Study on dietary constituents, hs-CRP serum levels and investigation of correlation between them in excess weight adolescents.

BACKGROUND:  The prevalence of childhood obesity has increased in Greece as well as worldwide. Mediterranean diet is considered the world's most popular healthy eating pattern. C-reactive protein (CRP) has been shown to play an important pathophysiological role between inflammation and cardiovascular diseases and has been linked to obesity. Our study aimed to investigate the adolescents' diet, their high-sensitivity CRP (hs-CRP) serum levels, and whether low-grade inflammation, present in obesity, is related to adolescents' diet. METHODS: The sample of the study consisted of 142 adolescents age- and gender- matched 13.4 ± 1.46 years, divided into two groups: the study group and the controls. The study group of 71 excess body weight adolescents was further divided into two subgroups of 28 overweight and 43 obese respectively; 71 normal weight age- and gender-matched served as controls. Dietary constituents (food weight, energy intake, protein, carbohydrate and fat consumption, fiber, and sugars) were analyzed. Adherence to the Mediterranean diet was investigated, and hs-CRP serum levels were determined. The findings were compared between/among groups. Furthermore, the correlation of hs-CRP serum levels and food constituents between/among groups was investigated. RESULTS:  We documented differences in several parameters among the groups: waist to hip ratio (p =0.001), food weight (p =0.040), energy intake (p =0.024), protein intake (p =0.001), total fibre (p =0.017), sugars (p =0.001), and the Mediterranean Diet Quality Index for children and adolescents (KIDMED; p =0.008). No statistically significant difference was found for hs-CRP serum levels among the three groups. No correlation was found between hs-CRP serum levels and any of the dietary constituents. CONCLUSIONS:   Comparing the three groups (obese, overweight, and controls), we found statistically significant differences for food constituents but not for hs-CRP serum levels. In our study, inflammation was not found to be correlated with any of the dietary constituents. Further studies in a larger sample are required to consolidate these findings. HIPPOKRATIA 2019, 23(1): 3-8.

Glomerular filtration rate estimation in patients with type 2 diabetes: creatinine- or cystatin C-based equations?

AIMS/HYPOTHESIS: It is argued that GFR estimation (eGFR) using cystatin C-based equations (eGFRcys) is superior to that using creatinine-based equations (eGFRcre). We investigated whether eGFRcys are superior to eGFRcre in patients with type 2 diabetes. METHODS: GFR was measured in 448 type 2 diabetic patients using (51)Cr-EDTA-measured GFR (mGFR) as the reference standard. Bias, precision and accuracy of eGFRcys and eGFRcre were compared. RESULTS: The most accurate eGFRcre equation (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]), which produced the highest proportion of estimates that were within 30% and 10% of the reference standard (80.7% and 38.0% of samples, respectively) had a bias of 7.1 and precision of 12.0 ml min(-1) 1.73 m(-2). The calibrated eGFRcys with the highest accuracy (Tan-C), which produced the highest proportion of estimates that were within 30% (78.8%) and within 10% (39.0%) of the reference standard had a bias of -3.5 and precision of 18.0 ml min(-1) 1.73 m(-2). Moreover, the areas under the receiver operating curve were higher with eGFRcre (CKD-EPI and Modification of Diet in Renal Disease [MDRD]) than with eGFRcys for the diagnosis of mild (mGFR <90 ml min(-1) 1.73 m(-2)) and moderate (mGFR <60 ml min(-1) 1.73 m(-2)) chronic kidney disease. In patients with mGFR ≥90 ml min(-1) 1.73 m(-2), CKD-EPI was the least biased, the most precise and the most accurate equation. CONCLUSIONS/INTERPRETATION: In patients with type 2 diabetes, eGFRcys do not currently provide better eGFR than eGFRcre. At present, compared with eGFRcys, eGFRcre are better at predicting the stage of chronic kidney disease. In addition, CKD-EPI seems to be the best equation for eGFR in patients with normal renal function.

Increased serum C-reactive protein levels in normal weight women with polycystic ovary syndrome.

