Enhanced nitric oxide production is closely associated with serum lipid concentrations in adolescents

BACKGROUND: To investigate whether nitric oxide (NO) production is associated with serum lipid concentrations and body mass index (BMI), we measured serum nitrate and nitrites (NOx) concentrations, serum lipid profiles, and anthropometric parameters in 319 adolescents. METHODS: Serum NOx concentrations were determined using the Griess reaction. Serum concentrations of triglyceride, total cholesterol, and low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were measured by standard enzymatic procedures. RESULTS: Subjects with increased serum cholesterol or triglyceride concentrations exhibited remarkably high NOx levels. Total cholesterol and triglyceride averaged 161.5+/-27.4 and 205.9+/-107.8 mg/dl in males with NOx >92.8 micromol/l (upper 20%), which were significantly above the values (132.4+/-17.2 and 58.1+/-20.3 mg/dl) in those with NOx <15.6 micromol/l (lower 20%). The prevalences of male adolescents with increased concentrations of cholesterol and triglyceride were significantly higher in the subjects with NOx > or =51.2 micromol/l than in those with NOx <51.2 micromol/l (8.9% and 22.2% vs. 1.6% and 2.3%, p<0.05, respectively). Correlation coefficients of serum lipid concentrations and anthropometric parameters vs. serum NOx concentrations were higher in males than in females for cholesterol (r=0.28 vs. 0.23), triglyceride (r=0.51 vs. 0.42), HDL-C (r=-0.25 vs. -0.16), and BMI (r=0.39 vs. 0.27). CONCLUSIONS: NO production is closely associated with serum lipid concentrations in adolescents, and these associations are stronger in males than in females.     

Serum uric acid concentration and thyroid-stimulating-hormone (TSH): results of screening for hyperuricaemia in 2359 consecutive patients with various degrees of thyroid dysfunction.

Serum uric acid concentration (sUA) and hyperthyroidism have been reported to positively correlate with each other. Furthermore, epidemiological data indicate that uric acid may be an independent risk factor for hypertension-associated morbidity and mortality. To evaluate whether screening for hyperuricaemia might be worthwhile in patients with hyperthyroidism we determined serum concentrations of uric acid in 2359 consecutive patients (1939 female, 420 male; age: 48 +/- 17 years, mean +/- SD) with various degrees of thyroid dysfunction (hyperthyroidism: n = 242; subclinical hyperthyroidism: n = 143, hypothyroidism: n = 71, subclinical hypothyroidism: n = 212) and in 1688 euthyroid subjects. No association (r = 0.03) between sUA and total T4/TSH was detected. The significant difference (p < 0.05) in serum uric acid between hyperthyroid (4.8 +/- 1.32 mg/dl) and euthyroid (4.5 +/- 1.32 mg/dl) patients was of no clinical significance. We conclude that routine determination of sUA in hyperthyroid patients is not warranted.     

Influences of hypercholesterolemia on red cell indices and erythrocyte sedimentation rate in elderly persons

BACKGROUND: We investigated whether hypercholesterolemia influenced the values of mean corpuscular volume (MCV) and erythrocyte sedimentation rate (ESR). METHODS: A total of 463 nonanemic elderly persons were evaluated regarding red cell indices, ESR, and ESR-related parameters, such as fibrinogen, albumin, and C-reactive protein (CRP). RESULTS: There were no significant differences in MCV between elderly men with and without hypercholesterolemia (>/=240 mg/dl) nor between the subjects with a marked increase of serum cholesterol concentrations (>/=260 mg/dl) and with severely lowered cholesterol concentrations (<155 mg/dl). ESR in elderly men with hypercholesterolemia averaged 12.3+/-6.8 mm/h, which were significantly higher than in those without hypercholesterolemia (6.0+/-4.7 mm/h, p<0.01). ESR averaged threefold higher in the elderly men with serum cholesterol concentration >/=260 mg/dl versus those with serum cholesterol concentrations <155 mg/dl, although no significant differences were observed in fibrinogen, albumin, and CRP values between the two groups. Serum cholesterol concentrations were higher in elderly men with ESR>/=15.0 mm/h (248.9+/-43.5 mg/dl), compared to those with ESR<2.0 mm/h (199.5+/-31.7 mg/dl, p<0.01). Serum cholesterol concentrations showed no associations with red cell indices but correlated significantly with ESR in elderly men (r=0.24, p<0.01) and postmenopausal women (r=0.21, p<0.01). CONCLUSION: Hypercholesterolemia does not appear to influence MCV but significantly accelerates ESR, especially in elderly men.     

