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Biomedical subjects

L Benzi

Publications and source records attributed to L Benzi.

At least 37 records · Page 2Linked to original sources
PubMed1997

Inhibition of endosomal acidification in normal cells mimics the derangements of cellular insulin and insulin-receptor metabolism observed in non-insulin-dependent diabetes mellitus.

Dissociation of the insulin-insulin receptor complex plays a crucial role in the processing of both insulin and the insulin receptor, and the acidification of endocytic vesicles may be the mechanism by which internalized insulin is dissociated from its receptor and properly sorted and processed. Internalized insulin-insulin receptor complexes are abnormally processed in cells from patients with non-insulin-dependent diabetes mellitus (NIDDM). Accordingly, to further investigate the mechanisms of the derangements observed in NIDDM cells, we examined the effects of the ionophore monensin, which inhibits endosomal acidification, on the cellular processing of insulin and insulin receptor in monocytes from control subjects (n = 12) and NIDDM patients (n = 14). This study confirms that monocytes from NIDDM patients, compared with cells from normal controls, had reduced binding (P < .01), internalization (P < .01), and degradation (P < .01) of insulin. In addition, the release of intracellular radioactivity was slower (P < .01), and recycling of the insulin receptor was inhibited (P < .01). Moreover, these defects were associated with a significant (P < .01) decrease of dissociation of the internalized insulin-insulin receptor complex. In cells from normal controls, incubation with monensin decreased insulin binding (P < .01), but not insulin internalization. High-performance liquid chromatography (HPLC) analysis of intracellular radioactivity showed that after monensin intracellular intact insulin significantly increased (P < .01), thus suggesting a decrease of intracellular insulin degradation. Moreover, insulin receptor recycling was completely disrupted. All of these derangements were associated with a significant decrease (P < .01) of dissociation of insulin-insulin receptor complexes. On the contrary, in diabetic monocytes, monensin had no significant additional effect on NIDDM-linked alterations. Comparison of the results obtained in cells from NIDDM patients to those found in monensin-treated normal cells demonstrates that NIDDM and monensin gave rise to a superimposable impairment of dissociation of the intracellular insulin-insulin receptor complex, associated with similar abnormal sorting and processing of insulin and its receptor. The only defect present in NIDDM cells but not in monensin-treated cells is the decrease of insulin internalization, which thus seems independent of the action of monensin on the processing of internalized insulin-insulin receptor complex. These results suggest that the impairment of dissociation of the insulin-insulin receptor complex may play a crucial role in the subsequent altered processing of insulin and insulin receptor. Moreover, they raise the question as to a possible similar alteration of the same intracellular mechanism by NIDDM and monensin, and point out that the derangements found in cells from NIDDM patients could be localized within the endosomal apparatus and consist mainly of a defective acidification of its interior.

Chromatography, High Pressure Liquid↗
PubMed1997

Screening of gestational diabetes in Tuscany: results in 2000 cases.

According to the guidelines of the "Third international workshop conference on GDM", we have examined 2000 pregnant women. The glucose challenge test (GCT) was positive in 408 cases (20.4%) and negative in 1592 (79.6%). The OGTT (Carpenter and Coustan's criteria) was performed in 647 pregnant women. GDM and IGGT prevalence was of 6.25% and 5.5% respectively and normal glucose tolerance (NGT) 88.25%. The GCT effectiveness for GDM and IGGT diagnosis is: sensibility 75.1%, specificity 44%, positive predictive value 46.4% and negative predictive value 74%. GDM and IGGT compared with NGT women were significantly older (p < 0.05) and prepregnancy BMI was higher (p < 0.01); the prevalence of previous macrosomia (p < 0.01), previous gestational diabetes (p < 0.01) and family history for diabetes mellitus (p < 0.05) was greater in GDM and IGCT. The prevalence of preterm delivery was higher in both GDM and IGCT (GDM 12.5% and IGGT 15.4% vs NGT 6%; p < 0.01), as well as the prevalence of cesarean sections (GDM 31.6% vs IGGT 23.5% and NGT 20.3%; p < 0.02), and the occurrence of macrosomia (GDM 27.6%, IGGT 16.6% and NGT 16.2%). In addition a higher prevalence (p < 0.01) of hyperbilirubinaemia, hypoglycemia and hypertrophy cardiomyopathy was observed in newborns from GDM women. Our data show that: GCT has a good specificity for GDM diagnosis, prevalence of GDM in our population is about 6%, GDM is still correlated to an elevated maternal and neonatal morbility.