BACKGROUND: The clinical spectrum of polycystic ovary syndrome (PCOS) includes components of the metabolic syndrome, such as central obesity, insulin resistance, dyslipidemia, arterial hypertension and, even, disturbances of the clotting mechanism. All these disorders are epidemiologically related to cardiovascular disease, most probably through low-grade intravascular chronic inflammation. The aim of this study was to evaluate the serum concentrations of high sensitivity C-reactive protein (hsCRP), a non-specific marker of low-grade inflammation and a predictive marker for cardiovascular disease, in normal weight women with (PCOS). PATIENTS AND METHODS: One hundred and eighty-eight (188) normal weight [body mass index (BMI) < 25 kg/m(2)] women with PCOS were included in the study. Forty-three (43) normal weight women without PCOS (normal ovulation without clinical or biochemical hyperandrogenemia) served as controls. Serum samples for luteinizing hormone, folliclestimulating hormone, prolactin, total testosterone, Δ4-androstenedione, 17α-hydroxy-progesterone, sex hormone-binding globulin (SHBG), insulin, glucose and hsCRP were collected in early follicular phase (third to sixth day) of a menstrual cycle in the control group or during a spontaneous bleeding episode in the PCOS group. RESULTS: Normal weight women with PCOS had higher concentrations of serum hsCRP as compared to normal weight women without PCOS (mean ± standard error of the mean 0.55 ± 0.08 versus 0.27 ± 0.08 mg/dL, p = 0.001). CONCLUSIONS: As normal weight women with PCOS are characterized by elevated serum concentrations of hsCRP, they have to be considered as carrying at least one marker of low-grade inflammation.

Effects of oral folate supplementation on serum total homocysteine and cholesterol levels in hyperhomocysteinemic children.

BACKGROUND: Hyperhomocysteinemia may be a risk factor for cardiovascular disease even among children. Increased levels of total serum homocysteine (tHcy) may initiate atherosclerosis by modulating increased cholesterol synthesis in the liver. Folate supplementation has been found to reduce homocysteine levels. However, no data have been reported about the relationship between folate supplementation and cholesterol levels in children. METHODS: Twenty of 26 hyperhomocysteinemic (>95th percentile for age) children underwent a therapeutic intervention of 5 mg of oral folate supplementation twice per week for 2 months. RESULTS: After the 2-month intervention with folate supplement, tHcy levels were statistically significantly decreased (P < .001), folate levels were significantly increased (P < .001), while total cholesterol levels were significantly improved from 183.8 (115-296 mg/dL) to 160.8 (109-265 mg/dL) (P < .05). CONCLUSIONS: Folate supplementation may reduce tHcy, serum folate, and total serum cholesterol levels in hyperhomocysteinemic children.

Oral supplementation of folic acid for two months reduces total serum homocysteine levels in hyperhomocysteinemic Greek children.

BACKGROUND & AIM: Hyperhomocysteimemia is a cardiovascular risk factor even among children. Supplementation of oral folic acid may reduce homocysteine levels to normal. However, data is limited at this point for healthy children and adolescents. METHODS: Five hundre and twenty four children participated in the study; Twenty six of them were found to be hyperho mocysteinemic(>95(th) percentile for age). Twenty of them received 5 mg of folic acid twice per week for two consecutive months while the other six received a diet rich in dietary folate. RESULTS: Serum homocysteine levels were statistically significantly decreased from 13.1 (10-24.2 micromol/L ) to 7.7 (4.9- 15.2 micromol/L), p<0.001. Serum folate levels were significantly rose from 4.3 (3-20 ng/mL) to 16.8 (7-20 ng/mL), p<0.001. On the contrary, no important changes were observed in the above parameters in children to whom a diet rich in folic acid was recommended. Homocysteine levels were found to be positively associated with age (r=0.314, p<0.001), BMI (r=0.192, p<0.001), WC (r = 0.215, p<0.001), simple sugars (r= 0.182, p<0.001 ) and negatively associated with folic acid (r = -0.331, p<0.001), vitamin B12 (r = -0.214, p<0.001) and dietary folic acid (r= -0.228, p=0.003). CONCLUSIONS: Oral folic acid 5 mg twice per week may efficiently reduce serum homocysteine levels and increase serum folic acid levels in healthy children with increased homocysteine levels (>95(th) percentile for age). Hyperhomocysteinemia in childhood may be a predictive factor of cardiovascular disease. In addition, these results may offer more help to health practioners in order to establish more prospective studies to elucidate the relationship between homocysteine, folic acid and heart disease in children.

Serum beta-endorphin response to stress before and after operation under fentanyl anesthesia in neonates, infants and preschool children.