Changes of plasma inflammatory markers after withdrawal of statin therapy in patients with hyperlipidemia

BACKGROUND: Atherosclerosis has been considered to be an inflammatory process. In addition to its lipid-lowering properties, statin has been shown to decrease the concentrations of inflammatory markers resulting in reduction of cardiovascular events. Emerging data suggest that withdrawal of statin might be associated with increased cardiac events. The mechanism for this phenomenon, however, is still unclear. We investigated whether acute termination of statin treatment could result in rebound of inflammatory markers, such as C-reactive protein (CRP) and interleukin-6 (IL-6), in patients with hyperlipidemia. METHODS: Seventeen patients (11 men and 6 women, mean age 51+/-7 years) with hyperlipidemia were given 40 mg/day of pravastatin for 6 weeks. The concentrations of plasma CRP and IL-6 were evaluated before receiving the statin therapy, immediately after 6 weeks of pravastatin therapy, and at days 1, 3 and 7 after withdrawal of pravastatin therapy. The lipid profile was also evaluated at baseline, 6 weeks of therapy, and at day 7 after terminating pravastatin. RESULTS: Pravastatin therapy induced significant reductions in total cholesterol (TC, 6.88+/-0.36 vs. 5.27+/-0.23 mmol/l, p<0.01), low-density lipoprotein (LDL) cholesterol (4.28+/-0.25 vs. 3.06+/-0.14 mmol/l, p<0.01), CRP (0.28+/-0.16 vs. 0.20+/-0.08 mg/l, p<0.01), and IL-6 (8.4+/-0.6 vs. 6.7+/-0.4 pg/dl, p<0.01). Although the TC and LDL-cholesterol did not change during the 7-day period after withdrawal of pravastatin therapy, the concentrations of CRP and IL-6 increased at day 3 (CRP: 0.20+/-0.08 vs. 0.27+/-0.12 mg/l, and IL-6: 6.7+/-0.4 vs. 7.7+/-0.6 pg/dl, p<0.05 respectively) and at day 7 (CRP: 0.20+/-0.08 vs. 0.30+/-0.14 mg/l, and IL-6: 6.7+/-0.4 vs. 8.7+/-0.8 pg/dl, p<0.01 respectively) after withdrawal of pravastatin therapy. No correlation between increase of CRP as well as IL-6 and small changes of LDL-cholesterol concentrations was found after withdrawal of pravastatin therapy at day 7 (r=-0.021 and r=-0.044 respectively, p>0.05 respectively). CONCLUSIONS: 6 weeks after pravastatin therapy could significant modify the lipid profile and decrease the inflammatory markers including CRP and IL-6 in patients with hyperlididemia. Moreover, statin therapy discontinuation could induce a rebound phenomenon of inflammatory response representing an increase in some inflammatory markers, which is independent of changes of lipid parameters.     

Adrenal function in non-septic long-stay critically ill patients: evaluation with the low-dose (1 micro g) corticotropin stimulation test

OBJECTIVE: To investigate the adrenal function in non-septic, long-stay critically ill patients. DESIGN: Prospective, consecutive study. SETTING: General intensive care unit in a university hospital. PATIENTS: Forty-three non-septic patients with protracted critical illness. INTERVENTIONS: A morning blood sample was first obtained to measure baseline plasma cortisol. Subsequently, 1 micro g of corticotropin (ACTH, Synacthene) was injected intravenously and 30 min later a second blood sample was drawn to determine stimulated plasma cortisol. Patients having a stimulated cortisol level of at least 18 micro g/dl were defined as responders. In 36 patients, morning interleukin-6 (IL-6) was also measured. MEASUREMENTS AND RESULTS: Baseline and stimulated plasma cortisol were 16.8+/-4.1 micro g/dl and 21.2+/-5.1 micro g/dl, respectively. Interleukin-6 was high (median 39.3 pg/ml, interquartile range 24.9-86.6 pg/ml) and correlated negatively with stimulated plasma cortisol (r=-0.40, p<0.05). Of the 43 patients studied, 31 patients (72%) were responders and 12 patients (28%) were non-responders to the ACTH stimulation test. Overall, 18 patients died and 25 patients survived to hospital discharge. Non-responders had significantly higher IL-6 levels compared to responders (106+/-73 versus 48+/-42 pg/ml, p<0.05), whereas mortality rate was comparable in the two groups (50% versus 38%, p=0.74). CONCLUSIONS: Circulating plasma IL-6 levels are high during protracted critical illness, and are partially responsible for the relative adrenal insufficiency found in a subset of severely ill patients.     