Adult↗
PubMed1997

Gestational diabetes: clinical characteristics and birth weight.

This retrospective study investigates the clinical characteristics of gestational diabetes mellitus (GDM) (time of diagnosis, different treatment, metabolic parameters, etc.) in relation to prepregnancy body mass index (BMI) and the influence of BMI on neonatal outcome. 93 GDM women and 110 control subjects were divided into three groups in relation to their prepregnancy BMI: normalweight (Nw), overweight (Ow) and obese (Ob). GDM was diagnosed significantly (p < 0.01) earlier in Ow and Ob than in Nw. Preterm deliveries and cesarean sections resulted significantly (p < 0.01) increased in all BMI categories of GDM respect to matched controls. Prevalence of neonatal macrosomia was higher in GDM patients (44.6%) compared with normal controls (15.4%) and correlated (p < 0.01) with prepregnancy BMI in both groups. Nevertheless in each BMI category the prevalence of macrosomia was significantly higher in GDM patients. The body weight increase during pregnancy was not associated with neonatal macrosomia. This study shows that prepregnancy BMI is an important risk factor for GDM and is predictive for macrosomia specially in women suffering from GDM.

Adult↗
PubMed1996

Neonatal outcome and obstetric complications in women with gestational diabetes: effects of maternal body mass index.

OBJECTIVE: To evaluate in a selected population the clinical characteristics (time of diagnosis, different treatment, metabolic parameters, etc.) of gestational diabetes in relation to prepregnancy body mass index (BMI) and the influence of BMI on neonatal outcome. DESIGN: This study was retrospectively led using a computerized data system for all deliveries that occurred at the Departments of Obstetrics and Gynecology of the University of Pisa (Italy) from 1 January 1987 to 31 December 1992. SUBJECTS: 93 women with GDM and 110 control subjects divided into three groups according to their pre-pregnancy BMI: normal weight (Nw), overweight (Ow) and obese (Ob). MEASUREMENTS: Time of diagnosis, mode of treatment and metabolic control of GDM; time and mode of delivery, neonatal outcome (macrosomia, respiratory distress syndrome, hyperbilirubinemia, hypoglycemia, polycythemia, hypocalcemia). RESULTS: GDM was diagnosed earlier in Ow and Ob than in Nw (p < 0.01) and insulin treatment was used in 86% of Ob-GDM, 91% of Ow-GDM and in 77% of Nw-GDM women (p < 0.001). Preterm deliveries and cesarean sections resulted significantly increased in all BMI categories of GDM patients with respect to matched normal controls. Prevalence of neonatal macrosomia was higher in GDM patients (44.6%) compared with normal controls (15.4%) and correlated (p > 0.01) with prepregnancy BMI in both groups. The body weight increase during pregnancy was not associated with neonatal macrosomia. CONCLUSIONS: The degree of overweight is associated with an earlier diagnosis of GDM; prepregnancy BMI is more predictive of macrosomia than weight gain, both in control and GDM women; GDM seems to play the most important role in increasing the possibility of the occurrence of macrosomia.

Body Mass Index↗
PubMed1996

Effects of tryptophan load on amino acid metabolism in type 1 diabetic patients.

Tolerance to an oral tryptophan load (50 mg/kg body weight) was evaluated in a group of 15 insulin-dependent diabetic patients of both sexes in poor metabolic control. Tryptophan was measured fluorometrically, and the plasma levels of the other physiological amino acids were determined by HPLC. The ratio of the plasma concentration of each large neutral amino acid (LNAA) to the sum of the others was calculated to serve as an index for the competitive transport of these amino acids into the brain. The results show that post-loading plasma tryptophan levels in diabetic patients increased less than in healthy controls, suggesting enhanced liver catabolism of this amino acid (as reported for diabetic animals). Small changes were observed in the post-loading plasma concentrations of other amino acids. Therefore, the increment in the tryptophan/LNAA ratio in controls (basal, 0.12 +/- 0.01; 120 min after the load, 0.89 +/- 0.04; 240 min, 0.51 +/- 0.03) was greatly attenuated in diabetic patients (basal, 0.11 +/- 0.01, NS; 120 min, 0.46 +/- 0.04, p < 0.01; 240 min, 0.31 +/- 0.04, p < 0.01). Post-loading excursions in some other ratios were slightly larger in control than diabetic subjects. These differences, which may occur to a lesser extent after a protein-rich meal, could modify the availability of precursor amino acids to the brain for synthesis of neurotransmitters. Thus, as happens in certain animal species, an impairment of the post-absorptive accumulation of tryptophan and serotonin in the brain may occur in diabetic patients as a result of altered metabolic disposal of tryptophan.