INTRODUCTION: The endogenous opioid beta-endorphin is a known indicator of stress and pain. Opioid anesthesia during operation may prevent postoperative beta-endorphin hypersecretion. We examine the effect on serum beta-endorphin of both preoperative stress and stress of operation under opioids in neonates, infants and preschool children. In order to eliminate the effect of hospitalization anxiety we compared with inpatients of similar age with non-surgical disease. MATERIAL AND METHODS: We included 74 surgical patients (25 neonates, 24 infants, 25 preschool children), and 44 non-surgical inpatients (14 neonates, 12 infants, 18 preschool children). Anesthesia comprised propofol and fentanyl. In presence of pain after extubation, supplementary morphine was administered. Sera were taken preoperatively and 2 h postoperatively in surgical patients, and once in non-surgical patients. Beta-endorphin was tested using ELISA (ng/ml). RESULTS: In all surgical patients beta-endorphin did not increase significantly after surgery. Neonates showed significantly elevated beta-endorphin preoperatively (mean+/-SD: 2.02+/-0.76) and postoperatively (2.07+/-0.90) compared to neonates with a non-surgical disease (1.05+/-0.34; p<0.005). In contrast, infants (preoperative values: 1.75+/-1.32, postoperative values: 2.00+/-1.83) did not differ from respective non-surgical inpatients (1.49+/-0.70). Before and after surgery, beta-endorphin was significantly elevated in preschool children (7.19+/-1.85, 6.42+/-1.31), as compared with neonates and infants (p<0.0005), and with preschool children with non-surgical disease (1.01+/-0.27; p<0.0005). CONCLUSIONS: Fentanyl/propofol anesthesia, supplemented by postoperative morphine where necessary, protects from surgical stress and postoperative pain, as denoted by no postoperative increase of beta-endorphin in all age groups. Preschool children, who exhibit increased emotional perception, have explicitly high serum beta-endorphin before and after surgery. Preoperative preparation programs might be worthy in this age group. Neonates show a moderate but still significantly high response of beta-endorphin to stress, retained after operation. In contrast, infants tolerated stress better (not increased beta-endorphin pre- and post-operatively).

Homocysteine lowering with folic acid supplements in children: effects on blood pressure.

Hyperhomocysteinemia is emerging as an independent predictor of cardiovascular disease and hypertension among children. The aim of the study was to examine the effects of oral folic acid on homocysteine and blood pressure. Folic acid supplementation has been found to reduce homocysteine levels and in some cases blood pressure. Five hundred and twenty children participated in the study, and 26 of them were found to be hyperhomocysteinemic; 20 of these children randomly received 5 mg oral folic acid supplement while the other six children were the controls. Serum homocysteine (P < 0.001) levels as well as systolic (P < 0.001) and diastolic (P = 0.045) blood pressure were statistically significantly decreased in the intervention group compared with the controls, while folic acid levels were statistically significantly increased (P < 0.001). Total serum homocysteine levels were correlated with age, serum folate, body mass index, and blood pressure. It appears that folic acid may be a safe and effective supplement to reduce homocysteine and possibly blood pressure, which consequently may prevent cardiovascular disease in children in early life.

Coagulation factors as biological risk markers of endothelial dysfunction. Association with the thrombotic episodes of chronic hemodialysis patients.

BACKGROUND AND AIM: The aim of our study was to assess the coagulation factors as endothelial dysfunction markers and prospectively their association with thrombotic episodes in chronic hemodialysis patients. PATIENTS AND METHODS: Fifty-four randomly selected patients on chronic hemodialysis (HD), 34 men and 20 women were included in this study. Their mean age was 56 years and the mean hemodialysis duration was 53.0861.92 months. The variations of tissue factor pathway inhibitor (TFPI), thrombomodulin (TM) and von Willebrand factor (vWF) were studied. The above-mentioned parameters were measured before and after HD session. Low molecular weight heparin (tinzaparin) was administered to all patients during hemodialysis. The results were compared with those obtained from 20 healthy volunteer-controls, age and sex matched. After the initial assessment, all patients were followed for a period of 15 months. RESULTS: Two patients experienced one hemorrhagic event each, regarding the upper and/or the lower gastrointestinal tract. Twenty patients showed at least one thrombotic episode. Eleven patients presented fistula thrombosis, four angina pectoris incidents and five thrombosis of the lower limbs. The rest of the patients did not experience any clinical symptomatology that could be attributed to coagulation disorders. Parameter differences between patients and controls were statistically significant (p<0.005 for TFPI and p<0.001 for TM and vWF) and were improved after hemodialysis session. The age and the elevated levels of the vWF were found to be significantly different (p<0.03 and p<0.02 respectively) between the groups of patients who experienced or not thrombotic episodes. CONCLUSIONS: Coagulation factors TFPI, TM, and vWF are increased in hemodialysis patients and the clinical disorders are mainly thrombotic episodes. The age of patients and the elevated levels of vWF are associated with the thrombotic incidents. Hemodialysis contributes in the improvement of these coagulation factors, which could be considered as biological risk markers of endothelial dysfunction in chronic HD patients.