LDL resistance to oxidation: effects of lipid phenotype, autologous HDL and alanine

BACKGROUND: Although LDL resistance to copper-induced oxidation is a time-honoured method, how it is modulated by the physiologic variability of lipid phenotype and what influences the protective action of homologous HDL and exogenous alanine is still unclear. METHODS: In 159 subjects without severe dyslipidemias, LDL resistance to copper-induced oxidation (lag phase) was measured under standardised conditions, with alanine and with autologous HDL. RESULTS: Lag phase was normally distributed and averaged 68+/-10 min (range: 40-105 min). Both VLDL-triglycerides (37+/-5, 52+/-7, 59+/-7, 53+/-5 mg/dl, p<0.05) and LDL-triglycerides (27+/-2, 27+/-1, 30+/-2, 35+/-3 mg/dl, p<0.01) increased across quartiles of lag phase. The relative LDL enrichment in triglycerides (triglycerides percent or triglycerides/cholesterol ratio) was strongly related to lag phase (r=0.29 and r=0.31, p<0.0005 for both) independently of age, gender, BMI, and presence of diabetes or hypertension. The protective effect of HDL was variable (+42+/-18 min) and largely dependent on the capacity of HDL to resist oxidation (r=0.69, p<0.0001). Alanine induced a rather constant lag phase prolongation (+32+/-7 min) that was weakly related only to baseline lag phase (r=0.17, p<0.05). CONCLUSIONS: Relative triglyceride abundance protects LDL from ex-vivo oxidation, HDL particles protect LDL mainly through substrate dilution and alanine probably through a direct anti-oxidant effect.     

Resistin is present in human breast milk and it correlates with maternal hormonal status and serum level of C-reactive protein.

BACKGROUND: The main objectives of our study were to determine whether resistin was present in human breast milk and to assess resistin status in breast milk and serum in breastfeeding women for up to 180 days post-partum. METHODS: Blood and breast milk samples were collected from 160 breastfeeding women enrolled on 1-3, 4-14, 15-30, 31-90 or 91-180 post-partum days. Blood samples were collected from 48 breast-fed infants at 8-24 days after birth. Milk and serum resistin levels were measured by ELISA. RESULTS: Serum and breast milk resistin concentrations were highest (5800+/-1100 and 1710+/-68 pg/mL, respectively) at 1-3 post-partum days and decreased to 1645+/-210 and 1130+/-115 pg/mL, 1600+/-105 and 710+/-25 pg/mL, 1980+/-155 and 595+/-20 pg/mL and to 2060+/-300 and 670+/-18 pg/mL at 4-14, 15-30, 31-90 and 91-180 post-partum days, respectively. Serum resistin concentrations were correlated with those of milk (r=0.822, p<0.001). Both milk and serum resistin concentrations were correlated positively with maternal serum estradiol, progesterone, prolactin, thyroxine, triiodothyronine, cortisol, leptin and C-reactive protein concentrations. Serum resistin concentration in breast-fed infants (4915+/-340 pg/mL) was higher than that observed in their consumed breast milk (1745+/-70 pg/mL, p<0.001) or in serum of their breastfeeding mothers (3760+/-360 pg/mL, p<0.05). CONCLUSIONS: Resistin is present in human breast milk and its concentration in breast milk decreases with time during lactation. Its concentrations in breast milk and serum are correlated with circulating levels of various reproductive and metabolic hormones and with those of the general inflammatory marker, C-reactive protein.     