Adult↗
PubMed1994

A prevalence study of known diabetes mellitus in Tuscany assessed from pharmaceutical prescriptions and other independent sources.

This study evaluates the prevalence of diabetes mellitus (DM) in Pisa (Tuscany, Italy) using four independent data sources. The main source, represented by computerized prescriptions for anti-diabetic agents collected over a 4-month period, was validated using three secondary sources: (a) the list of diabetic patients who receive material of self-care from the National Health Service; (b) the clinical records of diabetic patients obtained from a random sample of family doctors; (c) the clinical records of diabetic patients attending our outpatient clinic. The main source provided 3806 patients, and 697 patients were added from the secondary sources, thus identifying a total number of 4503. The prevalence of known DM in the "Pisa area" exclusively reckoned by the main source, was 2.01%, and the prevalence corrected by the addition of the various sources resulted in 2.4%. The capture-recapture method showed a completeness of ascertainment of the survey of 90.1%, and thus an estimated prevalence of known diabetes of 2.64%. Of these, 141 patients had insulin-dependent diabetes mellitus (IDDM) corresponding to 3.2% of identified diabetic subjects (prevalence 0.07% inhabitants); 4362 patients had non-insulin-dependent diabetes mellitus (NIDDM), 96.8% of identified diabetic subjects (prevalence 2.36%). Of patients with NIDDM 10.5% was treated by diet, 65% with oral hypoglycaemic agents (OHA), 23% with insulin and 1.5% with insulin plus OHA. This study shows that the method used in this survey is suitable for epidemiological studies because it does not demand the cooperation of the diabetic patients, is addressed to the entire diabetic population without age discrimination and singles out the diabetic population in a very reliable way.

Adult↗
PubMed1994

Insulin degradation in vitro and in vivo: a comparative study in men. Evidence that immunoprecipitable, partially rebindable degradation products are released from cells and circulate in blood.

The products of insulin metabolism generated in vitro and in vivo were compared in this study. Monocytes from 10 control subjects were incubated with 125IA14-labeled insulin, acid washed, and solubilized or reincubated in insulin-free binding buffer to study both intracellular radioactivity or radioactivity released from cells to medium. To evaluate in vivo insulin metabolism, labeled insulin (100-120 microCi) was injected as a single intravenous bolus in 5 of the 10 subjects. Cellular and plasma radioactivity was characterized by high-performance liquid chromatography (HPLC). The results of the study show the following: 1) Products with superimposable HPLC elution profiles are found within cells and in medium. Two new labeled products are observed in the latter, suggesting that a membrane degradation process exists in monocytes. 2) Intermediates found within monocytes, in medium from monocytes, and in plasma have identical elution profiles, supporting the possibility that insulin is metabolized in various cells by a common pathway. 3) Insulin metabolism produces intermediates that bind well to anti-insulin antibody. The presence in plasma of these products induces a significant difference in the value of the metabolic clearance rate of insulin when HPLC or immunoprecipitation is used to detect intact insulin. 4) Immunoprecipitable products maintain, in part, the capacity to bind to insulin receptors and to be internalized into monocytes.

Chromatography, High Pressure Liquid↗
PubMed1992

Change in glucose metabolism after long-term treatment with deflazacort and betamethasone.

We have compared the long-term effects of different corticosteroids on glucose metabolism by carrying out a 75 g oral glucose tolerance test in 27 subjects before and after the administration of deflazacort or betamethasone for two months in random balanced sequence. Fasting plasma glucose and insulin concentrations were significantly higher after betamethasone, whereas deflazacort increased only fasting plasma insulin. After oral glucose there were significant increases in blood glucose and insulin after betamethasone compared with deflazacort. These results suggest that the degree of glucose intolerance and insulin resistance depends on the steroid used and on the dose given, although long-term treatment with deflazacort has a smaller effect on glucose metabolism than betamethasone.

