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Biomedical subjects

S Panagiotopoulos

Publications and source records attributed to S Panagiotopoulos.

At least 37 records · Page 2Linked to original sources
PubMed1996

Effects of insulin on body composition in patients with insulin-dependent and non-insulin-dependent diabetes.

Insulin is used to control blood glucose but may have an adverse effect on the amount and distribution of fat mass and other cardiovascular risk factors. To test this hypothesis the effect of insulin therapy on blood glucose, body composition, and lipid levels was measured during 6 months in 9 patients with newly diagnosed insulin-dependent (Type 1) diabetes mellitus (IDDM) and 15 patients with non-insulin dependent (Type 2) diabetes (NIDDM) and secondary failure of therapy with oral hypoglycaemic agents. Both groups received similar daily doses of insulin (approximately 0.6 units kg-1 day-1). Glycaemic control improved during 6 months treatment in both groups, although the reduction in HbA1c was greater in IDDM (5.2 +/- 0.7%) than in NIDDM (2.0 +/- 0.4%, p < 0.001). All parameters of the lipid profile improved in IDDM but not in NIDDM. Body weight, lean mass, and fat mass, measured by dual energy x-ray absorptiometry, increased at 1 month in IDDM but not in NIDDM. By 6 months, body weight had increased more in IDDM than NIDDM (9.1 +/- 1.2 vs 3.77 +/- 0.5 kg, p < 0.01). The increase in weight was predominantly lean mass in IDDM (60.4 +/- 9.3%) and fat mass in NIDDM (59.9 +/- 8.4%). The increase in lean mass was greater in IDDM than NIDDM (5.6 +/- 1.1 vs 1.4 +/- 0.3 kg, p < 0.001). Fat mass increased by similar increments in IDDM and NIDDM (3.4 +/- 0.8 vs 2.4 +/- 0.5 kg, p = ns) and was predominantly an increase in trunk fat (IDDM: 2.3 +/- 0.6 kg, NIDDM: 2.0 +/- 0.4 kg, p = ns). The central/peripheral fat mass ratio prior to treatment was lower in IDDM than NIDDM (0.64 +/- 0.05 vs 1.09 +/- 0.09, p < 0.01) and then increased in IDDM by 0.32 +/- 0.15 (p = 0.07) and in NIDDM by 0.22 +/- 0.06 (p < 0.001). In conclusion, insulin therapy is associated with weight gain in both IDDM and NIDDM. In the former, weight gain reflects increases in lean mass whereas in NIDDM it reflects an increase in trunk fat mass. It remains to be determined whether this trend to central obesity partly offsets other benefits of insulin therapy in NIDDM.

Adipose Tissue↗
PubMed1996

Organ specificity of antihypertensive therapy on ocular albumin vascular clearance and albuminuria in the hypertensive diabetic rat.