Effects of tomatoes on the lipid profile

PURPOSE: The Mediterranean diet has been reported to reduce cardiovascular mortality and morbidity considerably. Tomatoes and lycopene are considered potent antioxidants. Our purpose was to study the effects of a tomatoe-rich diet on the lipid profile following 300g daily of tomatoes for one month. METHODS: Plasma concentrations of triglyceride, total cholesterol, HDL-cholesterol, LDL-cholesterol and VLDL-cholesterol were determined in 98 apparently healthy volunteers (mean age 45.5+/-14.1 yr) before and after one month of follow-up. Fifty volunteers (34 women and 16 men) ate tomatoes 300g daily and 48 volunteers (32 women and 16 men) continued their regular diet without eating tomatoes for a month. RESULTS: In the regular diet group, there were no changes in the lipid profile: triglyceride level (169.6+/-156.8 vs. 147.6+/-93.4mg/dl; P=0.33), total cholesterol level (198.3+/-41.2mg/dl vs. 204.2+/-70.9mg/dl; P=0.23), HDL-cholesterol level (50.6+/-12.2mg/dl vs. 47.6+/-10.8mg/dl; P=0.79), and LDL-cholesterol level (122.7+/-39.4mg/dl vs. 120.2+/-32.2mg/dl; P=0.24) before and after the 1 month offollow-up. In the tomato-rich diet group: triglyceride level 170.8+/-85.4mg/dl to 167.4+/-99.4mg/ dl (P=0.98), total cholesterol level 207.5+/-44.3mg/ dl to 204.1+/-45.1mg/dl (P=0.68), HDL-cholesterol level 46.1+/-10.6mg/dl to 53.4+/-13.3mg/dl (P=0.03), and LDL-cholesterol level 127.7+/-41.8mg/dl to 119.1+/-41.7mg/dl (P=0.57). CONCLUSION: We found that tomatoes'-rich diet (300g daily for one month) increased HDL-cholesterol level significantly by 15.2%.     

Systemic vascular resistance during brief withdrawal of angiotensin converting enzyme inhibition in heart failure

We tested the hypothesis that moderate increases in endogenous angiotensin II (Ang II) concentrations, induced by withdrawal of angiotensin converting enzyme inhibition (ACE-I) in patients with compensated heart failure (HF) on chronic medical therapy, do not increase or impair control of systemic vascular resistance (SVR). SVR was determined in supine and seated positions in 12 HF patients [NYHA class II-III; ejection fraction=0.29 +/- 0.03 (mean +/- SE)] and 9 control subjects. HF patients were investigated during high (n=11; withdrawal of ACE-I treatment for 24 h) and low (n=9; sustained ACE-I therapy) endogenous plasma Ang II concentrations. Withdrawal of ACE-I therapy in HF caused moderately increased Ang II concentrations of 30 +/- 5 pg/ml compared with 12 +/- 2 pg/ml in controls (p<0.05 vs. HF patients). Despite this, SVR was similar in HF (supine: 1503 +/- 159; seated: 1957 +/- 262 dyn s/cm5, p<0.05 vs. supine) and controls (supine: 1438 +/- 104; seated: 1847 +/- 127 dyn s/cm5, p<0.05 vs. supine). During sustained ACE-I therapy in HF, plasma Ang II concentrations were lower (6 +/- 2pg/ml, p<0.05 vs. withdrawal of ACE-I in HF) with no effect on supine SVR. However, the posture-induced increase in SVR in response to the seated position was attenuated. In conclusion, brief moderate increases in circulating plasma Ang II concentrations in compensated HF do not increase SVR compared to control subjects or impair control of SVR in response to a posture change.     

Formation of 8-nitroguanine in blood of patients with inflammatory gouty arthritis