Effects of succinylcholine on the recovery of block produced by mivacurium in rats.

This study investigates the effects of succinylcholine on the recovery of neuromuscular blockade produced by mivacurium in rats. In 48 anesthetized animals, the sciatic nerve was prepared and stimulated, and twitches of the flexor digitorum longus muscle were recorded. Animals were randomly divided into four groups (n = 12 each): bolus dose of succinylcholine 0.1 mg/kg (GroupSch), bolus dose of mivacurium 0.15 mg/kg (GroupMiv), bolus dose of mivacurium 0.15 mg/kg, followed by succinylcholine 0.1 mg/kg at 25% neuromuscular recovery from mivacurium (Group-MivSch(25)), or bolus dose of mivacurium 0.15 mg/kg, followed by succinylcholine 0.1 mg/kg at 75% neuromuscular recovery from mivacurium (GroupMivSch(75)). Onset times of neuromuscular block following succinylcholine in mivacurium-treated groups were comparable and significantly shorter than in GroupSch (p < 0.001). Duration of action of succinylcholine was more prolonged when it was given in the presence of deeper neuromuscular block induced by mivacurium (p < 0.001 in GroupMivSch(25) and p < 0.01 in GroupMivSch(75)). Our results suggest that, in rats, mivacurium administration has a significant potentiating effect on a subsequent succinylcholine-induced neuromuscular block.

Association of blood pressure, obesity and serum homocysteine levels in healthy children.

AIM: Obesity, hypertension and total serum homocysteine levels are well-known risk factors for cardiovascular disease in adults. However, there is limited data on the relation of these risk factors in children. METHODS: Five hundred twenty-four healthy school children aged 6-15 years participated in the study. BMI were used to categorize our subjects in normal overweight and obese groups based on Internationally Obesity Task Force criteria. RESULTS: The prevalence of overweight and obesity was 21.1% and 8.4% for boys and 17.6% and 7.3% for girls, respectively. Diastolic blood pressure (DBP), systolic blood pressure (SBP) and waist circumference (WC) were significantly higher in overweight and obese group compared to normal ones, whereas for homocysteine levels no difference was observed. Based on the results derived from the multiple regression analysis, BMI was positively related to energy intake (beta=0.247, p<0.001) and WC (beta=0.014, p<0.001). Both SBP and DBP were positively related to age ([beta=0.251, p<0.001] and [beta=0.301, p<0.001, respectively]), and BMI ([beta=0.096, p<0.001] and [beta=0.022, p<0.001], respectively). CONCLUSION: The current study revealed an association of blood pressure and WC with overweight and obesity in children, and even though these children may not have increased homocysteine levels, they still have enough reasons to reduce weight in order to avoid cardiovascular disease in their life later on.

Cardiac manifestations of inborn errors of metabolism.

AIM: The aim of the study was to investigate the frequency and type of cardiac manifestations in a defined group of patients with inborn errors of metabolism. This paper also explores the key role of cardiac manifestations in the diagnosis of inborn errors of metabolism in daily practice. METHODS: Out of the 287 patients with the potential for inborn errors of metabolism who had been referred to the University Hospital of Heraklion (202 children and adolescents and 85 adults), 41 were found to have a variety of cardiac manifestations, including cardiomyopathy, cardiomegaly, atrioventricular conduction disorders and coronary artery disease. RESULTS: In 15 out of the 41 patients a diagnosis of inborn errors of metabolism was established, while the total number of patients with inborn errors of metabolism was 60 out of the 287. In 6 out of the 15 patients the major symptoms were from the cardiovascular system and 7 of them were adults with symptoms initiating in childhood. CONCLUSION: The cardiac findings consist of a neglected area in the diagnosis of the inborn errors of metabolism. Neurologists, pediatricians and internists should cooperate with cardiologists in managing people with unexplained cardiac symptoms and signs and be aware that several inborn errors of metabolism are associated with cardiac abnormalities and mild neurologic findings.

Reference range of total serum homocysteine level and dietary indexes in healthy Greek schoolchildren aged 6-15 years.