PURPOSE: The contributions of hypertension and diabetes to microvascular dysfunction in the kidney and eye were investigated. Two indices of microvascular dysfunction, urinary albumin excretion rate (AER) and albumin vascular clearance (AVC) in the eye, were studied in control and streptozocin diabetic Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR). METHODS: Studies were performed on four groups of untreated rats--nondiabetic and diabetic WKY and nondiabetic and diabetic SHR--and on three groups of diabetic SHR treated with a converting enzyme inhibitor (perindopril), a calcium-channel blocker (lacidipine), or triple therapy (hydrochlorothiazide, reserpine, and hydralazine). In all rats, AER and AVC were measured at 16 weeks. RESULTS: There was a progressive increase in both parameters in the order WKY, diabetic WKY, SHR, and diabetic SHR. When compared with nondiabetic WKY, diabetic SHR showed an approximately 30-fold increase in AER and an approximately threefold increase in AVC. Treatment of diabetic SHR with perindopril or triple therapy normalized AER compared to an equihypotensive dose of lacidipine, which had no effect. By contrast, the three antihypertensive regimens showed a different order of efficacy in preventing increases in ocular AVC. In diabetic SHR, the increase in retinal AVC was prevented largely by lacidipine, whereas the other two antihypertensive regimens showed lesser effects [AVC expressed as percentage nondiabetic WKY: untreated diabetic SHR 278% +/- 47%, lacidipine 93% +/- 10% (P < 0.001), triple therapy 132% +/- 37% (P < 0.05), and perindopril 167% +/- 9% (P < 0.05)]. Lacidipine also prevented the increase in AVC of the anterior and posterior uvea. By contrast, increases in AVC observed in the diabetic SHR were not prevented by perindopril in the posterior uvea or by triple therapy in the anterior uvea. Thus, hypertension and diabetes increased ocular AVC and AER, and effective antihypertensive therapy substantially prevented changes in both parameters. However, despite equivalent levels of blood pressure control for each regimen, discordant effects were noted on AVC and AER. Perindopril was associated with significantly lower AER than lacidipine, whereas lacidipine was more potent in preventing increases in ocular AVC. CONCLUSIONS: Results of this study suggest that different antihypertensive regimens in the diabetic rat may exert organ-specific effects on the retina and kidney despite equivalent effects on systemic blood pressure. These data also raise the possibility that retinal microvascular dysfunction in diabetes is ameliorated more readily by calcium-channel blockade than by converting-enzyme inhibition, whereas the reverse applies to renal microvascular dysfunction, as reflected by albuminuria.

Albuminuria↗
PubMed1994

Complementary effects of pravastatin and nicotinic acid in the treatment of combined hyperlipidaemia in diabetic and non-diabetic patients.

BACKGROUND: Given that treatment with a single drug is frequently unsuccessful in patients with combined hyperlipidaemia, there is a rationale for the study of regimens using drugs that have complementary therapeutic profiles. We therefore set out to compare the efficacy of a combined pravastatin and nicotinic acid regimen with higher dose monotherapy using either drug in patients with non-insulin-dependent diabetes and in non-diabetic patients with combined hyperlipidaemia. METHODS: Forty-four patients with total-cholesterol levels of 6.5 mmol/l or higher and triglyceride levels of 2.5 mmol/l or above were randomly assigned to receive either pravastatin alone (40mg/day) or nicotinic acid alone (1500mg/day) for 12 weeks. At the end of this period, the participants received a combination of pravastatin (20mg/day) and nicotinic acid (1000mg/day) for a further 12 weeks. The lipid parameters measured included levels of total cholesterol, triglycerides, low-density-lipoprotein (LDL) cholesterol and high-density-lipoprotein (HDL) cholesterol. RESULTS: Thirty-three patients (22 without and 11 with diabetes) completed the protocol. Monotherapy with pravastatin was more effective than that with nicotinic acid in reducing levels of total cholesterol (-24.9 versus -9.8%, P<0.001) and LDL cholesterol (-32.1 versus -16.9%, P < 0.01), similar in reducing levels of triglyceride (-28.0 versus -31.8%, NS) and tended to be less effective in elevating levels of HDL cholesterol (+16.4 versus +30.8%, P = 0.06). Combination therapy was more effective than pravastatin monotherapy in reducing levels of triglyceride (-39.3 versus -28.0%, P < 0.05) and elevating those of HDL cholesterol (+35.6 versus +16.4%, P < 0.001) and was equally effective in reducing total-cholesterol (-22.3 versus -24.9%, NS) and LDL-cholesterol (-27.1 versus -32.1%, NS) levels. Combination therapy was more effective than nicotinic acid monotherapy in reducing levels of total cholesterol (-23.8 versus -9.8%, P < 0.001), triglyceride (-39.4 versus -31.8%, P < 0.05) and LDL cholesterol (-35.7 versus -16.9%, P < 0.05) and equally effective in elevating HDL-cholesterol levels (+33.6 versus +30.8%, NS). Diabetic and non-diabetic participants responded similarly to combination therapy. Eleven patients (25%) were withdrawn from the study: nine as a result of nicotinic acid intolerance (flushing and nausea) and one through pravastatin intolerance (nausea); one patient died of a myocardial infarction. Combination therapy elevated glycosylated haemoglobin A1c levels in non-diabetic patients (5.5 to 5.8%, P < 0.001); in diabetic patients, however, the observed rise (7.4 to 7.9%) was not statistically significant. Fasting plasma glucose levels, liver function tests and levels of creatine kinase or uric acid were unaffected by either monotherapy or by combination therapy, with the exception of an elevation of the glucose level in diabetic patients receiving nicotinic acid monotherapy. CONCLUSION: Pravastatin and nicotinic acid in lower-dose combination are more effective than pravastatin alone in reducing levels of triglyceride and elevating those of HDL cholesterol and are more effective than nicotinic acid alone in reducing total-cholesterol triglyceride and LDL-cholesterol levels. Combination therapy is equally effective in type-II diabetic and non-diabetic people. The complementary effects of the combination therapy on lipid levels suggest that this regimen should be considered as a therapeutic option in patients with combined hyperlipidaemia who tolerate the side effects of nicotinic acid.