Administration, Oral↗
PubMed1990

Insulin degradation in vivo: a high-performance liquid chromatographic analysis.

The metabolism of insulin in vivo was investigated using an isocratic reversed-phase high-performance liquid chromatographic (RP-HPLC) method. After intravenous injection of A14-[125I]insulin into normals, eight labelled insulin derivatives were found in plasma (peaks 1-8). Two of them (peaks 1 and 7) showed an elution pattern identical with those of reference [125I]monoiodotyrosine and intact A14-[125I]insulin, respectively. Of the other six peaks, five (2-6) eluted before and one (peak 8) after insulin. This pattern was highly reproducible in terms of capacity factors and peak heights. Radioactivity separated by RP-HPLC was further characterized for its trichloroacetic acid precipitability and immunoprecipitability. Fractions corresponding to peaks 4-6 and 8, which showed an immunoprecipitability higher than 50%, were pooled in order to obtain sufficient radioactivity and were found to be insulin separated by Sephadex G-50 chromatography, containing in its structure, after sulphitolysis, intact A-chain and to be partially rebindable to monocyte insulin receptors. These data demonstrate that in blood, products of insulin metabolism circulate which retain a part of the immunological and biological properties of the hormone. These products are clearly separated from one another and from intact insulin by RP-HPLC, suggesting that the appropriate use of this technique may allow a further and more accurate qualitative and quantitative characterization of in vivo insulin metabolism in physiological and pathological conditions.

Chromatography, High Pressure Liquid↗
PubMed1990

Ibopamine does not affect insulin resistance in patients with type I diabetes.

Diabetes mellitus was assessed by investigating 8 type I diabetic patients, in good metabolic control and with congestive heart failure, who were studied after 3 weeks of placebo and ibopamine (100 mg t.i.d.) treatment. Metabolic control and daily insulin dose did not change in any patient during the study. The insulin-mediated glucose uptake during the clamp studies showed no variation after placebo or ibopamine therapy. Total cholesterol, HDL-cholesterol and triglycerides concentrations remained unchanged. This study clearly suggests that ibopamine administered at a daily dose of 300 mg for 3 weeks presents a metabolic safety in type I diabetic patients.

Adult↗
PubMed1990

Improvement with metformin in insulin internalization and processing in monocytes from NIDDM patients.

This study investigated the relative effect of obesity alone and in combination with non-insulin-dependent diabetes mellitus (NIDDM) on the intracellular processing of insulin and evaluated the effect of metformin therapy on this process. Monocytes from 11 obese hyperinsulinemic subjects, 13 obese hyperinsulinemic NIDDM patients, and 7 nondiabetic control subjects were incubated with A14-125I-labeled insulin for 60 min at 37 degrees C, and intracellular insulin degradation was characterized by high-performance liquid chromatography. Total cell-associated insulin (insulin binding) and internalized and degraded insulin were decreased in obese subjects and significantly decreased in obese NIDDM patients compared with nondiabetic control subjects. In NIDDM patients, intracellular insulin degradation was inversely correlated with fasting plasma glucose (P less than 0.01). Eight obese subjects and 9 obese NIDDM patients were restudied after 4 wk of therapy with metformin (850 mg twice a day). Plasma levels of the drug were superimposable in the two groups. Metformin therapy did not change glucose and insulin levels in obese subjects but caused a decrease in blood glucose in obese NIDDM patients. Total cell-associated radioactivity (insulin binding) significantly increased in both groups (P less than 0.01). On the contrary, internalized radioactivity increased (0.83 +/- 0.3 vs. 1.31 +/- 0.35%, P less than 0.01), and similarly, insulin degradation was enhanced (54.6 +/- 8.9 vs. 74.22 +/- 9.15%, P less than 0.01) only in monocytes from obese NIDDM patients. However, the levels of these parameters were still lower than in control subjects (internalization, 2.94 +/- 0.68%; degradation, 93.03 +/- 3.7%).(ABSTRACT TRUNCATED AT 250 WORDS)

Biological Transport↗
PubMed1990

Diurnal pattern of plasma metformin concentrations and its relation to metabolic effects in type 2 (non-insulin-dependent) diabetic patients.