Elevated total serum homocysteine (tHcy) may be a possible risk factor for CVD. A 5 micromol/l increase in tHcy is associated with an approximately 70 % increase in relative risk of CVD in adults. Data for children and adolescents are, however, limited. The purpose of the present study was to provide a reference range for tHcy and investigate any relationship between tHcy and nutritional indexes in a Greek paediatric population. tHcy, folate, vitamin B12 levels and dietary indexes were measured in 520 healthy schoolchildren (274 boys, 246 girls) aged 6-15 years. As in adults, the tHcy distribution skewed to the right, with a geometric mean for both genders of 7.4 (range 3.4-29 micromol/l). Concentrations were lower in young children and increased with age. No statistically significant difference in tHcy level was observed between gender. The 95th percentiles for the three age groups were as follows: 6-9 years, 9.98 micromol/l; 10-12 years, 10.62 micromol/l; 13-15 years, 14.4 micromol/l. Using Pearson's coefficient analysis, tHcy level was correlated with age, serum folate, BMI and systolic blood pressure. Dietary analysis showed that folate, vitamin B12 and fibre intake were inversely related with tHcy; conversely, sugar and fat were positively associated with tHcy. However, in multiple linear regression analysis, only age (odds ratio 0.246, P < 0.05) and folate (odds ratio -0.346, P < 0.05) were significantly and independently associated with tHcy. This study provides age-specific reference data regarding tHcy concentration in a Greek paediatric population. tHcy levels increased as a function of age. Serum folate levels were significantly and independently associated with tHcy levels.

Combined treatment with low-dose pravastatin and fish oil in post-renal transplantation dislipidemia.

BACKGROUND: The most common cause of post-transplant dyslipidemia is the use of corticosteroids and cyclosporin-A (CyA). The HMG-CoA reductase inhibitors have emerged as the agents of first choice in the treatment of post-transplant hyperlipidemia in combination with low fat diet. The objective of this study was to evaluate the efficacy of combined treatment with low-dose pravastatin and fish oil in post-renal transplantation dislipidemia. PATIENTS AND METHODS: Twenty-four renal transplant patients, 15 men and 9 women aged from 30 to 60 years with stable renal function were included in this study. All patients were transplanted from living related donors and were given a stable triple immunosuppressive therapy, with methylprednisolone, azathioprine and CyA. All patients were also given a standard diet containing 1 g/kg BW protein, reducing the daily fat to less than 30%, and maintaining at least a 1:1 ratio of saturated to polyunsaturated (or monounsaturated) fats. A dosage of 20 mg pravastatin (pravachol) and 1 g of fish oil (prolipid) were added to the diet after dinner, according to our protocol. Blood samples were taken after each study period for total cholesterol, LDL-cholesterol, triglycerides, Apo A(1), Apo B, Lp(a), creatinine, CPK and fibrinogen determination. RESULTS: At the end of the therapeutic protocol with pravastatin a significant reduction (p < 0.02) of total and LDL-cholesterol was observed, but no significant change in triglycerides, HDL, Lp(a), Apo A(1), Apo B and fibrinogen was shown. At the end of the therapeutic protocol with pravastatin and fish oil supplement significant changes were seen in TC (p < 0.02), TG (p < 0.03), LDL-C (p < 0.03), Apo A(1) (p < 0.04) and Apo B (p < 0.05) concentrations. There were no significant changes in HDL-C and Lp(a) concentrations. Renal function and cyclosporine levels were not changed during and after the study. CPK was increased only in one case. CONCLUSIONS: It is suggested that if the response to the diet is inadequate, the use of combined treatment with low-dose pravastatin and fish oil is a more effective strategy than the pravastatin treatment alone for changing the lipid profile after renal transplantation.

Prognostic significance of adenosine deaminase in children with malignancies.