BACKGROUND: NOx causes DNA damage due to an inflammatory effect of gouty arthritis. We investigated the concentration of 8-nitroguanine (8-NO(2)-G) in the blood of patients with arthritis. METHODS: Subjects were divided into 3 groups: (1) high inflammatory (HI) group (n = 21) with hyperuricemia (mean, 8.9 mg/dl) and leukocytosis, (2) low inflammatory (LI) group (n = 14) with mild hyperuricemia (mean, 7.6 mg/dl) but normal leukocyte count, (3) non-inflammatory (NI) healthy control (n = 19) with mean serum uric acid concentration 5.3 mg/dl and normal leukocyte count. Serum C-reactive protein (CRP) concentrations were measured by a visual agglutination method. The blood concentrations of 8-NO(2)-G were determined by high performance liquid chromatography-electrochemical detection and were compared between groups. RESULTS: There was significant difference in percentage of positive CRP (NI: 55.6%, LI: 64.3%, HI: 100%, p = 0.003) between the 3 groups. The leukocyte count (mean +/- S.E., NI: 7400 +/- 528, LI: 7686 +/- 433, HI: 10952 +/- 691/mm(3), p < 0.001), uric acid (NI: 5.3 +/- 0.24, LI: 7.6 +/- 0.4, HI: 8.9 +/- 0.36 mg/dl, p < 0.001), NO(2) (NI: 6.5 +/- 1.2, LI: 11.1 +/- 2.9, HI: 35.6 +/- 5.1 microg/ml, p < 0.001) and the 8-NO(2)-G (NI: 0.08 +/- 0.03; LI: 0.34 +/- 0.13; HI: 0.59 +/- 0.09 ng/microg DNA, p = 0.002) were significantly increased by inflammation. CONCLUSION: Gouty inflammation induces DNA damage by increasing 8-NO(2)-G through endogenous NO and ROS formation.     

Absence of effect of secretin and cholecystokinin on plasma concentrations of vasoactive intestinal polypeptide and pancreatic glucagon

There is little information about the effect of peptides on the VIPergic system. Reports of the influence of secretin and cholecystokinin (CCK) on pancreatic alpha cells are contradictory. With the help of volunteers we investigated the influence of a new synthetic secretin (1 CU/kg/h, 0 to 120 min) alone and in combination with GIH-CCK (1 IU/kg/h, 60 to 120 min) on the concentrations of VIP (n = 13), pancreatic glucagon (PG) (n = 15) and blood sugar (n = 10). 6 of the volunteers were subjected to a randomized cross-over NaCl infusion study. Neither secretin (0 to 60 min) nor secretin and CCK (60 to 120 min) infusion caused a significant change in VIP (31 +/- 3 vs. 34 +/- 4.5 pg/ml, mean +/- SEM, p greater than 0.05), PG (102 +/- 9 vs. 116 +/- 12 vs. 114 +/- 12 pg/ml, p greater than 0.05) or blood sugar (about 90 mg/dl) concentrations. There is no evidence of an influence of secretin and CCK on te VIPergic system and the pancreatic alpha cells.     

Evidence that the brain of the conscious dog is insulin sensitive.

The aim of this study was to determine whether a selective increase in the level of insulin in the blood perfusing the brain is a determinant of the counterregulatory response to hypoglycemia. Experiments were carried out on 15 conscious 18-h-fasted dogs. Insulin was infused (2 mU/kg per min) in separate, randomized studies into a peripheral vein (n = 7) or both carotid and vertebral arteries (n = 8). This resulted in equivalent systemic insulinemia (84 +/- 6 vs. 86 +/- 6 microU/ml) but differing insulin levels in the head (84 +/- 6 vs. 195 +/- 5 microU/ml, respectively). Glucose was infused during peripheral insulin infusion to maintain the glucose level (56 +/- 2 mg/dl) at a value similar to that seen during head insulin infusion (58 +/- 2 mg/dl). Despite equivalent peripheral insulin levels and similar hypoglycemia; steady state plasma epinephrine (792 +/- 198 vs. 2394 +/- 312 pg/ml), norepinephrine (404 +/- 33 vs. 778 +/- 93 pg/ml), cortisol (6.8 +/- 1.8 vs. 9.8 +/- 1.6 micrograms/dl) and pancreatic polypeptide (722 +/- 273 vs. 1061 +/- 255 pg/ml) levels were all increased to a greater extent during head insulin infusion (P < 0.05). Hepatic glucose production, measured with [3-3H]glucose, rose from 2.6 +/- 0.2 to 4.3 +/- 0.4 mg/kg per min (P < 0.01) in response to head insulin infusion but remained unchanged (2.6 +/- 0.5 mg/kg per min) during peripheral insulin infusion. Similarly, gluconeogenesis, lipolysis, and ketogenesis were increased twofold (P < 0.001) during head compared with peripheral insulin infusion. Cardiovascular parameters were also significantly higher (P < 0.05) during head compared with peripheral insulin infusion. We conclude that during hypoglycemia in the conscious dog (a) the brain is directly responsive to physiologic elevations of insulin and (b) the response includes a profound stimulation of the autonomic nervous system with accompanying metabolic and cardiovascular changes.     