Adult↗
PubMed1994

Progressive decline in renal function in diabetic patients with and without albuminuria.

This study describes patterns of progression of albuminuria and renal function in a subgroup of 40 patients from a total cohort of 211 diabetic patients (118 type I, 93 type II) followed over a period of 8-14 years. Forty patients (18 with type I diabetes, 22 with type II diabetes) showed progressive increases in albumin excretion rate (AER) and/or decreases in creatinine clearance (CC) during the study period. Of these, AER alone increased in 15 patients, AER increased and CC decreased in 13 patients, and CC alone decreased in 12 patients, with a similar distribution of type I and type II diabetic patients in each group. Of the 28 patients who showed an increase in albuminuria, AER increased at an annual rate of 30-40%, resulting in a 4- to 8-fold increase in AER to > 20 micrograms/min during the study. Of the 25 patients who showed a decrease in renal function, CC decreased at an annual rate of 4-5 ml/min, resulting in an approximate halving of CC to < 90 ml/min during the study. The rate of fall in CC was not related to the presence or absence of concomitant increases in albuminuria. However, a significant preponderance of women in the group showed a decline in CC alone. The decline in CC was associated with an increase in plasma creatinine as well as a progressive decrease in urinary creatinine excretion, but the underlying mechanisms remain unexplained. These data support the concept that a subgroup of diabetic patients may show a decline in renal function in the absence of significant increases in AER.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

The antiatherosclerotic effect of the calcium antagonists and their implications in hypertension.

Calcium-dependent processes involved in atherosclerotic lesion formation include platelet aggregation, monocyte adhesion, release of growth factors, cell proliferation and migration, protein and collagen secretion and synthesis, and endothelial necrosis. In addition, the calcium (Ca2+) component of smooth muscle cell contraction contributes to one of the main risk factors, hypertension. The ability of the calcium channel blockers (CCBs) to interrupt the sequence of events that culminates in the formation of atherosclerotic lesions has been demonstrated in animal models and clinical trials. These studies have involved the short-acting CCBs. The results of this animal study show that manidipine, a new long-acting CCB, produces a dose-dependent reduction in atherosclerotic lesion formation without reducing plasma cholesterol.

Animals↗
PubMed1993

Long-term glycemic control and the rate of progression of early diabetic kidney disease.

In this prospective study of 11.9 years duration (range 9 to 14), we examined the progression of albuminuria prior to and after the onset of microalbuminuria [albumin excretion rate (AER): 20 to 200 micrograms/minute]. Glycated hemoglobin (HbA1), AER and blood pressure were measured every six months. Twenty-two (13 type I, 9 type II) patients were identified in whom AER increased progressively (progressors). These patients were compared with 22 others matched for age, duration and type of diabetes in whom AER did not change significantly during the study period (non-progressors). In the progressors, the rate of increase in AER correlated with mean HbA1 for the study period in patients with type I (r = 0.68, P < 0.01) and type II diabetes (r = 0.71, P < 0.05). Furthermore, AER began increasing well before the conventional 20 micrograms/minute threshold of microalbuminuria had been reached and within the first five years of diagnosis of type I diabetes. We conclude that in predisposed diabetic patients, long-term glycemic control is correlated with the rate of development of early renal abnormalities. Repeated measurements of AER from the time of diagnosis may be useful in the early detection of patients who will develop microalbuminuria and ultimately overt diabetic nephropathy.

