed between patients with normal and those with abnormal glucose tolerance. Multiple regression analysis confirmed that the significant independent determinants of NAG/creatinine ratio were age, parity, gestation and fasting state. Significant diurnal variation in urinary NAG/Cr ratio was observed, the highest levels being recorded in early morning fasting specimens, falling in each postprandial specimen and beginning to rise again by midnight. The urinary NAG/Cr ratio is influenced by fasting, parity, gestation and age. More consistent results for prediction of pre-eclampsia are therefore likely to be obtained using fasting (early morning) urine specimens and adjusting cut-off criteria for the other factors.

Stimulation of the Na+,K+-ATPase activity of K562 human erythroleukemia cells by triiodothyronine

The effect of triiodothyronine (T3) on Na+,K(+)-ATPase activity of K562 human erythroleukemic cell was studied to understand why the erythrocyte sodium pump activity is decreased in hyperthyroidism. Na+,K(+)-ATPase activity of K562 cell lysates was assayed by measuring the release of inorganic phosphate (Pi) from ATP. Na+,K(+)-ATPase activity of K562 cell grown in the presence of T3 for 48 hours was significantly higher than that of control (0.98 +/- 0.05 mumol Pi h-1 mg protein-1 vs 0.82 +/- 0.10 mumol Pi h-1 mg protein-1, p < 0.05). The Na+,K(+)-ATPase activity could be stimulated in a time- and concentration-dependent manner; maximum stimulatory effect of T3 was seen at a concentration of 10(-7) mol/L. When an inducer [cytosine-beta-D-arabino-furanoside (ARA-C)] was added to the culture medium, the K562 cells showed signs of differentiation and synthesised haemoglobin. At the same time, the Na+,K(+)-ATPase activity remained high. We conclude that T3 stimulates Na+,K(+)-ATPase activity of K562 cells and in the presence of T3 during differentiation, the enzyme activity remains high.

Platelet sodium pump and sodium potassium cotransport activity in nonpregnant, normotensive, and hypertensive pregnant women.

OBJECTIVE To determine ouabain-sensitive sodium pump and bumetanide-sensitive sodium potassium cotransport activity in platelets from nonpregnant and normotensive pregnant women and from women with pregnancy-induced hypertension (PIH). METHODS Blood was collected from 9 normotensive nonpregnant subjects, 24 normotensive pregnant subjects in both second and third trimesters, 9 subjects who developed proteinuric PIH, and 9 subjects who developed moderate nonproteinuric PIH. Platelet sodium pump activity was determined by the difference in the uptake of rubidium-86 in the presence and absence of ouabain; sodium potassium cotransport (SPC) activity is that component that is inhibitable by bumetanide. RESULTS SPC activity was similar in normotensive subjects in the second [median (range) 78 mmol Rb/h/mg protein (18-140)] and third trimesters [85 (39-134)] but was significantly (p < 0.001) higher than in nonpregnant subjects [22 (4-107)]. In addition, SPC was significantly (p < 0.001) lower in subjects with nonproteinuric [42 (4-67)] or proteinuric PIH [59 (33-102)] compared to those who remained normotensive. Sodium pump activity was significantly higher (p < 0.05) in nonpregnant subjects [263 (188-430)] compared with the other groups of subjects. Total rubidium uptake was significantly higher (p < 0.05) in third-trimester normotensive subjects [471 (243-560)] compared with second-trimester subjects [405 (278-608)]. CONCLUSION Our results suggest that the lower SPC activity in both nonproteinuric and proteinuric PIH may be an early sign of abnormality in the transport of sodium and potassium across the vascular smooth-muscle cell membrane, which is responsible for the maintenance of blood pressure.