Serum sialic acid concentration in patients with hypertriglyceridaemia showing the Frederickson's IIB phenotype.

1. Serum total sialic acid concentration, recently shown to be a cardiovascular risk factor, and also serum lipid-associated sialic acid concentration were measured in 15 patients with hypertriglyceridaemia (fasting serum triacyglycerol concentration > 2.3 mmol/l) showing a Frederickson's type IIB phenotype, 15 patients with hypercholesterolaemia showing a IIA phenotype and 15 age- and sex-matched normal control subjects. 2. Total serum sialic acid concentration was significantly raised in the hypertriglyceridaemic group (84.9 +/- 21.5 versus 64.9 +/- 20.8 mg/dl, P < 0.03, Mann-Whitney U-test) compared with the normal control group, as was serum lipid-associated sialic acid concentration (23.0 +/- 4.3 versus 12.0 +/- 3.2 mg/dl, respectively, P < 0.001, Mann-Whitney U-test). 3. Serum total sialic acid concentration was also significantly elevated in the hypertriglyceridaemic group as compared with the IIA phenotype hypercholesterolaemic group (84.9 +/- 21.5 versus 58.4 +/- 11.7 mg/dl, P < 0.03, Mann-Whitney U-test), as was serum lipid-associated sialic acid concentration (23.0 +/- 4.3 versus 14.9 +/- 4.7 mg/dl, P < 0.001, Mann-Whitney U-test). 4. We suggest that serum concentrations of both total sialic acid and lipid-associated sialic acid may be useful markers of cardiovascular risk which could, in part, be related to hypertriglyceridaemia.     

Increased plasma histamine levels in uraemic pruritus

1. We determined plasma levels of histamine in uraemic patients and examined their correlation with the presence of pruritus. 2. In 27 patients with chronic renal failure, plasma histamine levels were analysed by radioimmunoassay and were compared with those of 40 healthy adult subjects. The control population showed plasma histamine concentrations of 185 +/- 33 pg/ml, which were significantly lower than those of the patients with renal insufficiency. The highest levels (552 +/- 116 pg of histamine/ml) were found in 16 patients with chronic renal failure (mean serum creatinine 5.1 +/- 1.0 mg/dl) and severe itching. 3. Twelve patients with pronounced pruritus who were on maintenance haemodialysis (serum creatinine 9.2 +/- 1.2 mg/dl) had a mean plasma histamine concentration of 515 +/- 81 pg/ml. Fifteen patients on regular haemodialysis (serum creatinine 9.0 +/- 1.5 mg/dl) and who experienced itching had plasma histamine levels (322 +/- 40 pg/ml) which were significantly lower (P less than 0.01) than those of the patients with pruritus but which were elevated compared with those of the control population (P less than 0.01). 4. No correlation could be found between increased plasma histamine levels and the type of dialysis membrane used or the method of sterilization of the membrane. 5. Haemodialysis alone did not reduce plasma histamine concentrations, although high concentrations could be detected in the ultrafiltrate. In six patients a rapid decrease in plasma histamine concentration from 565 +/- 134 pg/ml to within the normal range could be detected after 60 min of combined haemodialysis and haemoperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum 1,25 dihydroxy vitamin D (1,25(OH)2D3), 25 hydroxy vitamin D (25(OH)D) and parathormone levels in diabetic retinopathy