Adolescent↗
PubMed1993

The effects of dietary cholesterol on experimental diabetic nephropathy.

Hyperlipidaemia has been previously shown to accelerate various models of renal disease. The present study has evaluated the effects of dietary cholesterol supplementation on functional and structural aspects of experimental diabetic nephropathy. Control and streptozotocin diabetic male Sprague Dawley rats were randomized to receive a normal diet or a high cholesterol (4% cholesterol + 1% cholic acid) diet. After 32 weeks, serum lipids, glycaemic control, urinary albumin excretion and glomerular ultrastructural parameters were evaluated in the 4 groups. Diabetes was associated with increased total cholesterol and triglyceride levels. Cholesterol supplementation increased total and decreased HDL-cholesterol in control and diabetic rats. Diabetes increased albuminuria but cholesterol supplementation did not influence urinary albumin excretion. In diabetic rats, glomerular basement membrane thickness and glomerular volume were increased but cholesterol supplementation did not influence any glomerular ultrastructural parameter. In control rats, increased dietary cholesterol intake led to an increase in blood pressure and glomerular volume. In contrast to other models of renal disease, experimental diabetic nephropathy does not appear to be exacerbated by dietary cholesterol supplementation.

Albuminuria↗
PubMed1990

Nifedipine and experimental cardioprotection.

Experimental studies using animal models designed to mimic the effect of ischemia and postischemic reperfusion have provided data indicating that the calcium antagonists might be cardioprotective. The laboratory studies have indicated consistently, however, that the timing of such drug administration is of critical importance. In the case of nifedipine (a dihydropyridine-based calcium antagonist), the laboratory studies have shown that when used prophylactically it has a protective effect during short (as in the "stunned heart") and long episodes (greater than 30 minutes) of ischemia. This protection has been quantitated in a variety of ways, including preservation of left ventricular function. A complete understanding of whether and how calcium antagonists can be used to protect the myocardium requires further detailed knowledge of not only of the voltage-activated calcium channel and its binding sites, but also of the sequence of events triggered by ischemia and reperfusion. Recent data from our laboratories indicate that cardiac membranes contain specific binding sites for the novel, endothelial-derived vasoconstrictor peptide, ET, and that the density of these sites increases during ischemia. ET promotes Ca2+ influx through the voltage-sensitive channels by a mechanism that does not involve a direct interaction with the dihydropyridine (DHP)-sensitive binding sites. Nevertheless, the ET-induced Ca2+ influx is attenuated by the dihydropyridine-based calcium channel blockers.

Animals↗
PubMed1990

Hyperlipidaemia increases albuminuria in hypertensive and normotensive rats.

1. The effects of a high cholesterol diet on urinary albumin excretion were examined in spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats over 36 weeks. 2. Cholesterol feeding resulted in an increase in total-cholesterol and a decrease in HDL-cholesterol without influencing triglyceride levels in both strains. 3. Urinary albumin excretion was significantly elevated in cholesterol-fed SHR and WKY rats. 4. These results suggest that hyperlipidaemia may be important in acceleration of experimental nephropathy.

Albuminuria↗
PubMed1990

Effect of acidosis and alkalosis on postischemic Ca gain in isolated rat heart.