In 33 children, 23 with acute lymphoblastic leukemia (ALL) and 10 with solid tumors, the phenotype of the enzyme adenosine deaminase (ADA) was detected in the erythrocytes by electrophoresis in cellulose acetate. In all children the ADA enzyme activity was also determined in the plasma by spectrophotometry at the onset of the disease, during remission, at the end of the therapy, and during relapse. The phenotype in all children was ADA1-1. There was a difference in enzyme activity between the mean values of children with ALI and those with solid tumors. There were also differences among the subtypes of ALL and also among the stages of ALL and the stages of solid tumors. In 23 children with ALL the mean value (MV) and the corresponding standard error (SEM) of enzyme activity at the onset of the disease were MV +/- SEM = 60.2 +/- 6.2 IU/L. This was higher than that of the control group (control group: MV +/- SEM = 27.8 +/- 3.3 IU/L). During remission the enzyme activity was lower than that of the control group (MV +/- SEM = 19.6 +/- 1.7 IU/L); at the end of the therapy it was MV +/- SEM = 24.0 +/- 1.3 IU/L, which is close to that of the control group; and during relapse it was much higher compared with the control group (MV +/- SEM = 73.1 +/- 4.6 IU/L). These values are discussed in connection to the leukaemic subtypes. In 10 children with solid tumors the mean value of enzyme activity at the onset of the disease was MV +/- SEM = 48.8 +/- 2.4 IU/L. During therapy it was MV +/- SEM = 32.4 +/- 1.9 IU/L and at the end of therapy MV +/- SEM = 22.1 +/- 2.5 IU/L. The aim of this work is to study the qualitative isoenzyme abnormalities to better understand the biological nature of the malignancies, to distinguish main groups and subsets of ALL and solid tumors on an enzymatic basis, and to identify possible sensitive key enzymes as targets for chemotherapy.

Intensive short course chemotherapy for treatment of Greek children with tuberculosis.

This prospective study with an 18-month posttreatment follow-up evaluated the efficacy of intensive short course chemotherapy in Greek children with pulmonary or extrapulmonary tuberculosis. Between November, 1988, and March 1991 a 2-month regimen of rifampin, 10 to 12 mg/kg/day, isoniazid, 10 to 12 mg/kg/day, and pyrazinamide, 30 to 35 mg/kg/day, followed by rifampin and isoniazid for the remaining 4 months, was administered orally to 36 children with tuberculosis. Twenty-three boys and 13 girls ages 8 months to 12 years (mean, 5 1/2 years) were enrolled in the study. The diagnostic criteria for establishing tuberculosis were tuberculin skin test reactivity, radiographic findings compatible with tuberculosis, epidemiological data and clinical and laboratory findings. Four children had extrapulmonary and 32 had pulmonary tuberculosis; 9 of the latter were asymptomatic. Among the pulmonary cases there were 2 children with pleural effusion. Clinical response to therapy was apparent within 7 to 14 days; the pleural effusions resolved in 2 to 6 weeks and the pulmonary infiltrates cleared in 2 to 6 months. Hilar adenopathy regressed within 18 months or longer. No serious problems with drug tolerance or toxicity were noted during the treatment period. Temporary hyperuricemia and transient elevation in serum transaminases were observed in 11 patients but no drug modification was required. There were no posttreatment relapses. These findings suggest that intensive short course chemotherapy for the treatment of Greek children with pulmonary or extrapulmonary tuberculosis appears to be effective, safe, of good patient compliance and comparable to the longer treatment regimens.

Interaction of ketoprofen and frusemide in man.

The effects of ketoprofen on frusemide-induced diuresis, natriuresis and renin release were studied in 12 healthy male volunteers. Each received frusemide 40 mg once daily with either ketoprofen 100 mg twice daily or placebo for two periods of 5 days separated by a treatment-free period according to a randomized, double-blind, cross-over study design. Ketoprofen significantly reduced frusemide-induced diuresis on Day 1 but not on Day 5 of treatment. The natriuresis induced by frusemide on Day 1 or Day 5 of treatment did not differ significantly whether ketoprofen or placebo was administered, although the mean urinary sodium excretion values were consistently lower following ketoprofen. Ketoprofen did not affect the kaliuretic response to frusemide on Day 1 or Day 5 of treatment. The increase in plasma renin activity after frusemide was inhibited by ketoprofen on both Day 1 and Day 5. These results suggest that ketoprofen reduces the diuresis and renin release induced by frusemide, but that the reduction in diuretic response may become less important after their repeated coadministration.

Comparison of chlortenoxicam and indomethacin on frusemide-induced diuresis.

A single oral dose of chlortenoxicam 4 mg, a new non-steroidal anti-inflammatory drug, significantly antagonized the diuretic and natriuretic actions of frusemide when compared with placebo in normal human volunteers. Indomethacin 50 mg significantly reduced the natriuretic, but not diuretic action of frusemide.

The influence of changes in buccal potential difference on the buccal absorption of propranolol.

A buccal potential difference (b.p.d.) exists across the mucous membrane of the mouth, which can be made less negative by contact with aspirin. The influence of changing the b.p.d. with aspirin on the buccal absorption of propranolol from a series of buffers of pH5-10 has been studied in eight volunteers. The study confirmed that the buccal absorption of propranolol was markedly pH dependent, but pretreatment of the buccal membrane with aspirin had no influence on the absorption of propranolol.