OBJECTIVES: To investigate whether there is a relationship between serum 1,25 dihydroxy vitamin D3 [1,25(OH)2D3], which is an inhibitor of angiogenesis, concentrations and severity of diabetic retinopathy (DR). DESIGN AND METHODS: Serum 1,25(OH)2D3, 25 hydroxy vitamin D [25(OH)D] and parathormone (PTH) concentrations were measured in diabetic patients (n = 66) and nondiabetic healthy subjects (n = 20). RESULTS: The mean serum 1,25(OH)2D3 concentration in diabetic patients was lower than that in nondiabetics (57.3+/-21.44 vs. 89.4+/-18.01 pmol/L, p<0.001); mean 1,25(OH)2D3 concentrations fell with increasing severity of DR [being 63.4+/-17.26 pmol/L for background DR (BDR), 47.7+/-13.27 pmol/L for preproliferative DR (pre-PDR), and 43.1+/-19.45 pmol/L for proliferative DR (PDR)]. Compared with the control group, serum 25(OH)D concentrations were found to be decreased in diabetic patients (p<0.001).There were negative correlations between 1,25(OH)2D3 and age (r = -0.331, p<0.01) and duration of diabetes (r = -0.255, p<0.05). CONCLUSION: From these findings, it was found that there was an inverse relationship between the severity of the retinopathy, i.e., neovascularization, and serum 1,25(OH)2D3 concentrations, being the lowest in PDR and the highest in diabetic patients without retinopathy (NDR) patients. The measurement of serum 1,25(OH)2D3 concentrations might be helpful to predict severity of DR in patients with diabetes mellitus.     

Hypocalcemia may not be essential for the development of secondary hyperparathyroidism in chronic renal failure.

Hypocalcemia is the main factor responsible for the genesis of secondary hyperparathyroidism in chronic renal disease. Studies with parathyroid cells obtained from uremic patients indicate that there is a shift in the set point for calcium-regulated hormone (parathyroid hormone [PTH] secretion. Studies were performed in dogs to further clarify this new potential mechanism. Hypocalcemia was prevented in uremic dogs by the administration of a high calcium diet. Initially, ionized calcium was 4.79 +/- 0.09 mg/dl and gradually increased up to 5.30 +/- 0.05 mg/dl. Despite a moderate increase in ionized calcium, immunoreactive PTH (iPTH) increased from 64 +/- 7.7 to 118 +/- 21 pg/ml. Serum 1,25(OH)2D3 decreased from 25.4 +/- 3.8 to 12.2 +/- 3.6 pg/ml. Further studies were performed in two other groups of dogs. One group received 150-200 ng and the second group 75-100 ng of 1,25(OH)2D3 twice daily. The levels of 1,25(OH)2D3 increased from 32.8 +/- 3.5 to a maximum of 69.6 +/- 4.4 pg/ml. In the second group the levels of serum 1,25(OH)2D3 after nephrectomy remained normal during the study. Amino-terminal iPTH did not increase in either of the two groups treated with 1,25(OH)2D3. In summary, the dogs at no time developed hypocalcemia; however, there was an 84% increase in iPTH levels, suggesting that hypocalcemia, per se, may not be the only factor responsible for the genesis of secondary hyperparathyroidism.     

Evidence for abnormal regulation of circulating 1 alpha,25-dihydroxyvitamin D in patients with sarcoidosis and normal calcium metabolism.

The effects of vitamin D, 2.5 mg (100,000 U)/d for 4 d, on serum calcium, serum 25-hydroxyvitamin D (25-OHD), and serum 1 alpha,25-dihydroxyvitamin D [1 alpha,25(OH)2D] were compared in 17 normal subjects and 6 patients with sarcoidosis who had normocalcemia and no history of hypercalcemia. The diagnosis was confirmed histologically in each of them. Vitamin D increased mean serum 25-PHD from 30 +/- 4 to 99 +/- 15 ng/ml (P < 0.001) and did not change mean serum 1 alpha,25(OH)2D (32 +/- 3 vs. 29 +/- 3 pg/ml) or mean serum calcium (9.5 +/- 0.1 vs. 9.6 +/- 0.1 mg/dl) in the normal subjects. In contrast, vitamin D increased mean serum 25-OHD from 19 +/- 3 to 65 +/- 19 ng/ml (p < 0.05), increased mean serum 1 alpha,25(OH)2D threefold from 40 +/- 7 to 120 +/- 24 pg/ml, and increased mean serum calcium from 9.4 +/- 0.2 to 9.8 +/- 0.2 mg/dl (P < 0.01). There was a significant positive correlation between the serum 1 alpha,25(OH)2D and serum calcium in these individuals (r = 0.663, P < 0.01) but not in the normal subjects. The results (a) provide further evidence for abnormal regulation of circulating 1 alpha,25(OH)2D in sarcoidosis and (b) indicate that the abnormality may exist in patients with normal calcium metabolism. Thus, the defect in vitamin D metabolism in sarcoid apparently is more common than was previously recognized.     