The effect of pH of the reperfusion buffer on postischemic changes in tissue Ca and Na was examined in isolated Langendorff-perfused Sprague-Dawley rat hearts. Reperfusion began after 15-, 25-, or 60-min ischemia at 37 degrees C. After 60-min ischemia, reperfusion at pH 6.4 or 6.6 attenuated the reperfusion-induced Ca gain so long as the acidotic conditions were maintained (3.08 +/- 0.22, 1.37 +/- 0.41, and 16.96 +/- 1.18 mumol Ca gain/g dry wt for pH 6.4, 6.6, and 7.4, respectively after 15-min reperfusion). Conversely, reperfusion under alkalotic conditions (pH 7.9) after 60-min ischemia exacerbated the gain (27.45 +/- 4.75 and 8.92 +/- 1.53 mumol Ca gain/g dry wt during 5-min reperfusion at pH 7.9 and 7.4, respectively). Similar, but less pronounced Ca gains occurred during reperfusion after 15- or 25-min ischemia. Sodium content during reperfusion, but not during aerobic perfusion, was also found to be pH sensitive with acidosis causing a reduction and alkalosis an increase. These results could not be explained in terms of an effect of pH on recovery of high-energy phosphates, percentage "reflow" during reperfusion, or reperfusion-induced increases in tissue water or resting tension. The results are in agreement with the hypothesis that the "inhibitory" effect of acidosis on postischemic Ca overload could involve an effect of pH on the Na(+)-H+ exchanger and intracellular Ca storage.

Acidosis↗
PubMed1989

Cyclosporine increases endothelin-1 binding site density in cardiac cell membranes.

When used in high concentrations, the immunosuppressive agent cyclosporine A has toxic side effects, including cardiac fibrosis and calcification. Cyclosporine-treated mice were used to investigate whether a cyclosporine dose regime which produces cardiac fibrosis and calcification alters the density of the specific binding sites for the endothelial-derived vasoconstrictor polypeptide, endothelin-1. After twenty-one days of treatment the endothelin-1 binding site density in cardiac cell membranes was increased, without any change in selectivity. This increase in endothelin-1 binding site density could contribute to the cytotoxic effects of cyclosporine.

Animals↗
PubMed1989

Reperfusion-induced calcium gain after ischemia.

Reperfusion-induced calcium gain provides a marker of irreversible injury, but whether the cells gain calcium because of irreversible injury caused by the ischemic episode, or whether it is the reperfusion-induced calcium gain that triggers the irreversible injury has yet to be established. Using isolated rat hearts made ischemic for either 30 or 60 minutes, and reperfusing with Krebs-Henseleit buffer or Krebs-Henseleit buffer containing either 2,3-butanedione monoxime (to inhibit contractile activity) or 2,4-dinitrophenol or nitrogen-gassed substrate-free Krebs-Henseleit buffer (to inhibit oxidative phosphorylation), the effect of reperfusion was monitored in terms of calcium gain and ultrastructural changes including loss of sarcolemmal integrity. The results establish that the routes of calcium entry during postischemic reperfusion are complex. The calcium gain can occur in the absence of mitochondrial oxidative phosphorylation and is modulated by interventions introduced at the moment of reperfusion which affect the contractile state. There are at least 2 routes of calcium entry: contraction-dependent and contraction independent. The former is probably associated with the development of sarcolemmal discontinuities. The results also establish that when sarcolemmal integrity has been destroyed, the cells can gain excess calcium under conditions that prevent mitochondrial calcium uptake. Accordingly, the mitochondria cannot be the only intracellular organelles that accumulate calcium under these conditions. Additional studies are needed to identify the other sites of calcium binding under conditions of adenosine triphosphate deprivation.

2,4-Dinitrophenol↗
PubMed1989

Streptozotocin-induced diabetes reduces the density of [125I]-endothelin-binding sites in rat cardiac membranes.

The effect of acute, streptozotocin-induced diabetes on the affinity (KD), density (Bmax) and selectivity of specific, high affinity binding sites for [125I]-endothelin [( 125I]-ET) in rat cardiac membrane fragments was determined. Three days after a single i.v. bolus dose of streptozotocin (60 mg kg-1), the density of [125I]ET binding sites was reduced (P less than 0.01) without changes in affinity or selectivity.

Animals↗
PubMed1988

Calcium-mediated damage during post-ischaemic reperfusion.