The authors describe the diurnal profile of plasma metformin concentrations in a group of 6 Type 2 (noninsulin-dependent) diabetic patients studied at two different daily metformin doses (500 mg and 850 mg b.d.) and report data on the relationships between plasma metformin and metabolic effects over a 14 h period. In addition, the effect of circulating metformin on insulin binding to isolated monocytes has been evaluated. At the two different daily doses fasting plasma metformin concentrations were similar (3.23 +/- 0.35 mumol/l and 3.86 +/- 0.72 mumol/l, mean values +/- SEM, at low and high dose respectively). Drug peak values and averaged concentrations (4.66 +/- 0.39 mumol/l vs 6.35 +/- 0.69 mumol/l) were significantly higher when more drug was administered. Mean plasma glucose was lower when 1,700 mg/day instead of 1,000 mg/day of metformin was given (7.3 +/- 0.4 mmol/l vs 9.1 +/- 0.9 mmol/l, p less than 0.05). After dosing, at higher plasma metformin concentrations corresponded lower plasma glucose values. The averaged blood lactate levels resulted 1.46 +/- 0.4 mmol/l (p less than 0.05 vs matched diet treated diabetic patients) at the higher drug dose. A significant positive correlation emerged between mean plasma metformin concentrations and mean blood lactate levels (r: 0.76, p less than 0.02). Alanine, glycerol and B-OH-butyrate levels were similar at the two metformin daily doses, and were not correlated to plasma metformin. The binding of insulin to isolated human monocytes was similar in metformin-treated diabetic patients (4.48 +/- 0.45) as in healthy volunteers (4.62 +/- 0.34); insulin binding was correlated (p less than 0.05) with plasma metformin levels.

Alanine↗
PubMed1989

Decreased salivary glucose secretory rate: usefulness for detection of diabetic patients with autonomic neuropathy.

In this study we investigated whether the presence of diabetic autonomic neuropathy (DAN) leads to an altered composition of saliva. DAN was evaluated in 33 normal subjects and 31 diabetic patients by means of the Valsalva manoeuvre, R-R variation during deep breathing, heart rate response to standing and lying down and blood pressure response to standing. Salivary flow (ml/h), salivary glucose levels (mumol/l) and salivary glucose secretory rate (mumol/h) were measured in each subject. Twelve diabetic patients were positive for DAN. Salivary flow (13 +/- 2 ml/h) and glucose concentration (330 +/- 50 mumol/l) were not significantly lower in patients with DAN than in normal subjects (18 +/- 2 ml/h, 500 +/- 50 mumol/l) and diabetic patients without DAN (16 +/- 1.9 ml/h, 500 +/- 40 mumol/l). The salivary glucose secretion rate was significantly lower (P less than 0.02) in diabetic patients with DAN (4.2 +/- 1.0 mumol/h) than in normal subjects and diabetic patients without DAN (9.0 +/- 1.0 mumol/h and 8.0 +/- 0.9 mumol/h respectively). The test had a good sensitivity and specificity, and appeared to be particularly indicated in discriminating patients without DAN. It is suggested that the measurement of salivary glucose may represent a simple, quick and inexpensive method for the screening of diabetic autonomic neuropathy.

Adult↗
PubMed1989

Defects in insulin-receptor internalization and processing in monocytes of obese subjects and obese NIDDM patients.

We investigated intracellular processing of the insulin-receptor complex in monocytes from 12 healthy control subjects, 11 obese nondiabetic subjects, and 13 obese patients with non-insulin-dependent diabetes mellitus (NIDDM) by measuring receptor internalization, recovery of cell-surface insulin binding after receptor internalization, and the release of intracellular intact insulin (insulin retroendocytosis). When monocytes from the three groups of subjects were exposed to 100 nM unlabeled insulin for 30 min at 37 degrees C, the subsequent cell-surface 125I-labeled insulin binding was reduced, but the total number of insulin receptors, measured by radioimmunoassay, was not changed. These findings indicate a redistribution of insulin receptors from the surface to the cell interior. Insulin-receptor internalization was significantly lower in monocytes of obese NIDDM patients (mean +/- SE 17.8 +/- 4.7%) than in obese subjects and healthy control subjects (33.5 +/- 4.5%, P less than .05, and 34.4 +/- 3.7%, P less than .02, respectively). Moreover, in downregulated cells, a complete recovery of the initial insulin binding was observed in control subjects but not in obese NIDDM patients or obese nondiabetic subjects. The release of internalized insulin was also reduced in obese NIDDM patients and obese subjects (t 1/2 = 49.0 +/- 2.4 min, P less than .02; 47.4 +/- 5.7 min, P less than .05; and 32.9 +/- 3.8 in NIDDM patients, obese subjects, and control subjects, respectively). In the radioactivity released from monocytes of obese subjects and obese NIDDM patients, the percentage of intact insulin was higher (P less than .05) than in control subjects, suggesting reduced intracellular insulin degradation in obese subjects and obese NIDDM patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Diabetes Mellitus↗
PubMed1989