Efficacy of Ipomoea batatas (Caiapo) on diabetes control in type 2 diabetic subjects treated with diet

OBJECTIVE: To investigate the tolerability, efficacy, and mode of action of Caiapo, an extract of white sweet potatoes, on metabolic control in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: A total of 61 type 2 diabetic patients treated by diet were given 4 g Caiapo (n = 30; mean age 55.2 +/- 2.1 years; BMI 28.0 +/- 0.4 kg/m(2)) or placebo (n = 31; mean age 55.6 +/- 1.5 years; BMI 27.6 +/- 0.3 kg/m(2)) once daily for 12 weeks. Each subject underwent a 75-g oral glucose tolerance test (OGTT) at baseline and after 1, 2, and 3 months to assess 2-h glucose levels. Additionally, fasting blood glucose, HbA(1c), total cholesterol, and triglyceride levels were measured. RESULTS: After treatment with Caiapo, HbA(1c) decreased significantly (P < 0.001) from 7.21 +/- 0.15 to 6.68 +/- 0.14%, whereas it remained unchanged (P = 0.23) in subjects given placebo (7.04 +/- 0.17 vs. 7.10 +/- 0.19%). Fasting blood glucose levels decreased (P < 0.001) in the Caiapo group (143.7 +/- 1.9 vs. 128.5 +/- 1.7 mg/dl) and did not change in the placebo group (144.3 +/- 1.9 vs. 138.2 +/- 2.1 mg/dl; P = 0.052). A decrease in body weight was observed in both the placebo group (P = 0.0027) and in the Caiapo group (P < 0.0001), probably due to a better- controlled lifestyle. In the Caiapo group, body weight was related to the improvement in glucose control (r = 0.618; P < 0.0002). Two-hour glucose levels were significantly (P < 0.001) decreased in the Caiapo group (193.3 +/- 10.4 vs. 162.8 +/- 8.2 mg/dl) compared with the placebo group (191.7 +/- 9.2 vs. 181.0 +/- 7.1 mg/dl). Mean cholesterol at the end of the treatment was significantly lower in the Caiapo group (214.6 +/- 11.2 mg/dl) than in the placebo group (248.7 +/- 11.2 mg/dl; P < 0.05). No significant changes in triglyceride levels or blood pressure were observed, and Caiapo was well tolerated without significant adverse effects. CONCLUSIONS: This study confirms the beneficial effects of Caiapo on plasma glucose as well as cholesterol levels in patients with type 2 diabetes. For the first time, the long-term efficacy of Caiapo on glucose control was demonstrated by the observed decrease in HbA(1c). Thus, the neutraceutical Caiapo seems to be a useful agent in the treatment of type 2 diabetes.     

Ascorbic acid and uric acid levels in lung cancer patients

OBJECTIVE: To study any possible association between serum ascorbic acid and uric acid levels with lung cancer. METHOD: Serum ascorbic acid and uric acid levels in lung cancer patients (n = 30) and healthy controls (n = 45) were measured. RESULTS: The mean values for serum ascorbic acid were found to be significantly lower (P< 0.05) in patients (0.112+/-0.020) than in controls (0.394+/-0.029). Serum uric acid levels of patients were also significantly lower than those of controls (P< 0.05). CONCLUSION: There was no association between serum levels of ascorbic acid and uric acid, cholesterol, triglyceride and albumin levels with lung cancer.     

Effects of sodium fluoride on total serum protein levels and transaminase activity in rats.

Transaminase activity and serum total protein level were investigated in adult rats after oral treating with sodium fluoride at three doses, 10, 20 and 30 mg/kg daily for 90 days. After 90 days, the average total serum protein level of the rats in the treatment group decreased significantly compared with that in the control [1.9 +/- 0.1 (mean +/- S.D., n = 140) vs. 3.1 +/- 0.2] mg/dl, P< 0.05. Serum transaminase activity in the treatment group increased compared with that in the control [5.3 +/- 0.4 (mean +/- S.D., n = 140) vs. 3.2 +/- 0.3] micromol/min per ml, P < 0.05.