Ca2+ gain during reperfusion after an ischaemic episode may be of primary importance in the development of cell death and tissue necrosis. These studies were undertaken to examine the possibility of modifying Ca2+ gain by introducing interventions only upon reperfusion. Electron microscopy did not reveal the presence of holes in the sarcolemma prior to reperfusion, indicating that Ca2+ entry at the moment of reperfusion is not through rents in the sarcolemma. Reperfusion with acidotic buffer (pH 6.4 or 6.6) after 60 min ischaemia attenuated Ca2+ gain. However, this attenuation persisted only as long as the acidotic conditions were maintained. Conversely, reperfusion under alkalotic conditions (pH 7.9) exacerbated Ca2+ gain. Reperfusion with hypoxic buffer after 60 min ischaemia did not alter Ca2+ gain, but readmission of oxygen after a period of hypoxic post-ischaemic reperfusion triggered a further gain in Ca2+. Addition of 5 microM nifedipine to the reperfusion medium slowed Ca2+ gain, while 1 microM Bay K 8644, a calcium agonist, enhanced the gain at early times of reperfusion. Addition of 20 microM W-7, a calmodulin antagonist, to the reperfusion medium had no effect on post-ischaemic Ca2+ gain. Therefore, we have shown that it is possible to alter post-ischaemic Ca2+ gain by introducing interventions only upon reperfusion. However, Ca2+ gain could only be delayed, rather than prevented and ultimately no long-term protection was achieved. These results indicate that post-ischaemic Ca2+ gain is highly pH-sensitive and that entry of Ca2+ through voltage-activated slow channels may contribute to the early gain.

Animals↗
PubMed1987

Fundamental mechanisms of action of calcium antagonists in myocardial ischemia.

The mammalian myocardium exhibits a spectrum of damage during an ischemic episode. After relatively short periods of ischemia the damage is reversible, but with longer periods of ischemia the number of cells that are lethally injured increases. When coronary flow is restored the lethally injured cells become overloaded with Ca++ and fail to regenerate adenosine triphosphate. The calcium antagonists provide protection under these circumstances, but only if used prophylactically. When added only upon reperfusion the calcium antagonists slow, but do not inhibit, the excessive gain in Ca++ that occurs during postischemic reperfusion. Nicotine, in a concentration equivalent to that found in the plasma of smokers (0.15 microgram/ml), exacerbates the reperfusion-induced Ca++ gain. Treatment with the long-acting calcium antagonist, anipamil, on a once-daily basis attenuates the reperfusion-induced Ca++ gain in spontaneously hypertensive rats and its exacerbation by nicotine in Sprague Dawley rats. The prolonged oral administration of at least 1 calcium antagonist, verapamil (50 mg/kg body weight/day), causes a significant (p less than 0.001) depletion of left ventricular norepinephrine.

Animals↗
PubMed1987

Nicotine-induced calcium overload during postischemic reperfusion.

The excessive gain in Ca2+ that occurs when hearts are reperfused after prolonged periods of ischemia contributes to cell death and tissue necrosis. The following experiments were undertaken to determine whether nicotine, in a concentration equivalent to the peak concentration present in plasma after cigarette smoke inhalation, alters reperfusion-induced Ca2+ gain in isolated rat hearts. Nicotine (0.15 microgram/ml) failed to increase tissue Ca2+ during aerobic perfusion but increased Ca2+ gain during reperfusion after 30 (p less than 0.02) or 60 (p less than 0.02) min of normothermic ischemia. The increase of Ca2+ gain was independent of a nicotine-induced release of norepinephrine (NE) or an altered "reflow area", heart rate, force of contraction, or end-diastolic resting tension. Pretreatment for 3 days with anipamil (20 mg/kg), a long-acting calcium channel blocker, attenuated the reperfusion-induced Ca2+ gain after 30 min of global ischemia, and reduced (p less than 0.001) the nicotine-induced exacerbation of that gain, without altering tissue ATP or creatine phosphate (CP). Verapamil (1 X 10(-6) M) reduced (p less than 0.02) the nicotine-induced exacerbation of Ca2+ gain caused by reperfusion after 30 min of ischemia.

Adenosine Triphosphate↗