Effects of metformin therapy on plasma amino acid pattern in patients with maturity-onset diabetes.

Plasma amino acid concentrations and metformin levels were measured by high-performance liquid chromatography in a group of diabetic patients on therapy with the biguanide drug. Diabetic patients treated with metformin showed higher concentrations of plasma glutamate, asparagine, alanine, methionine and tryptophan, and lower levels of ornithine in comparison with normal subjects, and higher levels of alanine when compared to diet-treated diabetic patients. No correlation emerged between amino acid concentrations and metformin dose or plasma concentration. It is concluded that besides the various metabolic abnormalities that are known to occur during metformin treatment, patients on therapy with metformin also show multiple changes of plasma amino acid pattern.

Aged↗
PubMed1988

Insulin degradation into monocytes from normal subjects: a high performance liquid chromatographic analysis.

In this work the fate of A14-125 I-insulin inside human cells has been investigated by the complementary use of gel permeation and reversed-phase high performance liquid chromatography to obtain a better resolution of the cell processed radioactive material resulting from the internalization of labeled insulin. Mononuclear leukocytes from 12 normals were incubated with pure A14-125 I insulin at 37 C and internalized radioactivity was characterized after 2, 15 and 60 min. Nearly 14% of intracellular radioactivity was associated to materials with a molecular weight of approximately 300,000. The remaining 86% had a molecular weight lower than 20,000. High molecular weight material showed an elution profile very similar to that obtained from purified human placental insulin receptor and was partially precipitable with antireceptor antibody. The reversed phase high performance liquid chromatography analysis of the low molecular weight material showed two main peaks corresponding to 125 I and A14-125 I-insulin and three intermediate peaks, a, b, c, accounting for about 8% of the recovered radioactivity. By increasing the incubation time of A14-125 I-insulin with monocytes a decrease of insulin peak (2 min: 38 +/- 18%; 15 min: 25 +/- 11%; 60 min: 6 +/- 4%) and a corresponding increase of iodide peak was observed. Immunoprecipitability with anti-insulin antibody was 0% for iodide and a peaks, 60% for peak b, 78% for peak c and 90% for A14-insulin peak. Our results show that intracellular insulin degradation procedes rapidly and in a time-dependent manner and that this process produces insulin derivatives which partially retain the immunological properties of intact A14-125 I insulin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Plasma biguanide levels are correlated with metabolic effects in diabetic patients.

Metabolic abnormalities occur in biguanide-treated diabetic patients. We investigated the relationship between plasma metformin and phenformin concentrations and metabolic effects. Drug levels were measured in 37 type II diabetic patients by HPLC. The method was sensitive, specific, and linear over a wide range of drug concentrations. Metformin and phenformin values ranged from 236 to 718 ng/ml and from 28 to 114 ng/ml, respectively. The plasma metformin level was correlated with triglycerides (r = -0.55; P less than 0.05) but not with drug dosage, plasma glucose, HbA1, creatinine, creatinine clearance, lactate, pyruvate, lipid, and clinical parameters. Plasma phenformin concentrations correlated with lactate (r = 0.49; P less than 0.05) and HbA1 (r = 0.50; P less than 0.05) but not with drug dosage, parameters of diabetes control, creatinine, creatinine clearance, pyruvate, and clinical parameters. The clinical usefulness of this HPLC method, the evidence that the increase of lactate is related to the circulating phenformin levels, and the demonstration that the metformin effect on triglyceride metabolism is correlated to plasma drug levels are the positive findings of this work.

Aged↗